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This article provides a focused update to the clinical practice guideline on the treatment and management of patients with coronavirus disease 2019, developed by the Infectious Diseases Society of America. The guideline panel presents a recommendation on the use of the anti-severe acute respiratory syndrome coronavirus 2 neutralizing antibody pemivibart as pre-exposure prophylaxis. The recommendation is based on evidence derived from a systematic review and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Information on pemivibart is included in the U.S. Food and Drug Administration Emergency Use Authorization for this agent., Competing Interests: Possible conflicts of interest. Evaluation of relationships as potential conflicts of interest is determined by a review process. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The following panelists have research-related advisor/consultant roles for indicated companies: R.B. for Shionogi, Merck, and Gilead Sciences; K.W.C. for Pardes Biosciences (concluded); E.D. for Gilead Sciences; D.V.G. for Gilead Sciences and Merck; A.K. for Shionogi; S.S. for Pfizer; P.T. for Merck and Shionogi. Importantly, these companies have developed COVID-19 treatment (but not prophylaxis) agents. No disclosures reported for all other authors including the chair and vice chair. Additional information. More detailed information on the analysis and development of recommendations is available in the Supplementary material., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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.)

Background: The Grading Recommendations, Assessment, Development, and Evaluations (GRADE) framework is widely applied in clinical guidelines to facilitate transparent evidence evaluation. While developing Infectious Diseases Society of America (IDSA) guidelines on the management of patients with coronavirus disease 2019 (COVID-19), panel members suggested developing and implementing a visual aid to enable quicker identification of key information by providers at bedside seeking guidance., Methods: We conducted a mixed-methods study evaluating the usability of a newly designed infographic/icon using a survey and focus groups. The survey incorporated a simulated COVID-19 IDSA guideline with and without the icon, followed by comprehension questions. Focus group discussions provided qualitative feedback on the GRADE methodology and icon usability., Results: The survey was returned by 289 health care providers. There was no statistical difference in the correct response rates between icon-aided and non-icon-aided guideline questions (McNemar's chi-square test, P > .1 for both questions). Interactions with the icon notably increased the time taken and number of clicks required to respond to the first question (Wilcoxon signed-rank test, P < .01). In contrast, response time did not differ between versions for the second question ( P = .38). Most subjects (85%) indicated that the icon improved the readability of the guidelines. A focus group follow-up suggested alternative designs for the icon., Conclusions: This study highlights the promise of iconography in clinical guidelines, although the specific icons tested did not measurably improve usability metrics. Future research should focus on icon design and testing within a formal usability framework, considering the impact of GRADE language on user experience., Competing Interests: Potential conflicts of interest. Y.F.Y., R.L.M., and R.A.M. disclose their affiliations as members of the GRADE working group and cofounders of the US GRADE network, with experience serving various societies as methodologists and GRADE experts. I.Y.C., J.C.O., J.E.G., M.M.M., and A.B. declare no disclosures., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: This guideline establishes clinical practice recommendations for Treatment of Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD) in adults and pediatric patients., Methods: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations., Good Practice Statement: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RLS., 1. In all patients with clinically significant RLS, clinicians should regularly test serum iron studies including ferritin and transferrin saturation (calculated from iron and total iron binding capacity, TIBC). The test should ideally be administered in the morning avoiding all iron-containing supplements and foods at least 24 hours prior to blood draw. Analysis of iron studies greatly influences the decision to use oral or intravenous (IV) iron treatment. Consensus guidelines, which have not been empirically tested, suggest that supplementation of iron in adults with RLS should be instituted with oral or IV iron if serum ferritin ≤75 ng/mL or transferrin saturation < 20%, and only with IV iron if serum ferritin is between 75 ng/mL and 100 ng/mL. In children, supplementation of iron should be instituted for serum ferritin < 50 ng/mL with oral or IV formulations. These iron supplementation guidelines are different than for the general population., 2. The first step in the management of RLS should be addressing exacerbating factors, such as alcohol, caffeine, antihistaminergic, serotonergic, anti-dopaminergic medications, and untreated obstructive sleep apnea (OSA)., 3. RLS is common in pregnancy; prescribers should consider the pregnancy-specific safety profile of each treatment being considered., Recommendations: The following recommendations are intended as a guide for clinicians in choosing a specific treatment for RLS and PLMD in adults and children. Each recommendation statement is assigned a strength ("Strong" or "Conditional"). A "Strong" recommendation (i.e., "We recommend…") is one that clinicians should follow under most circumstances. The recommendations listed below are ranked in the order of strength of recommendations and grouped by class of treatments within each PICO question. Some recommendations include remarks that provide additional context to guide clinicians with implementation of this recommendation., Adults with RLS ., 1. In adults with RLS, the AASM recommends the use of gabapentin enacarbil over no gabapentin enacarbil (Strong recommendation, moderate certainty of evidence)., 2. In adults with RLS, the AASM recommends the use of gabapentin over no gabapentin (Strong recommendation, moderate certainty of evidence)., 3. In adults with RLS, the AASM recommends the use of pregabalin over no pregabalin (Strong recommendation, moderate certainty of evidence)., 4. In adults with RLS, the AASM recommends the use of IV ferric carboxymaltose over no IV ferric carboxymaltose in patients with appropriate iron status (see good practice statement for iron parameters) (Strong recommendation, moderate certainty of evidence)., 5. In adults with RLS, the AASM suggests the use of IV low molecular weight (LMW) iron dextran over no IV LMW iron dextran in patients with appropriate iron status (see good practice statement for iron parameters) (Conditional recommendation, very low certainty of evidence)., 6. Recommendation 6: In adults with RLS, the AASM suggests the use of IV ferumoxytol over no IV ferumoxytol in patients with appropriate iron status (see good practice statement for iron parameters) (Conditional recommendation, very low certainty of evidence)., 7. In adults with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (Conditional recommendation, moderate certainty of evidence)., 8. In adults with RLS, the AASM suggests the use of dipyridamole over no dipyridamole (Conditional recommendation, low certainty of evidence)., 9. In adults with RLS, the AASM suggests the use of extended-release oxycodone and other opioids over no opioids (Conditional recommendation, moderate certainty of evidence)., 10. In adults with RLS, the AASM suggests the use of bilateral high-frequency peroneal nerve stimulation over no peroneal nerve stimulation (Conditional recommendation, low certainty of evidence)., 11. In adults with RLS, the AASM suggests against the standard use of levodopa (Conditional recommendation, very low certainty of evidence)., Remarks: Levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 12. In adults with RLS, the AASM suggests against the standard use of pramipexole (Conditional recommendation, moderate certainty of evidence)., Remarks: Pramipexole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 13. In adults with RLS, the AASM suggests against the standard use of transdermal rotigotine (Conditional recommendation, low certainty of evidence)., Remarks: Transdermal Rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 14. In adults with RLS, the AASM suggests against the standard use of ropinirole (Conditional recommendation, moderate certainty of evidence)., Remarks: Ropinirole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 15. In adults with RLS, the AASM suggests against the use of bupropion for the treatment of RLS (Conditional recommendation, moderate certainty of evidence)., 16. In adults with RLS, the AASM suggests against the use of carbamazepine (Conditional recommendation, low certainty of evidence)., 17. In adults with RLS, the AASM suggests against the use of clonazepam (Conditional recommendation, very low certainty of evidence)., 18. In adults with RLS, the AASM suggests against the use of valerian (Conditional recommendation, low certainty of evidence)., 19. In adults with RLS, the AASM suggests against the use of valproic acid (Conditional recommendation, low certainty of evidence)., 20. In adults with RLS, the AASM recommends against the use of cabergoline (Strong recommendation, moderate certainty of evidence)., Special adult populations with RLS ., 21. In adults with RLS and end-stage renal disease (ESRD), the AASM suggests the use of gabapentin over no gabapentin (conditional recommendation, very low certainty of evidence)., 22. In adults with RLS and ESRD, the AASM suggests the use of IV iron sucrose over no IV iron sucrose in patients with ferritin < 200 ng/mL and transferrin saturation < 20% (Conditional recommendation, moderate certainty of evidence)., 23. In adults with RLS and ESRD, the AASM suggests the use of vitamin C over no vitamin C (conditional recommendation, low certainty of evidence)., 24. In adults with RLS and ESRD, the AASM suggests against the standard use of levodopa (Conditional recommendation, low certainty of evidence)., Remarks: Levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., 25. In adults with RLS and ESRD, the AASM suggests against the standard use of rotigotine (Conditional recommendation, very low certainty of evidence)., Remarks: Rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation)., Adults with PLMD ., 26. In adults with PLMD, the AASM suggests against the use of triazolam (Conditional recommendation, very low certainty of evidence)., 27. In adults with PLMD, the AASM suggests against the use of valproic acid (Conditional recommendation, very low certainty of evidence)., Children with RLS ., 28. In children with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (Conditional recommendation, very low certainty of evidence)., (© 2024 American Academy of Sleep Medicine.)

