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 Cameroon Health Research and Evidence Database (CAMHRED): tools and methods for local evidence mapping.

BACKGROUND: Local evidence is important for contextualized knowledge translation. It can be used to adapt global recommendations, to identify future research priorities and inform local policy decisions. However, there are challenges in identifying local evidence in a systematic, comprehensive, and timely manner. There is limited guidance on how to map local evidence and provide it to users in an accessible and user-friendly way. In this study, we address these issues by describing the methods for the development of a centralized database of health research evidence for Cameroon and its applications for research prioritization and decision making. METHODS: We searched 10 electronic health databases and hand-searched the archives of non-indexed African and Cameroonian journals. We screened titles, abstracts, and full texts of peer reviewed journal articles published between 1999 and 2019 in English or French that assess health related outcomes in Cameroonian populations. We extracted relevant study characteristics based on a pre-established guide. We developed a coding scheme or taxonomy of content areas so that local evidence is mapped to corresponding domains and subdomains. Pairs of reviewers coded articles independently and resolved discrepancies by consensus. Moreover, we developed guidance on how to search the database, use search results to create evidence maps and conduct knowledge gap analyses. RESULTS: The Cameroon Health Research and Evidence Database (CAMHRED) is a bilingual centralized online portal of local evidence on health in Cameroon from 1999 onwards. It currently includes 4384 studies categorized into content domains and study characteristics (design, setting, year and language of publication). The database is searchable by keywords or through a guided search. Results including abstracts, relevant study characteristics and bibliographic information are available for users to download. Upon request, guidance on how to optimize search results for applications like evidence maps and knowledge gap analyses is also available. CONCLUSIONS: CAMHRED ( https://camhred.org/ ) is a systematic, comprehensive, and centralized resource for local evidence about health in Cameroon. It is freely available to stakeholders and provides an additional resource to support their work at various levels in the research process.

Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis.

There may be many predictors of venous thromboembolism (VTE) and bleeding in hospitalized medical patients, but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify prognostic factors for VTE and bleeding in hospitalized medical patients and searched Medline and EMBASE from inception through May 2018. We considered studies that identified potential prognostic factors for VTE and bleeding in hospitalized adult medical patients. Reviewers extracted data in duplicate and independently and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Of 69 410 citations, we included 17 studies in our analysis: 14 that reported on VTE, and 3 that reported on bleeding. For VTE, moderate-certainty evidence showed a probable association with older age; elevated C-reactive protein (CRP), D-dimer, and fibrinogen levels; tachycardia; thrombocytosis; leukocytosis; fever; leg edema; lower Barthel Index (BI) score; immobility; paresis; previous history of VTE; thrombophilia; malignancy; critical illness; and infections. For bleeding, moderate-certainty evidence showed a probable association with older age, sex, anemia, obesity, low hemoglobin, gastroduodenal ulcers, rehospitalization, critical illness, thrombocytopenia, blood dyscrasias, hepatic disease, renal failure, antithrombotic medication, and presence of a central venous catheter. Elevated CRP, a lower BI, a history of malignancy, and elevated heart rate are not included in most VTE risk assessment models. This study informs risk prediction in the management of hospitalized medical patients for VTE and bleeding; it also informs guidelines for VTE prevention and future research.

Control of Severe, Life-Threatening External Bleeding in the Out-of-Hospital Setting: A Systematic Review.

