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The delayed and modest uptake of evidence-based treatments following cardiovascular clinical trials highlights the need for greater attention to implementation early in the development and testing of treatments. However, implementation science is not well understood and is often an afterthought following phase 3 trials. In this review, we describe the goals, frameworks, and methods of implementation science, along with common multilevel barriers and facilitators of implementation. We propose that some of the approaches used for implementation well after a trial has ended can be incorporated into the design of phase 3 trials to foster early post-trial implementation. Approaches include, but are not limited to, engaging broad stakeholders including patients, clinicians, and decision-makers in trial advisory boards; using less restrictive eligibility criteria that ensure both internal validity and generalizability; having trial protocols reviewed by regulators; integrating trial execution with the health care system; evaluating and addressing barriers and facilitators to deployment of the intervention; and undertaking cost-effectiveness and cost utility analyses across jurisdictions. We provide case examples to highlight concepts and to guide end-of-trial implementation., Competing Interests: Funding Support and Author Disclosures CVCT meetings are supported by unrestricted educational grants with no allocation for speakers’ fees. Dr Van Spall has received grants from the Canadian Institutes of Health Research (CIHR) and the Heart and Stroke Foundation (HSF); has institution educational accounts with Boehringer Ingelheim and Novartis; has received consulting fees from the Baim Institute for Clinical Research; has trial committee roles with Medtronic, CardioVascular Research Foundation, and the Colorado Prevention Center Clinical Research; and has received travel and/or meeting attendance support from CVCT. Drs Desveaux, Finch, and Singh have received travel and/or meeting attendance support from CVCT. Dr Lewis has received royalties or licenses from Springer Publishing for Practical Implementation Science. Dr Venter has received Institutional grants from the Bill and Melinda Gates Foundation, SA Medical Research Council, National Institutes for Health, Unitaid, Foundation for Innovative New Diagnostics, Merck and the Children's Investment Fund Foundation, USAID, Merck, Johnson and Johnson, ViiV Healthcare, and Novo Nordisk; has received honoraria for educational events and advisory board participation from Gilead Sciences, ViiV Healthcare, Mylan/Viatris, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson and Johnson, Sanofi, Boehringer Ingelheim, Thermo-Fischer, and Virology Education; has received honorarium from the International National Institutes of Health HIV Data and Safety Monitoring Board; and has received drug donations from ViiV Healthcare, Merck, Johnson and Johnson, and Gilead Sciences for investigator-led clinical studies. Dr Zannad has received consulting fees from 89bio, Applied Therapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior Pharmaceuticals, Cellprothera, Cereno Scientific, CEVA, CVRx, Merck, Novartis, Novo Nordisk, Owkin, Pfizer, and Servier; has received honoraria for lectures from Bayer, Boehringer Ingelheim, CEVA, CVRx, Merck, and Novartis; has received fees for participation on a data safety monitoring board or advisory board from Acceleron/Merck; and has equity interests in G3 Pharmaceuticals, Cereno Pharmaceuticals, Cardiorenal, Eshmoun Clinical Research, and CVCT. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The views expressed in this paper are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Similarly, the views expressed in this paper by other authors are their personal views and may not be understood or quoted as being made on behalf of or reflecting the position of the organizations with which the authors are employed/affiliated., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

The strength of a systematic review hinges in large part on the quality of evidence it appraises. Observational studies, including cohort studies and case series, are positioned lower on the hierarchy of evidence, with cohort studies typically higher than case series. The often subtle differences between these study designs may lead to misclassification and can impact the strength of recommendations derived from such data. This manuscript offers an approach to delineate the differences between cohort studies and case series and provides clinical examples of these subtleties. By providing a simple approach for distinguishing cohort studies from case series, this manuscript seeks to assist researchers performing systematic reviews., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In evidence-based medicine frameworks, the highest level of evidence is derived from quantitative synthesis of double-masked, high-quality, randomly assigned controlled trials. Meta-analyses of randomly assigned controlled trials have demonstrated that screening mammography reduces breast cancer deaths. In the United States, every major guideline-producing organization has recommended screening mammography in average-risk women; however, there are controversies about age and frequency. Carefully controlled observational research studies and statistical modeling studies can address evidence gaps and inform evidence-based, contemporary screening practices. As breast imaging radiologists develop and evaluate existing and new screening tests and technologies, they will need to understand the key methodological considerations and scientific criteria used by policy makers and health service researchers to support dissemination and implementation of evidence-based screening tests. The Wilson and Jungner principles and the U.S. Preventive Services Task Force general analytic framework provide structured evaluations of the effectiveness of screening tests. Key considerations in both frameworks include public health significance, natural history of disease, cost-effectiveness, and characteristics of screening tests and treatments. Rigorous evaluation of screening tests using analytic frameworks can maximize the benefits of screening tests while reducing potential harms. The purpose of this article is to review key methodological considerations and analytic frameworks used to evaluate screening studies and develop evidence-based recommendations., (© Society of Breast Imaging 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Many dogmas influence daily clinical practice, and critical care medicine is no exception. We previously highlighted the weak, questionable, and often contrary evidence base underpinning four established medical managements-loop diuretics for acute heart failure, routine use of heparin thromboprophylaxis, rate of sodium correction for hyponatremia, and 'every hour counts' for treating bacterial meningitis. We now provide four further examples in this "Dogma II" piece (a week's course of antibiotics, diabetic ketoacidosis algorithms, sodium bicarbonate to improve ventricular contractility during severe metabolic acidosis, and phosphate replacement for hypophosphatemia) where routine practice warrants re-appraisal., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Patients with rheumatic diseases often enquire about the options for nutritional therapy. Nutritional factors have been empirically described that are associated with the occurrence of inflammatory rheumatic diseases or flare-ups or improved disease states. A growing number of epidemiological and clinical studies deal with the evaluation of nutrition and dietary restriction in