Search

Abstract Liquid-water management in polymer-electrolyte fuel cells (PEFCs) remains an area of ongoing research. To enhance water removal, certain flow-fields induce cross-flow, or flow through the gas-diffusion layer (GDL) via channel-to-channel pressure differences. While beneficial to water removal, cross-flow comes at the cost of higher pumping pressures and may lead to membrane dehydration and other deleterious issues. This paper examines the impact of cross-flow on component saturation levels as determined through in-plane high-resolution neutron radiography. Various humidities and operating conditions are examined, and the results demonstrate that cell saturation levels correlate strongly with the level of cross-flow rate, and lower GDL saturation levels are found to correlate with an increase in permeability at higher flow rates. Effective water removal is found to occur at channel-to-channel pressure gradients greater than the measured breakthrough pressure of the GDL, evidence that similar liquid-water transport mechanisms exist for under-land area transport as in transverse GDL flow.

Meta-analysis of diagnostic test accuracy data is more difficult than of effectiveness data because of 1) statistical challenges of dealing with multiple measures of accuracy (e.g., sensitivity and specificity) simultaneously and 2) incorporating threshold effects. A number of meta-analysis models are in use, ranging from naïve synthesis of independent sensitivity and specificity to optimization of a hierarchical summary receiver operating characteristic (SROC) curve. Little work has been done on how such analyses should inform decision models. This article aims to present a unified framework for the synthesis of primary data and economic evaluation of alternative diagnostic testing strategies using Bayesian Markov Chain Monte Carlo simulation methods. The authors extend this previous work by using systematic review to derive model parameters, fully allowing for uncertainty in their estimation, and formally incorporating variability between study results into the decision analysis. Using a simple decision model comparing alternative testing strategies for suspected deep vein thrombosis as an example, the authors consider how to use outputs of different alternative meta-analysis models in decision models. They also explore the limitations of diagnostic test studies, particularly when there is no obvious threshold value. To correct some of the limitations of diagnostic test studies, they propose that tests with implicit and explicit thresholds should be studied using distinctly different frameworks. Specifically, when a threshold exists, quantitative threshold information should be included in meta-analysis models to aid interpretation of SROCs. Setting policy to relate to a specific point may be much more difficult for studies with implicit thresholds. [ABSTRACT FROM AUTHOR]

Background: Traditionally, meta-analysis of time-to-event outcomes reports a single pooled hazard ratio assuming proportional hazards (PH). For health technology assessment evaluations, hazard ratios are frequently extrapolated across a lifetime horizon. However, when treatment effects vary over time, an assumption of PH is not always valid. The Royston-Parmar (RP), piecewise exponential (PE), and fractional polynomial (FP) models can accommodate non-PH and provide plausible extrapolations of survival curves beyond observed data., Methods: Simulation study to assess and compare the performance of RP, PE, and FP models in a Bayesian framework estimating restricted mean survival time difference (RMSTD) at 50 years from a pairwise meta-analysis with evidence of non-PH. Individual patient data were generated from a mixture Weibull distribution. Twelve scenarios were considered varying the amount of follow-up data, number of trials in a meta-analysis, non-PH interaction coefficient, and prior distributions. Performance was assessed through bias and mean squared error. Models were applied to a metastatic breast cancer example., Results: FP models performed best when the non-PH interaction coefficient was 0.2. RP models performed best in scenarios with complete follow-up data. PE models performed well on average across all scenarios. In the metastatic breast cancer example, RMSTD at 50-years ranged from -14.6 to 8.48 months., Conclusions: Synthesis of time-to-event outcomes and estimation of RMSTD in the presence of non-PH can be challenging and computationally intensive. Different approaches make different assumptions regarding extrapolation and sensitivity analyses varying key assumptions are essential to check the robustness of conclusions to different assumptions for the underlying survival function., (© 2024 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)

One of the stranger planetary rings is Saturn's narrow, clumpy F ring, lying just outside the main rings, in a region disturbed by chaotic orbital dynamics. We show that the F ring has a stable "true core" that dominates its mass and is confined into discontinuous short arcs of particles larger than a few millimeters in radius. The more obvious micron-size particles seen in images, outlining and obscuring the true core, contribute only a small fraction of its mass. We found that these arcs of large particles orbit Saturn in a specific corotational resonance with the nearby 100-kilometer diameter ringmoon Prometheus, which stabilizes the F ring material and allows it to persist within the disturbed region for decades or longer. Toward the end of the observing period, a small chaotic glitch in the orbit of Prometheus temporarily disrupted the confinement, but the arcs seem to be able to adapt.

Background: Remote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life., Methods: In a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933., Findings: Between May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8-4·4]; p<0·0001)., Interpretation: The Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions., Funding: Kidney Research UK., Competing Interests: Declaration of interests King's College Hospital NHS Trust and SAG were involved in the conception and development of Kidney BEAM. SB is a trustee of Kidney Research UK. DCW has an ongoing consultancy contract with AstraZeneca and has received honoraria or consultancy fees from Astellas, Boehringer Ingelheim, Bayer, Eledon, Galderma, GlaxoSmithKline, Gilead, Janssen, Mundipharma, ProKidney, Tricida, Vifor, and Zydus for activities related to education and clinical trials. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Competing interests: None declared.

Objective: To perform a large-scale pairwise and network meta-analysis on the effects of all relevant exercise training modes on resting blood pressure to establish optimal antihypertensive exercise prescription practices., Design: Systematic review and network meta-analysis., Data Sources: PubMed (Medline), the Cochrane library and Web of Science were systematically searched., Eligibility Criteria: Randomised controlled trials published between 1990 and February 2023. All relevant work reporting reductions in systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) following an exercise intervention of ≥2 weeks, with an eligible non-intervention control group, were included., Results: 270 randomised controlled trials were ultimately included in the final analysis, with a pooled sample size of 15 827 participants. Pairwise analyses demonstrated significant reductions in resting SBP and DBP following aerobic exercise training (-4.49/-2.53 mm Hg, p<0.001), dynamic resistance training (-4.55/-3.04 mm Hg, p<0.001), combined training (-6.04/-2.54 mm Hg, p<0.001), high-intensity interval training (-4.08/-2.50 mm Hg, p<0.001) and isometric exercise training (-8.24/-4.00 mm Hg, p<0.001). As shown in the network meta-analysis, the rank order of effectiveness based on the surface under the cumulative ranking curve (SUCRA) values for SBP were isometric exercise training (SUCRA: 98.3%), combined training (75.7%), dynamic resistance training (46.1%), aerobic exercise training (40.5%) and high-intensity interval training (39.4%). Secondary network meta-analyses revealed isometric wall squat and running as the most effective submodes for reducing SBP (90.4%) and DBP (91.3%), respectively., Conclusion: Various exercise training modes improve resting blood pressure, particularly isometric exercise. The results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Health and social care interventions are often complex and can be decomposed into multiple components. Multicomponent interventions are often evaluated in randomised controlled trials. Across trials, interventions often have components in common which are given alongside other components which differ across trials. Multicomponent interventions can be synthesised using component NMA (CNMA). CNMA is limited by the structure of the available evidence, but it is not always straightforward to visualise such complex evidence networks. The aim of this paper is to develop tools to visualise the structure of complex evidence networks to support CNMA., Methods: We performed a citation review of two key CNMA methods papers to identify existing published CNMA analyses and reviewed how they graphically represent intervention complexity and comparisons across trials. Building on identified shortcomings of existing visualisation approaches, we propose three approaches to standardise visualising the data structure and/or availability of data: CNMA-UpSet plot, CNMA heat map, CNMA-circle plot. We use a motivating example to illustrate these plots., Results: We identified 34 articles reporting CNMAs. A network diagram was