Introduction: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD)., Methods: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of pharmacological or nonpharmacological treatment to no treatment to improve patient-important outcomes. Statistical analyses were performed to determine the clinical significance of using various interventions to treat RLS and PLMD in adults and children. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations., Results: The literature search resulted in 3631 studies out of which 148 studies provided data suitable for statistical analyses. The task force provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations., (© 2024 American Academy of Sleep Medicine.)

Objectives: To explore the use of prediction interval (PI) for the simultaneous evaluation of the imprecision and inconsistency domains of Grading of Recommendations, Assessment, and Evaluation using stakeholder-provided decision thresholds., Study Design and Setting: We propose transforming the PI of a meta-analysis from a relative risk scale to an absolute risk difference using an appropriate baseline risk. The transformed PI is compared to stakeholder-provided thresholds on an absolute scale. We applied this approach to a large convenience sample of meta-analyses extracted from the Cochrane Database of Systematic Reviews and compared it against the traditional approach of rating imprecision and inconsistency separately using confidence intervals and statistical measures of heterogeneity, respectively. We used empirically derived thresholds following Grading of Recommendations, Assessment, and Evaluation guidance., Results: The convenience sample consisted of 2516 meta-analyses (median of 7 studies per meta-analysis; interquartile range: 5-11). The main analysis showed the percentage of meta-analyses in which both approaches had the same number of certainty levels rated down was 59%. The PI approach led to more levels of rating down (lower certainty) in 27% and to fewer levels of rating down (higher certainty) in 14%. Multiple sensitivity analyses using different thresholds showed similar results, but the PI approach had particularly increased width with a larger number of included studies and higher I 2 values., Conclusion: Using the PI for simultaneous evaluation of imprecision and inconsistency seems feasible and logical but can lead to lower certainty ratings. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria., Plain Language Summary: The prediction interval (PI) addresses both the imprecision and inconsistency domains of certainty. In this study, we applied this PI approach to simultaneously judge both domains and compared this to the traditional approach of making these separate judgments. The 2 approaches had moderate agreement. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Dystonia, typically characterized by slow repetitive involuntary movements, stiff abnormal postures, and hypertonia, is common among individuals with cerebral palsy (CP). Dystonia can interfere with activities and have considerable impact on motor function, pain/comfort, and ease of caregiving. Although pharmacological and neurosurgical approaches are used clinically in individuals with CP and dystonia that is causing interference, evidence to support these options is limited. This clinical practice guideline update comprises 10 evidence-based recommendations on the use of pharmacological and neurosurgical interventions for individuals with CP and dystonia causing interference, developed by an international expert panel following the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The recommendations are intended to help inform clinicians in their use of these management options for individuals with CP and dystonia, and to guide a shared decision-making process in selecting a management approach that is aligned with the individual's and the family's values and preferences., (© 2024 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Competing Interests: Declaration of competing interests The authors declare the following conflicts of interest (past 36 months): F.N.A.: member of the International Society on Thrombosis and Haemostasis (ISTH) Council and Vice-Chair of the ISTH Guideline and Guidance Committee; research funding (investigator-initiated studies, paid to university) from Bayer, Daiichi-Sankyo, and Sanofi; and consultancy fees (paid to university) from Boston Scientific. D.D.M.: member of the ISTH Council and consultant to the National Bleeding Disorders Foundation, the American Society of Hematology, and Believe Ltd on matters related to future research and workforce development in the areas of hematology and inherited bleeding disorders. A.C.: serves on the advisory board of Novo Nordisk and has received honoraria from Novo Nordisk, Grifols, Takeda, and Roche. E.V.D.P.: medical consultant for the area of the Brazilian Ministry of Health responsible for the national program of hereditary bleeding disorders. S.M.: member of the ISTH Council and reports participation in advisory or educational activities with AbbVie, Bayer, Astra Zeneca, Alveron (Advisory Board), Hemab, Norgine, Sanofi, Synapse, and Viatris; all honoraria are being paid to her institution. Y.F.-Y, T.S., and C.S. report no conflict of interest.

Competing Interests: Competing interests: The authors declare no financial conflicts of interest. MRS, RAM, RLM, YF-Y, PD, SS and MHM are members of the US GRADE Network. MRS is a fellow of the Evidence Foundation and receives a direct stipend. All other authors declare no conflicts of interest.

Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19) and for identifying asymptomatic carriage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of available SARS-CoV-2 nucleic acid detection tests continues to increase as does the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) developed an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients, and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss nuances of test result interpretation in a variety of practice settings, and highlight important unmet research needs related to COVID-19 diagnostic testing. IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 12 diagnostic recommendations. Access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention, and the public health response to COVID-19 infection. Information on the clinical performance of available tests continues to grow, but the quality of evidence of the current literature to support this updated molecular diagnostic guideline remains moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is suggested for asymptomatic individuals with known or suspected contact with a COVID-19 case when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions. Evidence in support of rapid testing and testing of upper respiratory specimens other than nasopharyngeal swabs, which offer logistical advantages, is sufficient to warrant conditional recommendations in favor of these approaches., Competing Interests: Potential conflicts of interest. The following list displays what has been reported to the IDSA. To provide thorough transparency, the IDSA requires full disclosure of all relationships, regardless of relevancy to the guideline topic. Evaluation of such relationships as potential conflicts of interest is determined by a review process which includes assessment by the Board of Directors’ liaison to the Standards and Practice Guideline Committee and, if necessary, the Conflicts of Interest (COI) and Ethics Committee. The assessment of disclosed relationships for possible COI is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The reader of these guidelines should be mindful of this when the list of disclosures is reviewed. M. K. H. receives research funding from the Centers for Disease Control and Prevention (CDC); and served as a member of Clinical Adjudication Panel for an investigational COVID-19 vaccine made by Sanofi Pasteur. K. E. H. served an advisor to Quidel, BioFire, Pfizer, and Takeda; received other numerations from Quidel, Pfizer, and Takeda; served as Editor to the American Society of Microbiology (ASM) and member of the Clinical and Laboratory Standards Institute Antifungal Committee; received research funding from the National Institutes of Health (NIH); and served on the exam committee for the American Board of Internal Medicine and associate editor for Open Forum Infectious Diseases. J. A. E. serves as a consultant for Sanofi Pasteur, Pfizer, and AstraZeneca and reports consulting fees from Moderna and Meissa Vaccines; is an advisor/consultant for Meissa Vaccines; receives research funding from the CDC, Pfizer, Brotman Baty Research Institute, Merck, Novavax, GlaxoSmithKline, and AstraZeneca; served as an advisor to Teva Pharmaceuticals; and served as a member of the Pediatric Infectious Diseases Society (PIDS) Publication Committee and Transplant ID Committee, and reports support for travel to the 2022 European Society for Paediatric Infectious Diseases (ESPID) meeting to present from ESPID/AstraZeneca. M. J. L. serves as an advisor for Sanofi, Seqirus, Medicago, GSK, Janssen, Novavax, Pfizer, and MD Brief; receives research funding from the Canadian Institutes of Health Research, World Health Organization (WHO), and Medical Research Council (United Kingdom); has received an in-kind supply of vaccine from Sanofi; has been paid for expert testimony on institutional and workplace vaccine policy; and has served on the DSMB for CanSino Biologics and an advisor to Merck. R. P. has a patent on a Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued; serves as a consultant to PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, Netflix, Abbott Laboratories, Oxford Nanopore Technologies, CARB-X, Qvella, and HealthTrackRx; receives other numeration (honoraria) from NBME, UpToDate, and the Infectious Disease Board Review Course; received grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate, ContraFect, TenNor Therapeutics Limited, Shionogi, NIH, Biofire, Adaptive Phage Therapeutics, National Science Foundation, and the Department of Defense; has served as a consultant to Curetis, Specific Technologies, NextGen Diagnostics, Pathoquest, Selux Diagnositcs, and 1928 Diagnostics; and reports support for attending meetings and/or travel from ASM Biofilms and ISAC and roles as Chair of ASM Governance Committee and as a member of the ASM Finance Committee. S. S. serves as a Board member for the Evidence Foundation; receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation; serves on guideline panels for the American Gastroenterological Association (AGA); reports unpaid roles as Co-Director for the Evidence Foundation and US Grade Network and former Chair Clinical Guidelines Committee for the AGA; and receives research funding from the Department of Veterans Affairs Evidence Synthesis Program. Y. F.-Y. serves as a Board member for the Evidence Foundation; receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation, the AGA for evidence reviews, and the Institute for Clinical and Economic Review (ICER) for committee meetings; serves as a Director for the Evidence Foundation and for the US GRADE Network; and served on an Independent Appraisal Committee for ICER. R. L. M. serves as a Board member for the Evidence Foundation and receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation. M. H. M. serves as a Board member for the Evidence Foundation; receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation; receives research funding from the Agency for Healthcare Research and Quality (AHRQ), the Endocrine Society, and the Society for Vascular Surgery; has received research funding from the American Society of Hematology and the WHO; and has served as a guideline methodologist for the WHO. A. B. received an honorarium from the ICER (clinical expert at an ICER public meeting [discussion in 2022 re: COVID-19 oral drug costs], honorarium $750). R. A. M. serves as a Board member for the Evidence Foundation; receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation and ICER for committee meetings; receives research funding from the NIH, the WHO, the American College of Rheumatology, the American Society of Hematology, and Bohringer Ingelheim; serves as Chair of the Midwest Comparative Effectiveness Public Advisory Council of the ICER; serves on the Methods Committee for Kidney Disease Improving Global Outcomes Work Group; serves on the Clinical Guidelines Committee for the Canadian Society of Nephrology; and previously served on the Clinical Guidelines Committee for the American College of Physicians (ACP). D. J. M. reports an NIH DP2 award, Shepherd contract, and is Co-Investigator on an Epicenter award from CDC, R01 on C. difficile from the AHRQ, and IIR on Diagnostic Stewardship from VA HSRD; support for conference planning and speaking from SHEA/IDSA; and an unpaid role as co-lead on the task force on diagnostic stewardship. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literature. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best-practice guidance related to SARS-CoV-2 Ag testing. This guideline is an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators, and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and nonmedical settings. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. A review of relevant, peer-reviewed published literature was conducted through 1 April 2022. