Search

Objectives: Actively addressing issues of equity, diversity, and inclusion (EDI) in healthcare guidelines provides an important avenue ensure that individuals and communities receive high-quality healthcare that meets their needs. In 2020, the National Clinical Evidence Taskforce was charged with developing Australian living guidelines for COVID-19 (the Guidelines). It was intended that the Guidelines would consider the biological and social determinants of health (BSDH) underpinning evidence-based recommendations for of the treatment of COVID-19. The objective of this paper is to describe the evidence available on BSDH that is reported in published trials of disease-modifying therapies for COVID-19., Study Design and Setting: Published papers of randomized controlled trials that informed clinical recommendations (for and against drug therapies for COVID-19) in the Guidelines were reviewed retrospectively using a case series design. We extracted reported characteristics relating to BSDH. These included age, sex, gender, geographical location, ethnicity (including indigenous), disability, migrant status, income, education, employment, and social support. A descriptive analysis was conducted to illustrate the characteristics available for use in guideline development., Results: A total of 115 peer-reviewed papers describing randomized control trials of drug interventions for the treatment of COVID-19 were included. BSDH characteristics were poorly reported. Geographical location of the study was the only category reported in all papers. While age and sex were reported in most papers (n = 109 and 108, respectively), ethnicity was reported in only one-third of papers (n = 40), social support was reported in only three papers, and employment in one paper. No paper reported on gender, disability, migrant status, income, or education., Conclusion: Consideration of EDI issues is a crucial component of guideline development. Although these issues were widely recognized to impact on health outcomes from COVID-19, reporting of these characteristics was poor in COVID trials. Urgent action is needed to improve reporting of EDI characteristics if they are to be meaningfully considered in guideline processes, and health inequity is overcome., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Surrogates of antiviral efficacy are needed for COVID-19. We aimed to investigate the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in outpatients treated for mild-to-moderate COVID-19., Methods: In this systematic review and meta-analysis, we searched PubMed, Scopus, and medRxiv from database inception to Aug 16, 2023, for randomised placebo-controlled trials that tested virus-directed treatments (ie, any monoclonal antibodies, convalescent plasma, or antivirals) in non-hospitalised individuals with COVID-19. We only included studies that reported both clinical outcomes (ie, rate of disease progression to hospitalisation or death) and virological outcomes (ie, viral load within the first 7 days of treatment). We extracted summary data from eligible reports, with discrepancies resolved through discussion. We used an established meta-regression model with random effects to assess the association between clinical efficacy and virological treatment effect, and calculated I 2 to quantify residual study heterogeneity., Findings: We identified 1718 unique studies, of which 22 (with a total of 16 684 participants) met the inclusion criteria, and were in primarily unvaccinated individuals. Risk of bias was assessed as low in 19 of 22 studies for clinical outcomes, whereas for virological outcomes, a high risk of bias was assessed in 11 studies, some risk in ten studies, and a low risk in one study. The unadjusted relative risk of disease progression for each extra log 10 copies per mL reduction in viral load in treated compared with placebo groups was 0·12 (95% CI 0·04-0·34; p<0·0001) on day 3, 0·20 (0·08-0·50; p=0·0006) on day 5, and 0·53 (0·30-0·94; p=0·030) on day 7. The residual heterogeneity in our meta-regression was estimated as low (I 2 =0% [0-53] on day 3, 0% [0-71] on day 5, and 0% [0-43] on day 7)., Interpretation: Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a potential surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy., Funding: Australian Government Department of Health, Medical Research Future Fund, and Australian National Health and Medical Research Council., Competing Interests: Declaration of interests MNP declares receiving provision of drugs for clinical trials from CSL Behring, Takeda, Grifols, Emergent Biosciences, and Gilead. DSK has received access to unpublished data via collaboration with employees of Merck & Co for research purposes on an unrelated pharmaceutical product. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Keeping best practice guidelines up-to-date with rapidly emerging research evidence is challenging. 'Living guidelines' approaches enable continual incorporation of new research, assisting healthcare professionals to apply the latest evidence to their clinical practice. However, information about how living guidelines are developed, maintained and applied is limited. The Stroke Foundation in Australia was one of the first organisations to apply living guideline development methods for their Living Stroke Guidelines (LSGs), presenting a unique opportunity to evaluate the process and impact of this novel approach., Methods: A mixed-methods study was conducted to understand the experience of LSGs developers and end-users. We used thematic analysis of one-on-one semi-structured interview and online survey data to determine the feasibility, acceptability, and facilitators and barriers of the LSGs. Website analytics data were also reviewed to understand usage., Results: Overall, the living guidelines approach was both feasible and acceptable to developers and users. Facilitators to use included collaboration with multidisciplinary clinicians and stroke survivors or carers. Increased workload for developers, workload unpredictability, and limited information sharing, and interoperability of technological platforms were identified as barriers. Users indicated increased trust in the LSGs (69%), likelihood of following the LSGs (66%), and frequency of access (58%), compared with previous static versions. Web analytics data showed individual access by 16,517 users in 2016 rising to 53,154 users in 2020, a threefold increase. There was also a fourfold increase in unique LSG pageviews from 2016 to 2020., Conclusions: This study, the first evaluation of living guidelines, demonstrates that this approach to stroke guideline development is feasible and acceptable, that these approaches may add value to developers and users, and may increase guideline use. Future evaluations should be embedded along with guideline implementation to capture data prospectively., (© 2024. The Author(s).)