rheumatology., Objective: Narrative presentation of the evidence of nutritional interventions and fasting and its clinical implications., Results and Discussion: Only limited data from smaller clinical studies are available for evidence assessment. A benefit in terms of symptoms and quality of life in rheumatoid arthritis was shown for the Mediterranean and plant-based diet as well as the anti-inflammatory diet. The effect sizes are small to moderate and the effectiveness in the context of complex lifestyle programs is probably sustainable. The evidence for elimination diets is weak. Initial clinical studies indicate a moderate benefit of plant-based nutrition for osteoarthritis in the context of the metabolic syndrome. There is moderate evidence for the benefit of dietary weight normalization in psoriasis. There is clear experimental evidence of a significant anti-inflammatory effect of prolonged fasting. Several clinical studies demonstrated a symptomatic benefit of prolonged modified fasting (therapeutic fasting) in rheumatoid arthritis (RA). If fasting is followed by a vegan and vegetarian diet, lasting effects of up to 1 year have been documented. Cardiometabolic but not antirheumatic effects have been proven for intermittent fasting. Nutrition and fasting can be classified as a possible useful addition to conventional treatment but are currently only rarely taken into account in practice., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The 2023 International Pediatric Ventilator Liberation Clinical Practice Guidelines provided evidence-based recommendations to guide pediatric critical care providers on how to perform daily aspects of ventilator liberation. However, because of the lack of high-quality pediatric studies, most recommendations were conditional based on very low to low certainty of evidence., Research Question: What are the research gaps related to pediatric ventilator liberation that can be studied to strengthen the evidence for future updates of the guidelines?, Study Design and Methods: We conducted systematic reviews of the literature in eight predefined Population, Intervention, Comparator, Outcome (PICO) areas related to pediatric ventilator liberation to generate recommendations. Subgroups responsible for each PICO question subsequently identified major research gaps by synthesizing the literature. These gaps were presented at an international symposium at the Pediatric Acute Lung Injury and Sepsis Investigators meeting in spring 2022 for open discussion. Feedback was incorporated, and final evaluation of research gaps are summarized herein. Although randomized controlled trials (RCTs) represent the highest level of evidence, the panel sought to highlight areas where alternative study designs also may be appropriate, given challenges with conducting large multicenter RCTs in children., Results: Significant research gaps were identified in six broad areas related to pediatric ventilator liberation. Several of these areas necessitate multicenter RCTs to provide definitive results, whereas other gaps can be addressed with multicenter observational studies or quality improvement initiatives. Furthermore, a need for some physiologic studies in several areas remains, particularly regarding newer diagnostic methods to improve identification of patients at high risk of extubation failure., Interpretation: Although pediatric ventilator liberation guidelines have been created, the certainty of evidence remains low and multiple research gaps exist that should be bridged through high-quality RCTs, multicenter observational studies, and quality improvement initiatives., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Increasing opportunities for prevention of infectious diseases by new, effective vaccines and the expansion of global immunization programs across the life course highlight the importance and value of evidence-informed decision-making (EIDM) by National Immunization Technical Advisory Groups (NITAGs). The U.S. Centers for Disease Control and Prevention (CDC) and Task Force for Global Health (TFGH) have developed and made available new tools to support NITAGs in EIDM. These include a toolkit for conducting facilitated training of NITAGs, Secretariats, or work groups on the use of the Evidence to Recommendations (EtR) approach to advise Ministries of Health (MoH) on specific vaccine policies, and an eLearning module on the EtR approach for NITAG members, Secretariat and others. The CDC and TFGH have also supported final development and implementation of the NITAG Maturity Assessment Tool (NMAT) for assessing maturity of NITAG capabilities in seven functional domains. The EtR toolkit and eLearning have been widely promoted in collaboration with the World Health Organization (WHO) Headquarters and Regional Offices through workshops engaging over 30 countries to date, and the NMAT assessment tool used in most countries in 3 WHO regions (Americas, Eastern Mediterranean, African). Important lessons have been learned regarding planning and conducting trainings for multiple countries and additional ways to support countries in applying the EtR approach to complete vaccine recommendations. Priorities for future work include the need to evaluate the impact of EtR training and NMAT assessments, working with partners to expand and adapt these tools for wider use, synergizing with other approaches for NITAG strengthening, and developing the best approaches to empower NITAGs to use the EtR approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Systematic review with meta-analysis integrates findings from multiple studies, offering robust conclusions on treatment effects and guiding evidence-based medicine. However, the process is often hampered by challenges such as inconsistent data reporting, complex calculations, and time constraints. Researchers must convert various statistical measures into a common format, which can be error-prone and labor-intensive without the right tools., Implementation: Meta-Analysis Accelerator was developed to address these challenges. The tool offers 21 different statistical conversions, including median & interquartile range (IQR) to mean & standard deviation (SD), standard error of the mean (SEM) to SD, and confidence interval (CI) to SD for one and two groups, among others. It is designed with an intuitive interface, ensuring that users can navigate the tool easily and perform conversions accurately and efficiently. The website structure includes a home page, conversion page, request a conversion feature, about page, articles page, and privacy policy page. This comprehensive design supports the tool's primary goal of simplifying the meta-analysis process., Results: Since its initial release in October 2023 as Meta Converter and subsequent renaming to Meta-Analysis Accelerator, the tool has gained widespread use globally. From March 2024 to May 2024, it received 12,236 visits from countries such as Egypt, France, Indonesia, and the USA, indicating its international appeal and utility. Approximately 46% of the visits were direct, reflecting its popularity and trust among users., Conclusions: Meta-Analysis Accelerator significantly enhances the efficiency and accuracy of meta-analysis of systematic reviews by providing a reliable platform for statistical data conversion. Its comprehensive variety of conversions, user-friendly interface, and continuous improvements make it an indispensable resource for researchers. The tool's ability to streamline data transformation ensures that researchers can focus more on data interpretation and less on manual calculations, thus advancing the quality and ease of conducting systematic reviews and meta-analyses., (© 2024. The Author(s).)

