Comparative benefits and harms of perioperative interventions to prevent chronic pain after orthopedic surgery: a systematic review and network meta-analysis of randomized trials.

BACKGROUND: Chronic postsurgical pain (CPSP) is common following musculoskeletal and orthopedic surgeries and is associated with impairment and reduced quality of life. Several interventions have been proposed to reduce CPSP; however, there remains uncertainty regarding which, if any, are most effective. We will perform a systematic review and network meta-analysis of randomised trials to assess the comparative benefits and harms of perioperative pharmacological and psychological interventions directed at preventing chronic pain after musculoskeletal and orthopedic surgeries. METHODS: We will search MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to present, without language restrictions. We will include randomised controlled trials that as follows: (1) enrolled adult patients undergoing musculoskeletal or orthopedic surgeries; (2) randomized them to any pharmacological or psychological interventions, or their combination directed at reducing CPSP, placebo, or usual care; and (3) assessed pain at 3 months or more after surgery. Screening for eligible trials, data extraction, and risk-of-bias assessment using revised Cochrane risk-of-bias tool (RoB 2.0) will be performed in duplicate and independently. Our main outcome of interest will be the proportion of surgical patients reporting any pain at ≥ 3 months after surgery. We will also collect data on other patient important outcomes, including pain severity, physical functioning, emotional functioning, dropout rate due to treatment-related adverse event, and overall dropout rate. We will perform a frequentist random-effects network meta-analysis to determine the relative treatment effects. When possible, the modifying effect of sex, surgery type and duration, anesthesia type, and veteran status on the effectiveness of interventions will be investigated using network meta-regression. We will use the GRADE approach to assess the certainty evidence and categorize interventions from most to least beneficial using GRADE minimally contextualised approach. DISCUSSION: This network meta-analysis will assess the comparative effectiveness of pharmacological and psychological interventions directed at preventing CPSP after orthopedic surgery. Our findings will inform clinical decision-making and identify promising interventions for future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023432503.

Endovascular Thrombectomy With or Without Thrombolysis for Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: To this date, whether to administer intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) for stroke patients still stirs some debate. We aimed to systematically update the evidence from randomized trials comparing EVT alone vs EVT with bridging IVT. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing EVT with or without IVT in patients presenting with stroke secondary to a large vessel occlusion. We conducted meta-analyses using random-effects models to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH), between EVT and EVT with IVT. We assessed risk of bias using the Cochrane risk-of-bias tool and certainty of evidence for each outcome using the GRADE approach. Results: Of 11,111 citations, we included 6 studies with a total of 2336 participants. We found low-certainty evidence of possibly a small decrease in the proportion of patients with functional independence (risk difference [RD] -2.0%, 95% CI -5.9% to 2.0%), low-certainty evidence that there is possibly a small increase in mortality (RD 1.0%, 95% CI -2.2% to 4.7%), and moderate-certainty evidence that there is probably a decrease in sICH (RD -1.0%, 95% CI -1.6% to .7%) for patients with EVT alone compared to EVT plus IVT, respectively. Conclusion: Low-certainty evidence shows that there is possibly a small decrease in functional independence, low-certainty evidence shows that there is possibly a small increase in mortality, and moderate-certainty evidence that there is probably a decrease in sICH for patients with EVT alone compared to EVT plus IVT.

Individuals' Values and Preferences Regarding Medical Cannabis for Chronic Pain: A Descriptive Qualitative Study.

Background: Cannabis for medical purposes has been legal in Canada since 2001; however, physicians receive no formal training in this modality, and clinical use of cannabis remains controversial. This study aims to explore the values and preferences of people living with chronic pain (PLwCP) in using medical cannabis for chronic pain to inform guideline development and shared decision-making in clinical practice. Methods: We conducted a descriptive qualitative study using in-depth interviews with PLwCP. Using a deductive/inductive approach, we developed concepts and themes related to values and preferences of PLwCP on their use (or avoidance) of medical cannabis for chronic pain. Results: We interviewed 52 PLwCP, including current medical cannabis users (40), previous users (10) and non-users (2). Most PLwCP who used cannabis therapeutically reported the need for experimentation to determine what cannabis products, routes, and doses worked for them. Perceived benefits of medical cannabis among current users included relief from pain, better sleep, and improved mental health. Reasons for discontinuing use of medical cannabis included lack of improvement in pain or sleep or undesirable side effects. Cannabidiol (CBD) dominant products were reported to result in minimal adverse effects (eg, physical or mental impairment) compared to tetrahydrocannabinol (THC) dominant products. Perceived barriers or facilitators to use included social acceptability, availability or access, cost, and attitudes and knowledge among healthcare providers. Participants noted different routes of cannabis use including oral routes that provided longer-lasting pain relief with a slower onset and inhaled routes with a more rapid onset with shorter-lived effects. Conclusion: Participants' decisions to use medical cannabis for chronic pain were varied, which suggests these decisions are likely to be sensitive to individuals' values and preferences. There is a call for further research and information-sharing to help PLwCP understand the complexities of cannabis use for medical purposes, including ideal dosing and timing.