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel made 10 diagnostic recommendations that address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. US Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared with nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms and, in symptomatic patients, on timing of testing after symptom onset. In most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved self-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared with testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remain the testing methods of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate., Competing Interests: Potential conflicts of interest. The following list displays what has been reported to the IDSA. To provide thorough transparency, the IDSA requires full disclosure of all relationships, regardless of relevancy to the guideline topic. Evaluation of such relationships as potential conflicts of interest is determined by a review process which includes assessment by the Board of Directors’ liaison to the Standards and Practice Guideline Committee and, if necessary, the Conflicts of Interest (COI) and Ethics Committee. The assessment of disclosed relationships for possible COI is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The reader of these guidelines should be mindful of this when the list of disclosures is reviewed. M. K. H. serves on a clinical adjudication panel for Sanofi; receives research funding from the Centers for Disease Control and Prevention (CDC) (grant and contract for investigator-initiated research) and the CDC Foundation (contract for investigator-initiated research); serves on the Society for Healthcare Epidemiology of America (SHEA) Board of Directors and Chair of the SHEA Education and Research Foundation (President of SHEA Board of Directors 2021; President, SHEA Foundation 2022); received other numerations from Sage, Medline, and Molnylycke; and served as Chair of the IDSA Diagnostics Committee; and reports participation as a member on a Clinical Adjudication Panel for investigational COVID-19 vaccine made by Sanofi. K. E. H. served as an advisor to Quidel, BioFire, Pfizer, and Takeda; received other numerations from Quidel, Pfizer, and Takeda; served as an editor to the American Society of Microbiology (ASM) and member of Clinical and Laboratory Standards Institute Antifungal Committee; received research funding from the National Institutes of Health (NIH); and served on the exam committee for the American Board of Internal Medicine, and associate editor for Open Forum Infectious Diseases. J. A. E. serves as a consultant for Sanofi Pasteur, Pfizer, Moderna, and AstraZeneca; serves as an advisor/consultant for Meissa Vaccines; receives research funding from the CDC, Pfizer, Brotman Baty Research Institute, Merck, Novavax, GlaxoSmithKline (GSK), and AstraZeneca; served as an advisor to Teva Pharmaceuticals; and served as member of Pediatric Infectious Diseases Society (PIDS) Publication Committee and Transplant ID Committee; and reports support for travel to the 2022 European Society for Paediatric Infectious Diseases (ESPID) meeting from ESPID/AstraZeneca. M. J. L. serves as an advisor for Sanofi, Seqirus, Medicago, GSK, Janssen, Novavax, Pfizer, and MD Brief; receives research funding from the Canadian Institutes of Health Research, World Health Organization (WHO), and Medical Research Council (United Kingdom); has received an in-kind supply of vaccine from Sanofi; has been paid for expert testimony on institutional and workplace vaccine policy; and has served on the Data Safety and Monitoring Board (DSMB) for CanSino Biologics and an advisor to Merck. R. P. has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued; serves as consultant to PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, Netflix, Abbott Laboratories, Oxford Nanopore Technologies, CARB-X, Qvella, and HealthTrackRx (monies from PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, and HealthTrackRx paid to Mayo Clinic); receives other numeration (honoraria) from National Board of Medical Examiners, UpToDate, and the Infectious Disease Board Review Course; received grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate, ContraFect, TenNor Therapeutics Limited, Shionogi, NIH, BioFire, Adaptive Phage Therapeutics, National Science Foundation, and the Department of Defense (monies from ContraFect, TenNor Therapeutics Limited, Adaptive Phage Therapeutics, and BioFire paid to Mayo Clinic); has served as a consultant to Curetis, Specific Technologies, NextGen Diagnostics, Pathoquest, Selux Diagnositcs, and 1928 Diagnostics; reports support for attending meetings and/or travel from ASM Biofilms and International Society of Antimicrobial Chemotherapy; and roles as Chair of ASM Governance Committee and as a member of the ASM Finance Committee. S. S. serves as a Board member for the Evidence Foundation and as Co-Director of Evidence Foundation and US Grade Network (no payments received for this role), and former Chair of the Clinical Guidelines Committee for the American Gastroenterological Association (no payments received for this); receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation; serves on guideline panels for the American Gastroenterological Association (AGA); and receives research funding from the Department of Veterans Affairs Evidence Synthesis Program (paid to their institution). Y. F.-Y. serves as a Board member for the Evidence Foundation; receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation, the AGA for evidence reviews, and the Institute for Clinical and Economic Review (ICER) for committee meetings; serves as a Director for the Evidence Foundation and for the US GRADE Network; and served on an Independent Appraisal Committee for ICER. R. M. serves as a Board member for the Evidence Foundation and receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation. M. H. M. serves as a Board member for the Evidence Foundation; receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation; receives research funding from the Agency for Healthcare Research and Quality, the Endocrine Society, and the Society for Vascular Surgery; has received research funding from the American Society of Hematology and the WHO; and has served as a guideline methodologist for the WHO. A. B. received an honorarium from the ICER. R. A. M. serves as a Board member for the Evidence Foundation; receives honoraria for evidence reviews, methodological support, and teaching from the Evidence Foundation, and ICER for committee meetings; receives research funding from the NIH, the WHO, the American College of Rheumatology, the American Society of Hematology, and Boehringer Ingelheim; serves as Chair of the Midwest Comparative Effectiveness Public Advisory Council of the ICER; serves on the Methods Committee for Kidney Disease Improving Global Outcomes Work Group; serves on the Clinical Guidelines Committee for the Canadian Society of Nephrology; and previously served on the Clinical Guidelines Committee for the American College of Physicians (ACP). D. J. M. reports grants or contracts from NIH (NIH DP2 award), CDC (Shepherd Contract and Co-Investigator on an Epicenter award), AHRQ (R01 on C. difficile), Veteran's Association Health Service Research and Development; support for conference planning and speaking from SHEA/IDSA; and a role as co-lead task force on diagnostic stewardship (unpaid) for SHEA. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. The objective was to develop evidence-based, rapid, living guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. In March 2020, the Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise to regularly review the evidence and make recommendations about the treatment and management of persons with COVID-19. The process used a living guideline approach and followed a rapid recommendation development checklist. The panel prioritized questions and outcomes. A systematic review of the peer-reviewed and grey literature was conducted at regular intervals. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Based on the most recent search conducted on 31 May 2022, the IDSA guideline panel has made 32 recommendations for the treatment and management of the following groups/populations: pre- and postexposure prophylaxis, ambulatory with mild-to-moderate disease, and hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines. At the inception of its work, the panel has expressed the overarching goal that patients be recruited into ongoing trials. Since then, many trials were conducted that provided much-needed evidence for COVID-19 therapies. There still remain many unanswered questions as the pandemic evolved, which we hope future trials can answer., Competing Interests: Potential conflicts of interest. The following list is a reflection of what has been reported to IDSA. To provide thorough transparency, IDSA requires full disclosure of all relationships, regardless of relevancy to the guideline topic. Evaluation of such relationships as potential conflicts of interest is determined by a review process which includes assessment by the Board of Directors liaison to the Standards and Practice Guidelines Committee and, if necessary, the Conflicts of Interest and Ethics Committee. The assessment of disclosed relationships for possible conflicts of interest is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The reader of these guidelines should be mindful of this when the list of disclosures is reviewed. L. B. receives research funding from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), Bill and Melinda Gates Foundation, Wellcome Trust, and Harvard Medical School; serves as chair of the Antimicrobial Drug Advisory Committee of the Food and Drug Administration; and is involved in HIV and COVID-19 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network, COVID Vaccine Prevention Network, International AIDS Vaccine Initiative, Crucell/Janssen Pharmaceuticals, Moderna, Military HIV Research Program, Bill and Melinda Gates Foundation, and the Ragon Institute. A. B. received an honorarium from the Institute for Clinical and Economic Review. V. C.