Early-phase trials and innovative care draw support from basic science, preclinical studies, and clinical research. Such evidential diversity presents a challenge for traditional ways of synthesizing evidence. In what follows, we review the limitations of existing approaches for communicating supporting evidence for early-phase trials. We then offer a structured approach, PATH (preclinical assessment for translation to humans). PATH is grounded in the premise that the case for administering novel strategies to patients requires connecting the dots between nine mechanistic steps supporting a clinical claim. Using PATH entails first parsing supporting evidence, assessing the strength of evidence at each step, and then assessing the strength of a chain of evidence linking drug administration to clinical effect. While PATH requires further refinement, the approach reduces some of the opacity, arbitrariness, and biases in current ways of presenting and assessing scientific support for early-phase trials and innovative care., Competing Interests: Declaration of interests J.K. serves on a data monitoring committee of NIAID, which reviews early-phase trials; honoraria for this sum to less than $1,000 USD/year., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Network meta-analysis is developed to compare all available treatments; therefore it enriches evidence for clinical decision-making, offering insights into treatment effectiveness and safety when faced with multiple options. However, the complexity and numerous treatment comparisons in network meta-analysis can challenge healthcare providers and patients. The purpose of this study aimed to introduce a graphic design to present complex rankings of multiple interventions comprehensively., Methods: Our team members developed a "beading plot" to summary probability of achieving the best treatment (P-best) and global metrics including surface under the cumulative ranking curve (SUCRA) and P-score. Implemented via the "rankinma" R package, this tool summarizes rankings across diverse outcomes in network meta-analyses, and the package received an official release on the Comprehensive R Archive Network (CRAN). It includes the `PlotBead()` function for generating beading plots, which represent treatment rankings among various outcomes., Results: Beading plot has been designed based on number line plot, which effectively displays collective metrics for each treatment across various outcomes. Order on the -axis is derived from ranking metrics like P-best, SUCRA, and P-score. Continuous lines represent outcomes, and color-coded beads signify treatments., Conclusion: The beading plot is a valuable graphic that intuitively displays treatment rankings across diverse outcomes, enhancing reader-friendliness and aiding decision-making in complex network evidence scenarios. While empowering clinicians and patients to identify optimal treatments, it should be used cautiously, alongside an assessment of the overall evidence certainty., (© 2024. The Author(s).)

Background: Real-world evidence (RWE) plays a key role in regulatory and healthcare decision-making, but the potentially fragmentated nature of generated evidence may limit its utility for clinical decision-making. Heterogeneity and a lack of reproducibility in RWE resulting from inconsistent application of methodologies across data sources should be minimized through harmonization., Methods: This paper's aim is to describe and reflect upon a multidisciplinary research platform (FOUNTAIN; FinerenOne mUlti-database NeTwork for evidence generAtIoN) with coordinated studies using diverse RWE generation approaches and explore the platform's strengths and limitations. With guidance from an executive advisory committee of multidisciplinary experts and patient representatives, the goal of the FOUNTAIN platform is to harmonize RWE generation across a portfolio of research projects, including research partner collaborations and a common data model (CDM)-based program. FOUNTAIN's overarching objectives as a research platform are to establish long-term collaborations among pharmacoepidemiology research partners and experts and to integrate diverse approaches for RWE generation, including global protocol execution by research partners in local data sources and common protocol execution in multiple data sources through federated data networks, while ensuring harmonization of medical definitions, methodology, and reproducible artifacts across all studies. Specifically, the aim of the multiple studies run within the frame of FOUNTAIN is to provide insight into the real-world utilization, effectiveness, and safety of finerenone across its life-cycle., Results: Currently, the FOUNTAIN platform includes 9 research partner collaborations and 8 CDM-mapped data sources from 7 countries (United States, United Kingdom, China, Japan, The Netherlands, Spain, and Denmark). These databases and research partners were selected after a feasibility fit-for-purpose evaluation. Six multicountry, multidatabase, cohort studies are ongoing to describe patient populations, current standard of care, comorbidity profiles, healthcare resource use, and treatment effectiveness and safety in different patient populations with chronic kidney disease and type 2 diabetes. Strengths and potential limitations of FOUNTAIN are described in the context of valid RWE generation., Conclusion: The establishment of the FOUNTAIN platform has allowed harmonized execution of multiple studies, promoting consistency both within individual studies that employ multiple data sources and across all studies run within the platform's framework. FOUNTAIN presents a proposal to efficiently improve the consistency and generalizability of RWE on finerenone., (© 2024. The Author(s).)

Purpose of Review: To provide an evidence-informed review weighing the pros and cons of particulate vs. nonparticulate steroids for lumbar transforaminal epidural steroid injections (TFESI)., Recent Findings: The relative use of nonparticulate vs. particulate steroids for lumbar TFESI has risen recently in light of catastrophic consequences reported for the latter during cervical TFESI. Among various causes of spinal cord infarct, an exceedingly rare event in the lower lumbar spine, embolization of particulate steroid is among the least likely. Case reports have documented cases of spinal cord infarct during lower lumbar TFESI with both particulate and nonparticulate steroids, with database reviews finding no difference in complication rates. There is some evidence for superiority of particulate over nonparticulate steroids in well-designed studies, which could lead to increase steroid exposure (i.e. more injections) and treatment failure resulting in surgical and/or opioid management when nonparticulate steroids are utilized., Summary: Similar to a paradigm shift in medicine, a personalized approach based on a shared decision model and the consequences of treatment failure, should be utilized in deciding which steroid to utilize. Alternatives to ESI include high-volume injections with nonsteroid solutions, and the use of hypertonic saline, which possesses anti-inflammatory properties and has been shown to be superior to isotonic saline in preliminary clinical studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Real-time clinical care, policy, and research decisions need real-time evidence synthesis. However, as we found during the COVID-19 pandemic, it is challenging to rapidly address key clinical and policy questions through rigorous, relevant, and usable evidence. Our objective is to present three exemplar cases of rapid evidence synthesis products from the Veterans Healthcare Administration Evidence Synthesis Program (ESP) and, in the context of these examples, outline ESP products, challenges, and lessons learned. We faced challenges in (1) balancing scientific rigor with the speed in which evidence synthesis was needed, (2) sorting through rapidly evolving large bodies of evidence, and (3) assessing the impact of evidence synthesis products on clinical care, policy, and research. We found solutions in (1) engaging stakeholders early, (2) utilizing artificial intelligence capabilities, (3) building infrastructure to establish living reviews, and (4) planning for dissemination to maximize impact., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