Objective: To describe the living systematic review (LSR) process and to share experience of planning, searches, screening, extraction, publishing and dissemination to inform and assist authors planning their own LSR. Many LSR do not publish more than one update, we hope this paper helps to increase this., Study Design and Setting: A Cochrane LSR with an international author team that has been 'living' for two years, with monthly search updates and three full updates published in this time. LSRs are regularly updated systematic reviews that allow new evidence to be incorporated as it becomes available. LSR are ideally suited to policy-relevant topics where there is uncertainty and new evidence will likely impact the interpretation and/or certainty of outcomes., Results: The key features of the process that require consideration are: specifying the frequency of searches and triggers for full updates in the protocol; stakeholder input; publishing and disseminating monthly search findings. A strong team, incorporating methodological and topic expertise, with core members that meet regularly is essential. Regular search updates make it important to have a clear cyclical schedule of activity. To achieve timely updates this process should be streamlined, for example, using automated monthly searches, and systematic reviewing software for screening. LSR provide a unique opportunity to incorporate stakeholder feedback., Conclusions: We recommend that LSRs should be: justified; carefully planned including the timing of search updates, triggers for publication and termination; published in a timely manner; have a clear dissemination plan; and a strong core team of authors., Competing Interests: Declaration of competing interest A.R.B., J.H.B., J.L.B., T.T., and N.L. have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The Australian National COVID-19 Clinical Evidence Taskforce has been developing, maintaining, and disseminating living guidelines and decision support tools (clinical flowcharts) for the care of people with suspected or confirmed COVID-19 since 2020. Living guidelines, a form of living evidence, are a relatively new approach; hence, more work is required to determine how to optimize their use to inform practice, policy, and decision-making and to explore implementation, uptake, and impact implications. An update of an earlier impact evaluation was conducted to understand sustained awareness and use of the guidelines; the factors that facilitate the widespread adoption of the guidelines and to explore the perceived strengths and opportunities for improvement of the guidelines., Study Design and Setting: A mixed-methods impact evaluation was conducted. Surveys collected both quantitative and qualitative data and were supplemented with qualitative interviews. Participants included Australian healthcare practitioners providing care to individuals with suspected or confirmed COVID-19 and people involved in policy-making. Data were collected on awareness, use, impact, strengths, and opportunities for improvement of the guidelines and flow charts., Results: A total of 148 participants completed the survey and 21 people were interviewed between January and March 2022. Awareness of the work of the Taskforce was high and more than 75% of participants reported that the guidelines were used within their workplace. Participants described the Taskforce website and guidelines as trustworthy, valuable, and reliable sources of up-to-date evidence-based information. The evaluation highlighted the varied ways the guidelines were being used across a range of settings and the diverse impacts they have from those at a clinical level to impacts at a policy level. Barriers to and enablers of impact and uptake of the guideline were explored., Conclusion: This evaluation highlights the value of living guidelines during a pandemic when the evidence base is rapidly changing and expanding. It presents useful understanding of the ways clinicians and others use living evidence to inform their clinical practice and decision-making and the diverse impacts the guidelines are having around Australia., Competing Interests: Declaration of competing interest The authors declare that they have no relevant conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Living guidelines provide reliable, ongoing evidence surveillance and regularly updated recommendations for healthcare decision-making. As a relatively new concept, most of the initial application of living approaches has been undertaken in high-income countries. However, in this scoping review, we looked at what is currently known about how living guidelines were developed, used and applied in low-income and middle-income countries., Methods: Searches for published literature were conducted in Medline, Global Health, Cochrane Library and Embase. Grey literature was identified using Google Scholar and the WHO website. In addition, the reference lists of included studies were checked for missing studies. Studies were included if they described or reflected on the development, application or utility of living guideline approaches for low-income and middle-income countries., Results: After a full-text review, 21 studies were included in the review, reporting on the development and application of living recommendations in low-income and middle-income countries. Most studies reported living guideline activities conducted by the WHO (15, 71.4%), followed by China (4, 19%), Chile (1, 4.8%) and Lebanon (1, 4.8%). All studies based on WHO reports relate to living COVID-19 management guidelines., Conclusions: Most of the studies in this review were WHO-reported studies focusing solely on COVID-19 disease treatment living guidelines. However, there was no clear explanation of how living guidelines were used nor information on the prospects for and obstacles to the implementation of living guidelines in low-income and middle-income countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. People who smoke, healthcare providers and regulators want to know if ECs can help people quit smoking, and if they are safe to use for this purpose. This is a review update conducted as part of a living systematic review., Objectives: To examine the safety, tolerability and effectiveness of using electronic cigarettes (ECs) to help people who smoke tobacco achieve long-term smoking abstinence, in comparison to non-nicotine EC, other smoking cessation treatments and no treatment., Search Methods: We searched the Cochrane Tobacco Addiction Group's Specialized Register to 1 February 2023, and Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 July 2023, and reference-checked and contacted study authors., Selection Criteria: We included trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention as these studies have the potential to provide further information on harms and longer-term use. Studies had to report an eligible outcome., Data Collection and Analysis: We followed standard Cochrane methods for screening and data extraction. Critical outcomes were abstinence from smoking after at least six months, adverse events (AEs), and serious adverse events (SAEs). We used a fixed-effect Mantel-Haenszel model to calculate risk ratios (RRs) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data in pairwise and network meta-analyses (NMA)., Main Results: We included 88 completed studies (10 new to this update), representing 27,235 participants, of which 47 were randomized controlled trials (RCTs). Of the included studies, we rated ten (all but one contributing to our main comparisons) at low risk of bias overall, 58 at high risk overall (including all non-randomized studies), and the remainder at unclear risk. There is high certainty that nicotine EC increases quit rates compared to nicotine replacement therapy (NRT) (RR 1.59, 95% CI 1.29 to 1.93; I 2 = 0%; 7 studies, 2544 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 2 to 6 more). There is moderate-certainty evidence (limited by imprecision) that the rate of occurrence of AEs is similar between groups (RR 1.03, 95% CI 0.91 to 1.17; I 2 = 0%; 5 studies, 2052 participants). SAEs were rare, and there is insufficient evidence to determine whether rates differ between groups due to very serious imprecision (RR 1.20, 95% CI 0.90 to 1.60; I 2 = 32%; 6 studies, 2761 participants; low-certainty evidence). There is moderate-certainty evidence, limited by imprecision, that nicotine EC increases quit rates compared to non-nicotine EC (RR 1.46, 95% CI 1.09 to 1.96; I 2 = 4%; 6 studies, 1613 participants). In absolute terms, this might lead to an additional three quitters per 100 (95% CI 1 to 7 more). There is moderate-certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I 2 = 0%; 5 studies, 1840 participants). There is insufficient evidence to determine whether rates of SAEs differ between groups, due to very serious imprecision (RR 1.00, 95% CI 0.56 to 1.79; I 2 = 0%; 9 studies, 1412 participants; low-certainty evidence). Due to issues with risk of bias, there is low-certainty evidence that, compared to behavioural support only/no support, quit rates may be higher for participants randomized to nicotine EC (RR 1.88, 95% CI 1.56 to 2.25; I 2 = 0%; 9 studies, 5024 participants). In absolute terms, this represents an additional four quitters per 100 (95% CI 2 to 5 more). There was some evidence that (non-serious) AEs may be more common in people randomized to nicotine EC (RR 1.22, 95% CI 1.12 to 1.32; I 2 = 41%, low-certainty evidence; 4 studies, 765 participants) and, again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 0.89, 95% CI 0.59 to 1.34; I 2 = 23%; 10 studies, 3263 participants; very low-certainty evidence). Results from the NMA were consistent with those from pairwise meta-analyses for all critical outcomes, and there was no indication of inconsistency within the networks. Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued EC use. Very few studies reported data on other outcomes or comparisons, hence, evidence for these is limited, with CIs often encompassing both clinically significant harm and benefit., Authors' Conclusions: There is high-certainty evidence that ECs with nicotine increase quit rates compared to NRT and moderate-certainty evidence that they increase quit rates compared to ECs without nicotine. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain due to risk of bias inherent in the study design. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, with no difference in AEs between nicotine and non-nicotine ECs nor between nicotine ECs and NRT. Overall incidence of SAEs was low across all study arms. We did not detect evidence of serious harm from nicotine EC, but the longest follow-up was two years and the number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information to decision-makers, this review is a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: While there has been widespread global acceptance of the importance of evidence-informed policy, many opportunities to inform health policy with research are missed, often because of a mismatch between when and where reliable evidence is needed, and when and where it is available. 'Living evidence' is an approach where systematic evidence syntheses (e.g. living reviews, living guidelines, living policy briefs, etc.) are continually updated to incorporate new relevant evidence as it becomes available. Living evidence approaches have the potential to overcome a major barrier to evidence-informed policy, making up-to-date systematic summaries of policy-relevant research available at any time that policy-makers need them. These approaches are likely to be particularly beneficial given increasing calls for policy that is responsive, and rapidly adaptive to changes in the policy context. We describe the opportunities presented by living evidence for evidence-informed policy-making and highlight areas for further exploration., Discussion: There are several elements of living approaches to evidence synthesis that might support increased and improved use of evidence to inform policy. Reviews are explicitly prioritised to be 'living' by partnerships between policy-makers and researchers based on relevance to decision-making, as well as uncertainty of existing evidence, and likelihood that new evidence will arise. The ongoing nature of the work means evidence synthesis teams can be dynamic and engage with policy-makers in a variety of ways over time; and synthesis topics, questions and methods can be adapted as policy interests or contextual factors shift. Policy-makers can sign-up to be notified when relevant new evidence is found, and can be confident that living syntheses are up-to-date and contain all research whenever they access them. The always up-to-date nature of living evidence syntheses means producers can rapidly demonstrate availability of relevant, reliable evidence when it is needed, addressing a frequently cited barrier to evidence-informed policymaking., Conclusions: While there are challenges to be overcome, living evidence provides opportunities to enable policy-makers to access up-to-date evidence whenever they need it and also enable researchers to respond to the issues of the day with up-to-date research; and update policy-makers on changes in the evidence base as they arise. It also provides an opportunity to build flexible partnerships between researchers and policy-makers to ensure that evidence syntheses reflect the changing needs of policy-makers., (© 2023. The Author(s).)

Background: Continual evidence surveillance is an integral feature of living guidelines. The Australian Stroke Guidelines include recommendations on 100 clinical topics and have been 'living' since 2018., Objectives: To describe the approach for establishing and evaluating an evidence surveillance system for the living Australian Stroke Guidelines., Methods: We developed a pragmatic surveillance system based on an analysis of the searches for the 2017 Stroke Guidelines and evaluated its reliability by assessing the potential impact on guideline recommendations. Search retrieval and screening workload are monitored monthly, together with the frequency of changes to the guideline recommendations., Results: Evidence surveillance was guided by practical considerations of efficiency and sustainability. A single PubMed search covering all guideline topics, limited to systematic reviews and randomised trials, is run monthly. The search retrieves about 400 records a month of which a sixth are triaged to the guideline panels for further consideration. Evaluations with Epistemonikos and the Cochrane Stroke Trials Register demonstrated the robustness of adopting this more restrictive approach. Collaborating with the guideline team in designing, implementing and evaluating the surveillance is essential for optimising the approach., Conclusion: Monthly evidence surveillance for a large living guideline is feasible and sustainable when applying a pragmatic approach., (© 2023 The Authors. Health Information and Libraries Journal published by John Wiley & Sons Ltd on behalf of Health Libraries Group.)

Background: Randomised controlled trials of passive antibodies as treatment and prophylaxis for COVID-19 have reported variable efficacy. However, the determinants of efficacy have not been identified. We aimed to assess how the dose and timing of administration affect treatment outcome., Methods: In this systematic review and meta-analysis, we extracted data from published studies of passive antibody treatment from Jan 1, 2019, to Jan 31, 2023, that were identified by searching multiple databases, including MEDLINE, PubMed, and ClinicalTrials.gov. We included only randomised controlled trials of passive antibody administration for the prevention or treatment of COVID-19. To compare administered antibody dose between different treatments, we used data on in-vitro neutralisation titres to normalise dose by antibody potency. We used mixed-effects regression and model fitting to analyse the relationship between timing, dose and efficacy., Findings: We found 58 randomised controlled trials that investigated passive antibody therapies for the treatment or prevention of COVID-19. Earlier clinical stage at treatment initiation was highly predictive of the efficacy of both monoclonal antibodies (p<0·0001) and convalescent plasma therapy (p=0·030) in preventing progression to subsequent stages, with either prophylaxis or treatment in outpatients showing the greatest effects. For the treatment of outpatients with COVID-19, we found a significant association between the dose administered and efficacy in preventing hospitalisation (relative risk 0·77; p<0·0001). Using this relationship, we predicted that no approved monoclonal antibody was expected to provide more than 30% efficacy against some omicron (B.1.1.529) subvariants, such as BQ.1.1., Interpretation: Early administration before hospitalisation and sufficient doses of passive antibody therapy are crucial to achieving high efficacy in preventing clinical progression. The relationship between dose and efficacy provides a framework for the rational assessment of future passive antibody prophylaxis and treatment strategies for COVID-19., Funding: The Australian Government Department of Health, Medical Research Future Fund, National Health and Medical Research Council, the University of New South Wales, Monash University, Haematology Society of Australia and New Zealand, Leukaemia Foundation, and the Victorian Government., Competing Interests: Declaration of interests MNP declares receiving provision of drug for clinical trials from CSL Behring, Takeda, Grifols, Emergent Biosciences, and Gilead. ZKM and EMW declare research funding from CSL Behring to Monash University for work outside this project. All other authors declare no competing interests., (Copyright © 2023 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.)