the most common plot type used to visualise the data structure for CNMA (26/34 papers), but was unable to express the complex data structures and large number of components and potential combinations of components associated with CNMA. Therefore, we focused visualisation development around representing the data structure of a CNMA more completely. The CNMA-UpSet plot presents arm-level data and is suitable for networks with large numbers of components or combinations of components. Heat maps can be utilised to inform decisions about which pairwise interactions to consider for inclusion in a CNMA model. The CNMA-circle plot visualises the combinations of components which differ between trial arms and offers flexibility in presenting additional information such as the number of patients experiencing the outcome of interest in each arm., Conclusions: As CNMA becomes more widely used for the evaluation of multicomponent interventions, the novel CNMA-specific visualisations presented in this paper, which improve on the limitations of existing visualisations, will be important to aid understanding of the complex data structure and facilitate interpretation of the CNMA results., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety., Methods: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate., Discussion: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future., Trial Registration: Trial registration number: ISRCTN87042063. Registered: 14/07/2020., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Chronic postsurgical pain is common after surgery. Identification of non-opioid analgesics with potential for preventing chronic postsurgical pain is important, although trials are often underpowered. Network meta-analysis offers an opportunity to improve power and to identify the most promising therapy for clinical use and future studies., Methods: We conducted a PRISMA-NMA-compliant systematic review and network meta-analysis of randomised controlled trials of non-opioid analgesics for chronic postsurgical pain. Outcomes included incidence and severity of chronic postsurgical pain, serious adverse events, and chronic opioid use., Results: We included 132 randomised controlled trials with 23 902 participants. In order of efficacy, i.v. lidocaine (odds ratio [OR] 0.32; 95% credible interval [CrI] 0.17-0.58), ketamine (OR 0.64; 95% CrI 0.44-0.92), gabapentinoids (OR 0.67; 95% CrI 0.47-0.92), and possibly dexmedetomidine (OR 0.36; 95% CrI 0.12-1.00) reduced the incidence of chronic postsurgical pain at ≤6 months. There was little available evidence for chronic postsurgical pain at >6 months, combinations agents, chronic opioid use, and serious adverse events. Variable baseline risk was identified as a potential violation to the network meta-analysis transitivity assumption, so results are reported from a fixed value of this, with analgesics more effective at higher baseline risk. The confidence in these findings was low because of problems with risk of bias and imprecision., Conclusions: Lidocaine (most effective), ketamine, and gabapentinoids could be effective in reducing chronic postsurgical pain ≤6 months although confidence is low. Moreover, variable baseline risk might violate transitivity in network meta-analysis of analgesics; this recommends use of our methods in future network meta-analyses., Systematic Review Protocol: PROSPERO CRD42021269642., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The statistical models developed for meta-analysis of diagnostic test accuracy studies require specialised knowledge to implement. This is especially true since recent guidelines, such as those in Version 2 of the Cochrane Handbook of Systematic Reviews of Diagnostic Test Accuracy, advocate more sophisticated methods than previously. This paper describes a web-based application - MetaBayesDTA - that makes many advanced analysis methods in this area more accessible., Results: We created the app using R, the Shiny package and Stan. It allows for a broad array of analyses based on the bivariate model including extensions for subgroup analysis, meta-regression and comparative test accuracy evaluation. It also conducts analyses not assuming a perfect reference standard, including allowing for the use of different reference tests., Conclusions: Due to its user-friendliness and broad array of features, MetaBayesDTA should appeal to researchers with varying levels of expertise. We anticipate that the application will encourage higher levels of uptake of more advanced methods, which ultimately should improve the quality of test accuracy reviews., (© 2023. The Author(s).)

Objectives: Network meta-analysis (NMA) is becoming a popular statistical tool for analyzing a network of evidence comparing more than two interventions. A particular advantage of NMA over pairwise meta-analysis is its ability to simultaneously compare multiple interventions including comparisons not previously trialed together, permitting intervention hierarchies to be created. Our aim was to develop a novel graphical display to aid interpretation of NMA to clinicians and decision-makers that incorporates ranking of interventions., Study Design and Setting: Current literature was searched, scrutinized, and provided direction for developing the novel graphical display. Ranking results were often found to be misinterpreted when presented alone and, to aid interpretation and effective communication to inform optimal decision-making, need to be displayed alongside other important aspects of the analysis including the evidence networks and relative intervention effect estimates., Results: Two new ranking visualizations were developed-the 'Litmus Rank-O-Gram' and the 'Radial SUCRA' plot-and embedded within a novel multipanel graphical display programmed within the MetaInsight application, with user feedback gained., Conclusion: This display was designed to improve the reporting, and facilitate a holistic understanding, of NMA results. We believe uptake of the display would lead to better understanding of complex results and improve future decision-making., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Haemodialysis (HD) treatment causes a significant decrease in quality of life (QoL). When enrolled in a clinical trial, some patients are lost prior to follow-up because they die or they receive a kidney transplant. It is unclear how these patients are dealt with in the analysis of QoL data. There are questions surrounding the consistency of how QoL measures are used, reported and analysed., Methods: A systematic search of electronic databases for trials measuring QoL in HD patients using any variation of the Kidney Disease Quality of Life (KDQoL) Questionnaire was conducted. The review was conducted in Covidence version 2. Quantitative analysis was conducted in Stata version 16., Results: We included 61 trials in the review, of which 82% reported dropouts. The methods to account for missing data due to dropouts include imputation (7%) and complete case analysis (72%). Few trials (7%) conducted a sensitivity analysis to assess the impact of missing data on the study results. Single imputation techniques were used, but are only valid under strong assumptions regarding the type and pattern of missingness. There was inconsistency in the reporting of the KDQoL, with many articles (70%) amending the validated questionnaires or reporting only statistically significant results., Conclusions: Missing data are not dealt with according to the missing data mechanism, which may lead to biased results. Inconsistency in the use of patient-reported outcome measures raises questions about the validity of these trials. Methodological issues in nephrology trials could be a contributing factor to why there are limited effective interventions to improve QoL in this patient group., Prospero Registration: CRD42020223869., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Aims: The optimal timing of an invasive strategy (IS) in non-ST-elevation acute coronary syndrome (NSTE-ACS) is controversial. Recent randomized controlled trials (RCTs) and long-term follow-up data have yet to be included in a contemporary meta-analysis., Methods and Results: A systematic review of RCTs that compared an early IS vs. delayed IS for NSTE-ACS was conducted by searching MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. A meta-analysis was performed by pooling relative risks (RRs) using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), recurrent ischaemia, admission for heart failure (HF), repeat re-vascularization, major bleeding, stroke, and length of hospital stay. This study was registered with PROSPERO (CRD42021246131). Seventeen RCTs with outcome data from 10 209 patients were included. No significant differences in risk for all-cause mortality [RR: 0.90, 95% confidence interval (CI): 0.78-1.04], MI (RR: 0.86, 95% CI: 0.63-1.16), admission for HF (RR: 0.66, 95% CI: 0.43-1.03), repeat re-vascularization (RR: 1.04, 95% CI: 0.88-1.23), major bleeding (RR: 0.86, 95% CI: 0.68-1.09), or stroke (RR: 0.95, 95% CI: 0.59-1.54) were observed. Recurrent ischaemia (RR: 0.57, 95% CI: 0.40-0.81) and length of stay (median difference: -22 h, 95% CI: -36.7 to -7.5 h) were reduced with an early IS., Conclusion: In all-comers with NSTE-ACS, an early IS does not reduce all-cause mortality, MI, admission for HF, repeat re-vascularization, or increase major bleeding or stroke when compared with a delayed IS. Risk of recurrent ischaemia and length of stay are significantly reduced with an early IS., Competing Interests: Conflict of interest: S.A.K. reports personal fees from Bayer. C.P.G. reports personal fees from AstraZeneca, personal fees from Amgen, personal fees from