-C. C. receives research funding from the Health and Medical Research Fund; serves on the Research Committee of the Society for Healthcare Epidemiology of America (SHEA); and serves on the international editorial boards for the Journal of Hospital Infection, Infection Prevention in Practice, and Antimicrobial Stewardship and Healthcare Epidemiology. K. M. E. serves as a scientific advisor for Merck, Bionet, IBM, Sanofi, X4 Pharmaceuticals, Inc, Seqirus, Inc, Moderna, Inc, GSK plc, Roche, and Pfizer; and receives research funding from the Centers for Disease Control and Prevention and the NIH. J. C. G. serves in an advisory role for Qpex, Shionogi, and Merck; receives research funding from Merck; previously served in an advisory role for Accelerate Diagnostics, Achaogen, Astellas Pharma, Melinta Therapeutics, Nabriva Therapeutics, Paratek Pharma, scPharmaceuticals, Spero Therapeutics, and Tetraphase Pharmaceuticals; and previously served on the speaker’s bureau for Astellas Pharma, Melinta Therapeutics, Merck, and Shionogi. R. T. G. serves as a panel member on the NIH COVID-19 Treatment Guidelines Panel; serves as the immediate Past Chair for the HIV Medicine Association; receives research funding from the NIH; and has served on the scientific advisory board for Gilead Sciences, Inc, and Merck. W. J. M. serves in an advisory role for Seqirus, Inc; receives research funding from Ansun Biopharma, Astellas Pharma, AstraZeneca, Eli Lilly and Company, Enanta Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Karius, Melinta Therapeutics, Merck, Moderna, Nabriva Therapeutics, Paratek Pharma, Pfizer, Roche, and Tetraphase Pharmaceuticals; and has previously received research funding from Abbott Laboratories. M. H. M receives research funding from the Agency for Healthcare Research and Quality, the Endocrine Society, and the Society for Vascular Surgery; serves as a Board member for the Evidence Foundation; has received research funding from the American Society of Hematology and the World Health Organization (WHO); and has served as a guideline methodologist for the WHO. R. A. M. receives research funding from the NIH, the WHO, the American College of Rheumatology, the American Society of Hematology, and Bohringer Ingelheim; serves as Chair of the Midwest Comparative Effectiveness Public Advisory Council of the Institute for Clinical and Economic Review (ICER); serves on the Methods Committee for Kidney Disease Improving Global Outcomes Work Group; serves on the Clinical Guidelines Committee for the Canadian Society of Nephrology; and previously served on the Clinical Guidelines Committee for the American College of Physicians (ACP). M. M. N. co-chairs the Pediatric Infectious Diseases Society COVID-19 Therapies Task Force, will receive support to attend as a speaker the American Academy of Pediatrics National Conference & Exhibition in October 2022, and has received research funding from Gilead Sciences. J. C. O. serves as an advisor for Bates College; holds stocks in Doximity, Inc; receives research funding from the MITRE Corporation and Nference, Inc; and serves on committees for the Society for Critical Care Medicine, SHEA, and University Lake School. R. W. S. served in an advisory role for GSK plc and Gilead Sciences. S. Soham serves in advisory roles for Amplyx Pharmaceuticals, Inc, ReViral Ltd, Adamis Pharmaceuticals, and Immunome; holds stocks in Immunome; receives research funding from Ansun BioPharma, Zeteo Tech, Inc, F2G, Emergent Biosolutions, Shionogi, Shire (now Takeda), Cidara Therapeutics, US Department of Defense (Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense), Defense Health Agency, Bloomberg Philanthropies, the State of Maryland, NIH/NIAID, NIH National Center for Advancing Translational Sciences, Mental Wellness Foundation, Moriah Fund, Octopharma, HealthNetwork Foundation, Shear Family Foundation, Johns Hopkins University, and Mayo Clinic; serves as the Governor of the ACP; has received research funding from the University of Nebraska; and has served as an advisor for Janssen Pharmaceuticals, Acidophil, LLC, Adagio Therapeutics, Inc, Celltrion Healthcare, and Intermountain Health. A. H. S. receives research funding from the US Department of Veterans Affairs. S. Sultan serves on guideline panels for the American Gastroenterological Association (AGA) and receives research funding from the Department of Veterans Affairs Evidence Synthesis Program. Y. F.-Y. receives honoraria from the Evidence Foundation for evidence reviews and teaching, the AGA for evidence reviews, and ICER for committee meetings; serves as a Director for the Evidence Foundation and for the US GRADE Network; and served on an Independent Appraisal Committee for ICER. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The role of serologic testing for SARS-CoV-2 has evolved during the pandemic as seroprevalence in global populations has increased. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA., Objective: To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity., Methods: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature reviewed, identified, and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations., Results: The panel recommends against serologic testing to diagnose SARS-CoV-2 infection in the first two weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for IgG, IgG/IgM, or total antibodies to nucleocapsid protein three to five weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, we suggest against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence.) The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy., Conclusions: The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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.)

Background: Assessing certainty of evidence is a key element of any systematic review. The aim of this meta-epidemiology study was to understand the frequency and ways with which certainty of evidence is assessed in contemporary systematic reviews published in high-impact sports science journals., Methods: We searched PubMed and relevant journal web sites from 1 August 2016 to 11 October 2022 for systematic reviews published in the top-ten highest-impact journals within the 2020 Journal Citation Report for the Sports Sciences category. Pairs of independent reviewers screened items using a priori established criteria., Results: Of 1250 eligible documents, 258 (20.6%) assessed the certainty of evidence, defined as using two or more distinct domains to provide an overall rating of the trustworthiness of findings across studies. Nine methods were cited for assessing certainty, with the most common being the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach (61.6%). The proportion of systematic reviews assessing certainty of evidence appeared to increase over the 6-year timeframe analyzed. Across all reviews analyzed, a large majority addressed the domains of risk of bias, imprecision, and inconsistency of the results. Other certainty domains including indirectness/applicability were less commonly assessed., Discussion: Only one in five recent contemporary systematic reviews in the field of exercise and sports science assessed certainty of evidence. Organizational and institutional education on methods for assessing evidence may help further increase uptake of these methods and improve both the quality and clinical impact of systematic reviews in the field., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: This updated guidance from the Grading of Recommendations Assessment, Development, and Evaluation addresses rating up certainty of evidence due to a dose-response gradient (DRG) observed in synthesis of intervention and exposure studies., Study Design and Setting: This guidance was developed using iterative discussions and consensus in multiple meetings and was presented to attendees of the Grading of Recommendations Assessment, Development, and Evaluation Working Group meeting for feedback in November 2022 and for final approval in May 2023., Results: The guidance consists of two steps. The first is to determine whether the DRG is credible. We describe five items for assessing credibility: a) is DRG identified using a proper analytical approach; b) is confounding the cause of the DRG; c) is there serious concern about ecological bias; d) is the DRG consistent across studies; and e) is there indirect evidence supporting the DRG. The first two of these items are the most critical. If the DRG was judged to be credible, then the second step is to apply the DRG domain and consider rating up, but only by one level due to the concern about residual confounding., Conclusion: Systematic review authors should only rate up certainty in evidence when a DRG is deemed credible., Competing Interests: Declaration of competing interest Authors of this paper are GRADE Working Group members. Gordon H. Guyatt and Holger J. Schünemann are the co-founders and co-chairs of GRADE Working Group. Gordon H. Guyatt is a member of the Journal of Clinical Epidemiology Editorial Board., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: All authors are members of the U.S. GRADE Network and the Evidence Foundation. They declare no relevant conflicts of interest. MRS is a fellow of the Evidence Foundation and receives direct financial support.