A "living" approach to clinical practice guidelines is when the identification, appraisal and synthesis of evidence is maintained and repeated at an agreed frequency, with a clear process for when and how new evidence is to be incorporated. The value of a living approach to guidelines was emphasised during the COVID-19 pandemic when health professionals and policymakers needed to make decisions regarding patient care in the context of a nascent but rapidly evolving evidence base. In this perspective, we draw on our recent experience developing Australian and international living guidelines and reflect on the feasibility of applying living guideline methods and processes to a lifecycle approach to health technology assessment (HTA). We believe the opportunities and challenges of adopting a living approach in HTA fall into five key themes: identification, appraisal and synthesis of evidence; optimising the frequency of updates; embedding ongoing multi-stakeholder engagement; linking the emergence of new evidence to reimbursement; and system capacity to support a living approach. We acknowledge that the suitability of specific living approaches to HTA will be heavily influenced by the type of health technology, its intended use in the health system, local reimbursement pathways, and other policy settings. But we believe that the methods and processes applied successfully to guideline development to manage evidentiary uncertainty could be applied in the context of HTA and reimbursement decision-making to help manage similar sources of uncertainty., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cheyne, Chakraborty, Lewis, Campbell, Turner and Norris.)

Background: COVID-19 led to a rapid acceleration in the number of systematic reviews. Readers need to know how up to date evidence is when selecting reviews to inform decisions. This cross-sectional study aimed to evaluate how easily the currency of COVID-19 systematic reviews published early in the pandemic could be determined and how up to date these reviews were at the time of publication., Methods: We searched for systematic reviews and meta-analyses relevant to COVID-19 added to PubMed in July 2020 and January 2021, including any that were first published as preprints. We extracted data on the date of search, number of included studies, and date first published online. For the search date, we noted the format of the date and where in the review this was reported. A sample of non-COVID-19 systematic reviews from November 2020 served as a comparator., Results: We identified 246 systematic reviews on COVID-19. In the abstract of these reviews, just over half (57%) reported the search date (day/month/year or month/year) while 43% failed to report any date. When the full text was considered, the search date was missing from 6% of reviews. The median time from last search to publication online was 91 days (IQR 63-130). Time from search to publication was similar for the subset of 15 rapid or living reviews (92 days) but shorter for the 29 reviews published as preprints (37 days). The median number of studies or publications included per review was 23 (IQR 12-40). In the sample of 290 non-COVID SRs, around two-thirds (65%) reported the search date while a third (34%) did not include any date in the abstract. The median time from search to publication online was 253 days (IQR 153-381) and each review included a median of 12 studies (IQR 8-21)., Conclusions: Despite the context of the pandemic and the need to easily ascertain the currency of systematic reviews, reporting of the search date information for COVID-19 reviews was inadequate. Adherence to reporting guidelines would improve the transparency and usefulness of systematic reviews to users., (© 2023. The Author(s).)

Objectives: To introduce methods for living guidelines based on practical experiences by the Australian Living Evidence Consortium (ALEC), the National Institute of Health and Care Excellence (NICE), and the Infectious Diseases Society of America (IDSA), with methodological support from the US Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Network., Study Design and Setting: Members of ALEC, NICE, and the US GRADE Network, convened a working group to share experiences of the methods used to develop living guidelines and outline the key differences between traditional and living guidelines methods., Results: The guidance includes the following steps: 1) deciding if the guideline is a priority for a living approach, 2) preparing for living guideline development, 3) literature surveillance and frequency of searching, 4) assessment and synthesis of the evidence, 5) publication and dissemination, and 6) transitioning recommendations out of living mode., Conclusion: This paper introduces methods for living guidelines and provides examples of the similarities and differences in approach across multiple organizations conducting living guidelines. It also introduces a series of papers exploring methods for living guidelines based on our practical experiences, including consumer involvement, selecting and prioritizing questions, search decisions, and methods decisions., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe and reflect on the consumer engagement approaches used in five living guidelines from the perspectives of consumers (i.e., patients, carers, the public, and their representatives) and guideline developers., Study Design and Setting: In a descriptive report, we used a template to capture engagement approaches and the experiences of consumers and guideline developers in living guidelines in Australia and the United Kingdom. Responses were summarized using descriptive synthesis., Results: One guideline used a Consumer Panel, three included two to three consumers in the guideline development group, and one did both. Much of our experience was common to all guidelines (e.g., consumers felt welcomed but that their role initially lacked clarity). We identified six challenges and opportunities specific to living guidelines: managing the flow of work; managing engagement in online environments; managing membership of the panel; facilitating more flexibility, variety and depth in engagement; recruiting for specific skills-although these can be built over time; developing living processes to improve; and adapting consumer engagement together., Conclusion: Consumer engagement in living guidelines should follow established principles of consumer engagement in guidelines. Conceiving the engagement as living, underpinned by a living process evaluation, allows the approach to be developed with consumers over time., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Producing living guidelines requires making important decisions about methods for evidence identification, appraisal, and integration to allow the living mode to function. Clarifying what these decisions are and the trade-offs between options is necessary. This article provides living guideline developers with a framework to enable them to choose the most suitable model for their living guideline topic, question, or context., Study Design and Setting: We developed this guidance through an iterative process informed by interviews, feedback, and a consensus process with an international group of living guideline developers., Results: Several key decisions need to be made both before commencing and throughout the continual process of living guideline development and maintenance. These include deciding what approach is taken to the systematic review process; decisions about methods to be applied for the evidence appraisal process, including the use of unpublished data; and selection of "triggers" to incorporate new studies into living guideline recommendations. In each case, there are multiple options and trade-offs., Conclusion: We identify trade-offs and important decisions to be considered throughout the living guideline development process. The most appropriate, and most sustainable, mode of development and updating will be dependent on the choices made in each of these areas., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This article is part of a series on methods for living guidelines, consolidating practical experiences from developing living guidelines. It focuses on methods for identification, selection, and prioritization of clinical questions for a living approach to guideline development., Study Design and Setting: Members of the Australian Living Evidence Consortium, the National Institute of Health and Care Excellence and the US Grading of Recommendations, Assessment, Development and Evaluations Network, convened a working group. All members have expertize and practical experience in the development of living guidelines. We collated methods, documents on prioritization from each organization's living guidelines, conducted interviews and held working group discussions. We consolidated these to form best practice principles which were then edited and agreed on by the working group members., Results: We developed best practice principles for (1) identification, (2) selection, and (3) prioritization, of questions for a living approach to guideline development. Several different strategies for undertaking prioritizing questions are explored., Conclusion: The article provides guidance for prioritizing questions in living guidelines. Subsequent articles in this series explore consumer involvement, search decisions, and methods decisions that are appropriate for questions with different priority levels., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate how quickly evidence was incorporated into the Australian living guidelines for COVID-19 during the first 12 months of the pandemic., Study Design and Setting: For each study concerning drug therapies included in the guideline from April 3, 2020 to April 1, 2021, we extracted the publication date of the study, and the guideline version the study was included in. We analyzed two subgroups of studies as follows: those published in high impact factor journals and those with 100 or more participants., Results: In the first year, we published 37 major versions of the guidelines, incorporating 129 studies that investigated 48 drug therapies informing 115 recommendations. The median time from first publication of a study to incorporation in the guideline was 27 days (interquartile range [IQR], 16 to 44), ranging from 9 to 234 days. For the 53 studies in the highest impact factor journals, the median was 20 days (IQR 15 to 30), and for the 71 studies with 100 or more participants the median was 22 days (IQR 15 to 36)., Conclusion: Developing and sustaining living guidelines where evidence is rapidly incorporated is a resource- and time-intensive undertaking; however, this study demonstrates that it is feasible, even over a long period., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. Some people who smoke use ECs to stop or reduce smoking, although some organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit smoking, and if they are safe to use for this purpose. This is a review update conducted as part of a living systematic review., Objectives: To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke tobacco achieve long-term smoking abstinence., Search Methods: We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 July 2022, and reference-checked and contacted study authors.  SELECTION CRITERIA: We included randomized controlled trials (RCTs) and randomized cross-over trials, in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. Studies had to report abstinence from cigarettes at six months or longer or data on safety markers at one week or longer, or both., Data Collection and Analysis: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included the proportion of people still using study product (EC or pharmacotherapy) at six or more months after randomization or starting EC use, changes in carbon monoxide (CO), blood pressure (BP), heart rate, arterial oxygen saturation, lung function, and levels of carcinogens or toxicants, or both. We used a fixed-effect Mantel-Haenszel model to calculate risk ratios (RRs) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data in meta-analyses., Main Results: We included 78 completed studies, representing 22,052 participants, of which 40 were RCTs. Seventeen of the 78 included studies were new to this review update. Of the included studies, we rated ten (all but one contributing to our main comparisons) at low risk of bias overall, 50 at high risk overall (including all non-randomized studies), and the remainder at unclear risk. There was high certainty that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (RR 1.63, 95% CI 1.30 to 2.04; I 2 = 10%; 6 studies, 2378 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 2 to 6). There was moderate-certainty evidence (limited by imprecision) that the rate of occurrence of AEs was similar between groups (RR 1.02, 95% CI 0.88 to 1.19; I 2 = 0%; 4 studies, 1702 participants). SAEs were rare, but there was insufficient evidence to determine whether rates differed between groups due to very serious imprecision (RR 1.12, 95% CI 0.82 to 1.52; I 2 = 34%; 5 studies, 2411 participants). There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.94, 95% CI 1.21 to 3.13; I 2 = 0%; 5 studies, 1447 participants). In absolute terms, this might lead to an additional seven quitters per 100 (95% CI 2 to 16). There was moderate-certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I 2 = 0%; 5 studies, 1840 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 1.00, 95% CI 0.56 to 1.79; I 2 = 0%; 8 studies, 1272 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.66, 95% CI 1.52 to 4.65; I 2 = 0%; 7 studies, 3126 participants). In absolute terms, this represents an additional two quitters per 100 (95% CI 1 to 3). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was some evidence that (non-serious) AEs were more common in people randomized to nicotine EC (RR 1.22, 95% CI 1.12 to 1.32; I 2 = 41%, low certainty; 4 studies, 765 participants) and, again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 1.03, 95% CI 0.54 to 1.97; I 2 = 38%; 9 studies, 1993 participants).  Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued EC use. Very few studies reported data on other outcomes or comparisons, hence evidence for these is limited, with CIs often encompassing clinically significant harm and benefit., Authors' Conclusions: There is high-certainty evidence that ECs with nicotine increase quit rates compared to NRT and moderate-certainty evidence that they increase quit rates compared to ECs without nicotine. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the effect size. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, with no difference in AEs between nicotine and non-nicotine ECs nor between nicotine ECs and NRT. Overall incidence of SAEs was low across all study arms. We did not detect evidence of serious harm from nicotine EC, but longest follow-up was two years and the number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates, but further RCTs are underway. To ensure the review continues to provide up-to-date information to decision-makers, this review is a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: In 2019, WHO prioritized updating recommendations relating to three labour induction topics: labour induction at or beyond term, mechanical methods for labour induction, and outpatient labour induction. As part of this process, we aimed to review the evidence addressing factors beyond clinical effectiveness (values, human rights and sociocultural acceptability, health equity, and economic and feasibility considerations) to inform WHO Guideline Development Group decision-making using the WHO-INTEGRATE evidence-to-decision framework, and to reflect on how methods for identifying, synthesizing and integrating this evidence could be improved., Methods: We adapted the framework to consider the key criteria and sub-criteria relevant to our intervention. We searched for qualitative and other evidence across a variety of sources and mapped the eligible evidence to country income setting and perspective. Eligibility assessment and quality appraisal of qualitative evidence syntheses was undertaken using a two-step process informed by the ENTREQ statement. We adopted an iterative approach to interpret the evidence and provided both summary and detailed findings to the decision-makers. We also undertook a review to reflect on opportunities to improve the process of applying the framework and identifying the evidence., Results: Using the WHO-INTEGRATE framework allowed us to explore health rights and equity in a systematic and transparent way. We identified a lack of qualitative and other evidence from low- and middle-income settings and in populations that are most impacted by structural inequities or traditionally excluded from research. Our process review highlighted opportunities for future improvement, including adopting more systematic evidence mapping methods and working with social science researchers to strengthen theoretical understanding, methods and interpretation of the evidence., Conclusions: Using the WHO-INTEGRATE evidence-to-decision framework to inform decision-making in a global guideline for induction of labour, we identified both challenges and opportunities relating to the lack of evidence in populations and settings of need and interest; the theoretical approach informing the development and application of WHO-INTEGRATE; and interpretation of the evidence. We hope these insights will be useful for primary researchers as well as the evidence synthesis and health decision-making communities, and ultimately contribute to a reduction in health inequities., (© 2022. The Author(s).)