Bayer, grants from BMS, personal fees from Boehrinher-Ingelheim, personal fees from Chiesi, personal fees from Daiichi Sankyo, personal fees from Vifor Pharma, grants from Abbott, personal fees from Menarini, personal fees from Wondr Medical, personal fees from Raisio Group, personal fees from Zydus, personal fees from Oxford University Press, grants from Abbott Diabetes, grants from BMS grants from British Heart Foundation, grants from NIHR, grant from Horizon 2020, grants from ESC, outside the submitted work. N.C. reports unrestricted research grants from Boston Scientific, HeartFlow, Beckman Coulter, and speaker/consultancy fees from Boston, Abbott, HeartFlow outside the submitted work. A.P.B. reports speaker fees from Boston Scientific, Medtronic, Abbott, and Miracor. G.P.M. reports research grants from NIHR, BHF, MRC, and AstraZeneca outside the submitted the work. The remaining authors have no conflicts of interest to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Standard methods for the meta-analysis of medical tests, without assuming a gold standard, are limited to dichotomous data. Multivariate probit models are used to analyse correlated dichotomous data, and can be extended to model ordinal data. Within the context of an imperfect gold standard, they have previously been used for the analysis of dichotomous and ordinal test data from a single study, and for the meta-analysis of dichotomous tests. However, they have not previously been used for the meta-analysis of ordinal tests. In this article, we developed a Bayesian multivariate probit latent class model for the simultaneous meta-analysis of ordinal and dichotomous tests without assuming a gold standard, which also allows one to obtain summary estimates of joint test accuracy. We fitted the models using the software Stan, which uses a state-of-the-art Hamiltonian Monte Carlo algorithm, and we applied the models to a dataset in which studies evaluated the accuracy of tests, and test combinations, for deep vein thrombosis. We demonstrate the issues with dichotomising ordinal test accuracy data in the presence of an imperfect gold standard, before applying and comparing several variations of our proposed model which do not require the data to be dichotomised. The models proposed will allow researchers to more appropriately meta-analyse ordinal and dichotomous tests without a gold standard, potentially leading to less biased estimates of test accuracy. This may lead to a better understanding of which tests, and test combinations, should be used for any given medical condition., (© 2022 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)

Securing decarbonized economies for energy and commodities will require abundant and widely available green H 2 . Ubiquitous wastewaters and nontraditional water sources could potentially feed water electrolyzers to produce this green hydrogen without competing with drinking water sources. Herein, we show that the energy and costs of treating nontraditional water sources such as municipal wastewater, industrial and resource extraction wastewater, and seawater are negligible with respect to those for water electrolysis. We also illustrate that the potential hydrogen energy that could be mined from these sources is vast. Based on these findings, we evaluate the implications of small-scale, distributed water electrolysis using disperse nontraditional water sources. Techno-economic analysis and life cycle analysis reveal that the significant contribution of H 2 transportation to costs and CO 2 emissions results in an optimal levelized cost of hydrogen at small- to moderate-scale water electrolyzer size. The implications of utilizing nontraditional water sources and decentralized or stranded renewable energy for distributed water electrolysis are highlighted for several hydrogen energy storage and chemical feedstock applications. Finally, we discuss challenges and opportunities for mining H 2 from nontraditional water sources to achieve resilient and sustainable economies for water and energy.

Background: Synthesis of clinical effectiveness from multiple trials is a well-established component of decision-making. Time-to-event outcomes are often synthesised using the Cox proportional hazards model assuming a constant hazard ratio over time. However, with an increasing proportion of trials reporting treatment effects where hazard ratios vary over time and with differing lengths of follow-up across trials, alternative synthesis methods are needed., Objectives: To compare and contrast five modelling approaches for synthesis of time-to-event outcomes and provide guidance on key considerations for choosing between the modelling approaches., Methods: The Cox proportional hazards model and five other methods of estimating treatment effects from time-to-event outcomes, which relax the proportional hazards assumption, were applied to a network of melanoma trials reporting overall survival: restricted mean survival time, generalised gamma, piecewise exponential, fractional polynomial and Royston-Parmar models., Results: All models fitted the melanoma network acceptably well. However, there were important differences in extrapolations of the survival curve and interpretability of the modelling constraints demonstrating the potential for different conclusions from different modelling approaches., Conclusion: The restricted mean survival time, generalised gamma, piecewise exponential, fractional polynomial and Royston-Parmar models can accommodate non-proportional hazards and differing lengths of trial follow-up within a network meta-analysis of time-to-event outcomes. We recommend that model choice is informed using available and relevant prior knowledge, model transparency, graphically comparing survival curves alongside observed data to aid consideration of the reliability of the survival estimates, and consideration of how the treatment effect estimates can be incorporated within a decision model.

Low-salt-rejection reverse osmosis (LSRRO) is a novel reverse osmosis (RO)-based technology that can highly concentrate brines using moderate operating pressures. In this study, we investigate the performance of LSRRO membrane modules and systems using module-scale analysis. Specifically, we correlate the observed salt rejection of an LSRRO module with the water and salt permeabilities of the RO membrane. We then elaborate the impact of membrane properties and operating conditions on the performance of a 2-stage LSRRO, providing design guidelines for LSRRO systems. We further compare the performance of 2-stage and 3-stage LSRRO systems, showing that an LSRRO system with more stages is not always favored due to a larger energy consumption. The performance of a 3-stage LSRRO in treating different feed solutions for minimal/zero liquid discharge (MLD/ZLD) applications is then evaluated. Based on our results, when treating feed waters with a relatively low salinity (e.g., 0.1 M or ∼5,800 mg L -1 NaCl), the 3-stage LSRRO can achieve a concentrated brine that can be directly sent to the thermal brine crystallizers (i.e., brine concentration > 4 M or ∼240,000 mg L -1 NaCl), and the corresponding specific energy consumption (SEC) is only ∼3 kWh m -3 . When treating feed waters with a relatively high salinity (e.g., 0.6 M or ∼35,000 mg L -1 NaCl), the brine from the 3-stage LSRRO can be ∼80 % more concentrated compared to that from conventional RO, while the corresponding SEC does not exceed 6 kWh m -3 . Our results demonstrate that LSRRO can substantially advance minimal/zero liquid discharge (MLD/ZLD) applications because it can significantly minimize the use of thermal brine concentrators. We conclude with a discussion on the practicability of LSRRO and highlight future research needs., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Network meta-analysis (NMA) has been increasingly adopted worldwide by Cochrane reviews, guideline developers and decision-making bodies to identify optimal treatment choices. However, NMA results are often produced statically, not allowing stakeholders to 'dig deeper' and interrogate with their own judgement. Additionally, amid the COVID-19 pandemic, unnecessary or duplicated reviews have been proposed which analyse from the same pool of evidence. We developed the 'MetaInsight COVID-19' app as a prototype for an interactive platform to eliminate such duplicated efforts, by empowering users to freely analyse the data and improve scientific transparency., Methods: MetaInsight COVID-19 ( https://crsu.shinyapps.io/metainsightcovid/ ) was developed to conduct NMA with the evolving evidence on treatments for COVID-19. It was updated weekly between 19th May - 19th Oct 2020, incorporating new evidence identified from a living systematic review., Results: The app includes embedded functions to facilitate study selection based on study characteristics, and displays the synthesised results in real time. It allows both frequentist and Bayesian NMA to be conducted as well as consistency and heterogeneity assessments. A demonstration of the app is provided and experiences of building such a platform are discussed., Conclusions: MetaInsight COVID-19 allows users to take control of the evidence synthesis using the analytic approach they deem appropriate to ascertain how robust findings are to alternative analysis strategies and study inclusion criteria. It is hoped that this app will help avoid many of the duplicated efforts when reviewing and synthesising the COVID-19 evidence, and, in addition, establish the desirability of an open platform format such as this for interactive data interrogation, visualisation, and reporting for any traditional or 'living' NMA., (© 2022. The Author(s).)

Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients (KTRs). CVD risk scores underestimate risk in this population as CVD is driven by clustering of traditional and non-traditional risk factors, which lead to prognostic pathological changes in cardiovascular structure and function. While exercise may mitigate CVD in this population, evidence is limited, and physical activity levels and patient activation towards exercise and self-management are low. This pilot study will assess the feasibility of delivering a structured, home-based exercise intervention in a population of KTRs at increased cardiometabolic risk and evaluate the putative effects on cardiovascular structural and functional changes, cardiorespiratory fitness, quality of life, patient activation, healthcare utilisation and engagement with the prescribed exercise programme., Methods and Analysis: Fifty KTRs will be randomised 1:1 to: (1) the intervention; a 12week, home-based combined resistance and aerobic exercise intervention; or (2) the control; usual care. Intervention participants will have one introductory session for instruction and practice of the recommended exercises prior to receiving an exercise diary, dumbbells, resistance bands and access to instructional videos. The study will evaluate the feasibility of recruitment, randomisation, retention, assessment procedures and the intervention implementation. Outcomes, to be assessed prior to randomisation and postintervention, include: cardiac structure and function with stress perfusion cardiac MRI, cardiorespiratory fitness, physical function, blood biomarkers of cardiometabolic health, quality of life and patient activation. These data will be used to inform the power calculations for future definitive trials., Ethics and Dissemination: The protocol was reviewed and given favourable opinion by the East Midlands-Nottingham 2 Research Ethics Committee (reference: 19/EM/0209; 14 October 2019). Results will be published in peer-reviewed academic journals and will be disseminated to the patient and public community via social media, newsletter articles and presentations at conferences., Trial Registration Number: NCT04123951., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: It is estimated that 25 000 people in the UK receive dialysis. Dialysis is an intrusive and time-consuming intervention that causes significant reductions in quality of life. When enrolled in a clinical trial, often some patients drop out of the study either because they die, receive a kidney transplant or are lost to follow-up for other reasons. It is unclear how these events are dealt with when analysing quality of life measures within clinical trials. This review will assess current practice for dealing with loss to follow-up in trials including patients on haemodialysis. The methods currently used will be analysed in terms of their adequacy and will form the basis of future work assessing the most appropriate methods to employ under these circumstances. The results of this review will feed into recommendations for future nephrology trials., Methods and Analysis: A systematic search of electronic databases including MEDLINE and the Cochrane Library will be conducted to find clinical trials enrolling patients on haemodialysis that measure quality of life using either the kidney disease quality of life (KDQoL) or the short form 36 health survey (SF-36) (or any variation of these two measures). Ongoing trials will be identified through a search of trial registers. Articles will be screened against inclusion/exclusion criteria and data will be extracted using a predetermined data extraction form. General information such as the title, location, trial design will be extracted along with more specific information on how the study dealt with patients that died or received a transplant before the end of the follow-up period. Two independent reviewers will perform screening and extraction. Disagreements will be resolved by discussion or by a third independent reviewer. Data synthesis will be performed as a narrative summary., Ethics and Dissemination: Ethics approval is not required. Dissemination will be by publication in a peer-reviewed journal., Prospero Registration Number: CRD42020223869., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Dementia remains a clinical diagnosis with a degree of subjective assessment and potential for interrater disagreement. We described interrater agreement of clinical dementia diagnosis for various diagnostic criteria., Methods: We conducted a PROSPERO-registered (CRD42020168245) systematic review and meta-analysis. We searched multiple cross-disciplinary databases from inception until April 2020 for relevant papers, extracted data and described study quality in duplicate. Study quality was assessed using the Guidelines for Reporting Reliability and Agreement Studies. We used random-effects models to obtain summary estimates of interrater agreement using kappa and, where possible, Gwet's AC1/2 coefficients., Results: We found 7577 titles and 22 eligible studies. Meta-analysis was possible for all-cause dementia using the Diagnostic and Statistical Manual of Mental Disorders third edition revised (DSM-III-R) criteria (kappa = 0.66, 95% CI = [0.53,0.78]), Alzheimer's disease using the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria (kappa = 0.71, 95% CI = [0.65,0.77] for presence/absence and AC2 = 0.61, 95% CI = [0.53,0.70] when distinguishing probable/possible cases), and vascular dementia using the International Classification of Diseases version 10 (ICD-10) criteria kappa = 0.79 (95% CI = [0.70,0.87]). Data was more limited for other criteria and dementia types. AC1/2 coefficients generally indicated higher agreement. One study was rated as high quality., Conclusions: Diagnostic criteria for clinical dementia may have good but imperfect agreement. This has important implications for clinical practice and research studies, which frequently assume these criteria are perfect tests, such as diagnostic test accuracy studies frequently conducted for biomarkers and neuropsychological tests, and for trials where incident dementia is the outcome., (© 2021 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD., Objectives: • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD., Selection Criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation., Data Collection and Analysis: We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance., Main Results: We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low-certainty evidence). The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates. Data were probably because of the very short follow-up period (2 months to 28 months). It takes follow-up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow-up., Authors' Conclusions: The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non-alcohol-related fatty liver disease. Accordingly, high-quality randomised comparative clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow-up of 8 years (to find meaningful differences in clinically important outcomes)., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The prevalence of nonalcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases the risks of liver cirrhosis, hepatocellular carcinoma, and requirement for liver transplantation. There is uncertainty surrounding the relative benefits and harms of various lifestyle interventions for people with NAFLD., Objectives: To assess the comparative benefits and harms of different lifestyle interventions in the treatment of NAFLD through a network meta-analysis, and to generate rankings of the different lifestyle interventions according to their safety and efficacy., Search Methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD., Selection Criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) in people with NAFLD, whatever the method of diagnosis, age, and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation., Data Collection and Analysis: We planned to perform a network meta-analysis with OpenBUGS using Bayesian methods and to calculate the differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios (RaRs) with 95% credible intervals (CrIs) based on an available-participant analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. However, the data were too sparse for the clinical outcomes. We therefore performed only direct comparisons (head-to-head comparisons) with OpenBUGS using Bayesian methods., Main Results: We included a total of 59 randomised clinical trials (3631 participants) in the review. All but two trials were at high risk of bias. A total of 33 different interventions, ranging from advice to supervised exercise and special diets, or a combination of these and no additional intervention were compared in these trials. The reference treatment was no active intervention. Twenty-eight trials (1942 participants) were included in one or more comparisons. The follow-up ranged from 1 month to 24 months. The remaining trials did not report any of the outcomes of interest for this review. The follow-up period in the trials that reported clinical outcomes was 2 months to 24 months. During this short follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. This is probably because of the very short follow-up periods. It takes a follow-up of 8 years to 28 years to detect differences in mortality between people with NAFLD and the general population. It is therefore unlikely that differences by clinical outcomes will be noted in trials with less than 5 years to 10 years of follow-up. In one trial, one participant developed an adverse event. There were no adverse events in any of the remaining participants in this trial, or in any of the remaining trials, which seemed to be directly related to the intervention., Authors' Conclusions: The evidence indicates considerable uncertainty about the effects of the lifestyle interventions compared with no additional intervention (to general public health advice) on any of the clinical outcomes after a short follow-up period of 2 months to 24 months in people with nonalcohol-related fatty liver disease. Accordingly, high-quality randomised clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (a study design in which multiple interventions are trialed within large longitudinal cohorts of participants to gain efficiencies and align trials more closely to standard clinical practice), comparing aerobic exercise and dietary advice versus standard of care (exercise and dietary advice received as part of national health promotion). The reason for the choice of aerobic exercise and