An assessment of the validity of studies is an essential component of most evidence syntheses (systematic reviews) to understand the risk of bias (ROB) and applicability of the evidence. A formal validity assessment requires a structured and comprehensive approach, which can be implemented using an assessment tool, specifically developed for this purpose. Many different tools are available, marking it difficult for researchers to choose the best tool for their evidence synthesis. We have established the LATITUDES Network to assist researchers in identifying the most appropriate tool to use in their evidence synthesis and to support researchers using these tools. The LATITUDES website (www.latitudes-network.org) includes a searchable library of validity assessment tools designed for use in evidence syntheses, bringing tools together in one place and providing researchers with clear information on suitable tools, categorized by study design. The website also provides links to training on the process of validity assessment and a list of tools currently under development. To be included in the LATITUDES library, tools must meet the following criteria: be designed for use in evidence syntheses; assess multidimensional aspects of validity of individual studies or reviews; and be developed for use by the wider research community rather than for a single research group. We highlight 'key' tools, those that are considered to be the most robust and reliable tools based on prespecified criteria agreed in conjunction with our advisory board, an international group of experts in the area of evidence synthesis and ROB tools., Competing Interests: Declaration of competing interest All authors are members of the LATITUDES Network leadership group. None of the authors have any additional competing interests to clear., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Evidence synthesis organisations are trying to meet commissioners' needs for rapid responses to their evidence synthesis commissions. In this project we piloted an intensive process, working to complete evidence syntheses within six-weeks, rather than the standard lead time of 4-6 months. Our objective was to explore how researchers experience working intensively, identify barriers and facilitators, and determine how a more intensive approach to evidence synthesis could be more systematically introduced in the future., Methods: In a pre-planning phase, an intensive work group was established, and two commissions were selected for this pilot project. The evidence synthesis process was divided into two phases: planning and intensive. The planning phase, involved scheduling the intensive phase, exploring new digital tools, and identifying peer reviewers. The intensive phase encompassed the entire evidence synthesis process. Two review teams were formed, each with a team lead supported by a process lead and leadership contact point. Throughout the project, teams engaged in reflective meetings to evaluate and adjust processes as needed., Results: During the planning phase, teams identified significant uncertainties regarding scopes, research questions, and inclusion criteria. To address this, they engaged with commissioners earlier than originally planned, clarified these aspects, and prepared protocols. Despite some minor deviations from the original plan, both reviews were completed on schedule, with one team expanding their scope due to the absence of eligible studies. Teams operated flexibly, held regular meetings, and found the process seamless due to fewer interruptions. Machine learning tools facilitated rapid study selection. The process lead role, created to guide and evaluate the project, proved beneficial, providing structure and support, although clearer role delineation with the leadership contact point could have improved efficiency., Conclusions: Overall, the intensive process fostered focus and productivity, allowing teams to manage short-term deliverables effectively. The researchers preferred working intensively with one evidence synthesis over being involved with many projects at the same time. They felt that time use was more effective, and they were able to complete the tasks in a focused way. However, there are several implications that should be considered before implementing an intensive approach in future evidence syntheses., (© 2024. The Author(s).)

Guidelines help to facilitate treatment decisions based on available evidence, and also to provide recommendations in areas of uncertainty. In this paper, we compare the recommendations for stroke workup and secondary prevention of ischemic stroke and transient ischemic attack of the American Heart Association (AHA)/American Stroke Association (ASA) with the European Stroke Organization (ESO) guidelines. The primary aim of this paper is to offer clinicians guidance by identifying areas where there is consensus and where consensus is lacking, in the absence or presence of high-level evidence. We compared AHA/ASA with the ESO guideline recommendations for 7 different topics related to diagnostic stroke workup and secondary prevention. We categorized the recommendations based on class and level of evidence to determine whether there were relevant differences in the ratings of evidence that the guidelines used for its recommendations. Finally, we summarized major topics of agreement and disagreement, while also prominent knowledge gaps were identified. In total, we found 63 ESO and 82 AHA/ASA recommendations, of which 38 were on the same subject. Most recommendations are largely similar, but not all are based on high-level evidence. For many recommendations, AHA/ASA and ESO assigned different levels of evidence. For the 10 recommendations with Level A evidence (high quality) in AHA/ASA, ESO only labeled 4 of these as high quality . There are many remaining issues with either no or insufficient evidence, and some topics that are not covered by both guidelines. Most ESO and AHA/ASA Guideline recommendations for stroke workup and secondary prevention were similar. However not all were based on high-level evidence and the appointed level of evidence often differed. Clinicians should not blindly follow all guideline recommendations; the accompanying level of evidence informs which recommendations are based on robust evidence. Topics with lower levels of evidence, or those with recommendations that disagree or are missing, may be an incentive for further clinical research., Competing Interests: Dr Dippel reports grants from Stryker, Medtronic, Penumbra, Cerenovus, and Thrombolytic Science, paid to the institution for research outside the submitted work.

Patients with diseases of the musculoskeletal system are confronted with a large quantity of treatment offers based on methods of complementary medicine. Despite a considerable number of publications on this topic, the scientific evidence is still poor. This article focuses on Ayurvedic medicine (AM), traditional Chinese medicine (TCM), mind-body medicine and homeopathy. These procedures have a longstanding tradition of practice and each claims to have its own theoretical concept; however, the application in the field of rheumatology can only be recommended either for specific entities or, in the case of homeopathy, not at all. In addition, this article summarizes the evidence for dietary recommendations, nutritional supplements and herbal medicine in rheumatology. The latter topics are frequently discussed in the popular press and are a much-debated issue between physicians and patients; however, clear-cut recommendations for the application on a scientific basis are the exception and mainly consist of the endorsement to adhere to the principles of a Mediterranean diet., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: The aim of this paper is to provide clinicians and authors of clinical guidelines or patient information with practical guidance on searching and choosing systematic reviews(s) (SR[s]) and, where adequate, on making use of SR(s)., Study Design and Setting: At the German conference of the Evidence-Based Medicine Network (EbM Network) a workshop on the topic was held to identify the most important areas where guidance for practice appears necessary. After the workshop, we established working groups. These included SR users with different backgrounds (eg, information specialists, epidemiologists) and working areas. Each working group developed and consented a draft guidance based on their expert knowledge and experiences. The results were presented to the entire group and finalized in an iterative process., Results: We developed a practical guidance that answers questions that usually arise when choosing and using