Romina Brignardello-Petersen

Background: Post-COVID-19 condition (PCC) is a complication following acute COVID-19 infection, which may lead to long-term cardiac abnormalities. This review aimed to assess the prevalence of structural/functional deviations in echocardiography in individuals with PCC compared to patients without PCC. Methods: We searched three databases. Two reviewers independently screened articles using LASER Al and extracted relevant data using a piloted Excel sheet. We performed meta-analysis using OpenMeta and RevManWeb and a subgroup analysis based on patients’ settings during acute COVID-19. We assessed the risk of bias using the Hoy et al. tool and the certainty using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 16 studies that reported on differences in echocardiographic findings in patients with or without PCC. Individuals with PCC were more likely to have structural/functional deviations in echocardiographic readings of unclear clinical significance, particularly those who were hospitalized during acute COVID-19. The overall certainty of the evidence was very low due to the high risk of bias, indirectness, and imprecision. Conclusions: This review provides insight into the use of echocardiograms and the frequency of test deviations in individuals with PCC. Despite existing evidence, there is a need for future studies to assess the diagnostic test accuracy of echocardiograms in PCC.

This systematic review summarizes the evidence informing 2 recommendations from the updated American Society of Hematology guidelines for the treatment of newly diagnosed acute myeloid leukemia in older adults, comparing conventional induction and postremission therapy vs hypomethylating agents (HMA)- or low-dose cytarabine (LDAC)-based strategies, with or without venetoclax. We searched Ovid MEDLINE and Embase, and Cochrane CENTRAL through February 2024, and monitored these databases for new studies throughout November 2024. We included randomized controlled trials (RCTs) and nonrandomized studies (NRS). Reviewers screened studies, extracted data, assessed risk of bias, conducted random-effects meta-analyses, and rated certainty of evidence using GRADE (grading of recommendations, assessment, development, and evaluation). We included 21 studies (3 RCTs, 18 NRS). Compared with HMA- or LDAC-based monotherapy, conventional 7+3-type remission induction therapy may reduce mortality at longest follow-up (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.85-1.04; low certainty), increase complete remission rates (odds ratio, 1.75; 95% CI, 1.25-2.38; high certainty), and may reduce recurrence at longest follow-up (RR, 0.81; 95% CI, 0.64-1.04; low certainty). Conventional therapies probably increase most severe toxicities (moderate certainty). Compared with HMA or LDAC combined with venetoclax, very low certainty evidence suggests that conventional therapy may reduce 1-year mortality (RR, 0.72; 95% CI, 0.60-0.87), increase allogeneic transplant rates (RR, 2.28; 95% CI, 1.70-3.06), result in no important differences in complete remission or recurrence, and have variable effects on severe toxicities. Conventional therapy may have benefits over HMA or LDAC alone; however, compared with HMA or LDAC plus venetoclax, the evidence remains of very low certainty.

Older adults with newly diagnosed acute myeloid leukemia (AML) are often ineligible for conventional “7+3” induction chemotherapy. Despite recent drug approvals, treatment outcomes remain poor in this population. We conducted an updated systematic review to inform the 2025 American Society of Hematology (ASH) AML update guidelines in older adults. This review compared the efficacy and safety of low-dose cytarabine (LDAC), azacitidine (AZA), 5- and 10-day decitabine (DEC), and gemtuzumab ozogamicin, alone or combined with drugs such as venetoclax (VEN), in older adults with AML ineligible for conventional chemotherapy. We included randomized controlled trials (RCTs) and nonrandomized studies (NRSs) of adults aged ≥55 years with AML, and synthesized evidence on mortality, remission, quality of life (QoL), functional status, and severe toxicity. We applied GRADE (grading of recommendations assessment, development, and evaluation) to assess the certainty of evidence. We included 47 studies (30 RCTs and 17 NRSs). AZA or LDAC combined with VEN probably reduces mortality and improves remission and QoL. AZA plus isocitrate dehydrogenase 1 (IDH1) inhibitors may reduce 1-year mortality and improve remission and survival in patients with IDH1-mutated AML. Compared with DEC alone, combining DEC with other agents showed inconsistent effects with mostly low certainty of conclusions. VEN combinations showed promising effects on mortality and remission but lacked data on QoL and functional status. In older adults with AML ineligible for conventional therapy, evidence suggests that hypomethylating agents or LDAC combined with VEN likely improves survival and remission outcomes. Treatment decisions should consider patient goals and functional status. These findings informed 8 recommendations in updated ASH-AML guidelines.

Background: Myocardial infarction (MI) remains a major global health burden, with percutaneous coronary intervention (PCI) as the primary revascularization strategy. However, complications such as no‐reflow, reperfusion injury and in‐stent restenosis persist, requiring adjunctive therapies. Traditional Chinese Medicine (TCM), especially blood‐activating and stasis‐resolving Chinese patent medicine (CPM), is increasingly used in MI management. Objective: To develop a living clinical practice guideline for the perioperative use of CPMs in the perioperative period of PCI for MI, based on rigorous and transparent methodology. Methods: The guideline followed the WHO Handbook for Guideline Development, methods for developing integrated Chinese–Western medicine guidelines, and the living guideline framework. It will be reported in accordance with the RIGHT‐TCM extension. Clinical questions and outcomes were framed, selected and rated through structured discussions with the Guideline Steering Committee and the Guideline Development Group. A systematic review and Bayesian network meta‐analysis will evaluate the efficacy and safety of CPM. The certainty of evidence will be assessed using the GRADE approach, and recommendations will be formulated via the Evidence‐to‐Decision framework, incorporating benefits, harms, evidence certainty, feasibility and costs. When new clinical studies are included and critical outcomes' combined effect demonstrates directional or magnitude changes, the consensus and guideline development groups will jointly decide on new updates. Conclusion: By addressing key clinical uncertainties and leveraging real‐time evidence updates, the guideline aims to enhance patient outcomes and support clinicians in decision‐making. Trial Registration: Guideline Registration Number: PREPARE‐2024CN596