dietary advice is the impact of these interventions on indirect outcomes which may translate to clinical benefit. The outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource use measures including costs of intervention and decreased healthcare use after a minimum follow-up of eight years, to find meaningful differences in the clinically important outcomes., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Approximately 40% to 95% of people with liver cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed within about one to three years after diagnosis. Several different treatments are available, including, among others, endoscopic sclerotherapy, variceal band ligation, somatostatin analogues, vasopressin analogues, and balloon tamponade. However, there is uncertainty surrounding the individual and relative benefits and harms of these treatments., Objectives: To compare the benefits and harms of different initial treatments for variceal bleeding from oesophageal varices in adults with decompensated liver cirrhosis, through a network meta-analysis; and to generate rankings of the different treatments for acute bleeding oesophageal varices, according to their benefits and harms., Search Methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until 17 December 2019, to identify randomised clinical trials (RCTs) in people with cirrhosis and acute bleeding from oesophageal varices., Selection Criteria: We included only RCTs (irrespective of language, blinding, or status) in adults with cirrhosis and acutely bleeding oesophageal varices. We excluded RCTs in which participants had bleeding only from gastric varices, those who failed previous treatment (refractory bleeding), those in whom initial haemostasis was achieved before inclusion into the trial, and those who had previously undergone liver transplantation., Data Collection and Analysis: We performed a network meta-analysis with OpenBUGS software, using Bayesian methods, and calculated the differences in treatments using odds ratios (OR) and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. We performed also the direct comparisons from RCTs using the same codes and the same technical details., Main Results: We included a total of 52 RCTs (4580 participants) in the review. Forty-eight trials (4042 participants) were included in one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those with and without a previous history of bleeding. We included outcomes assessed up to six weeks. All trials were at high risk of bias. A total of 19 interventions were compared in the trials (sclerotherapy, somatostatin analogues, vasopressin analogues, sclerotherapy plus somatostatin analogues, variceal band ligation, balloon tamponade, somatostatin analogues plus variceal band ligation, nitrates plus vasopressin analogues, no active intervention, sclerotherapy plus variceal band ligation, balloon tamponade plus sclerotherapy, balloon tamponade plus somatostatin analogues, balloon tamponade plus vasopressin analogues, variceal band ligation plus vasopressin analogues, balloon tamponade plus nitrates plus vasopressin analogues, balloon tamponade plus variceal band ligation, portocaval shunt, sclerotherapy plus transjugular intrahepatic portosystemic shunt (TIPS), and sclerotherapy plus vasopressin analogues). We have reported the effect estimates for the primary and secondary outcomes when there was evidence of differences between the interventions against the reference treatment of sclerotherapy, but reported the other results of the primary and secondary outcomes versus the reference treatment of sclerotherapy without the effect estimates when there was no evidence of differences in order to provide a concise summary of the results. Overall, 15.8% of the trial participants who received the reference treatment of sclerotherapy (chosen because this was the commonest treatment compared in the trials) died during the follow-up periods, which ranged from three days to six weeks. Based on moderate-certainty evidence, somatostatin analogues alone had higher mortality than sclerotherapy (OR 1.57, 95% CrI 1.04 to 2.41; network estimate; direct comparison: 4 trials; 353 participants) and vasopressin analogues alone had higher mortality than sclerotherapy (OR 1.70, 95% CrI 1.13 to 2.62; network estimate; direct comparison: 2 trials; 438 participants). None of the trials reported health-related quality of life. Based on low-certainty evidence, a higher proportion of people receiving balloon tamponade plus sclerotherapy had more serious adverse events than those receiving only sclerotherapy (OR 4.23, 95% CrI 1.22 to 17.80; direct estimate; 1 RCT; 60 participants). Based on moderate-certainty evidence, people receiving vasopressin analogues alone and those receiving variceal band ligation had fewer adverse events than those receiving only sclerotherapy (rate ratio 0.59, 95% CrI 0.35 to 0.96; network estimate; direct comparison: 1 RCT; 219 participants; and rate ratio 0.40, 95% CrI 0.21 to 0.74; network estimate; direct comparison: 1 RCT; 77 participants; respectively). Based on low-certainty evidence, the proportion of people who developed symptomatic rebleed was smaller in people who received sclerotherapy plus somatostatin analogues than those receiving only sclerotherapy (OR 0.21, 95% CrI 0.03 to 0.94; direct estimate; 1 RCT; 105 participants). The evidence suggests considerable uncertainty about the effect of the interventions in the remaining comparisons where sclerotherapy was the control intervention., Authors' Conclusions: Based on moderate-certainty evidence, somatostatin analogues alone and vasopressin analogues alone (with supportive therapy) probably result in increased mortality, compared to endoscopic sclerotherapy. Based on moderate-certainty evidence, vasopressin analogues alone and band ligation alone probably result in fewer adverse events compared to endoscopic sclerotherapy. Based on low-certainty evidence, balloon tamponade plus sclerotherapy may result in large increases in serious adverse events compared to sclerotherapy. Based on low-certainty evidence, sclerotherapy plus somatostatin analogues may result in large decreases in symptomatic rebleed compared to sclerotherapy. In the remaining comparisons, the evidence indicates considerable uncertainty about the effects of the interventions, compared to sclerotherapy., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: No formal cost-effectiveness analysis has been performed for programs of cycling exercise during dialysis (intradialytic cycling [IDC]). The objective of this analysis is to determine the effect of a 6-month program of IDC on health care costs., Methods: This is a retrospective formal cost-effectiveness analysis of adult participants with end-stage kidney disease undertaking in-center maintenance hemodialysis enrolled in the CYCLE-HD trial. Data on hospital utilization, primary care consultations, and prescribed medications were extracted from medical records for the 6 months before, during, and after a 6-month program of thrice-weekly IDC. The cost-effectiveness analysis was conducted from a health care service perspective and included the cost of implementing the IDC intervention. The base-case analyses included a 6-month "within trial" analysis and a 12-month "within and posttrial" analysis considering health care utilization and quality of life (QoL) outcomes., Results: Data from the base-case within trial analysis, based on 109 participants ( n  = 56 control subjects and n  = 53 IDC subjects) showed a reduction in health care utilization costs between groups, favoring the IDC group, and a 73% chance of IDC being cost-effective compared with control subjects at a willingness to pay of £20,000 and £30,000 per quality-adjusted life year (QALY) gained. When QoL data points were extrapolated forward to 12 months, the probability of IDC being cost-effective was 93% and 94% at £20,000 and £30,000 per QALY gained. Sensitivity analysis broadly confirms these findings., Conclusion: A 6-month program of IDC is cost-effective and the implementation of these programs nationally should be a priority., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Background: Approximately 40% to 95% of people with cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed in about one to three years. There are several different treatments to prevent bleeding, including: beta-blockers, endoscopic sclerotherapy, and variceal band ligation. However, there is uncertainty surrounding their individual and relative benefits and harms., Objectives: To compare the benefits and harms of different treatments for prevention of first variceal bleeding from oesophageal varices in adults with liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for prevention of first variceal bleeding from oesophageal varices according to their safety and efficacy., Search Methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers to December 2019 to identify randomised clinical trials in people with cirrhosis and oesophageal varices with no history of bleeding., Selection Criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and oesophageal varices with no history of bleeding. We excluded randomised clinical trials in which participants had previous bleeding from oesophageal varices and those who had previously undergone liver transplantation or previously received prophylactic treatment for oesophageal varices., Data Collection and Analysis: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the differences in treatments using hazard ratios (HR), odds ratios (OR), and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute for Health and Care Excellence Decision Support Unit guidance. We performed the direct comparisons from randomised clinical trials using the same codes and the same technical details., Main Results: We included 66 randomised clinical trials (6653 participants) in the review. Sixty trials (6212 participants) provided data for one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those at high risk of bleeding from oesophageal varices. The follow-up in the trials that reported outcomes ranged from 6 months to 60 months. All but one of the trials were at high risk of bias. The interventions compared included beta-blockers, no active intervention, variceal band ligation, sclerotherapy, beta-blockers plus variceal band ligation, beta-blockers plus nitrates, nitrates, beta-blockers plus sclerotherapy, and portocaval shunt. Overall, 21.2% of participants who received non-selective beta-blockers ('beta-blockers') - the reference treatment (chosen because this was the most common treatment compared in the trials) - died during 8-month to 60-month follow-up. Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates all had lower mortality versus no active intervention (beta-blockers: HR 0.49, 95% CrI 0.36 to 0.67; direct comparison HR: 0.59, 95% CrI 0.42 to 0.83; 10 trials, 1200 participants; variceal band ligation: HR 0.51, 95% CrI 0.35 to 0.74; direct comparison HR 0.49, 95% CrI 0.12 to 2.14; 3 trials, 355 participants; sclerotherapy: HR 0.66, 95% CrI 0.51 to 0.85; direct comparison HR 0.61, 95% CrI 0.41 to 0.90; 18 trials, 1666 participants; beta-blockers plus nitrates: HR 0.41, 95% CrI 0.20 to 0.85; no direct comparison). No trials reported health-related quality of life. Based on low-certainty evidence, variceal band ligation had a higher number of serious adverse events (number of events) than beta-blockers (rate ratio 10.49, 95% CrI 2.83 to 60.64; 1 trial, 168 participants). Based on low-certainty evidence, beta-blockers plus nitrates had a higher number of 'any adverse events (number of participants)' than beta-blockers alone (OR 3.41, 95% CrI 1.11 to 11.28; 1 trial, 57 participants). Based on low-certainty evidence, adverse events (number of events) were higher in sclerotherapy than in beta-blockers (rate ratio 2.49, 95% CrI 1.53 to 4.22; direct comparison rate ratio 2.47, 95% CrI 1.27 to 5.06; 2 trials, 90 participants), and in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison rate ratio 1.72, 95% CrI 1.08 to 2.76; 1 trial, 140 participants). Based on low-certainty evidence, any variceal bleed was lower in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison HR 0.21, 95% CrI 0.04 to 0.71; 1 trial, 173 participants). Based on low-certainty evidence, any variceal bleed was higher in nitrates than beta-blockers (direct comparison HR 6.40, 95% CrI 1.58 to 47.42; 1 trial, 52 participants). The evidence indicates considerable uncertainty about the effect of the interventions in the remaining comparisons., Authors' Conclusions: Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates may decrease mortality compared to no intervention in people with high-risk oesophageal varices in people with cirrhosis and no previous history of bleeding. Based on low-certainty evidence, variceal band ligation may result in a higher number of serious adverse events than beta-blockers. The evidence indicates considerable uncertainty about the effect of beta-blockers versus variceal band ligation on variceal bleeding. The evidence also indicates considerable uncertainty about the effect of the interventions in most of the remaining comparisons., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Approximately 40% to 95% of people with cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed in about one to three years of diagnosis. Several different treatments are available, which include endoscopic sclerotherapy, variceal band ligation, beta-blockers, transjugular intrahepatic portosystemic shunt (TIPS), and surgical portocaval shunts, among others. However, there is uncertainty surrounding their individual and relative benefits and harms., Objectives: To compare the benefits and harms of different initial treatments for secondary prevention of variceal bleeding in adults with previous oesophageal variceal bleeding due to decompensated liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for secondary prevention according to their safety and efficacy., Search Methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until December 2019 to identify randomised clinical trials in people with cirrhosis and a previous history of bleeding from oesophageal varices., Selection Criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and previous history of bleeding from oesophageal varices. We excluded randomised clinical trials in which participants had no previous history of bleeding from oesophageal varices, previous history of bleeding only from gastric varices, those who failed previous treatment (refractory bleeding), those who had acute bleeding at the time of treatment, and those who had previously undergone liver transplantation., Data Collection and Analysis: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the differences in treatments using hazard ratios (HR), odds ratios (OR) and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance., Main Results: We included a total of 48 randomised clinical trials (3526 participants) in the review. Forty-six trials (3442 participants) were included in one or more comparisons. The trials that provided the information included people with cirrhosis due to varied aetiologies. The follow-up ranged from two months to 61 months. All the trials were at high risk of bias. A total of 12 interventions were compared in these trials (sclerotherapy, beta-blockers, variceal band ligation, beta-blockers plus sclerotherapy, no active intervention, TIPS (transjugular intrahepatic portosystemic shunt), beta-blockers plus nitrates, portocaval shunt, sclerotherapy plus variceal band ligation, beta-blockers plus nitrates plus variceal band ligation, beta-blockers plus variceal band ligation, sclerotherapy plus nitrates). Overall, 22.5% of the trial participants who received the reference treatment (chosen because this was the commonest treatment compared in the trials) of sclerotherapy died during the follow-up period ranging from two months to 61 months. There was considerable uncertainty in the effects of interventions on mortality. Accordingly, none of the interventions showed superiority over another. None of the trials reported health-related quality of life. Based on low-certainty evidence, variceal band ligation may result in fewer serious adverse events (number of people) than sclerotherapy (OR 0.19; 95% CrI 0.06 to 0.54; 1 trial; 100 participants). Based on low or very low-certainty evidence, the adverse events (number of participants) and adverse events (number of events) may be different across many comparisons; however, these differences are due to very small trials at high risk of bias showing large differences in some comparisons leading to many differences despite absence of direct evidence. Based on low-certainty evidence, TIPS may result in large decrease in symptomatic rebleed than variceal band ligation (HR 0.12; 95% CrI 0.03 to 0.41; 1 trial; 58 participants). Based on moderate-certainty evidence, any variceal rebleed was probably lower in sclerotherapy than in no active intervention (HR 0.62; 95% CrI 0.35 to 0.99, direct comparison HR 0.66; 95% CrI 0.11 to 3.13; 3 trials; 296 participants), beta-blockers plus sclerotherapy than sclerotherapy alone (HR 0.60; 95% CrI 0.37 to 0.95; direct comparison HR 0.50; 95% CrI 0.07 to 2.96; 4 trials; 231 participants); TIPS than sclerotherapy (HR 0.18; 95% CrI 0.08 to 0.38; direct comparison HR 0.22; 95% CrI 0.01 to 7.51; 2 trials; 109 participants), and in portocaval shunt than sclerotherapy (HR 0.21; 95% CrI 0.05 to 0.77; no direct comparison) groups. Based on low-certainty evidence, beta-blockers alone and TIPS might result in more, other compensation, events than sclerotherapy (rate ratio 2.37; 95% CrI 1.35 to 4.67; 1 trial; 65 participants and rate ratio 2.30; 95% CrI 1.20 to 4.65; 2 trials; 109 participants; low-certainty evidence). The evidence indicates considerable uncertainty about the effect of the interventions including those related to beta-blockers plus variceal band ligation in the remaining comparisons., Authors' Conclusions: The evidence indicates considerable uncertainty about the effect of the interventions on mortality. Variceal band ligation might result in fewer serious adverse events than sclerotherapy. TIPS might result in a large decrease in symptomatic rebleed than variceal band ligation. Sclerotherapy probably results in fewer 'any' variceal rebleeding than no active intervention. Beta-blockers plus sclerotherapy and TIPS probably result in fewer 'any' variceal rebleeding than sclerotherapy. Beta-blockers alone and TIPS might result in more other compensation events than sclerotherapy. The evidence indicates considerable uncertainty about the effect of the interventions in the remaining comparisons. Accordingly, high-quality randomised comparative clinical trials are needed., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The complexity of public health interventions create challenges in evaluating their effectiveness. There have been huge advancements in quantitative evidence synthesis methods development (including meta-analysis) for dealing with heterogeneity of intervention effects, inappropriate 'lumping' of interventions, adjusting for different populations and outcomes and the inclusion of various study types. Growing awareness of the importance of using all available evidence has led to the publication of guidance documents for implementing methods to improve decision making by answering policy relevant questions., Methods: The first part of this paper reviews the methods used to synthesise quantitative effectiveness evidence in public health guidelines by the National Institute for Health and Care Excellence (NICE) that had been published or updated since the previous review in 2012 until the 19th August 2019.The second part of this paper provides an update of the statistical methods and explains how they address issues related to evaluating effectiveness evidence of public health interventions., Results: The proportion of NICE public health guidelines that used a meta-analysis as part of the synthesis of effectiveness evidence has increased since the previous review in 2012 from 23% (9 out of 39) to 31% (14 out of 45). The proportion of NICE guidelines that synthesised the evidence using only a narrative review decreased from 74% (29 out of 39) to 60% (27 out of 45).An application in the prevention of accidents in children at home illustrated how the choice of synthesis methods can enable more informed decision making by defining and estimating the effectiveness of more distinct interventions, including combinations of intervention components, and identifying subgroups in which interventions are most effective., Conclusions: Despite methodology development and the publication of guidance documents to address issues in public health intervention evaluation since the original review, NICE public health guidelines are not making full use of meta-analysis and other tools that would provide decision makers with fuller information with which to develop policy. There is an evident need to facilitate the translation of the synthesis methods into a public health context and encourage the use of methods to improve decision making.