Operationalizing the GRADE-equity criterion to inform guideline recommendations: application to a medical cannabis guideline.

OBJECTIVES: Incorporating health equity considerations into guideline development often requires information beyond that gathered through traditional evidence synthesis methodology. This article outlines an operationalization plan for the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-equity criterion to gather and assess evidence from primary studies within systematic reviews, enhancing guideline recommendations to promote equity. We demonstrate its use in a clinical guideline on medical cannabis for chronic pain. STUDY DESIGN AND SETTING: We reviewed GRADE guidance and resources recommended by team members regarding the use of evidence for equity considerations, drafted an operationalization plan, and iteratively refined it through team discussion and feedback and piloted it on a medicinal cannabis guideline. RESULTS: We propose a seven-step approach: 1) identify disadvantaged populations, 2) examine available data for specific populations, 3) evaluate population baseline risk for primary outcomes, 4) assess representation of these populations in primary studies, 5) appraise analyses, 6) note barriers to implementation of effective interventions for these populations, and 7) suggest supportive strategies to facilitate implementation of effective interventions. CONCLUSION: Our approach assists guideline developers in recognizing equity considerations, particularly in resource-constrained settings. Its application across various guideline topics can verify its feasibility and necessary adjustments.

Endovascular Thrombectomy with or without Bridging Thrombolysis in Acute Ischemic Stroke: A Cost-Effectiveness Analysis.

BACKGROUND: There is unclear added benefit of intravenous thrombolysis (IVT) with endovascular thrombectomy (EVT). We performed a cost-effectiveness analysis to assess the cost-effectiveness of comparing EVT with IVT versus EVT alone. METHODS: We used a decision tree to examine the short-term costs and outcomes at 90 days after the occurrence of index stroke to compare the cost-effectiveness of EVT alone with EVT plus IVT for patients with stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1-year, 5-year, and 20-year time horizons. We estimated total and incremental cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio. RESULTS: The average costs per patient were estimated to be $47,304, $49,510, $59,770, and $76,561 for EVT-only strategy and $55,482, $57,751, $68,314, and $85,611 for EVT with IVT over 90 days, 1 year, 5 years, and 20 years, respectively. The cost saving of EVT-only strategy was driven by the avoided medication costs of IVT (ranging from $8,178 to $9,050). The additional IVT led to a slight decrease in QALY estimate during the 90-day time horizon (loss of 0.002 QALY), but a small gain over 1-year and 5-year time horizons (0.011 and 0.0636 QALY). At a willingness-to-pay threshold of $50,000 per QALY gained, the probabilities of EVT only being cost-effective were 100%, 100%, and 99.3% over 90-day, 1-year, and 5-year time horizons. CONCLUSION: Our cost-effectiveness model suggested that EVT only may be cost-effective for patients with acute ischemic stroke secondary to large vessel occlusion.

The design of studies testing the effectiveness of risk-guided care has many challenges: a scoping review addressing key considerations.