OBJECTIVE: Trauma, with resultant bleeding, is a significant cause of morbidity and mortality throughout the world; however, the best possible method of bleeding control by immediate responders is unknown. We performed a systematic review of the effectiveness of treatment modalities for severe, life-threatening external bleeding in the out-of-hospital first aid setting. Methods: We followed the Cochrane Handbook for Systematic Reviews of Interventions methodology and report results according to PRISMA guidelines. We included randomized controlled trials, non-randomized comparative studies and case series investigating adults and children with severe, life-threatening external bleeding who were treated with therapies potentially suitable for first aid providers. We assessed the certainty of the evidence and risk of bias. Outcomes were prioritized by first aid specialists based on importance for patients and decision-makers and included mortality due to bleeding, all-cause mortality, cessation of bleeding, time to cessation of bleeding, a decrease in bleeding, and complications/adverse effects. Results were reported in Evidence Profiles. Results: Of the 1,051 full-text articles screened, 107 were included for analysis including 22,798 patients. The primary methods of bleeding control were tourniquets (n = 49), hemostatic dressings (n = 34), hemostatic devices (n = 14), pressure dressings/bandages/devices (n = 8), pressure points (n = 4), including 2 studies that reported multiple hemorrhage control methods. Overall, certainty of evidence was very low and often relied on indirect evidence and poorly controlled studies. Tourniquets were associated with a decrease in mortality when compared with direct manual pressure. Hemostatic dressings resulted in a shorter time to hemostasis than direct manual pressure using standard dressings. Direct manual compression resulted in a shorter time to hemostasis than pressure dressings/devices. Conclusion: Overall, data regarding the control of life-threatening bleeding is of very low certainty, making it difficult to draw robust conclusions for treatment by immediate responders. While more robust data is needed on first aid treatments of life-threatening bleeding, this systematic review aggregates the most comprehensive to date to help guide recommendations. Key words: bleeding; hemorrhage; tourniquet; hemostatic dressing; direct pressure.

Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence.

BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).

Approaches of integrating the development of guidelines and quality indicators: a systematic review.

BACKGROUND: Guidelines and quality indicators (for example as part of a quality assurance scheme) aim to improve health care delivery and health outcomes. Ideally, the development of quality indicators should be grounded in evidence-based, trustworthy guideline recommendations. However, anecdotally, guidelines and quality assurance schemes are developed independently, by different groups of experts who employ different methodologies. We conducted an extension and update of a previous systematic review to identify, describe and evaluate approaches to the integrated development of guidelines and related quality indicators. METHODS: On May 24th, 2019 we searched in Medline, Embase and CINAHL and included studies if they reported a methodological approach to guideline-based quality indicator development and were published in English, French, or German. RESULTS: Out of 16,034 identified records, we included 17 articles that described a method to integrate guideline recommendations development and quality indicator development. Added to the 13 method articles from original systematic review we included a total 30 method articles. We did not find any evaluation studies. In most approaches, guidelines were a source of evidence to inform the quality indicator development. The criteria to select recommendations (e.g. level of evidence or strength of the recommendation) and to generate, select and assess quality indicators varied widely. We found methodological approaches that linked guidelines and quality indicator development explicitly, however none of the articles reported a conceptual framework that fully integrated quality indicator development into the guideline process or where quality indicator development was part of the question formulation for developing the guideline recommendations. CONCLUSIONS: In our systematic review we found approaches which explicitly linked guidelines with quality indicator development, nevertheless none of the articles reported a comprehensive and well-defined conceptual framework which integrated quality indicator development fully into the guideline development process.

Strategies for eliciting and synthesizing evidence for guidelines in rare diseases.

BACKGROUND: Rare diseases are a global public health priority. Though each disease is rare, when taken together the thousands of known rare diseases cause significant morbidity and mortality, impact quality of life, and confer a social and economic burden on families and communities. These conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment. Clinical practice guidelines are necessary to support clinical and policy decisions. However, creating guidelines for rare diseases presents specific challenges, including a paucity of high certainty evidence to inform panel recommendations. METHODS: This paper draws from the authors' experience in the development of clinical practice guidelines for three rare diseases: hemophilia, sickle cell disease, and catastrophic antiphospholipid syndrome. RESULTS: We have summarized a number of strategies for eliciting and synthesizing evidence that are compatible with the rigorous, internationally accepted standards for guideline development set out by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. These strategies include: use of pre-existing and ad hoc qualitative research, use of systematic observation forms, use of registry data, and thoughtful use of indirect evidence. Their use in three real guideline development efforts, as well as their theoretical underpinnings, are discussed. Avenues for future research to improve clinical practice guideline creation for rare diseases - and any disease affected by a relative lack of evidence - are also identified. CONCLUSIONS: Rigorous clinical practice guidelines are needed to improve the care of the millions of people worldwide who suffer from rare diseases. Innovative evidence elicitation and synthesis methods will benefit not only the rare disease community, but also individuals with common diseases who have rare presentations, suffer rare complications, or require nascent therapies. Further refinement and improved uptake of these innovative methods should lead to higher quality clinical practice guidelines in rare diseases.

Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment.