Evidence-based decision making in health often requires comparison of multiple options for a given condition. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence-to-decision (EtD) framework provides a structured approach for moving from evidence to decisions but was originally designed for pairwise comparisons. Hence, there is a need to accommodate decision making based on multiple comparisons, especially with the increasing use of systematic reviews and network meta-analyses in guideline development. Furthermore, since the original EtD framework was developed, further relevant GRADE guidance has been developed. The aim of this work was to develop a new EtD framework to accommodate multiple comparisons and reflect current GRADE guidance. The new EtD framework was revised and developed through iterative discussion, feedback, and refinement by the GRADE EtD Project Group and the GRADE Working Group. Experiences and examples from guideline developers, methodological experts, and other stakeholders informed improvements in its structure and usability for multiple comparisons and were subsequently approved by the GRADE Working Group. This article describes the new EtD framework, which now includes 2 corresponding parts for reviews of pairwise and multiple comparisons. The authors describe application to a review with multiple comparisons for the different parts of the EtD framework: the question definition, which now includes the presentation of values of health outcomes and decision thresholds; the assessment section, where the new "net effect" criterion has been included; and the conclusion section, which includes an adaptation for multiple comparisons. The article provides examples and suggestions for presentation of findings. The framework does have limitations, in that its usability has not been tested across a broad spectrum of guideline development contexts.

Background: Older adults with acute myeloid leukemia (AML) represent a cancer population in which disease-based risk factors, comorbidities, patient goals, and treatment risks and benefits influence treatment recommendations. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health professionals in their decisions about management of AML in older adults. Methods: ASH formed a multidisciplinary guideline panel, including patient representatives, that minimized bias from conflicts of interest. Clarity Research Group at McMaster University supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development and evaluation approach, including evidence-to-decision frameworks, to assess evidence and make recommendations. Results: The panel agreed on 9 critical clinical recommendations for managing AML in older adults, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management; traditional induction and postremission therapy vs hypomethylating agent or low-dose cytarabine, or combinations with venetoclax; the role and duration of postremission therapy; combinations with venetoclax vs monotherapy; the use of targeted therapy, including isocitrate dehydrogenase and FMS-like tyrosine kinase 3 (FLT3) inhibitors, in appropriate patients; the role of hematopoietic stem cell transplantation in nonfavorable prognosis AML; and the role of transfusion support for patients no longer receiving antileukemic therapy. Conclusions: Key recommendations of these guidelines include treatment over best supportive care; venetoclax-based regimens over monotherapies; and incorporation of FLT3 inhibitors into traditional induction and postremission therapy.

Despite published guidance by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group on the use of good practice statements (GPSs), their appropriate development remains challenging. This article provides updated guidance with nuanced operationalization. The updated guidance was developed on the basis of examples and iterative discussions. The lead authors refined the approach according to the feedback from GRADE Working Group meetings and presented the summary of the results to all attendees of the GRADE Working Group meeting for feedback in September 2023 and for final approval in September 2024. The 5 signaling questions from the original guidance were leveraged, and the authors recommend that guideline developers select relevant Evidence to Decision criteria to assess the potential downstream consequences of implementing the statement. They have updated the definition of a GPS, classifying GPSs into the following 3 categories: those grounded in ethics and human rights; those grounded in essential principles, practices, and protocols; and those grounded in established scientific evidence. Practical examples accompany the steps as they relate to each type of GPS. In addition, the authors introduce a tool to streamline GPS development and enhance the reporting process. This GRADE guidance article provides an update on when and how to develop a GPS. Adherence to the guidance will add to the trustworthiness of guidelines and may facilitate reducing the inappropriate use or overuse of the GPS.

Introduction: Antimicrobial resistance (AMR) is a widely recognized threat to global health, mainly driven by the inappropriate use of antimicrobials. Recommendations from evidence‐based practice guidelines (EBPGs) can promote appropriate antimicrobial use. Currently, no guidance exists for considering AMR in EBPGs. This is the protocol for two studies that aim to (1) develop a checklist of AMR considerations for EBPGs and (2) conduct a case study to evaluate existing EBPGs regarding the extent to which AMR is considered among other methodological assessments. Methods: Using the Delphi technique, we will consult with individuals from four interest‐holder groups to develop and refine a checklist of AMR considerations for EBPGs. To assess EBPGs, we will search various databases for guidelines on four prioritized syndromes (i.e., community‐acquired pneumonia, urinary tract infection, skin and soft tissue infections and exacerbations of chronic obstructive pulmonary disease). We will screen articles in duplicate and in stages to include EBPGs for the prioritized syndromes and will use piloted data extraction forms to extract characteristics of the EBPGs. For each EBPG, we will evaluate whether AMR was considered (using the developed checklist), its trustworthiness (i.e., methodological quality) (using the modified National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards instrument) and its adaptability (using items from existing adaptability frameworks). Discussion: This work will develop a checklist of AMR considerations for EBPGs and evaluate a subsequent sample of EBPGs to investigate the extent to which AMR is considered. Furthermore, by conducting a methodological appraisal of trustworthiness and adaptability, this study will contextualize results to promote the uptake and appropriate interpretation of existing guidelines. Thus, these findings will be useful to decision‐makers as well as guideline development groups as they highlight what existing work can be trusted and leveraged while also identifying what limitations and gaps need to be addressed.