Objective: The objective of the study is to establish how often continuous and time-to-event outcomes are synthesized in health technology assessment (HTA), the statistical methods and software used in their analysis and how often evidence synthesis informs decision models., Study Design and Setting: This is a review of National Institute of Health Research HTA reports, National Institute for Health and Care Excellence (NICE) technology appraisals, and NICE guidelines reporting quantitative meta-analysis or network meta-analysis of at least one continuous or time-to-event outcome published from April 01, 2018 to March 31, 2019., Results: We identified 47 eligible articles. At least one continuous or time-to-event outcome was synthesized in 51% and 55% of articles, respectively. Evidence synthesis results informed decision models in two-thirds of articles. The review and expert knowledge identified five areas where methodology is available for improving the synthesis of continuous and time-to-event outcomes: i) outcomes reported on multiple scales, ii) reporting of multiple related outcomes, iii) appropriateness of the additive scale, iv) reporting of multiple time points, and v) nonproportional hazards. We identified three anticipated barriers to the uptake and implementation of these methods: i) statistical expertise, ii) software, and iii) reporting of trials., Conclusion: Continuous and time-to-event outcomes are routinely reported in HTA. However, increased uptake of methodological advances could maximize the evidence base used to inform the decision making process., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Organophosphorus chemical warfare agents function as potent neurotoxins. Whilst the destruction of nerve agents is most readily achieved by hydrolysis, their storage and transport are hazardous and lethal in milligram doses, with any spillage resulting in fatalities. Furthermore, current decontamination and remediation measures are limited by a need for stoichiometric reagents, solvents, and buffered solutions, complicating the process for the treatment of bulk contaminants. Herein, we report a composite polymer material capable of rendering bulk VX unusable by immobilization within a porous polymer until a metal-organic framework (MOF) catalyst fully hydrolyzes the neurotoxin. This is an all-in-one capability that minimizes the use of multiple reagents, facilitated by a porous high internal phase emulsion-based polystyrene monolith housing an active zirconia MOF catalyst (MOF-808); the porous polymer absorbs and immobilizes the liquid agents, while the MOF enables hydrolysis. The dichotomous hierarchy of porous materials facilitates the containment and rapid hydrolysis of VX (>80% degradation in 8 h) in the presence of excess H 2 O. This composite can further enable the hydrolysis of neat VX with reliance on ambient humidity (>95% in 11 days). Potentially, 4.5 kg of the composite can absorb, immobilize, and degrade the contents of a standard chemical drum/barrel (208 L, 55 gal) of the chemical warfare agent (CWA). We believe that this composite is the first example of what will be the go-to approach for CWA immobilization and degradation in the future. Furthermore, we believe that this demonstration of a catalytically reusable absorbent sponge provides a signpost for the development of similar materials where immobilization of a substrate in a catalytically active environment is desirable.

Background: Approximately 2.5% of all hospitalisations in people with liver cirrhosis are for spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis is associated with significant short-term mortality; therefore, it is important to prevent spontaneous bacterial peritonitis in people at high risk of developing it. Antibiotic prophylaxis forms the mainstay preventive method, but this has to be balanced against the development of drug-resistant spontaneous bacterial peritonitis, which is difficult to treat, and other adverse events. Several different prophylactic antibiotic treatments are available; however, there is uncertainty surrounding their relative efficacy and optimal combination., Objectives: To compare the benefits and harms of different prophylactic antibiotic treatments for prevention of spontaneous bacterial peritonitis in people with liver cirrhosis using a network meta-analysis and to generate rankings of the different prophylactic antibiotic treatments according to their safety and efficacy., Search Methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers to November 2018 to identify randomised clinical trials in people with cirrhosis at risk of developing spontaneous bacterial peritonitis., Selection Criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis undergoing prophylactic treatment to prevent spontaneous bacterial peritonitis. We excluded randomised clinical trials in which participants had previously undergone liver transplantation, or were receiving antibiotics for treatment of spontaneous bacterial peritonitis or other purposes., Data Collection and Analysis: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance., Main Results: We included 29 randomised clinical trials (3896 participants; nine antibiotic regimens (ciprofloxacin, neomycin, norfloxacin, norfloxacin plus neomycin, norfloxacin plus rifaximin, rifaximin, rufloxacin, sparfloxacin, sulfamethoxazole plus trimethoprim), and 'no active intervention' in the review. Twenty-three trials (2587 participants) were included in one or more outcomes in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies, with or without other features of decompensation, having ascites with low protein or previous history of spontaneous bacterial peritonitis. The follow-up in the trials ranged from 1 to 12 months. Many of the trials were at high risk of bias, and the overall certainty of evidence was low or very low. Overall, approximately 10% of trial participants developed spontaneous bacterial peritonitis and 15% of trial participants died. There was no evidence of differences between any of the antibiotics and no intervention in terms of mortality (very low certainty) or number of serious adverse events (very low certainty). However, because of the wide CrIs, clinically important differences in these outcomes cannot be ruled out. None of the trials reported health-related quality of life or the proportion of people with serious adverse events. There was no evidence of differences between any of the antibiotics and no intervention in terms of proportion of people with 'any adverse events' (very low certainty), liver transplantation (very low certainty), or the proportion of people who developed spontaneous bacterial peritonitis (very low certainty). The number of 'any' adverse events per participant was fewer with norfloxacin (rate ratio 0.74, 95% CrI 0.59 to 0.94; 4 trials, 546 participants; low certainty) and sulfamethoxazole plus trimethoprim (rate ratio 0.19, 95% CrI 0.02 to 0.81; 1 trial, 60 participants; low certainty) versus no active intervention. There was no evidence of differences between the other antibiotics and no intervention in the number of 'any' adverse events per participant (very low certainty). There were fewer other decompensation events with rifaximin versus no active intervention (rate ratio 0.61, 65% CrI 0.46 to 0.80; 3 trials, 575 participants; low certainty) and norfloxacin plus neomycin (rate ratio 0.06, 95% CrI 0.00 to 0.33; 1 trial, 22 participants; low certainty). There was no evidence of differences between the other antibiotics and no intervention in the number of decompensations events per participant (very low certainty). None of the trials reported health-related quality of life or development of symptomatic spontaneous bacterial peritonitis. One would expect some correlation between the above outcomes, with interventions demonstrating effectiveness across several outcomes. This was not the case. The possible reasons for this include sparse data and selective reporting bias, which makes the results unreliable. Therefore, one cannot draw any conclusions from these inconsistent differences based on sparse data. There was no evidence of any differences in the subgroup analyses (performed when possible) based on whether the prophylaxis was primary or secondary., Funding: the source of funding for five trials were organisations who would benefit from the results of the study; six trials received no additional funding or were funded by neutral organisations; and the source of funding for the remaining 18 trials was unclear., Authors' Conclusions: Based on very low-certainty evidence, there is considerable uncertainty about whether antibiotic prophylaxis is beneficial, and if beneficial, which antibiotic prophylaxis is most beneficial in people with