Introduction: Pregnant women are at higher risk of severe illness from coronavirus disease 2019 (COVID-19) than non-pregnant women of a similar age. Early in the COVID-19 pandemic, it was clear that evidenced-based guidance was needed, and that it would need to be updated rapidly. The National COVID-19 Clinical Evidence Taskforce provided a resource to guide care for people with COVID-19, including during pregnancy. Care for pregnant and breastfeeding women and their babies was included as a priority when the Taskforce was set up, with a Pregnancy and Perinatal Care Panel convened to guide clinical practice., Main Recommendations: As of May 2022, the Taskforce has made seven specific recommendations on care for pregnant women and those who have recently given birth. This includes supporting usual practices for the mode of birth, umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, and using antenatal corticosteroids and magnesium sulfate as clinically indicated. There are 11 recommendations for COVID-19-specific treatments, including conditional recommendations for using remdesivir, tocilizumab and sotrovimab. Finally, there are recommendations not to use several disease-modifying treatments for the treatment of COVID-19, including hydroxychloroquine and ivermectin. The recommendations are continually updated to reflect new evidence, and the most up-to-date guidance is available online (https://covid19evidence.net.au)., Changes in Management Resulting From the Guidelines: The National COVID-19 Clinical Evidence Taskforce has been a critical component of the infrastructure to support Australian maternity care providers during the COVID-19 pandemic. The Taskforce has shown that a rapid living guidelines approach is feasible and acceptable., (© 2022 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Introduction: The Australian National COVID-19 Clinical Evidence Taskforce was established in March 2020 to maintain up-to-date recommendations for the treatment of people with coronavirus disease 2019 (COVID-19). The original guideline (April 2020) has been continuously updated and expanded from nine to 176 recommendations, facilitated by the rapid identification, appraisal, and analysis of clinical trial findings and subsequent review by expert panels., Main Recommendations: In this article, we describe the recommendations for treating non-pregnant adults with COVID-19, as current on 1 August 2022 (version 61.0). The Taskforce has made specific recommendations for adults with severe/critical or mild disease, including definitions of disease severity, recommendations for therapy, COVID-19 prophylaxis, respiratory support, and supportive care., Changes in Management as a Result of the Guideline: The Taskforce currently recommends eight drug treatments for people with COVID-19 who do not require supplemental oxygen (inhaled corticosteroids, casirivimab/imdevimab, molnupiravir, nirmatrelvir/ritonavir, regdanvimab, remdesivir, sotrovimab, tixagevimab/cilgavimab) and six for those who require supplemental oxygen (systemic corticosteroids, remdesivir, tocilizumab, sarilumab, baricitinib, casirivimab/imdevimab). Based on evidence of their achieving no or only limited benefit, ten drug treatments or treatment combinations are not recommended; an additional 42 drug treatments should only be used in the context of randomised trials. Additional recommendations include support for the use of continuous positive airway pressure, prone positioning, and endotracheal intubation in patients whose condition is deteriorating, and prophylactic anticoagulation for preventing venous thromboembolism. The latest updates and full recommendations are available at www.covid19evidence.net.au., (© 2022 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Background: Non-communicable diseases (NCDs) are a leading cause of maternal mortality and morbidity worldwide. The World Health Organization is developing new recommendations focusing on the management of NCDs for pregnant, intrapartum, and postnatal women. Thus, to support the development of new guidelines and recommendations, we aimed to determine the availability, focus, and scope of recommendations of current guidelines for the management of NCDs during pregnancy, intrapartum, and postnatal period., Methods: PubMed, Global Index Medicus, TRIP, and Guideline International Network databases were searched on 31 May 2021, to identify any NCD-related guidelines published between 2011 and 2021 with no language or country restrictions. Websites of 165 professional organizations were also searched. Characteristics of included guidelines were analyzed, and recommendations were extracted from guidelines of five high-priority NCD conditions (diabetes, chronic hypertension, respiratory conditions, hemoglobinopathies and sickle cell disease, and mental and substance use disorders)., Results: From 6026 citations and 165 websites, 405 guidelines were included of which 132 (33%) were pregnancy-specific and 285 (88%) were developed in high-income countries. Among pregnancy-specific guidelines, the most common conditions for which recommendations were provided were gestational diabetes, circulatory diseases, thyroid disorders, and hypertensive disorders of pregnancy. For the five high-priority conditions, 47 guidelines were identified which provided 1834 recommendations, largely focused on antenatal care interventions (62%) such as early detection, screening tools, pharmacological treatment, and lifestyle education. Postnatal recommendations largely covered postnatal clinical assessments, lifestyle education, and breastfeeding. Health system recommendations largely covered multidisciplinary care teams and strengthening referral pathways., Conclusions: This study provides a robust assessment of currently available guidelines and mapping of recommendations on NCD management within maternal health services, which will inform the scope of the World Health Organization's future guideline development activities. This study identified a need to develop guidelines that consider NCDs holistically, with an integrated approach to antenatal, intrapartum, and postnatal care, and that are relevant for resource-limited contexts. Any such guidelines should consider what interventions are most essential to improving outcomes for women with NCDs and their newborns, and how variations in quality of NCD-related care can be addressed., (© 2022. The Author(s).)