Background: The start of the COVID-19 pandemic presented a situation in which there was an urgent need for decision-making that relates to diagnosis, but the evidence was lacking, of low certainty or constantly changing. Rapid and living guideline development methods were needed and had to be applied to rigorous guideline approaches, such as the Grading of Recommendations Assessment, Development, and Evaluation approach., Objectives: To describe the process of developing rapid diagnosis guidelines when there is limited and imperfect available data at the time of crisis., Sources: Case example from four Infectious Disease Society of America COVID-19 diagnostic guidelines., Content: As the world was experiencing panic with COVID-19, there were serious doubts about the feasibility of following a rigorous process for guideline development when timeliness was of extreme value. The Infectious Disease Society of America guideline panels supported by several methodologists strongly believed that at times of crisis, it is more important than ever to follow a rigorous process. The panel adopted a rapid and living systematic review methodology and applied the Grading of Recommendations Assessment, Development and Evaluation approach to four diagnosis guidelines despite the challenges of scarce and dynamic evidence. We describe the methodological details of the rapid and living approach (data extraction, meta-analysis, Evidence to Decision framework, and recommendation development), the challenge of resources, the challenge of scarce evidence, the challenge of rapidly changing evidence, as well as 'wins' from the Infectious Disease Society of America experience., Implications: Mitigation of pandemics relies on rapid and accurate diagnosis, which is challenged by many knowledge gaps. This necessitates emerging evidence is rapidly incorporated in a living fashion with several decisional and contextual factors to ensure the best public health strategies and care for patients. This process must be systematic and transparent for developing trustworthy guidelines and should be supported by all stakeholders, including researchers, editors, publishers, professional societies, and policymakers., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To empirically evaluate five commonly used meta-analysis methods and their impact on imprecision judgements about effect estimates. The two fixed-effect model methods were the inverse variance method based on normal distribution and the Mantel-Haenszel method. The three random-effects model methods were the DerSimonian and Laird, the Hartung-Knapp-Sidik-Jonkman and the profile likelihood approaches., Design: Meta-epidemiological study., Setting: Meta-analyses published between 2007 and 2019 in the 10 general medical journals with the highest impact factors that evaluated a medication or device for chronic medical conditions and included at least 5 randomised trials., Main Outcome Measures: Discordance in the judgements of imprecision of effect estimates based on two definitions: when either boundary of 95% CI of the OR changed by more than 15% or changed in relation to the null., Results: We analysed 88 meta-analyses including 1114 trials with an average of 12.60 trials per meta-analysis and average I 2 of 26% (range: 0%-96%). The profile likelihood failed to converge in three meta-analyses (3%). Discordance in imprecision judgements based on the two definitions, respectively, occurred between the fixed normal distribution and fixed Mantel-Haenszel method (8% and 2%), between the DerSimonian and Laird and Hartung-Knapp-Sidik-Jonkman methods (19% and 10%), between the DerSimonian and Laird and profile likelihood methods (9% and 5%), and between the Hartung-Knapp-Sidik-Jonkman and profile likelihood methods (5% and 13%). Discordance was greater when fewer studies and greater heterogeneity was present., Conclusion: Empirical evaluation of studies of chronic medical conditions showed that conclusions about the precision of the estimates of the efficacy of a drug or device frequently changed when different pooling methods were used, particularly when the number of studies within a meta-analysis was small and statistical heterogeneity was substantial. Sensitivity analyses using more than one method may need to be considered in these two scenarios., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The development of guidelines by gastroenterology societies increasingly stresses evidence-based endoscopic practice., Aims: We performed a systematic assessment to determine whether endoscopic video teaching platforms incorporate evidence-based educational strategies and methods in order to disseminate guideline-based endoscopic management strategies., Methods: Platforms with a video component were systematically identified using the Google search engine, Apple and Android application stores, and searching four major gastroenterology society websites and three known platforms, to identify all relevant platforms. Two video samples from each teaching platform were reviewed independently by two authors and assessed for use of a priori defined principles of evidence-based medicine, as determined by consensus agreement and for the use of simulation., Results: Fourteen platforms were included in the final analysis, and two videos from each were analyzed. One of the 14 platforms used simulation and incorporated evidence-based medicine principles consistently. Nine of the 14 platforms were not transparent in regard to citation. None of the platforms consistently cited the certainty of evidence or explained how evidence was selected., Conclusions: Education of guideline-based endoscopic management strategies using principles of evidence-based medicine is under-utilized in endoscopic videos. In addition, the use of cognitive simulation is absent in this arena. There is a paucity of evidence-based cognitive endoscopy simulators designed for fellows that incorporate systematic evaluation, and efforts should be made to create this platform., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Both non-alcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection commonly result in hepatic fibrosis and may lead to cirrhosis. This study aims to determine the incidence of HCC in patients with HCV or NAFLD complicated by advanced fibrosis, inferred from measurements of liver stiffness., Methods: Using Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI), we identified a nationwide cohort of patients with an existing diagnosis of HCV or NAFLD with liver transient elastography (TE) testing from 2015 to 2019. HCC cases, along with a random sample of non-HCC patients, were identified and validated, leading to calculation of incidence rates for HCC after adjustment for confounders., Results: 26,161 patients carried a diagnosis of HCV and 13,629 were diagnosed with NAFLD at the time of testing. In those with HCV, rates of HCC increased with liver stiffness with incidences of 0.28 (95% CI 0.24, 0.34), 0.93 (95% CI 0.72, 1.17), 1.28 (95% CI 0.89, 1.79), and 2.79 (95% CI 2.47, 3.14)/100,000 person years for TE score ranges <9.5 kPa, 9.5-12.5 kPa, 12.5-14.5 kPa and >14.5 kPa, respectively, after a median follow-up of 2.3 years. HCC incidence also increased with higher TE liver stiffness measures in NAFLD after a median follow-up of 1.1 years., Conclusion: In this retrospective cohort, the incidence of HCC in HCV and NAFLD increases with higher TE liver stiffness measures, confirming that advanced fibrosis portends risk in viral and non-viral fibrotic liver diseases. Additional comparative studies are needed to determine the optimal cut point of TE liver stiffness to inform HCC screening guidelines and approaches., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of advanced liver disease in the USA. Liver biopsy, the gold standard diagnostic test for evaluating liver fibrosis, is associated with significant risk and expense. The accuracy of ultrasound elastography and Fibrosis-4 index (FIB-4) in the obese NAFLD population is unknown. We aimed to compare the accuracy of ultrasound elastography and FIB-4 to liver biopsy in ruling out cirrhosis in NAFLD patients at a tertiary, transplant referral center in the US., Methods: We retrospectively evaluated 93 patients with a mean age of 53 years (SD: 13 years) who underwent liver ultrasound elastography and liver biopsy, and additionally calculated their FIB-4 at the time of biopsy. We compared the liver stiffness measurement (LSM) obtained from ultrasound elastography and FIB-4 with the pathology results for ruling out cirrhosis., Results: 85% of the patients were white, 53% were female, average BMI was 34.7 (SD: 6.7), 52% had diabetes, and 53% had hypertension. For biopsy-proven cirrhosis (prevalence 15%), a cut-off value of 12.5 kilopascals (kPa) for F4 had a sensitivity of 92% and a specificity of 54%. Values below this threshold excluded cirrhosis with 98% certainty. Compared to FIB-4, ultrasound elastography showed higher accuracy in ruling out cirrhosis (92% vs. 80% sensitivity, 98% vs. 95% negative predictive value (NPV), respectively)., Conclusion: To our knowledge, this is the first study in a tertiary transplant referral center in the USA to show that ultrasound elastography was superior to FIB-4 and can be used as a reliable screening test to rule out cirrhosis in obese NAFLD patients at a 12.5 kPa cut-off. Therefore, helping to avoid the risk and expense associated with liver biopsy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Damjanovska et al.)

