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AbstractObjectiveTo compare the effectiveness of interventions for the management of long covid (post-covid condition).DesignLiving systematic review.Data sourcesMedline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023.Eligibility criteriaTrials that randomised adults (≥18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care.Results24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation. Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference −8.4, 95% confidence interval (CI) −13.11 to −3.69; Checklist for Individual Strength fatigue subscale; range 8-56, higher scores indicate greater impairment) and probably improves concentration (mean difference −5.2, −7.97 to −2.43; Checklist for Individual Strength concentration problems subscale; range 4-28; higher scores indicate greater impairment). Moderate certainty evidence suggested that, compared with usual care, an online, supervised, combined physical and mental health rehabilitation programme probably leads to improvement in overall health, with an estimated 161 more patients per 1000 (95% CI 61 more to 292 more) experiencing meaningful improvement or recovery, probably reduces symptoms of depression (mean difference −1.50, −2.41 to −0.59; Hospital Anxiety and Depression Scale depression subscale; range 0-21; higher scores indicate greater impairment), and probably improves quality of life (0.04, 95% CI 0.00 to 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; range −0.022-1; higher scores indicate less impairment). Moderate certainty evidence suggested that intermittent aerobic exercise 3-5 times weekly for 4-6 weeks probably improves physical function compared with continuous exercise (mean difference 3.8, 1.12 to 6.48; SF-36 physical component summary score; range 0-100; higher scores indicate less impairment). No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, a mobile application providing education on long covid.ConclusionModerate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid.Systematic review registrationOpen Science Framework https://osf.io/9h7zm/.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Background Determinants of practice are factors that might prevent or enable improvements. Several checklists, frameworks, taxonomies, and classifications of determinants of healthcare professional practice have been published. In this paper, we describe the development of a comprehensive, integrated checklist of determinants of practice (the TICD checklist). Methods We performed a systematic review of frameworks of determinants of practice followed by a consensus process. We searched electronic databases and screened the reference lists of key background documents. Two authors independently assessed titles and abstracts, and potentially relevant full text articles. We compiled a list of attributes that a checklist should have: comprehensiveness, relevance, applicability, simplicity, logic, clarity, usability, suitability, and usefulness. We assessed included articles using these criteria and collected information about the theory, model, or logic underlying how the factors (determinants) were selected, described, and grouped, the strengths and weaknesses of the checklist, and the determinants and the domains in each checklist. We drafted a preliminary checklist based on an aggregated list of determinants from the included checklists, and finalized the checklist by a consensus process among implementation researchers. Results We screened 5,778 titles and abstracts and retrieved 87 potentially relevant papers in full text. Several of these papers had references to papers that we also retrieved in full text. We also checked potentially relevant papers we had on file that were not retrieved by the searches. We included 12 checklists. None of these were completely comprehensive when compared to the aggregated list of determinants and domains. We developed a checklist with 57 potential determinants of practice grouped in seven domains: guideline factors, individual health professional factors, patient factors, professional interactions, incentives and resources, capacity for organisational change, and social, political, and legal factors. We also developed five worksheets to facilitate the use of the checklist. Conclusions Based on a systematic review and a consensus process we developed a checklist that aims to be comprehensive and to build on the strengths of each of the 12 included checklists. The checklist is accompanied with five worksheets to facilitate its use in implementation research and quality improvement projects.

Background The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) coherence, (3) adequacy of data and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on making an overall assessment of confidence in a review finding and creating a CERQual Evidence Profile and a CERQual Summary of Qualitative Findings table. Methods We developed this guidance by examining the methods used by other GRADE approaches, gathering feedback from relevant research communities and developing consensus through project group meetings. We then piloted the guidance on several qualitative evidence syntheses before agreeing on the approach. Results Confidence in the evidence is an assessment of the extent to which a review finding is a reasonable representation of the phenomenon of interest. Creating a summary of each review finding and deciding whether or not CERQual should be used are important steps prior to assessing confidence. Confidence should be assessed for each review finding individually, based on the judgements made for each of the four CERQual components. Four levels are used to describe the overall assessment of confidence: high, moderate, low or very low. The overall CERQual assessment for each review finding should be explained in a CERQual Evidence Profile and Summary of Qualitative Findings table. Conclusions Structuring and summarising review findings, assessing confidence in those findings using CERQual and creating a CERQual Evidence Profile and Summary of Qualitative Findings table should be essential components of undertaking qualitative evidence syntheses. This paper describes the end point of a CERQual assessment and should be read in conjunction with the other papers in the series that provide information on assessing individual CERQual components.