SR(s). (1) How to efficiently find high-quality SRs? (2) How to choose the most appropriate SR? (3) What to do if no SR of sufficient quality could be identified? In addition, we developed an algorithm that links these steps and accounts for their interaction. The resulting guidance is primarily directed at clinicians and developers of clinical practice guidelines or patient information resources., Conclusion: We suggest practical guidance for making the best use of SRs when answering a specific research question. The guidance may contribute to the efficient use of existing SRs. Potential benefits when using existing SRs should be always weighted against potential limitations., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To map whether and how systematic reviews (SRs) with network meta-analysis (NMA) use presentation formats to report (a) structured evidence summaries - here defined as reporting of effects estimates in absolute effects with certainty ratings and with a method to rate interventions across one or more outcome(s) - and (b) NMA results in general., Study Design and Setting: We conducted a systematic survey, searching MEDLINE (Ovid) for SRs with NMA published between January 1, 2020, and December 31, 2021. We planned to include a random sample of publications, with predefined mechanisms in place for saturation, and included SRs that met prespecified quality criteria and extracted data on presentation formats that reported: (a) estimates of effects, (b) certainty of the evidence, or (c) rating of interventions., Results: The 200 eligible SRs, from 158 unique Journals, utilized 1133 presentation formats. We found structured evidence summaries in 10 publications (5.0%), with 3 (1.5%) reporting structured evidence summaries across all outcomes, including benefits and harms. Sixteen of the 133 SRs (11.7%) reporting dichotomous outcomes included estimates of absolute effects. Seventy-six SRs (38.0%) reported both benefits and harms and 26 SRs (13.0%) reported certainty ratings in presentation formats, 20 (76.9%) used Grading of Recommendations Assessment, Development and Evaluation and 6 (23.1%) used Confidence In Network Meta-analysis. Surface Under the Cumulative Ranking Curve was the most common method to rate interventions (69 SRs, 34.5%). NMA results were most often reported using forest plots (108 SRs, 54.0%) and league tables (93 SRs, 46.5%)., Conclusion: Most SRs with NMA do not report structured evidence summaries and only rarely do such summaries include reporting of both benefits and harms; those that do offer effective user-friendly communication and provide models for optimal NMA presentation practice., Competing Interests: Declaration of competing interest T.A. reports a relationship with MAGIC Evidence Ecosystem Foundation that includes: board membership and employment. P.O.V. reports a relationship with MAGIC Evidence Ecosystem Foundation that includes: board membership and employment. P.O.V. and T.A. are CEO and deputy CEO of the nonprofit organization MAGIC Evidence Ecosystem Foundation (https://www.magicevidence.org). In collaboration with P.O.L. at Lovisenberg Diaconal Hospital, MAGIC is conducting the research project Making Alternative Treatment Choices Intuitive and Trustworthy (MATCH-IT). The overarching aim of MATCH-IT is to develop a new interactive SoF table and decision support tool, displaying multiple structured evidence summaries from NMAs. The tool may be integrated as part of MAGICapp (https://app.magicapp.org/#/guidelines), an online author and publication platform for guidelines, evidence summaries and decision aids. A.A.V. is Statistical Associate Editor for the Journal of Clinical Epidemiology, but had no involvement with the peer review process or decision for publication. A.C.T. is Coeditor-in-Chief for the Journal of Clinical Epidemiology, but had no involvement with the peer review process or decision for publication. X.W., T.P., M.Ø., and C.L. declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The American Diabetes Association and the European Association for the Study of Diabetes published a 2022 consensus report recommending changes in diabetes care. This Perspective raises three concerns: with how the report summarizes evidence, how it frames the social determinants of health (SDOH), and with its transnational composition and conflicts of interest. The Perspective analyzes three new clinical recommendations that change the role of metformin from first-line therapy to a first-line option, for the inclusion of weight management as a co-primary treatment goal with glycemic control for patients without cardiac or renal complications, and for addition of the SDOH as a universal component of diabetes care together with lifestyle changes and self-management support. The Perspective considers how the poor evidence assessments of the recommendations and the imprecise framing of the SDOH introduce bias. The composition of the panel's membership poorly represents and accounts for the challenges faced by vulnerable US communities or safety net providers. The report is placed in a historical context for diabetes of organized medicine's failures to overcome prejudices and promote health equity. The Perspective concludes that the report perpetuates a pattern of prejudice within organized medicine at the expense of scientific precision and health equity., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Fluid therapy is an integral component of perioperative management. In light of emerging evidence in this area, the Perioperative Quality Initiative (POQI) convened an international multiprofessional expert meeting to generate evidence-based consensus recommendations for fluid management in patients undergoing surgery. This article provides a summary of the recommendations for perioperative fluid management of surgical patients from the preoperative period until hospital discharge and for all types of elective and emergency surgery, apart from burn injuries and head and neck surgery. Where evidence was lacking, recommendations for future research were generated. Specific recommendations are made for fluid management in elective major noncardiac surgery, cardiopulmonary bypass, thoracic surgery, neurosurgery, minor noncardiac surgery under general anaesthesia, and critical illness. There are ongoing gaps in knowledge resulting in variation in practice and some disagreement with our consensus recommendations. Perioperative fluid management should be individualised, taking into account the type of surgery and important patient factors, including intravascular volume status and acute and chronic comorbidities. Recommendations are made for further research in perioperative fluid management to address important gaps., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

For older adults with serious, life-limiting illnesses near the end of life, clinicians frequently face difficult decisions about the medical care they provide because of clinical uncertainty. This difficulty is further complicated by unique challenges and medical advancements for patients with advanced heart diseases. In this article, we describe common mistakes encountered by clinicians when having goals-of-care conversations (e.g. conversations between clinicians and seriously ill patients/surrogates to discuss patient's values and goals for clinical care near the end of life.). Then, we delineate an evidence-based approach in goals-of-care conversations and highlight the unique challenges around decision-making in the cardiac intensive care unit., Competing Interests: Conflict of interest: K.O. has received advisory fees from Jolly Good, Inc (a virtual reality company). All other authors have nothing to report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This report aimed to examine temporal changes in the number of recommendations on management of infective endocarditis in the European and American guidelines. The number of recommendations has increased since 2004 without an increment in evidence base in the European iteration. American guidelines have reduced the number of recommendations with a main evidence base of level B., Competing Interests: Conflict of interest Lauge Østergaard: Independent research grant from the Novo Nordisk Foundation for the research of mitral valve regurgitation. Lars Køber: Speakers honorarium from Novo, Novartis, AstraZeneca, Boehringer and Bayer Emil Loldrup Fosbøl: Novo Nordisk Foundation and the Danish Heart Association: Independent research grant related to valvular heart disease and endocarditis. Sofie Truong, Eva Havers-Borgersen and Jeppe Petersen: None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Evidence-based practice is the principle governing a range of healthcare practices and beyond. However, it has suffered from a lack of philosophical rigour. This paper sets out to analyse the epistemological basis of evidence-based practice., Method: The paper uses a conceptual analysis. First, it describes the implicit epistemology at work in evidence-based practice. Second, it evaluates the implicit epistemological basis., Results: The analysis indicates that evidence-based practice lacks an explicit epistemological basis. It shows, moreover, that the implicit epistemological basis is untenable., Conclusion: There is a need to re-think the epistemological basis for evidence-based practice. Evidence-based practice is out of touch with developments within philosophy of science., (© 2024 The Author(s). Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Clinicians often suspect that a treatment effect can vary across individuals. However, they usually lack "evidence-based" guidance regarding potential heterogeneity of treatment effects (HTE). Potentially actionable HTE is rarely discovered in clinical trials and is widely believed (or rationalized) by researchers to be rare. Conventional statistical methods to test for possible HTE are extremely conservative and tend to reinforce this belief. In truth, though, there is no realistic way to know whether a common, or average, effect estimated from a clinical trial is relevant for all, or even most, patients. This absence of evidence, misinterpreted as evidence of absence, may be resulting in sub-optimal treatment for many individuals. We first summarize the historical context in which current statistical methods for randomized controlled trials (RCTs) were developed, focusing on the conceptual and technical limitations that shaped, and restricted, these methods. In particular, we explain how the common-effect assumption came to be virtually unchallenged. Second, we propose a simple graphical method for exploratory data analysis that can provide useful visual evidence of possible HTE. The basic approach is to display the complete distribution of outcome data rather than relying uncritically on simple summary statistics. Modern graphical methods, unavailable when statistical methods were initially formulated a century ago, now render fine-grained interrogation of the data feasible. We propose comparing observed treatment-group data to "pseudo data" engineered to mimic that which would be expected under a particular HTE model, such as the common-effect model. A clear discrepancy between the distributions of the common-effect pseudo data and the actual treatment-effect data provides prima facie evidence of HTE to motivate additional confirmatory investigation. Artificial data are used to illustrate implications of ignoring heterogeneity in practice and how the graphical method can be useful., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: Access to evidence-based pharmacotherapy (EBP) is crucial in effectively managing allergies. Allergy conditions, including rhinitis, asthma, and dermatitis, require treatment guided by scientific evidence. However, healthcare professionals face challenges in accessing relevant information., Recent Findings: The dynamic nature of allergy research, coupled with limited resources and variability in practice guidelines, complicates decision-making., Summary: To enhance access, healthcare institutions should invest in comprehensive online resources tailored to allergy management, such as databases and platforms. Advances in algorithm development have shown that artificial intelligence and machine learning can enhance clinical decision-making. Integrating allergy-specific Clinical Decision Support Systems (CDSS) into electronic health records can assist professionals in making EBP decisions at the point of care. Continuing education and training programs focused on allergy management can keep healthcare providers updated on the latest research and guidelines. Multidisciplinary teams facilitate knowledge exchange and standardize practice approaches. Social media outlets can be a great route to publicize work carried out or in progress to a target audience of interest. By bridging the gap between evidence and practice in allergy management, healthcare systems can ensure optimal care for patients, alleviating the burden of allergic diseases on individuals and society., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To understand the current usage of eviQ Cancer Treatments Online (www.eviQ.org.au), an Australian, open-access website providing evidence-based and consensus-driven cancer treatment protocols and information, and the extent to which it is meeting its intended outcomes and providing value to its users., Methods: A mixed-method evaluation was conducted in 2020-2022 which included a review of key program documentation and website usage data, and delivery of a focused online survey to its users., Results: In 2022, 329 clinicians representing all Australian states and territories contributed to eviQ content development and review. eviQ content continues to grow with a 15.2% increase in total content from 2019 to 2022.  eviQ website users continue to grow with 90,000 total monthly users in 2022, representing a 166% increase from 2018. The proportion of international users compared to Australian users continues to grow with 57% of total users in Australia and 43% international in 2022. Of 466 survey responses, the most cited reason for eviQ use was for information on side effects/toxicity (67%). Ninety-three percent (93%) of respondents either agreed or strongly agreed that eviQ contributed to both health professionals providing the best evidence-based treatment and care and improving the standardization of treatment and care provided., Conclusion:  eviQ is embedded in Australian clinical practice, highly valued, and relied upon by users. Users agree that eviQ has a positive impact on patients by supporting the delivery of evidence-based treatment and that eviQ contributed to patients' improved health outcomes and quality of life. eviQ's increasing international usage should be explored., (© 2024 John Wiley & Sons Australia, Ltd.)

Purpose: It has been proposed that a higher habitual protein intake may increase cancer risk, possibly via upregulated insulin-like growth factor signalling. Since a systematic evaluation of human studies on protein intake and cancer risk based on a standardised assessment of systematic reviews (SRs) is lacking, we carried out an umbrella review of SRs on protein intake in relation to risks of different types of cancer., Methods: Following a pre-specified protocol (PROSPERO: CRD42018082395), we retrieved SRs on protein intake and cancer risk published before January 22th 2024, and assessed the methodological quality and outcome-specific certainty of the evidence using a modified version of AMSTAR 2 and NutriGrade, respectively. The overall certainty of evidence was rated according to predefined criteria., Results: Ten SRs were identified, of which eight included meta-analyses. Higher total protein intake was not associated with risks of breast, prostate, colorectal, ovarian, or pancreatic cancer incidence. The methodological quality of the included SRs ranged from critically low (kidney cancer), low (pancreatic, ovarian and prostate cancer) and moderate (breast and prostate cancer) to high (colorectal cancer). The outcome-specific certainty of the evidence underlying the reported findings on protein intake and cancer risk ranged from very low (pancreatic, ovarian and prostate cancer) to low (colorectal, ovarian, prostate, and breast cancer). Animal and plant protein intakes were not associated with cancer risks either at a low (breast and prostate cancer) or very low (pancreatic and prostate cancer) outcome-specific certainty of the evidence. Overall, the evidence for the lack of an association between protein intake and (i) colorectal cancer risk and (ii) breast cancer risk was rated as possible. By contrast, the evidence underlying the other reported results was rated as insufficient., Conclusion: The present findings suggest that higher total protein intake may not be associated with the risk of colorectal and breast cancer, while conclusions on protein intake in relation to risks of other types of cancer are restricted due to insufficient evidence., (© 2024. The Author(s).)