OBJECTIVES: Studies evaluating the effectiveness of care based on patients' risk of adverse outcomes (risk-guided care) use a variety of study designs. In this scoping review, using examples, we review characteristics of relevant studies and present key design features to optimize the trustworthiness of results. STUDY DESIGN AND SETTING: We searched five online databases for studies evaluating the effect of risk-guided care among adults on clinical outcomes, process, or cost. Pairs of reviewers independently performed screening and data abstraction. We descriptively summarized the study design and characteristics. RESULTS: Among 14,561 hits, we identified 116 eligible studies. Study designs included randomized controlled trials (RCTs), post hoc analysis of RCTs, and retrospective or prospective cohort studies. Challenges and sources of bias in the design included limited performance of predictive models, contamination, inadequacy to address the credibility of subgroup effects, absence of differences in care across risk strata, reporting only process measures as opposed to clinical outcomes, and failure to report benefits and harms. CONCLUSION: To assess the benefit of risk-guided care, RCTs provide the most trustworthy evidence. Observational studies offer an alternative but are hampered by confounding and other limitations. Reaching valid conclusions when testing risk-guided care requires addressing the challenges identified in our review.

Equity issues rarely addressed in the development of COVID-19 formal recommendations and good practice statements: a cross-sectional study.

BACKGROUND AND OBJECTIVE: To identify COVID-19 actionable statements (e.g., recommendations) focused on specific disadvantaged populations in the living map of COVID-19 recommendations (eCOVIDRecMap) and describe how health equity was assessed in the development of the formal recommendations. METHODS: We employed the place of residence, race or ethnicity or culture, occupation, gender or sex, religion, education, socio-economic status, and social capital-Plus framework to identify statements focused on specific disadvantaged populations. We assessed health equity considerations in the evidence to decision frameworks (EtD) of formal recommendations for certainty of evidence and impact on health equity criteria according to the Grading of Recommendations, Assessment, Development, and Evaluations criteria. RESULTS: We identified 16% (124/758) formal recommendations and 24% (186/819) good practice statements (GPS) that were focused on specific disadvantaged populations. Formal recommendations (40%, 50/124) and GPS (25%, 47/186) most frequently focused on children. Seventy-six percent (94/124) of the recommendations were accompanied with EtDs. Over half (55%, 52/94) of those considered indirectness of the evidence for disadvantaged populations. Considerations in impact on health equity criterion most frequently involved implementation of the recommendation for disadvantaged populations (17%, 16/94). CONCLUSION: Equity issues were rarely explicitly considered in the development COVID-19 formal recommendations focused on specific disadvantaged populations. Guidance is needed to support the consideration of health equity in guideline development during health emergencies.

Endovascular thrombectomy with or without thrombolysis bridging in patients with acute ischaemic stroke: protocol for a systematic review, meta-analysis of randomised trials and cost-effectiveness analysis.

INTRODUCTION: Current published guidelines and meta-analyses comparing endovascular thrombectomy (EVT) alone versus EVT with bridging intravenous thrombolysis (IVT) suggest that EVT alone is non-inferior to EVT with bridging thrombolysis in achieving favourable functional outcome. Because of this controversy, we aimed to systematically update the evidence and meta-analyse data from randomised trials comparing EVT alone versus EVT with bridging thrombolysis, and performed an economic evaluation comparing both strategies. METHODS AND ANALYSIS: We will conduct a systematic review of randomised controlled trials comparing EVT with or without bridging thrombolysis in patients presenting with large vessel occlusions. We will identify eligible studies by systematically searching the following databases from inception without any language restrictions: MEDLINE (through Ovid), Embase and the Cochrane Library. The following criteria will be used to assess eligibility for inclusion: (1) adult patients ≥18 years old; (2) randomised patients to EVT alone or to EVT with IVT; and (3) measured outcomes, including functional outcomes, at least 90 days after randomisation. Pairs of reviewers will independently screen the identified articles, extract information and assess the risk of bias of eligible studies. We will use the Cochrane Risk-of-Bias tool to evaluate risk of bias. We will also use the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome. We will then perform an economic evaluation based on the extracted data. ETHICS AND DISSEMINATION: This systematic review will not require a research ethics approval because no confidential patient data will be used. We will disseminate our findings by publishing the results in a peer-reviewed journal and via presentation at conferences. PROSPERO REGISTRATION NUMBER: CRD42022315608.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis for patients with COVID-19: March 2022 update on the use of anticoagulation in critically ill patients.

BACKGROUND: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for patients with COVID-19. METHODS: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing systematic evidence reviews (up to January 2022). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 and May 2021 as part of the living phase of these guidelines. RESULTS: The panel made 1 additional recommendation: a conditional recommendation for the use of prophylactic-intensity over therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of thrombotic and bleeding risk. CONCLUSIONS: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation for patients with COVID-19-related critical illness.