Background: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence., Objective: To develop a framework that characterizes the processes of development of living practice guidelines in health care., Design: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders., Setting: International., Participants: Multidisciplinary group of 51 persons who have experience with guidelines., Measurements: Not applicable., Results: A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the organization's adoption of the living methodology as well as each specific guideline project. The production process consists of initiation, maintenance, and retirement phases. The reporting should cover the evidence surveillance time stamp, the outcome of reassessment of the body of evidence (when applicable), and the outcome of revisiting a recommendation (when applicable). The dissemination process may necessitate the use of different venues, including one for formal publication., Limitation: This study does not provide detailed or practical guidance for how the described concepts would be best implemented., Conclusion: The framework will help guideline developers in planning, producing, reporting, and disseminating living guideline projects. It will also help research methodologists study the processes of living guidelines., Primary Funding Source: None.

Objectives: To identify and map all trials in maternal health conducted in low and middle-income countries (LMIC) over the 10-year period from 2010 to 2019, to identify geographical and thematic trends, as well as comparing to global causes of maternal death and preidentified priority areas., Design: Systematic scoping review., Primary and Secondary Outcome Measures: Extracted data included location, study characteristics and whether trials corresponded to causes of mortality and identified research priority topics., Results: We searched the Cochrane Central Register of Controlled Trials database, a combined registry of trials from multiple sources. Our search identified 7269 articles, 874 of which were included for analysis. Between 2010 and 2019, maternal health trials conducted in LMICs more than doubled (50-114). Trials were conducted in 61 countries-231 trials (26.4%) were conducted in Iran. Only 225 trials (25.7%) were aligned with a cause of maternal mortality. Within these trials, pre-existing medical conditions, embolism, obstructed labour and sepsis were all under-represented when compared with number of maternal deaths globally. Large numbers of studies were conducted on priority topics such as labour and delivery, obstetric haemorrhage and antenatal care. Hypertensive disorders of pregnancy, diabetes and health systems and policy-despite being high-priority topics-had relatively few trials., Conclusion: Despite trials conducted in LMICs increasing from 2010 to 2019, there were significant gaps in geographical distribution, alignment with causes of maternal mortality and known research priority topics. The research gaps identified provide guidance and insight for future research conduct in low-resource settings., Trial Registration Number: 10.17605/OSF.IO/QUJP5., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: "Living guidelines" are guidelines which are continually kept up to date as new evidence emerges. Living guideline methods are evolving. The aim of this study was to determine how frequently searches for new evidence should be undertaken for the Australian Living Stroke Guidelines., Methods: Members of the Living Stroke Guidelines Development Group were invited to complete an online survey. Participants nominated one or more recommendation topics from the Living Stroke Guidelines with which they had been involved and answered questions about that topic, assessing whether it met criteria for living evidence synthesis, and how frequently searches for new evidence should be undertaken and why. For each topic we also determined how many studies had been assessed and included, and whether recommendations had been changed., Results: Fifty-seven assessments were received from 33 respondents, covering half of the 88 guideline topic areas. Nearly all assessments (49, 86%) were that the continual updating process should be maintained. Only three assessments (5%) deemed that searches should be conducted monthly; 3-monthly (14, 25%), 6-monthly (13, 23%) and yearly (17, 30%) searches were far more frequently recommended. Rarely (9, 16%) were topics deemed to meet all three criteria for living review. The vast majority of assessments (45, 79%) deemed the topic a priority for decision-making. Nearly half indicated that there was uncertainty in the available evidence or that new evidence was likely to be available soon. Since 2017, all but four of the assessed topic areas have had additional studies included in the evidence summary. For eight topics, there have been changes in recommendations, and revisions are underway for an additional six topics. Clinical importance was the most common reason given for why continual evidence surveillance should be undertaken. Workload for reviewers was a concern, particularly for topics where there is a steady flow of publication of small trials., Conclusions: Our study found that participants felt that the vast majority of topics assessed in the Living Stroke Guidelines should be continually updated. However, only a fifth of topic areas were assessed as conclusively meeting all three criteria for living review, and the definition of "continual" differed widely. This work has informed decisions about search frequency for the Living Stroke Guidelines and form the basis of further research on methods for frequent updating of guidelines., (© 2022. The Author(s).)

Background: Guideline developers are encouraged to engage patients, carers and their representatives ('consumers') from diverse backgrounds in guideline development to produce more widely applicable guidelines. However, consumers from diverse backgrounds are infrequently included in guidelines and there is scant research to support guideline developers to do this., Objectives: To identify principles and approaches to broaden the diversity of consumers engaged in guideline development., Design: Scoping review and semi-structured interviews., Methods: We conducted comprehensive searches to March 2020 for studies, reports and guidance documents. Inclusion criteria included the terms 'consumer' (patients, carers and their representatives), 'diversity' (defined using the PROGRESS-PLUS mnemonic) and 'consumer engagement' (the active involvement of consumers at any stage of guideline development). We also conducted four interviews with consumers and guideline developers. We used descriptive synthesis to identify themes, and summarised information about implemented approaches used to broaden diversity of consumers in guidelines., Results: From 10 included documents, we identified eight themes. Themes covered general engagement concepts (Respectful partnerships; Recruitment; Expectations, process and review); specific concepts about guideline development group (GDG) engagement (Characteristics of guideline personnel; Consumers' role, characteristics and prominence; Preparing and supporting consumers); and other (non-GDG) approaches (Online methods; Consultations and research-based approaches). The most commonly included PROGRESS-PLUS categories were Disability, Race/culture/ethnicity/language, Place of residence and Other vulnerable (eg, 'disadvantaged groups'). Each theme included the views of both consumers and guideline developers. We found descriptions of 12 implemented engagement approaches to broaden diversity of consumers in guidelines., Conclusions: Relationship-building, mitigating power imbalances and meeting consumers where they are at underpin our findings. Engaging with diverse groups may require greater attention to building formal, respectful partnerships and employing inclusive engagement methods., Competing Interests: Competing interests: None declared, (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the completeness and currency of published systematic reviews of remdesivir for COVID-19 and to compare this with a living guidelines approach., Study Design and Setting: In this cross-sectional study, we searched Europe PMC on May 20, 2021 for systematic reviews of remdesivir (including preprints, living review updates). Completeness and currency were based on the inclusion of four major randomized trials of remdesivir available at the time of publication of the review (including as preliminary results and preprints)., Results: We included 38 reviews (45 reports), equivalent to a new publication every 9 days. 23 (51%) reports were out of date at the time of publication. Eleven reviews that were current on publication had a median survival time of 10 days (range 4-57). A third of reviews cited other systematic reviews, but only four provided justifications for why another review was necessary. Eight (21%) of the reviews were registered in PROSPERO. The Australian COVID-19 Clinical Evidence Taskforce living guidelines were updated within 14 days for three of the remdesivir trials, and within 28 days for the fourth., Conclusion: There was considerable duplication of systematic reviews of remdesivir, and half were already out of date at the time of publication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Early diagnosis and prompt antibiotic treatment are crucial to reducing morbidity and mortality of early-onset sepsis (EOS) in neonates. However, this strategy remains challenging due to non-specific clinical findings and limited facilities. Inappropriate antibiotics use is associated with ineffective therapy and adverse outcomes. This study aims to determine the characteristics of EOS and use of antibiotics in the neonatal-intensive care units (NICUs) in Indonesia, informing efforts to drive improvements in the prevention, diagnosis, and treatment of EOS., Methods: A descriptive study was conducted based on pre-intervention data of the South East Asia-Using Research for Change in Hospital-acquired Infection in Neonates project. Our study population consisted of neonates admitted within 72 h of life to the three participating NICUs. Neonates who presented with three or more clinical signs or laboratory results consistent with sepsis and who received antibiotics for 5 consecutive days were considered to have EOS. Culture-proven EOS was defined as positive blood or cerebrospinal fluid culture. Type and duration of antibiotics used were also documented., Results: Of 2,509 neonates, 242 cases were suspected of having EOS (9.6%) with culture-proven sepsis in 83 cases (5.0% of neonatal admissions in hospitals with culture facilities). The causative organisms were mostly gram-negative bacteria (85/94; 90.4%). Ampicillin / amoxicillin and amikacin were the most frequently prescribed antibiotics in hospitals with culture facilities, while a third-generation cephalosporin was mostly administered in hospital without culture facilities. The median durations of antibiotic therapy were 19 and 9 days in culture-proven and culture-negative EOS groups, respectively., Conclusions: The overall incidence of EOS and culture-proven EOS was high in Indonesia, with diverse and prolonged use of antibiotics. Prospective antibiotic surveillance and stewardship interventions are required., (© 2022. The Author(s).)