cirrhosis and ascites with low protein or history of spontaneous bacterial peritonitis. Future randomised clinical trials should be adequately powered, employ blinding, avoid postrandomisation dropouts (or perform intention-to-treat analysis), and use clinically important outcomes such as mortality, health-related quality of life, and decompensation events., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Liver transplantation is considered the definitive treatment for people with liver failure. As part of post-liver transplantation management, immunosuppression (suppressing the host immunity) is given to prevent graft rejections. Immunosuppressive drugs can be classified into those that are used for a short period during the beginning phase of immunosuppression (induction immunosuppression) and those that are used over the entire lifetime of the individual (maintenance immunosuppression), because it is widely believed that graft rejections are more common during the first few months after liver transplantation. Some drugs such as glucocorticosteroids may be used for both induction and maintenance immunosuppression because of their multiple modalities of action. There is considerable uncertainty as to whether induction immunosuppression is necessary and if so, the relative efficacy of different immunosuppressive agents., Objectives: To assess the comparative benefits and harms of different induction immunosuppressive regimens in adults undergoing liver transplantation through a network meta-analysis and to generate rankings of the different induction immunosuppressive regimens according to their safety and efficacy., Search Methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until July 2019 to identify randomised clinical trials in adults undergoing liver transplantation., Selection Criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults undergoing liver transplantation. We excluded randomised clinical trials in which participants had multivisceral transplantation and those who already had graft rejections., Data Collection and Analysis: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, and hazard ratio (HR) with 95% credible intervals (CrIs) based on an available case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance., Main Results: We included a total of 25 trials (3271 participants; 8 treatments) in the review. Twenty-three trials (3017 participants) were included in one or more outcomes in the review. The trials that provided the information included people undergoing primary liver transplantation for various indications and excluded those with HIV and those with renal impairment. The follow-up in the trials ranged from three to 76 months, with a median follow-up of 12 months among trials. All except one trial were at high risk of bias, and the overall certainty of evidence was very low. Overall, approximately 7.4% of people who received the standard regimen of glucocorticosteroid induction died and 12.2% developed graft failure. All-cause mortality and graft failure was lower with basiliximab compared with glucocorticosteroid induction: all-cause mortality (HR 0.53, 95% CrI 0.31 to 0.93; network estimate, based on 2 direct comparison trials (131 participants; low-certainty evidence)); and graft failure (HR 0.44, 95% CrI 0.28 to 0.70; direct estimate, based on 1 trial (47 participants; low-certainty evidence)). There was no evidence of differences in all-cause mortality and graft failure between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). There was also no evidence of differences in serious adverse events (proportion), serious adverse events (number), renal failure, any adverse events (proportion), any adverse events (number), liver retransplantation, graft rejections (any), or graft rejections (requiring treatment) between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). However, because of the wide CrIs, clinically important differences in these outcomes cannot be ruled out. None of the studies reported health-related quality of life., Funding: the source of funding for 14 trials was drug companies who would benefit from the results of the study; two trials were funded by neutral organisations who have no vested interests in the results of the study; and the source of funding for the remaining nine trials was unclear., Authors' Conclusions: Based on low-certainty evidence, basiliximab induction may decrease mortality and graft failure compared to glucocorticosteroids induction in people undergoing liver transplantation. However, there is considerable uncertainty about this finding because this information is based on small trials at high risk of bias. The evidence is uncertain about the effects of different induction immunosuppressants on other clinical outcomes, including graft rejections. Future randomised clinical trials should be adequately powered, employ blinding, avoid post-randomisation dropouts (or perform intention-to-treat analysis), and use clinically important outcomes such as mortality, graft failure, and health-related quality of life., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Approximately 20% of people with cirrhosis develop ascites. Several different treatments are available; including, among others, paracentesis plus fluid replacement, transjugular intrahepatic portosystemic shunts, aldosterone antagonists, and loop diuretics. However, there is uncertainty surrounding their relative efficacy., Objectives: To compare the benefits and harms of different treatments for ascites in people with decompensated liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for ascites according to their safety and efficacy., Search Methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until May 2019 to identify randomised clinical trials in people with cirrhosis and ascites., Selection Criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and ascites. We excluded randomised clinical trials in which participants had previously undergone liver transplantation., Data Collection and Analysis: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance., Main Results: We included a total of 49 randomised clinical trials (3521 participants) in the review. Forty-two trials (2870 participants) were included in one or more outcomes in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies, without other features of decompensation, having mainly grade 3 (severe), recurrent, or refractory ascites. The follow-up in the trials ranged from 0.1 to 84 months. All the trials were at high risk of bias, and the overall certainty of evidence was low or very low. Approximately 36.8% of participants who received paracentesis plus fluid replacement (reference group, the current standard treatment) died within 11 months. There was no evidence of differences in mortality, adverse events, or liver transplantation in people receiving different interventions compared to paracentesis plus fluid replacement (very low-certainty evidence). Resolution of ascites at maximal follow-up was higher with transjugular intrahepatic portosystemic shunt (HR 9.44; 95% CrI 1.93 to 62.68) and adding aldosterone antagonists to paracentesis plus fluid replacement (HR 30.63; 95% CrI 5.06 to 692.98) compared to paracentesis plus fluid replacement (very low-certainty evidence). Aldosterone antagonists plus loop diuretics had a higher rate of other decompensation events such as hepatic encephalopathy, hepatorenal syndrome, and variceal bleeding compared to paracentesis plus fluid replacement (rate ratio 2.04; 95% CrI 1.37 to 3.10) (very low-certainty evidence). None of the trials using paracentesis plus fluid replacement reported health-related quality of life or symptomatic recovery from ascites., Funding: the source of funding for four trials were industries which would benefit from the results of the study; 24 trials received no additional funding or were funded by neutral organisations; and the source of funding for the remaining 21 trials was unclear., Authors' Conclusions: Based on very low-certainty evidence, there is considerable uncertainty about whether interventions for ascites in people with decompensated liver cirrhosis decrease mortality, adverse events, or liver transplantation compared to paracentesis plus fluid replacement in people with decompensated liver cirrhosis and ascites. Based on very low-certainty evidence, transjugular intrahepatic portosystemic shunt and adding aldosterone antagonists to paracentesis plus fluid replacement may increase the resolution of ascites compared to paracentesis plus fluid replacement. Based on very low-certainty evidence, aldosterone antagonists plus loop diuretics may increase the decompensation rate compared to paracentesis plus fluid replacement., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)