Systematic use of Clinical Decision Support (CDS), which provides timely information to assist healthcare practitioners in decision-making, is recommended in the implementation of fall prevention among older adults. This systematic review aimed to evaluate the effects of CDS for fall prevention on healthcare practitioners' adherence to recommended practice, medication outcomes, and patient outcomes. We searched Medline, EMBASE, CINAHL, Cochrane Library, Web of Science, AMED, PEDro, and Google Scholar from the earliest available dates through January 2025. We included randomised and non-randomised studies that directly compared interventions consisting of CDS presented on-screen or on paper to healthcare practitioners aiming to prevent falls in persons aged 65 years or older. We analysed healthcare practitioner performance, medication review and prescribing, fall risk, fall rate, and fall injury rate as primary outcomes. Two reviewers independently screened studies and assessed for risk of bias. We synthesised results using meta-analyses and vote-counting based on direction of effect, when possible, otherwise narratively, and we rated the certainty of the evidence using the GRADE approach. Of 25 included studies, 20 were randomised and five were non-randomised. Most CDS tools supported healthcare practitioners in performing multifactorial fall risk assessments and follow-up interventions based on identified risks (60%) and most were delivered electronically (60%). CDS may improve healthcare practitioners' adherence to recommended practice (all eight comparisons favouring CDS; 95% confidence interval [CI] 68% to 100%; low certainty) and likely improve medication review and prescribing (all nine comparisons favouring CDS; 95% CI 70% to 100%; moderate certainty), although the effect sizes are uncertain. CDS may reduce fall risk, but the effect may be small (odds ratio 0.93; 95% CI 0.81 to 1.01; low certainty). CDS likely reduces fall rates in hospitals or residential care (rate ratio [RaR] 0.74; 95% CI 0.63 to 0.88; moderate certainty) and in patients aged 80 years or older (RaR 0.72; 95% CI 0.61 to 0.86; moderate certainty). CDS may reduce fall rates in community-dwelling older adults (RaR 0.97; 95% CI 0.93 to 1.00; moderate certainty) and in patients aged between 65 and 80 years (RaR 0.92; 95% CI 0.84 to 1.01; low certainty), though the effects in both of these subgroups may be small. CDS may reduce fall injury rates in older adults aged between 65 and 80 years (RaR 0.80; 95% CI 0.59 to 1.09; low certainty). The evidence on fall injury rates in patients aged 80 years or older was very uncertain. CDS likely enhances healthcare practitioners' performance in fall prevention among older adults; however, the effect sizes remain unknown. Although CDS may improve patient outcomes in fall prevention, both the effect sizes and the certainty of evidence vary. Results from this study may inform the planning and implementation of CDS in fall prevention. Future studies should strive for clearer reporting of CDS design factors to allow for an evaluation of which factors may influence the success of CDS interventions in fall prevention. Registration: PROSPERO, CRD42021250500.

Objective To describe a framework for people making and using evidence-informed health system and public health recommendations and decisions. Background We developed the GRADE Evidence to Decision (EtD) framework for health system and public health decisions as part of the DECIDE project, in which we simultaneously developed frameworks for these and other types of healthcare decisions, including clinical recommendations, coverage decisions and decisions about diagnostic tests. Developing the framework Building on GRADE EtD tables, we used an iterative approach, including brainstorming, consultation of the literature and with stakeholders, and an international survey of policy-makers. We applied the framework to diverse examples, conducted workshops and user testing with health system and public health guideline developers and policy-makers, and observed and tested its use in real-life guideline panels. Findings All the GRADE EtD frameworks share the same basic structure, including sections for formulating the question, making an assessment and drawing conclusions. Criteria listed in the assessment section of the health system and public health framework cover the important factors for making these types of decisions; in addition to the effects and economic impact of an option, the priority of the problem, the impact of the option on equity, and its acceptability and feasibility are important considerations that can inform both whether and how to implement an option. Because health system and public health interventions are often complex, detailed implementation considerations should be made when making a decision. The certainty of the evidence is often low or very low, but decision-makers must still act. Monitoring and evaluation are therefore often important considerations for these types of decisions. We illustrate the different components of the EtD framework for health system and public health decisions by presenting their application in a framework adapted from a real-life guideline. Discussion This framework provides a structured and transparent approach to support policy-making informed by the best available research evidence, while making the basis for decisions accessible to those whom they will affect. The health system and public health EtD framework can also be used to facilitate dissemination of recommendations and enable decision-makers to adopt, and adapt, recommendations or decisions.

To provide Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidance for assessing inconsistency, imprecision, and other domains for the certainty of evidence about the relative importance of outcomes. We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance, and consulted GRADE members and other stakeholders for feedback. We describe the rationale for considering the remaining GRADE domains when rating the certainty in a body of evidence for the relative importance of outcomes. As meta-analyses are not common in this context, inconsistency and imprecision assessments are challenging. Furthermore, confusion exists about inconsistency, imprecision, and true variability in the relative importance of outcomes. To clarify this issue, we suggest that the true variability is neither equivalent to inconsistency nor imprecision. Specifically, inconsistency arises from population, intervention, comparison and outcome and methodological elements that should be explored and, if possible, explained. The width of the confidence interval and sample size inform judgments about imprecision. We also provide suggestions on how to detect publication bias and discuss the domains to rate up the certainty. We provide guidance and examples for rating inconsistency, imprecision, and other domains for a body of evidence describing the relative importance of outcomes.