Background: Millions of people have acquired and died from SARS-CoV-2 infection during the COVID-19 pandemic. Healthcare workers (HCWs) are required to wear personal protective equipment (PPE), including surgical masks and P2/N95 respirators, to prevent infection while treating patients. However, the comparative effectiveness of respirators and masks in preventing SARS-CoV-2 infection and the likelihood of experiencing adverse events (AEs) with wear are unclear., Methods: Searches were carried out in PubMed, Europe PMC and the Cochrane COVID-19 Study Register to 14 June 2021. A systematic review of comparative epidemiological studies examining SARS-CoV-2 infection or AE incidence in HCWs wearing P2/N95 (or equivalent) respirators and surgical masks was performed. Article screening, risk of bias assessment and data extraction were duplicated. Meta-analysis of extracted data was carried out in RevMan., Results: Twenty-one studies were included, with most having high risk of bias. There was no statistically significant difference in respirator or surgical mask effectiveness in preventing SARS-CoV-2 infection (OR 0.85, [95%CI 0.72, 1.01]). Healthcare workers experienced significantly more headaches (OR 2.62, [95%CI 1.18, 5.81]), respiratory distress (OR 4.21, [95%CI 1.46, 12.13]), facial irritation (OR 1.80, [95%CI 1.03, 3.14]) and pressure-related injuries (OR 4.39, [95%CI 2.37, 8.15]) when wearing respirators compared to surgical masks., Conclusion: The existing epidemiological evidence does not enable definitive assessment of the effectiveness of respirators compared to surgical masks in preventing infection. Healthcare workers wearing respirators may be more likely to experience AEs. Effective mitigation strategies are important to ensure the uptake and correct use of respirators by HCWs., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: The Australian National COVID-19 Clinical Evidence Taskforce is developing living, evidence-based, national guidelines for treatment of people with COVID-19. These living guidelines are updated each week. We undertook an impact evaluation to understand the extent to which health professionals providing treatment to people with COVID 19 were aware of, valued and used the guidelines, and the factors that enabled or hampered this., Methods: A mixed methods approach was used for the evaluation. Surveys were conducted to collect both quantitative and qualitative data and were supplemented with qualitative interviews. Australian healthcare practitioners potentially providing care to individuals with suspected or confirmed COVID-19 were invited to participate. Data were collected on guideline awareness, relevance, ease of use, trustworthiness, value, importance of updating, use, and strengths and opportunities for improvement., Results: A total of 287 people completed the surveys and 10 interviews were conducted during November 2020. Awareness of the work of the Taskforce was high and the vast majority of respondents reported that the guidelines were very or extremely relevant, easy to use, trustworthy and valuable. More than 50% of respondents had used the guidelines to support their own clinical decision-making; and 30% were aware of other examples of the guidelines being used. Qualitative data revealed that amongst an overwhelming morass of evidence and opinions during the COVID-19 pandemic, the guidelines have been a reliable, united source of evidence-based advice; participants felt the guidelines built confidence and provided reassurance in clinical decision-making. Opportunities to improve awareness and accessibility to the guidelines were also explored., Conclusions: As of June 2021, the guidelines have been published and updated more than 40 times, include more than 140 recommendations and are being used to inform clinical decisions. The findings of this impact evaluation will be used to improve processes and outputs of the Taskforce and guidelines project, and to inform future living guideline projects., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Maintaining clinical guideline currency has been one challenge to traditional guideline development. This paper describes the methods used to maintain a large national guideline for stroke management., Study Design and Setting: The Australian Stroke Clinical Guidelines are developed to meet Australian National Health and Medical Research Council (NHMRC) standards. Monthly surveillance is conducted for new systematic reviews and randomised controlled studies. Included studies undergo data extraction followed by preparation of updated evidence-to-decision frameworks which are used to inform updates, or development of new recommendations. Small writing groups made up of clinical experts and those with lived experience review and agree on changes, which are finally reviewed by a multidisciplinary Guidelines Steering Group. Draft changes are developed and published using the online MAGICapp platform, with dissemination and promotion via traditional methods as well as social media., Results: Each month approximately 350 abstracts are considered, covering 96 clinical topics and taking on average 16 h to review. There have been four major guideline updates covering 34 new and updated recommendations., Conclusion: It is feasible to use 'living' methods to maintain the Australian Clinical Guidelines for Stroke Management. Further work is now needed to understand the impact of living guidelines., Competing Interests: Conflicts of interest declaration Kelvin Hill -program manager for lead agency, no other conflicts of interest Coralie English -co-chair of the guidelines content team, no other conflicts of interest Bruce C.V. Campbell -co-chair of the guidelines content team, no other conflicts of interest Steve McDonald - involved in Cochrane living methods, no other conflicts of interest Loyal Pattuwage -no conflicts of interest Peta Bates -no conflicts of interest Chris Lassig -no conflicts of interest Tari Turner -involved in Cochrane living methods, no other conflicts of interest, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The Australian National COVID-19 Clinical Evidence Taskforce is producing living, evidence-based, national guidelines for treatment of people with COVID-19 which are updated each week. To continually improve the process and outputs of the Taskforce, and inform future living guideline development, we undertook a concurrent process evaluation examining Taskforce activities and experience of team members and stakeholders during the first 5 months of the project., Methods: The mixed-methods process evaluation consisted of activity and progress audits, an online survey of all Taskforce participants; and semi-structured interviews with key contributors. Data were collected through five, prospective 4-weekly timepoints (beginning first week of May 2020) and three, fortnightly retrospective timepoints (March 23, April 6 and 20). We collected and analysed quantitative and qualitative data., Results: An updated version of the guidelines was successfully published every week during the process evaluation. The Taskforce formed in March 2020, with a nominal start date of March 23. The first version of the guideline was published two weeks later and included 10 recommendations. By August 24, in the final round of the process evaluation, the team of 11 staff, working with seven guideline panels and over 200 health decision-makers, had developed 66 recommendations addressing 58 topics. The Taskforce website had received over 200,000 page views. Satisfaction with the work of the Taskforce remained very high (>90% extremely or somewhat satisfied) throughout. Several key strengths, challenges and methods questions for the work of the Taskforce were identified., Conclusions: In just over 5 months of activity, the National COVID-19 Clinical Evidence Taskforce published 20 weekly updates to the evidence-based national treatment guidelines for COVID-19. This process evaluation identified several factors that enabled this achievement (e.g. an extant skill base in evidence review and convening), along with challenges that needed to be overcome (e.g. managing workloads, structure and governance) and methods questions (pace of updating, and thresholds for inclusion of evidence) which may be useful considerations for other living guidelines projects. An impact evaluation is also being conducted separately to examine awareness, acceptance and use of the guidelines., Competing Interests: The authors have declared that no competing interests exist.