Background: Hepatitis C virus (HCV) therapy lowers risk of hepatocellular carcinoma (HCC). Little is known about factors driving/preceding HCC in treated persons. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate host response and pathogenesis of disease. We investigated plasma levels of these RNAs and select serum markers before, during, and after HCV therapy, preceding HCC. Methods: Of 187 DAA treated HCV patients where therapy oriented longitudinal sampling was performed at a time without HCC diagnosis, 9 were subsequently diagnosed with HCC within 2 years of therapy. They were matched with 7 patients not diagnosed with HCC over the same time period. RNASeq was performed on plasma, and serum was assessed for biomarkers of inflammation by ELISA. Results: HCC diagnosis was 19 months (6-28) after therapy start in the HCC group. 73 and 63 miRs were differentially expressed at baseline (before DAA therapy) and 12 weeks after DAA therapy comparing HCC and non-HCC groups. Several lncRNA- showed differential expression as well. Several miRNA suppressors of cancer-related pathways, lncRNA- and mRNA-derived stabilized short RNAs were consistently absent in the plasma of patients who developed HCC. Serum IP10, and MCP-1 level was higher in the HCC group 12 weeks after therapy, and distinct miRNAs correlated with IP10 and MCP-1. Finally, in a focused analysis of 8 miRNAs best associated with HCC we observed expression of mi576 and mi-5189 correlation with expression of a select group of PBMC mRNA. Conclusions: These results are consistent with complex interplay between RNA-mediated host immune regulation and cancer suppression, strikingly skewed 12 weeks following therapy, prior to HCC diagnosis.

Background: The development of rigorous, high-quality clinical guidelines increases the need for resources and skilled personnel within guideline-producing organizations. While collaboration between organizations provides a unique opportunity to pool resources and save time and effort, the collaboration presents its own unique challenges., Objective: To assess the perceived needs and current challenges of guideline producers worldwide related to guideline development and collaboration efforts., Design: Survey questions were developed by the Guidelines International Network and the US GRADE Network, pilot-tested among attendees of a guideline development workshop, and disseminated electronically using convenience and snowball sampling methods., Participants: A total of 171 respondents representing 30 countries and more than 112 unique organizations were included in this analysis., Main Measures: The survey included free-response, multiple-choice, and seven-point Likert-scale questions. Questions assessed respondents' perceived value of guidelines, resource availability and needs, guideline development processes, and collaboration efforts of their organization., Key Results: Time required to develop high-quality systematic reviews and guidelines was the most relevant need (median=7; IQR=5.5-7). In-house resources to conduct literature searches (median=4; IQR=3-6) and the resources to develop rigorous guidelines rapidly (median=4; IQR=2-5) were perceived as the least available resources. Difficulties reconciling differences in guideline methodology (median=6; IQR=4-7) and the time required to establish collaborative agreements (median=6; IQR=5-6) were the most relevant barriers to collaboration between organizations. Results also indicated a general need for improvement in conflict of interest (COI) disclosure policies., Conclusion: The survey identified organizational challenges in supporting rigorous guideline development, including the time, resources, and personnel required. Connecting guideline developers to existing databases of high-quality systematic reviews and the use of freely available online platforms may facilitate guideline development. Guideline-producing organizations may also consider allocating resources to hiring or training personnel with expertise in systematic review methodologies or utilizing resources more effectively by establishing collaborations with other organizations., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Patent foramen ovale (PFO) is a common anatomic variant associated with intermittent right-to-left shunting. Transcatheter PFO closure has been proposed to address multiple clinical conditions including stroke, transient ischemic attack, migraine, and decompression illness., Methods: A systematic review was conducted using the GRADE approach to address 5 questions formulated by the Society for Cardiovascular Angiography and Interventions (SCAI) Guideline Panel in patient, intervention, comparator, outcome (PICO) format. Medical literature from January 2015 through May 2021 was searched. Extracted data underwent review and risk-of-bias assessment by 2 independent researchers. Pooled effect estimates were calculated. Certainty of evidence was determined for each query., Results: Our search identified 2701 titles and abstracts, of which 30 met eligibility criteria and informed the technical review. Data were abstracted to address outcomes of PFO closure for patients with and without prior stroke, in comparison to antiplatelet therapy, in comparison to anticoagulation, and with various post-procedure antithrombotic regimens., Conclusion: In appropriately selected patients with prior stroke, transcatheter PFO closure reduces the risk of recurrent stroke more than antiplatelet therapy alone. Evidence to support PFO closure is weaker regarding older patients, anticoagulation, thrombophilia, transient ischemic attack, migraine, and decompression illness. Data from this technical review will inform the SCAI Guideline for Transcatheter Patent Foramen Ovale Closure., (© 2022 The Authors.)

Background: Patent foramen ovale (PFO) is a vestigial congenital cardiovascular structure present in around 25% of adults. In most cases, PFO is entirely benign and requires no treatment. However, it may cause serious complications under certain circumstances., Objective: These evidence-based guidelines from the Society for Cardiovascular Angiography and Interventions (SCAI) aim to support patients, clinicians, and other stakeholders in decisions about management of PFO., Methods: SCAI convened a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The Evidence Foundation, a registered 501(c)(3) nonprofit organization, provided methodological support for the guideline-development process. Following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, the guideline panel formulated and prioritized clinical questions in population, intervention, comparison, outcome (PICO) format. A separate technical review team of clinical and methodological experts conducted systematic reviews of the evidence, synthesized data, and graded the certainty of the evidence across outcomes. The guideline panel then reconvened to formulate recommendations and supporting remarks informed by the results of the technical review and additional contextual factors described in the GRADE evidence-to-decision framework., Results: The panel agreed on 13 recommendations to address variations on 5 clinical scenarios., Conclusions: Key recommendations address patient selection for PFO closure in the prevention of recurrent PFO-associated stroke, including populations not commonly included in randomized studies, and scenarios where the PFO closure might serve a role in the prevention of other outcomes such as migraine headaches and decompression illness. The panel has also identified future research priorities to advance the field., (© 2022 The Authors.)