BACKGROUND: It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the published American College of Rheumatology (ACR) Rheumatoid Arthritis (RA) treatment guideline to the Eastern Mediterranean Region (EMR). The objective of this paper is to describe the process used for the adaptation of the 2015 ACR guideline on the treatment of RA for the EMR. METHODS: We used the GRADE-Adolopment methodology for the guideline adaptation process. We describe in detail how adolopment enhanced the efficiency of the following steps of the guideline adaptation process: (1) groups and roles, (2) selecting guideline topics, (3) identifying and training guideline panelists, (4) prioritizing questions and outcomes, (5) identifying, updating or conducting systematic reviews, (6) preparing GRADE evidence tables and EtD frameworks, (7) formulating and grading strength of recommendations, (8) using the GRADEpro-GDT software. RESULTS: The adolopment process took 6 months from January to June 2016 with a project coordinator dedicating 40% of her time, and the two co-chairs dedicating 5% and 10% of their times respectively. In addition, a research assistant worked 60% of her time over the last 3 months of the project. We held our face-to-face panel meeting in Qatar. Our literature update included five newly published trials. The certainty of the evidence of three of the eight recommendations changed: one from moderate to very low and two from low to very low. The factors that justified a very low certainty of the evidence in the three recommendations were: serious risk of bias and very serious imprecision. The strength of five of the recommendations changed from strong to conditional. The factors that justified the conditional strength of these 5 recommendations were: cost (n = 5 [100%]), impact on health equities (n = 4 [80%]), the balance of benefits and harms (n = 1 [20%]) and acceptability (n = 1 [20%]). CONCLUSION: This project confirmed the feasibility of GRADE-Adolopment. It also highlighted the value of collaboration with the organization that had originally developed the treatment guideline. We discuss the implications for both guideline adaptation and future research to advance the field.

Using patient values and preferences to inform the importance of health outcomes in practice guideline development following the GRADE approach.

BACKGROUND: There are diverse opinions and confusion about defining and including patient values and preferences (i.e. the importance people place on the health outcomes) in the guideline development processes. This article aims to provide an overview of a process for systematically incorporating values and preferences in guideline development. METHODS: In 2013 and 2014, we followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to adopt, adapt and develop 226 recommendations in 22 guidelines for the Ministry of Health of the Kingdom of Saudi Arabia. To collect context-specific values and preferences for each recommendation, we performed systematic reviews, asked clinical experts to provide feedback according to their clinical experience, and consulted patient representatives. RESULTS: We found several types of studies addressing the importance of outcomes, including those reporting utilities, non-utility measures of health states based on structured questionnaires or scales, and qualitative studies. Guideline panels used the relative importance of outcomes based on values and preferences to weigh the balance of desirable and undesirable consequences of alternative intervention options. However, we found few studies addressing local values and preferences. CONCLUSIONS: Currently there are different but no firmly established processes for integrating patient values and preferences in healthcare decision-making of practice guideline development. With GRADE Evidence-to-Decision (EtD) frameworks, we provide an empirical strategy to find and incorporate values and preferences in guidelines by performing systematic reviews and eliciting information from guideline panel members and patient representatives. However, more research and practical guidance are needed on how to search for relevant studies and grey literature, assess the certainty of this evidence, and best summarize and present the findings.

Stakeholders' perceptions of rehabilitation services for individuals living with disability: a survey study.

BACKGROUND: The World Health Organization (WHO) was tasked with developing health system guidelines for the implementation of rehabilitation services. Stakeholders' perceptions are an essential factor to take into account in the guideline development process. The aim of this study was to assess stakeholders' perceived feasibility and acceptability of eighteen rehabilitation services and the values they attach to ten rehabilitation outcomes. METHODS: We disseminated an online self-administered questionnaire through a number of international and regional organizations from the different WHO regions. Eligible individuals included persons with disability, caregivers of persons with disability, health professionals, administrators and policy makers. The answer options consisted of a 9-point Likert scale. RESULTS: Two hundred fifty three stakeholders participated. The majority of participants were health professional (64 %). In terms of outcomes, 'Increasing access' and 'Optimizing utilization' were the top service outcomes rated as critical (i.e., 7, 8 or 9 on the Likert scale) by >70 % of respondents. 'Fewer hospital admissions', 'Decreased burden of care' and 'Increasing longevity' were the services rated as least critical (57 %, 63 % and 58 % respectively). In terms of services, 'Community based rehabilitation' and 'Home based rehabilitation' were found to be both definitely feasible and acceptable (75 % and 74 % respectively). 'Integrated and decentralized rehabilitation services' was found to be less feasible than acceptable according to stakeholders (61 % and 71 % respectively). As for 'Task shifting', most stakeholders did not appear to find task shifting as either definitely feasible or definitely acceptable (63 % and 64 % respectively). CONCLUSION: The majority of stakeholder's perceived 'Increasing access' and 'Optimizing utilization' as most critical amongst rehabilitation outcomes. The feasibility of the 'Integrated and decentralized rehabilitation services' was perceived to be less than their acceptability. The majority of stakeholders found 'Task shifting' as neither feasible nor acceptable.