Chronic hepatitis B (CHB) remains a major global public health problem. The functional cure is the ideal therapeutic target recommended by the latest guidelines, and pursuing a functional cure has become the key treatment end point of current therapy and for upcoming clinical trials. In this review, based on the latest published clinical research evidence, we analyzed the concept and connotation of clinical cures and elaborated on the benefits of clinical cures in detail. Secondly, we have summarized various potential treatment methods for achieving clinical cures, especially elaborating on the latest research progress of interferon-based optimized treatment strategies in achieving clinical cures. We also analyzed which populations can achieve clinical cures and conducted a detailed analysis of relevant virological and serological markers in screening clinical cure advantage populations and predicting clinical cure achievement. In addition, we also introduced the difficulties that may be encountered in the current pursuit of achieving a clinical cure., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Objectives: To evaluate and improve "Making Alternative Treatment Choices Intuitive and Trustworthy" (MATCH-IT)-a digital, interactive decision support tool displaying structured evidence summaries for multiple comparisons-to help physicians interpret and apply evidence from network meta-analysis (NMA) for their clinical decision-making., Study Design and Setting: We conducted a qualitative user testing study, applying principles from user-centered design in an iterative development process. We recruited a convenience sample of practicing physicians in Norway, Belgium, and Canada, and asked them to interpret structured evidence summaries for multiple comparisons-linked to clinical guideline recommendations-displayed in MATCH-IT. User testing included (a) introduction of a clinical scenario, (b) a think-aloud session with participant-tool interaction, and (c) a semistructured interview. We video recorded, transcribed, and analyzed user tests using directed content analysis. The results informed new updates in MATCH-IT., Results: Distributed across 5 development cycles we tested MATCH-IT with 26 physicians. Of these, 24 (94%) reported either no or sparse prior experience with interpretation of NMA. Physicians perceived MATCH-IT as easy to interpret and navigate, and appreciated its ability to provide an overview of the evidence. Visualization of effects in pictograms and inclusion of information on burden of treatment ("practical issues") were highlighted as potentially useful features in interacting with patients. We also identified problems, including undiscovered functionalities (drag and drop), suboptimal tutorial, and cumbersome navigation of the tool. In addition, physicians wanted definition/explanation of key terms (eg, outcomes and "certainty"), and there were concerns that overwhelming evidence from a large NMA would complicate applicability to clinical practice. This led to several updates with development of a new start page, tutorial, updated user interface for more efficient maneuvering, solutions to display definition of key terms and a "frequently asked questions" section. To facilitate interpretation of large networks, we improved categorization of results using color coding and added filtering functionality. These modifications allowed physicians to focus on interventions of interest and reduce information overload., Conclusion: This study provides proof of concept that physicians can use MATCH-IT to understand NMA evidence. Key features of MATCH-IT in a clinical context include providing an overview of the evidence, visualization of effects, and the display of information on burden of treatments. However, unfamiliarity with the Grading of Recommendations Assessment, Development and Evaluation concepts, time constraints, and accessibility at the point of care may be challenges for use. To what extent our results are transferable to real-world clinical contexts remains to be explored., Competing Interests: Declaration of competing interest T.A. is the Chair of the board and Deputy CEO of the nonprofit organization MAGIC Evidence Ecosystem Foundation (https://www.magicevidence.org). F.A. is a paid consultant for the MAGIC Evidence Ecosystem Foundation and is a part of the research team in MAGIC conducting the research project “Making Alternative Treatment Choices Intuitive and Trustworthy” (MATCH-IT). P.O.V is the CEO of the nonprofit organization MAGIC Evidence Ecosystem Foundation (https://www.magicevidence.org). P.O.L, B.S.H, and A.F.H are all part of the research team in MAGIC conducting the research project Making Alternative Treatment Choices Intuitive and Trustworthy (MATCH-IT). J.W.B. is partly supported by the Canadian Institutes of Health Research Canada Research Chair in the prevention and management of chronic pain. There are no competing interests for any other author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The ClinGen Actionability Working Group (AWG) developed an evidence-based framework to generate actionability reports and scores of gene-condition pairs in the context of secondary findings from genome sequencing. Here we describe the expansion of the framework to include actionability assertions., Methods: Initial development of the actionability rubric was based on previously scored adult gene-condition pairs and individual expert evaluation. Rubric refinement was iterative and based on evaluation, feedback, and discussion. The final rubric was pragmatically evaluated via integration into actionability assessments for 27 gene-condition pairs., Results: The resulting rubric has a 4-point scale (limited, moderate, strong, and definitive) and uses the highest-scoring outcome-intervention pair of each gene-condition pair to generate a preliminary assertion. During AWG discussions, predefined criteria and factors guide discussion to produce a consensus assertion for a gene-condition pair, which may differ from the preliminary assertion. The AWG has retrospectively generated assertions for all previously scored gene-condition pairs and are prospectively asserting on gene-condition pairs under assessment, having completed over 170 adult and 188 pediatric gene-condition pairs., Conclusion: The AWG expanded its framework to provide actionability assertions to enhance the clinical value of their resources and increase their utility as decision aids regarding return of secondary findings., Competing Interests: Conflict of Interest A. Buchanan has equity in MeTree and You, Inc. S. Rego is an employee and has options at BillionToOne, Inc. Dr Steiner is an employee with equity of PreventionGenetics, part of Exact Sciences, and reports consulting fees from Leadiant, Mirum, and PTC Therapeutics. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Systematic reviews and meta-analyses are essential tools in contemporary evidence-based medicine, synthesizing evidence from various sources to better inform clinical decision-making. However, the conclusions from different meta-analyses on the same topic can be discrepant, which has raised concerns about their reliability. One reason is that the result of a meta-analysis is sensitive to factors such as study inclusion/exclusion criteria and model assumptions. The arm-based meta-analysis model is growing in importance due to its advantage of including single-arm studies and historical controls with estimation efficiency and its flexibility in drawing conclusions with both marginal and conditional effect measures. Despite its benefits, the inference may heavily depend on the heterogeneity parameters that reflect design and model assumptions. This article aims to evaluate the robustness of meta-analyses using the arm-based model within a Bayesian framework. Specifically, we develop a tipping point analysis of the between-arm correlation parameter to assess the robustness of meta-analysis results. Additionally, we introduce some visualization tools to intuitively display its impact on meta-analysis results. We demonstrate the application of these tools in three real-world meta-analyses, one of which includes single-arm studies., (© 2024. The Author(s).)