Background The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE working group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) relevance, (3) coherence and (4) adequacy of data. This paper is part of a series providing guidance on how to apply CERQual and focuses on CERQual’s coherence component. Methods We developed the coherence component by searching the literature for definitions, gathering feedback from relevant research communities and developing consensus through project group meetings. We tested the CERQual coherence component within several qualitative evidence syntheses before agreeing on the current definition and principles for application. Results When applying CERQual, we define coherence as how clear and cogent the fit is between the data from the primary studies and a review finding that synthesises that data. In this paper, we describe the coherence component and its rationale and offer guidance on how to assess coherence in the context of a review finding as part of the CERQual approach. This guidance outlines the information required to assess coherence, the steps that need to be taken to assess coherence and examples of coherence assessments. Conclusions This paper provides guidance for review authors and others on undertaking an assessment of coherence in the context of the CERQual approach. We suggest that threats to coherence may arise when the data supporting a review finding are contradictory, ambiguous or incomplete or where competing theories exist that could be used to synthesise the data. We expect the CERQual approach, and its individual components, to develop further as our experiences with the practical implementation of the approach increase.

Background The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) coherence, (3) adequacy of data and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on CERQual’s methodological limitations component. Methods We developed the methodological limitations component by searching the literature for definitions, gathering feedback from relevant research communities and developing consensus through project group meetings. We tested the CERQual methodological limitations component within several qualitative evidence syntheses before agreeing on the current definition and principles for application. Results When applying CERQual, we define methodological limitations as the extent to which there are concerns about the design or conduct of the primary studies that contributed evidence to an individual review finding. In this paper, we describe the methodological limitations component and its rationale and offer guidance on how to assess methodological limitations of a review finding as part of the CERQual approach. This guidance outlines the information required to assess methodological limitations component, the steps that need to be taken to assess methodological limitations of data contributing to a review finding and examples of methodological limitation assessments. Conclusions This paper provides guidance for review authors and others on undertaking an assessment of methodological limitations in the context of the CERQual approach. More work is needed to determine which criteria critical appraisal tools should include when assessing methodological limitations. We currently recommend that whichever tool is used, review authors provide a transparent description of their assessments of methodological limitations in a review finding. We expect the CERQual approach and its individual components to develop further as our experiences with the practical implementation of the approach increase.

Objective To identify case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and explore how the validity of case definitions can be evaluated in the absence of a reference standard. Design Systematic review. Setting International. Participants A literature search, updated as of November 2013, led to the identification of 20 case definitions and inclusion of 38 validation studies. Primary and secondary outcome measure Validation studies were assessed for risk of bias and categorised according to three validation models: (1) independent application of several case definitions on the same population, (2) sequential application of different case definitions on patients diagnosed with CFS/ME with one set of diagnostic criteria or (3) comparison of prevalence estimates from different case definitions applied on different populations. Results A total of 38 studies contributed data of sufficient quality and consistency for evaluation of validity, with CDC-1994/Fukuda as the most frequently applied case definition. No study rigorously assessed the reproducibility or feasibility of case definitions. Validation studies were small with methodological weaknesses and inconsistent results. No empirical data indicated that any case definition specifically identified patients with a neuroimmunological condition. Conclusions Classification of patients according to severity and symptom patterns, aiming to predict prognosis or effectiveness of therapy, seems useful. Development of further case definitions of CFS/ME should be given a low priority. Consistency in research can be achieved by applying diagnostic criteria that have been subjected to systematic evaluation.

Background The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) working group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations; (2) coherence; (3) adequacy of data; and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on CERQual’s adequacy of data component. Methods We developed the adequacy of data component by searching the literature for definitions, gathering feedback from relevant research communities and developing consensus through project group meetings. We tested the CERQual adequacy of data component within several qualitative evidence syntheses before agreeing on the current definition and principles for application. Results When applying CERQual, we define adequacy of data as an overall determination of the degree of richness and the quantity of data supporting a review finding. In this paper, we describe the adequacy component and its rationale and offer guidance on how to assess data adequacy in the context of a review finding as part of the CERQual approach. This guidance outlines the information required to assess data adequacy, the steps that need to be taken to assess data adequacy, and examples of adequacy assessments. Conclusions This paper provides guidance for review authors and others on undertaking an assessment of adequacy in the context of the CERQual approach. We approach assessments of data adequacy in terms of the richness and quantity of the data supporting each review finding, but do not offer fixed rules regarding what constitutes sufficiently rich data or an adequate quantity of data. Instead, we recommend that this assessment is made in relation to the nature of the finding. We expect the CERQual approach, and its individual components, to develop further as our experiences with the practical implementation of the approach increase.