Given the urgent need for treatments during the coronavirus disease 2019 pandemic, the US Food and Drug Administration issued emergency use authorizations (EUAs) for multiple therapies. In several instances, however, these EUAs were issued before sufficient evidence of a given therapy's efficacy and safety were available, potentially promoting ineffective or even harmful therapies and undermining the generation of definitive evidence. We describe the strengths and weaknesses of the different therapeutic EUAs issued during this pandemic. We also contrast them to the vaccine EUAs and suggest a framework and criteria for an evidence-based, trustworthy, and publicly transparent therapeutic EUA process for future pandemics., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Despite the challenges of the pandemic, there has been substantial progress with coronavirus disease 2019 (COVID-19) therapies. Pivotal COVID-19 trials like SOLIDARITY, RECOVERY, and ACCT-1 were rapidly conducted and data disseminated to support effective therapies. However, critical shortcomings remain on trial conduct, dissemination and interpretation of study results, and regulatory guidance in pandemic settings. The lessons that we learned have implications for both the current pandemic and future emerging infectious diseases. There is a need for establishing and standardizing clinical meaningful outcomes in therapeutic trials and for targeting defined populations and phenotypes that will most benefit from specific therapies. Standardized processes should be established for rapid and critical data review and dissemination to ensure scientific integrity. Clarity around the evidence standards needed for issuance of both emergency use authorization (EUA) and biologic license application (BLA) should be established and an infrastructure for executing rapid trials in epidemic settings maintained., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and Aims: In the digital era of evidence-based medicine, there is a paucity of video endoscopy teaching platforms that use evidence-based medicine principles, or that allow for cognitive simulation of endoscopic management strategies. We created a guideline-based teaching platform for fellows that incorporates these features, and tested it., Methods: A pilot video module with embedded questions was drafted, and after incorporation of feedback from several attending gastroenterologists, an additional 2 modules were created. The embedded questions were designed to simulate cognitive management decisions as if the viewer were doing the endoscopy procedure in the video. A narrator explained the evidence behind the task being performed, and its certainty based on endoscopic guidelines. Quizzes and surveys were developed and administered to a sample of attendings and fellows who completed the video modules to test efficacy, usability, and likeability., Results: Three video modules, named evidence-based endoscopy (EBE), incorporating low fidelity simulation, and utilizing evidence-based medicine principles, were created. Eight fellows and 10 attendings completed the video modules and all quizzes and surveys. Mean test scores improved from before to after completing the video modules (56% to 92%; mean difference = -35%; 95% confidence interval, 27%-47%). Surveys indicated that the product was viewed favorably by participants, and that there is a strong desire for this type of educational product., Conclusions: The EBE simulator is a unique, desirable, and effective educational platform based on evidence-based medicine principles that fills a gap in available tools for endoscopy education. Further studies are needed to assess whether EBE can aid in long-term knowledge retention and increase adherence to guideline recommendations., (Copyright © 2022 AGA Institute. All rights reserved.)

Background: Elevated rheumatoid factor (RF) levels and systemic immune activation are highly prevalent during chronic hepatitis C virus (HCV) infection. Direct-acting antiviral (DAA) therapy has been associated with normalization of various soluble immune activation parameters. Whether the RF levels relate to soluble immune activation markers during chronic HCV infection, and over what time frame RF levels normalize during and after DAA treatment is unknown and was investigated here., Methods: In a longitudinal study, plasma and serum was obtained from HCV infected RF positive (RF+) and RF negative (RF-) participants. The levels of RF, HCV RNA and soluble markers of inflammation were determined before (week 0), during (weeks 4, 8 and 12) and after (week 24) treatment with HCV DAA therapy. In a subset of RF+ participants, the analysis was extended to over 70 weeks after therapy initiation. Hepatic and other clinical parameters were determined at baseline (week 0) in all participants., Results: Before therapy, transient elastography (TE) score was greater in RF+ compared to RF- HCV infected participants, while the systemic levels of soluble inflammatory markers were comparable. Following DAA therapy initiation, HCV RNA levels became undetectable within 4 weeks in both the RF+ and RF- groups. RF levels declined in the first 6 months in most RF+ persons but most commonly remained positive. The levels of some soluble inflammatory markers declined, mainly within 4 weeks of DAA therapy start, in both the RF+ and RF- groups. The baseline (week 0) TE score correlated with RF levels before, during and after DAA therapy, while plasma IL-18 levels correlated with RF level after DAA therapy., Conclusion: During chronic HCV infection, TE score is elevated in RF+ HCV infected individuals and factors other than HCV viremia (including liver stiffness or fibrosis and select markers of inflammation) likely contribute to persistence of RF after treatment of HCV with DAA., Competing Interests: The authors have declared no competing interests exist.

Background & Aims: Hepatocellular carcinoma (HCC), the most common primary liver cancer, remains a deadly cancer, with an incidence that has tripled in the United States since 1980. In recent years, new systemic therapies for HCC have been approved and a critical assessment of the existing data is necessary to balance benefits and harms and inform the development of evidence-based guidelines., Methods: The American Gastroenterological Association formed a multidisciplinary group consisting of a Technical Review Panel and a Guideline Panel. The Technical Review Panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of systemic therapies in patients with advanced-stage HCC. The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence. The Guideline Panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations., Results: The Panel reviewed the evidence, summarized in the Technical Review, for the following medications approved by the US Food and Drug Administration for HCC: first-line therapies: bevacizumab+atezolizumab, sorafenib, and lenvatinib; second-line therapies: cabozantinib, pembrolizumab, ramucirumab, and regorafenib; and other agents: bevacizumab, nivolumab, and nivolumab+ipilimumab., Conclusions: The Panel agreed on 11 recommendations focused on systemic therapy for HCC in patients who are not eligible for locoregional therapy or resection, those with metastatic disease and preserved liver function, those with poor liver function, and those on systemic therapy as adjuvant therapy., (Copyright © 2022. Published by Elsevier Inc.)

Background: Since its emergence in late 2019, SARS-CoV-2 continues to pose a risk to healthcare personnel (HCP) and patients in healthcare settings. Although all clinical interactions likely carry some risk of transmission, human actions like coughing and care activities like aerosol-generating procedures likely have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 continues to create significant challenges in healthcare facilities, particularly with shortages of personal protective equipment (PPE) used by HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care continue to be needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators., Objective: Develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known COVID-19., Methods: IDSA formed a multidisciplinary guideline panel including frontline clinicians, infectious disease specialists, experts in infection control, and guideline methodologists with representation from the disciplines of public health, medical microbiology, pediatrics, critical care medicine and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations., Results: The IDSA guideline panel agreed on eight recommendations, including two updated recommendations and one new recommendation added since the first version of the guideline. Narrative summaries of other interventions undergoing evaluations are also included., Conclusions: Using a combination of direct and indirect evidence, the panel was able to provide recommendations for eight specific questions on the use of PPE for HCP providing care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. There remain significant gaps in the understanding of the transmission dynamics of SARS-CoV-2 and PPE recommendations may need to be modified in response to new evidence. These recommendations should serve as a minimum for PPE use in healthcare facilities and do not preclude decisions based on local risk assessments or requirements of local health jurisdictions or other regulatory bodies., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)