Purpose: Cancer is associated with an urgent need for understandable and reliable information, which is often not satisfied by information available online. Therefore, as part of the PIKKO project, a web-based knowledge database (WDB) was introduced to provide cancer patients with quality-assured, evidence-based information. This paper aims to provide insights into the usage (Who? How? What?) and the effects regarding health literacy of the WDB., Methods: A patient survey and automatically generated logfile data were evaluated. Two user groups, patients and patient navigators (PNs), were compared., Results: The 13 PNs were responsible for 1/3 of all accesses over the entire duration of the project. The 413 patients used WDB twice on average and spent an average of 12 min per session online (PNs: 9 min per session, more frequently). The top 3 topics of interest were 'therapy', 'nutrition' and 'carcinogenesis' for the patients, and 'therapy', 'naturopathy' and 'legal regulations/support' for the PNs. Of the patients surveyed, 69% said that WDB was helpful in making informed decisions, 76% found the information they wanted and 90% thought WDB was an appropriate way to provide information., Conclusion: Our WDB provided important information about cancer and its treatment on a digital way both, to patients and PNs. In routine cancer care, the WDB can improve health literacy and informed decision-making., Trial Registration: This study was retrospectively registered in the German Clinical Trial Register under DRKS00016703 (21 Feb 2019, retrospectively registered). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016703., (© 2024. The Author(s).)

Pragmatism in clinical trials is focused on increasing the generalizability of research findings for routine clinical care settings. Hybridism in clinical trials (i.e., assessing both clinical effectiveness and implementation success) is focused on speeding up the process by which evidence-based practices are developed and adopted into routine clinical care. Even though pragmatic trial methodologies and implementation science evolved from very different disciplines, Pragmatic Trials and Hybrid Effectiveness-Implementation Trials share many similar design features. In fact, these types of trials can easily be conflated, creating the potential for investigators to mislabel their trial type or mistakenly use the wrong trial type to answer their research question. Blurred boundaries between trial types can hamper the evaluation of grant applications, the scientific interpretation of findings, and policy-making. Acknowledging that most trials are not pure Pragmatic Trials nor pure Hybrid Effectiveness-Implementation Trials, there are key differences in these trial types and they answer very different research questions. The purpose of this paper is to clarify the similarities and differences of these trial types for funders, researchers, and policy-makers. In addition, recommendations are offered to help investigators choose, label, and operationalize the most appropriate trial type to answer their research question. These recommendations complement existing reporting guidelines for clinical effectiveness trials (TIDieR) and implementation trials (StaRI)., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

There is a growing demand for the use of high-quality real-world evidence (RWE) to support regulatory decision-making worldwide and in China, which highlights the need for conducting literature reviews to evaluate the available data and evidence. This study aims to review the use of RWE in Chinese regulatory decisions and to summarize relevant regulatory and methodological considerations to inform the future use of RWE in China. We identified policy documents, technical guidance documents, and cases on official Chinese government websites and extracted their contents separately. We consulted experts from the National Medical Products Administration (NMPA) and academic institutes and searched case-related articles for enrichment. We also searched and included articles related to the use of RWE/Real-world data in Chinese regulatory decisions. Six trial versions of technical guidance documents, 7 case studies, and 40 articles related to the Chinese regulatory decisions were included in this study. Based on the technical guidance, data quality, and appropriate study design and statistical analysis are the main concerns for RWE generation. The cases and articles related to regulatory decisions revealed 9 main concerns, including data sources and applicability, data quality, strength of existing evidence, appropriate study design and statistical analysis, regulated and transparent process for analysis and evidence generation, product safety and efficacy, product characteristics and clinical needs, ethical considerations and data security, and communicate adequately with regulatory authorities. Among these concerns, data issues are central. Preliminary attempts have been made by the NMPA to promote the use of RWE, but substantial challenges still remain., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Objectives: To assess to what extent the overall quality of evidence indicates changes to observe intervention effect estimates when new data become available., Methods: We conducted a meta-epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same health-care question that was updated with inclusion of additional data between January 2016 and May 2021. We extracted the reported effect estimates with 95% confidence intervals (CIs) from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ratio of odds ratio (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance., Results: High CoE without limitations characterized 19.3% (n = 29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95% CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; interquartile range [IQR]: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78-0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations)., Conclusion: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated., Competing Interests: Declaration of competing interest I.H.: has one-year consulting contract for research projects at the Medical University of South Carolina, Charleston, SC, USA. D.N.: declares having led/coauthored/coauthoring Cochrane Reviews and conducted GRADE assessments as part of completing some of these reviews. He also declares having been part of the Cochrane Convenes initiative organized by Cochrane to consider the issue of misinformation, its impact on the health evidence ecosystem and solutions to address it. L.G.H.’s Institution (RC2NB) is supported by Foundation Clinical Neuroimmunology and Neuroscience Basel. There are no competing interests for any other author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

"Lifestyle medicine (LM) is an evidence-based therapeutic intervention delivered by clinicians trained and certified in this specialty to prevent, treat, and often reverse chronic disease". Eighty percent of the conditions primary care physicians routinely encounter in their offices, e.g., diabetes mellitus, hypertension, COPD, cardiovascular disease, have root causes in poor lifestyle choices such as smoking, insufficient sleep, being sedentary, or eating highly processed foods. Lifestyle is the foundation of most chronic disease management guidelines aimed at reducing morbidity and mortality. Studies have shown that changes in lifestyle can be achieved and link almost directly to reduction in risk for chronic illness. Primary care physicians are ideally positioned to incorporate LM into their practices. It is important to recognize and find solutions to the many barriers to implementing LM at the patient, physician, and system level. There is an urgent need to increase opportunities for practicing physicians to increase their knowledge and skills related to LM and include this in medical school and residency curricula. Many resources exist that can provide the necessary training for seasoned physicians and students/residents to become competent in practicing LM and address barriers to implementing LM. LM has the potential to revolutionize clinical practice by placing a greater emphasis on disease prevention and the role of healthy lifestyle behaviors in disease management., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.