Analytical frameworks in colorectal cancer guidelines: development of methods for systematic reviews, their application and practical guidance for their use.

OBJECTIVES: Analytical frameworks are graphical representation of the key questions answered by a systematic review and can support the development of guideline recommendations. Our objectives were to a) conduct a systematic review to identify, describe and compare all analytical frameworks published as part of a systematic and guideline development process related to colorectal cancer (CRC), and b) to use this case study to develop guidance on how to conduct systematic reviews of analytical frameworks. METHODS: We developed a search strategy to identify eligible studies in Medline and Embase from 1996 until December 2020. We also manually searched guideline databases and websites to identify all guidelines and systematic reviews in CRC that used an analytical framework. We assessed the quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II tool. The systematic review was registered in International Prospective Register of Systematic Reviews, registration CRD42020172117. RESULTS: We screened 34,505 records and identified 1,166 guidelines and 3,127 systematic reviews on CRC of which five met our inclusion criteria. These five publications included four analytical frameworks in colorectal cancer (one update). We also describe our methodological approach to systematic reviews for analytical frameworks and underlying concepts for developing analytical framework using a bottom-up or top-down approach. CONCLUSION: Few guidelines and systematic reviews are utilizing analytical frameworks in the development of recommendations. Development of analytical frameworks should begin with a systematic search for existing analytical frameworks and follow a structured conceptual approach for their development to support guideline recommendations. Our methods may be helpful in achieving these objectives.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: January 2022 update on the use of therapeutic-intensity anticoagulation in acutely ill patients.

BACKGROUND: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19. METHODS: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines. RESULTS: The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19-related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of risk of thrombosis and bleeding. The panel also noted that heparin (unfractionated or low molecular weight) may be preferred because of a preponderance of evidence with this class of anticoagulants. CONCLUSION: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19-related acute illness.

Defining decision thresholds for judgments on health benefits and harms using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks: a protocol for a randomised methodological study (GRADE-THRESHOLD).

INTRODUCTION: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and similar Evidence to Decision (EtD) frameworks require its users to judge how substantial the effects of interventions are on desirable and undesirable people-important health outcomes. However, decision thresholds (DTs) that could help understand the magnitude of intervention effects and serve as reference for interpretation of findings are not yet available.The objective of this study is an approach to derive and use DTs for EtD judgments about the magnitude of health benefits and harms. We hypothesise that approximate DTs could have the ability to discriminate between the existing four categories of EtD judgments (Trivial, Small, Moderate, Large), support panels of decision-makers in their work, and promote consistency and transparency in judgments. METHODS AND ANALYSIS: We will conduct a methodological randomised controlled trial to collect the data that allow deriving the DTs. We will invite clinicians, epidemiologists, decision scientists, health research methodologists, experts in Health Technology Assessment (HTA), members of guideline development groups and the public to participate in the trial. Then, we will investigate the validity of our DTs by measuring the agreement between judgments that were made in the past by guideline panels and the judgments that our DTs approach would suggest if applied on the same guideline data. ETHICS AND DISSEMINATION: The Hamilton Integrated Research Ethics Board reviewed this study as a quality improvement study and determined that it requires no further consent. Survey participants will be required to read a consent statement in order to participate in this study at the beginning of the trial. This statement reads: You are being invited to participate in a research project which aims to identify indicative DTs that could assist users of the GRADE EtD frameworks in making judgments. Your input will be used in determining these indicative thresholds. By completing this survey, you provide consent that the anonymised data collected will be used for the research study and to be summarised in aggregate in publication and electronic tools. PROTOCOL REGISTRATION NUMBER: NCT05237635.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: July 2021 update on postdischarge thromboprophylaxis.

BACKGROUND: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19 who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development, and evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation against the use of outpatient anticoagulant prophylaxis in patients with COVID-19 who are discharged from the hospital and who do not have suspected or confirmed VTE or another indication for anticoagulation. CONCLUSIONS: This recommendation was based on very low certainty in the evidence, underscoring the need for high-quality randomized controlled trials assessing the role of postdischarge thromboprophylaxis. Other key research priorities include better evidence on assessing risk of thrombosis and bleeding outcomes in patients with COVID-19 after hospital discharge.

Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021). STUDY SELECTION: Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate. METHODS: After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm. RESULTS: As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) -4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD -4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD -3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD -4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative. CONCLUSION: In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a data supplement. FUNDING: This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321). READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (www.covid19lnma.com).

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients.

BACKGROUND: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. RESULTS: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. CONCLUSIONS: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.

A modeling approach to derive baseline risk estimates for GRADE recommendations: Concepts, development, and results of its application to the American Society of Hematology 2019 guidelines on prevention of venous thromboembolism in surgical hospitalized patients.

OBJECTIVE: The goal of this study was to develop an approach that can be used where baseline risk estimates that are directly applicable to prioritized patient-important outcomes are not available from published studies. STUDY DESIGN: The McMaster University GRADE Centre and the ASH guideline panel for the prevention of VTE in surgical patients developed a modeling approach based on explicit assumptions about the distribution of symptoms, anatomical location, and severity of VTE events. RESULTS: We applied the approach to derive modeled estimates of baseline risk. These estimates were used to calculated absolute measures of anticipated effects that informed the discussion of the evidence and the formulation of 30 guideline recommendations. CONCLUSION: Our approach can assist guideline developers facing a lack of information about baseline risk estimates that directly apply to outcomes of interest. The use of modeled estimates increases transparency in the process and makes the baseline risk used by guideline experts explicit during their decision-making.

Interventional treatments for chronic, axial or radicular, non-cancer, spinal pain: a protocol for a systematic review and network meta-analysis of randomised trials.

INTRODUCTION: Chronic, non-cancer, axial or radicular spinal pain is a common condition associated with considerable socioeconomic burden. Clinicians frequently offer patients various interventional procedures for the treatment of chronic spine pain; however, the comparative effectiveness and safety of available procedures remains uncertain. METHODS: We will conduct a systematic review of randomised controlled trials that explores the effectiveness and harms of interventional procedures for the management of axial or radicular, chronic, non-cancer, spine pain. We will identify eligible studies through a systematic search of Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and Web of Science from inception without language restrictions. Eligible trials will: (1) enrol primarily adult patients (≥18 years old) with axial or radicular, chronic, non-cancer, spine pain, (2) randomise patients to different, currently available, interventional procedures or to an interventional procedure and a placebo/sham procedure or usual care, and (3) measure outcomes at least 1 month after randomisation.Pairs of reviewers will independently screen articles identified through searches and extract information and assess risk of bias of eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias. We will use frequentist random-effects network meta-analyses to assess the relative effects of interventional procedures, and five a priori hypotheses to explore between studies subgroup effects. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome, including direct, indirect and network estimates. ETHICS AND DISSEMINATION: No research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence. PROSPERO REGISTRATION NUMBER: CRD42020170667.

Effect of desmopressin on hematoma expansion in antiplatelet-associated intracerebral hemorrhage: A systematic review and meta-analysis.

The purpose of this study was to perform a systematic review and meta-analysis on the effect of desmopressin on hematoma expansion (HE) in antiplatelet-associated intracerebral hemorrhage (AA-ICH). Secondary outcomes examined were the rate of thrombotic complications and neurologic outcome. Three databases were searched (Pubmed, Scopus, and Cochrane) for randomized clinical trials and controlled studies comparing desmopressin versus controls in adult patients with AA-ICH. The Mantel-Haenszel method was applied to calculate an overall effect estimate for each outcome by combining stratum-specific risk ratio (RR). Risk of bias was computed using the Newcastle-Ottawa Scale. The protocol was registered in PROSPERO (42020190234). Three retrospective controlled studies involving 263 patients were included in the meta-analysis. Compared to controls, desmopressin was associated with a non-significant reduction in HE (19.1% vs. 30%; RR:0.61; 95%CI, 0.27-1.39; P = 0.24), a similar rate of thrombotic events (5.5% vs. 9.9%; RR:0.47; 95%CI, 0.17-1.31; P = 0.15), and significantly worse neurologic outcome (mRS ≥ 4) (66.3% vs. 50%; RR:1.36; 95%CI, 1.08-1.7; P = 0.008). Qualitative analysis of included studies for each outcome revealed low to moderate risk of bias. The available literature does not support the routine use of desmopressin in the setting of AA-ICH. Until larger prospective trials are performed, the administration of desmopressin should be judiciously considered on a case-by-case basis.