Systematic reviews are difficult to keep up to date, but failure to do so leads to poor review currency and accuracy. "Living systematic review" (LSR) is an approach that aims to continually update a review, incorporating relevant new evidence as it becomes available. LSRs may be particularly important in fields where research evidence is emerging rapidly, current evidence is uncertain, and new research may change policy or practice decisions.This chapter describes the concept and processes of living systematic reviews. It describes the general principles of LSRs, when they might be of particular value, and how their procedures differ from conventional systematic reviews. The chapter focuses particularly on two methods of sequential meta-analysis that may be particularly useful for LSRs: Trial Sequential Analysis and Sequential Meta-Analysis, which both control for Type I error, Type II error (failing to detect a genuine effect) and take account of heterogeneity., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Mindfulness interventions are increasingly popular as an approach to improve mental well-being. To date, no Cochrane Review examines the effectiveness of mindfulness in medical students and junior doctors. Thus, questions remain regarding the efficacy of mindfulness interventions as a preventative mechanism in this population, which is at high risk for poor mental health.  OBJECTIVES: To assess the effects of psychological interventions with a primary focus on mindfulness on the mental well-being and academic performance of medical students and junior doctors., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and five other databases (to October 2021) and conducted grey literature searches.  SELECTION CRITERIA: We included randomised controlled trials of mindfulness that involved medical students of any year level and junior doctors in postgraduate years one, two or three. We included any psychological intervention with a primary focus on teaching the fundamentals of mindfulness as a preventative intervention. Our primary outcomes were anxiety and depression, and our secondary outcomes included stress, burnout, academic performance, suicidal ideation and quality of life.  DATA COLLECTION AND ANALYSIS: We used standard methods as recommended by Cochrane, including Cochrane's risk of bias 2 tool (RoB2).  MAIN RESULTS: We included 10 studies involving 731 participants in quantitative analysis.  Compared with waiting-list control or no intervention, mindfulness interventions did not result in a substantial difference immediately post-intervention for anxiety (standardised mean difference (SMD) 0.09, 95% CI -0.33 to 0.52; P = 0.67, I 2  = 57%; 4 studies, 255 participants; very low-certainty evidence). Converting the SMD back to the Depression, Anxiety and Stress Scale 21-item self-report questionnaire (DASS-21) showed an estimated effect size which is unlikely to be clinically important. Similarly, there was no substantial difference immediately post-intervention for depression (SMD 0.06, 95% CI -0.19 to 0.31; P = 0.62, I 2 = 0%; 4 studies, 250 participants; low-certainty evidence). Converting the SMD back to DASS-21 showed an estimated effect size which is unlikely to be clinically important. No studies reported longer-term assessment of the impact of mindfulness interventions on these outcomes.  For the secondary outcomes, the meta-analysis showed a small, substantial difference immediately post-intervention for stress, favouring the mindfulness intervention (SMD -0.36, 95% CI -0.60 to -0.13; P < 0.05, I 2  = 33%; 8 studies, 474 participants; low-certainty evidence); however, this difference is unlikely to be clinically important. The meta-analysis found no substantial difference immediately post-intervention for burnout (SMD -0.42, 95% CI -0.84 to 0.00; P = 0.05, I² = 0%; 3 studies, 91 participants; very low-certainty evidence). The meta-analysis found a small, substantial difference immediately post-intervention for academic performance (SMD -0.60, 95% CI -1.05 to -0.14; P < 0.05, I² = 0%; 2 studies, 79 participants; very low-certainty evidence); however, this difference is unlikely to be clinically important. Lastly, there was no substantial difference immediately post-intervention for quality of life (mean difference (MD) 0.02, 95% CI -0.28 to 0.32; 1 study, 167 participants; low-certainty evidence). There were no data available for three pre-specified outcomes of this review: deliberate self-harm, suicidal ideation and suicidal behaviour. We assessed the certainty of evidence to range from low to very low across all outcomes. Across most outcomes, we most frequently judged the risk of bias as having 'some concerns'. There were no studies with a low risk of bias across all domains.  AUTHORS' CONCLUSIONS: The effectiveness of mindfulness in our target population remains unconfirmed. There have been relatively few studies of mindfulness interventions for junior doctors and medical students. The available studies are small, and we have some concerns about their risk of bias. Thus, there is not much evidence on which to draw conclusions on effects of mindfulness interventions in this population. There was no evidence to determine the effects of mindfulness in the long term., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. Some people who smoke use ECs to stop or reduce smoking, but some organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This is an update conducted as part of a living systematic review., Objectives: To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke tobacco achieve long-term smoking abstinence., Search Methods: We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 May 2021, and reference-checked and contacted study authors. We screened abstracts from the Society for Research on Nicotine and Tobacco (SRNT) 2021 Annual Meeting.   SELECTION CRITERIA: We included randomized controlled trials (RCTs) and randomized cross-over trials, in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. Studies had to report abstinence from cigarettes at six months or longer or data on safety markers at one week or longer, or both., Data Collection and Analysis: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included the proportion of people still using study product (EC or pharmacotherapy) at six or more months after randomization or starting EC use, changes in carbon monoxide (CO), blood pressure (BP), heart rate, arterial oxygen saturation, lung function, and levels of carcinogens or toxicants or both. We used a fixed-effect Mantel-Haenszel model to calculate risk ratios (RRs) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data in meta-analyses., Main Results: We included 61 completed studies, representing 16,759 participants, of which 34 were RCTs. Five of the 61 included studies were new to this review update. Of the included studies, we rated seven (all contributing to our main comparisons) at low risk of bias overall, 42 at high risk overall (including all non-randomized studies), and the remainder at unclear risk. There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.53, 95% confidence interval (CI) 1.21 to 1.93; I 2 = 0%; 4 studies, 1924 participants). In absolute terms, this might translate to an additional three quitters per 100 (95% CI 1 to 6). There was low-certainty evidence (limited by very serious imprecision) that the rate of occurrence of AEs was similar (RR 0.98, 95% CI 0.80 to 1.19; I 2 = 0%; 2 studies, 485 participants). SAEs were rare, but there was insufficient evidence to determine whether rates differed between groups due to very serious imprecision (RR 1.30, 95% CI 0.89 to 1.90: I 2 = 0; 4 studies, 1424 participants). There was moderate-certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.94, 95% CI 1.21 to 3.13; I 2 = 0%; 5 studies, 1447 participants). In absolute terms, this might lead to an additional seven quitters per 100 (95% CI 2 to 16). There was moderate-certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I 2 = 0%; 3 studies, 601 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 1.06, 95% CI 0.47 to 2.38; I 2 = 0; 5 studies, 792 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.61, 95% CI 1.44 to 4.74; I 2 = 0%; 6 studies, 2886 participants). In absolute terms this represents an additional six quitters per 100 (95% CI 2 to 15). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was some evidence that non-serious AEs were more common in people randomized to nicotine EC (RR 1.22, 95% CI 1.12 to 1.32; I 2 = 41%, low certainty; 4 studies, 765 participants), and again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 1.51, 95% CI 0.70 to 3.24; I 2 = 0%; 7 studies, 1303 participants).  Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued use. Very few studies reported data on other outcomes or comparisons, hence evidence for these is limited, with CIs often encompassing clinically significant harm and benefit., Authors' Conclusions: There is moderate-certainty evidence that ECs with nicotine increase quit rates compared to NRT and compared to ECs without nicotine. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the effect size. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, with no difference in AEs between nicotine and non-nicotine ECs. Overall incidence of SAEs was low across all study arms. We did not detect  evidence of harm from nicotine EC, but longest follow-up was two years and the  number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates, but further RCTs are underway. To ensure the review continues to provide up-to-date information to decision-makers, this review is now a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Implementation of evidence-based care remains a key challenge in clinical practice. Determining "what" to implement can guide implementation efforts. This paper describes a process developed to identify priority recommendations from clinical guidelines for implementation, incorporating the perspectives of both consumers and health professionals. A case study is presented where the process was used to prioritize recommendations for implementation from the Australian Stroke Clinical Guidelines., Methods: The process was developed by a multidisciplinary group of researchers following consultation with experts in the field of implementation and stroke care in Australia. Use of the process incorporated surveys and facilitated workshops. Survey data were analysed descriptively; responses to ranking exercises were analysed via a graph theory-based voting system., Results: The four-step process to identify high-priority recommendations for implementation comprised the following: (1) identifying key implementation criteria, which included (a) reliability of the evidence underpinning the recommendation, (b) capacity to measure change in practice, (c) a recommendation-practice gap, (d) clinical importance and (e) feasibility of making the recommended changes; (2) shortlisting recommendations; (3) ranking shortlisted recommendations and (4) reaching consensus on top priorities. The process was applied to the Australian Stroke Clinical Guidelines between February 2019 and February 2020. Seventy-five health professionals and 16 consumers participated. Use of the process was feasible. Three recommendations were identified as priorities for implementation from over 400 recommendations., Conclusion: It is possible to implement a robust process which involves consumers, clinicians and researchers to systematically prioritize guideline recommendations for implementation. The process is generalizable and could be applied in clinical areas other than stroke and in different geographical regions to identify implementation priorities. The identification of three clear priority recommendations for implementation from the Australian Stroke Clinical Guidelines will directly inform the development and delivery of national implementation strategies.

Background: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. Some people who smoke use ECs to stop or reduce smoking, but some organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This is an update of a review first published in 2014., Objectives: To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke achieve long-term smoking abstinence., Search Methods: We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 February 2021, together with reference-checking and contact with study authors., Selection Criteria: We included randomized controlled trials (RCTs) and randomized cross-over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer., Data Collection and Analysis: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta-analyses., Main Results: We included 56 completed studies, representing 12,804 participants, of which 29 were RCTs. Six of the 56 included studies were new to this review update. Of the included studies, we rated five (all contributing to our main comparisons) at low risk of bias overall, 41 at high risk overall (including the 25 non-randomized studies), and the remainder at unclear risk. There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I 2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low-certainty evidence (limited by very serious imprecision) that the rate of occurrence of AEs was similar) (RR 0.98, 95% CI 0.80 to 1.19; I 2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I 2 = n/a; 2 studies, 727 participants). There was moderate-certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.70, 95% CI 1.03 to 2.81; I 2 = 0%; 4 studies, 1057 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 11). These trials mainly used older EC with relatively low nicotine delivery. There was moderate-certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I 2 = 0%; 3 studies, 601 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.60, 95% CI 0.15 to 2.44; I 2 = n/a; 4 studies, 494 participants). Compared to behavioral support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.70, 95% CI 1.39 to 5.26; I 2 = 0%; 5 studies, 2561 participants). In absolute terms this represents an increase of seven per 100 (95% CI 2 to 17). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs differed, but some evidence that non-serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.22, 95% CI 1.12 to 1.32; I 2 = 41%, low certainty; 4 studies, 765 participants; SAEs: RR 1.17, 95% CI 0.33 to 4.09; I 2 = 5%; 6 studies, 1011 participants, very low certainty). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit., Authors' Conclusions: There is moderate-certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the size of effect, particularly when using modern EC products. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, though evidence indicated no difference in AEs between nicotine and non-nicotine ECs. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow-up was two years and the overall number of studies was small. The evidence is limited mainly by imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information, this review is now a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background and Objectives: The Australian National COVID-19 Clinical Evidence Taskforce is a consortium of 31 Australian health professional organisations developing living, evidence-based guidelines for care of people with COVID-19, which are updated weekly. This article describes the methods used to develop and maintain the guidelines., Methods: The guidelines use the GRADE methods and are designed to meet Australian NHMRC standards. Each week, new evidence is reviewed, current recommendations are revised, and new recommendations made. These are published in MAGIC and disseminated through traditional and social media. Relevant new questions to be addressed are continually sought from stakeholders and practitioners. For prioritized questions, the evidence is actively monitored and updated. Evidence surveillance combines horizon scans and targeted searches. An evidence team appraises and synthesizes evidence and prepares evidence-to-decision frameworks to inform development of recommendations. A guidelines leadership group oversees the development of recommendations by multidisciplinary guidelines panels and is advised by a consumer panel., Results: The Taskforce formed in March 2020, and the first recommendations were published 2 weeks later. The guidelines have been revised and republished on a weekly basis for 24 weeks, and as of October 2020, contain over 90 treatment recommendations, suggesting that living methods are feasible in this context., Conclusions: The Australian guidelines for care of people with COVID-19 provide an example of the feasibility of living guidelines and an opportunity to test and improve living evidence methods., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Respiratory failure, multiple organ failure, shortness of breath, recovery, and mortality have been identified as critically important core outcomes by more than 9300 patients, health professionals, and the public from 111 countries in the global coronavirus disease 2019 core outcome set initiative. The aim of this project was to establish the core outcome measures for these domains for trials in coronavirus disease 2019., Design: Three online consensus workshops were convened to establish outcome measures for the four core domains of respiratory failure, multiple organ failure, shortness of breath, and recovery., Setting: International., Patients: About 130 participants (patients, public, and health professionals) from 17 countries attended the three workshops., Interventions: None., Measurements and Main Results: Respiratory failure, assessed by the need for respiratory support based on the World Health Organization Clinical Progression Scale, was considered pragmatic, objective, and with broad applicability to various clinical scenarios. The Sequential Organ Failure Assessment was recommended for multiple organ failure, because it was routinely used in trials and clinical care, well validated, and feasible. The Modified Medical Research Council measure for shortness of breath, with minor adaptations (recall period of 24 hr to capture daily fluctuations and inclusion of activities to ensure relevance and to capture the extreme severity of shortness of breath in people with coronavirus disease 2019), was regarded as fit for purpose for this indication. The recovery measure was developed de novo and defined as the absence of symptoms, resumption of usual daily activities, and return to the previous state of health prior to the illness, using a 5-point Likert scale, and was endorsed., Conclusions: The coronavirus disease 2019 core outcome set recommended core outcome measures have content validity and are considered the most feasible and acceptable among existing measures. Implementation of the core outcome measures in trials in coronavirus disease 2019 will ensure consistency and relevance of the evidence to inform decision-making and care of patients with coronavirus disease 2019., Competing Interests: Dr. Tong is supported by The University of Sydney Robinson Fellowship. Dr. Morris is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z). The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article. Dr. Douglas is the principal investigator of clinical and translational research studies of acute respiratory distress syndrome, sepsis, and coronavirus disease 2019 from National Institutes of Health, Roche Pharmaceuticals, and Genentech. Research grants are to his institution, Denver Health Medical Center. Dr. Povoa had received lecture fees from Orion, Pfizer, and Technofage. Dr. Azevedo received funding from Halex Istar and Baxter. Dr. Marshall received funding from AM Pharma, and he disclosed he is Cochair of the World Health Organization Working Group on Clinical Characterization and Management. Dr. Mer received funding from honoraria for serving on speakers bureaus and advisory boards as an invited “key opinion leader,” including from Pfizer, MSD, Astellas, and Sun. Dr. Morris received support from WT/Charity Open Access Fund. Dr. Morris’ institution received funding from WT. Dr. Smyth’s institution received funding from Vertex outside the submitted work; he disclosed having a patent “Alkyl quinolones as biomarkers of Pseudomonas aeruginosa infection and uses thereof”; and he received funding from Teva, Novartis, and Vertex, outside the submitted work. Dr. Simpson disclosed he is a coapplicant on independent grants with Becton Dickinson Biosciences and he is the Director of a National Institute for Health Research In Vitro Diagnostics Co-operative, which works with companies across the diagnostics industry. Dr. Turner’s institution received funding from Burnet Institute and United States Agency for International Development, and she received funding from World Health Organization. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: The increasingly rapid rate of evidence publication has made it difficult for evidence synthesis-systematic reviews and health guidelines-to be continually kept up to date. One proposed solution for this is the use of automation in health evidence synthesis. Guideline developers are key gatekeepers in the acceptance and use of evidence, and therefore, their opinions on the potential use of automation are crucial., Methods: The objective of this study was to analyze the attitudes of guideline developers towards the use of automation in health evidence synthesis. The Diffusion of Innovations framework was chosen as an initial analytical framework because it encapsulates some of the core issues which are thought to affect the adoption of new innovations in practice. This well-established theory posits five dimensions which affect the adoption of novel technologies: Relative Advantage, Compatibility, Complexity, Trialability, and Observability. Eighteen interviews were conducted with individuals who were currently working, or had previously worked, in guideline development. After transcription, a multiphase mixed deductive and grounded approach was used to analyze the data. First, transcripts were coded with a deductive approach using Rogers' Diffusion of Innovation as the top-level themes. Second, sub-themes within the framework were identified using a grounded approach., Results: Participants were consistently most concerned with the extent to which an innovation is in line with current values and practices (i.e., Compatibility in the Diffusion of Innovations framework). Participants were also concerned with Relative Advantage and Observability, which were discussed in approximately equal amounts. For the latter, participants expressed a desire for transparency in the methodology of automation software. Participants were noticeably less interested in Complexity and Trialability, which were discussed infrequently. These results were reasonably consistent across all participants., Conclusions: If machine learning and other automation technologies are to be used more widely and to their full potential in systematic reviews and guideline development, it is crucial to ensure new technologies are in line with current values and practice. It will also be important to maximize the transparency of the methods of these technologies to address the concerns of guideline developers.

Objectives: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019., Design: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set., Setting: International., Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers)., Interventions: None., Measurements: None., Main Results: Six themes were identified. "Responding to the critical and acute health crisis" reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. "Capturing different settings of care" highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. "Encompassing the full trajectory and severity of disease" was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). "Distinguishing overlap, correlation and collinearity" meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). "Recognizing adverse events" refers to the potential harms of new and evolving interventions. "Being cognizant of family and psychosocial wellbeing" reflected the pervasive impacts of coronavirus disease 2019., Conclusions: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials.

Objectives: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials., Design: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically., Setting: International., Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers)., Interventions: None., Measurements: None., Main Results: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes., Conclusions: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.

Background: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. People who smoke report using ECs to stop or reduce smoking, but some organisations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This review is an update of a review first published in 2014., Objectives: To evaluate the effect and safety of using electronic cigarettes (ECs) to help people who smoke achieve long-term smoking abstinence., Search Methods: We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO for relevant records to January 2020, together with reference-checking and contact with study authors., Selection Criteria: We included randomized controlled trials (RCTs) and randomized cross-over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer., Data Collection and Analysis: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, AEs, and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta-analyses., Main Results: We include 50 completed studies, representing 12,430 participants, of which 26 are RCTs. Thirty-five of the 50 included studies are new to this review update. Of the included studies, we rated four (all which contribute to our main comparisons) at low risk of bias overall, 37 at high risk overall (including the 24 non-randomized studies), and the remainder at unclear risk. There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I 2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low-certainty evidence (limited by very serious imprecision) of no difference in the rate of adverse events (AEs) (RR 0.98, 95% CI 0.80 to 1.19; I 2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I 2 = n/a; 2 studies, 727 participants). There was moderate-certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.71, 95% CI 1.00 to 2.92; I 2 = 0%; 3 studies, 802 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 12). These trials used EC with relatively low nicotine delivery. There was low-certainty evidence, limited by very serious imprecision, that there was no difference in the rate of AEs between these groups (RR 1.00, 95% CI 0.73 to 1.36; I 2 = 0%; 2 studies, 346 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.25, 95% CI 0.03 to 2.19; I 2 = n/a; 4 studies, 494 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.50, 95% CI 1.24 to 5.04; I 2 = 0%; 4 studies, 2312 participants). In absolute terms this represents an increase of six per 100 (95% CI 1 to 14). However, this finding was very low-certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs varied, but some evidence that non-serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.17, 95% CI 1.04 to 1.31; I 2 = 28%; 3 studies, 516 participants; SAEs: RR 1.33, 95% CI 0.25 to 6.96; I 2 = 17%; 5 studies, 842 participants). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit., Authors' Conclusions: There is moderate-certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the degree of effect, particularly when using modern EC products. Confidence intervals were wide for data on AEs, SAEs and other safety markers. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow-up was two years and the overall number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information for decision-makers, this review is now a living systematic review. We will run searches monthly from December 2020, with the review updated as relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)