Health system and community level interventions for improving antenatal care coverage and health outcomes.

BACKGROUND: The World Health Organization (WHO) recommends at least four antenatal care (ANC) visits for all pregnant women. Almost half of pregnant women worldwide, and especially in developing countries do not receive this amount of care. Poor attendance of ANC is associated with delivery of low birthweight babies and more neonatal deaths. ANC may include education on nutrition, potential problems with pregnancy or childbirth, child care and prevention or detection of disease during pregnancy.This review focused on community-based interventions and health systems-related interventions. OBJECTIVES: To assess the effects of health system and community interventions for improving coverage of antenatal care and other perinatal health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 June 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-randomised trials and cluster-randomised trials. Trials of any interventions to improve ANC coverage were eligible for inclusion. Trials were also eligible if they targeted specific and related outcomes, such as maternal or perinatal death, but also reported ANC coverage. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included 34 trials involving approximately 400,000 women. Some trials tested community-based interventions to improve uptake of antenatal care (media campaigns, education or financial incentives for pregnant women), while other trials looked at health systems interventions (home visits for pregnant women or equipment for clinics). Most trials took place in low- and middle-income countries, and 29 of the 34 trials used a cluster-randomised design. We assessed 30 of the 34 trials as of low or unclear overall risk of bias. Comparison 1: One intervention versus no interventionWe found marginal improvements in ANC coverage of at least four visits (average odds ratio (OR) 1.11, 95% confidence interval (CI) 1.01 to 1.22; participants = 45,022; studies = 10; Heterogeneity: Tau² = 0.01; I² = 52%; high quality evidence). Sensitivity analysis with a more conservative intra-cluster correlation co-efficient (ICC) gave similar marginal results. Excluding one study at high risk of bias shifted the marginal pooled estimate towards no effect. There was no effect on pregnancy-related deaths (average OR 0.69, 95% CI 0.45 to 1.08; participants = 114,930; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; low quality evidence), perinatal mortality (average OR 0.98, 95% CI 0.90 to 1.07; studies = 15; Heterogeneity: Tau² = 0.01; I² = 58%; moderate quality evidence) or low birthweight (average OR 0.94, 95% CI 0.82 to 1.06; studies = five; Heterogeneity: Tau² = 0.00; I² = 5%; high quality evidence). Single interventions led to marginal improvements in the number of women who delivered in health facilities (average OR 1.08, 95% CI 1.02 to 1.15; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; high quality evidence), and in the proportion of women who had at least one ANC visit (average OR 1.68, 95% CI 1.02 to 2.79; studies = six; Heterogeneity: Tau² = 0.24; I² = 76%; moderate quality evidence). Results for ANC coverage (at least four and at least one visit) and for perinatal mortality had substantial statistical heterogeneity. Single interventions did not improve the proportion of women receiving tetanus protection (average OR 1.03, 95% CI 0.92 to 1.15; studies = 8; Heterogeneity: Tau² = 0.01; I² = 57%). No study reported onintermittent prophylactic treatment for malaria. Comparison 2: Two or more interventions versus no interventionWe found no improvements in ANC coverage of four or more visits (average OR 1.48, 95% CI 0.99 to 2.21; participants = 7840; studies = six; Heterogeneity: Tau² = 0.10; I² = 48%; low quality evidence) or pregnancy-related deaths (average OR 0.70, 95% CI 0.39 to 1.26; participants = 13,756; studies = three; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). However, combined interventions led to improvements in ANC coverage of at least one visit (average OR 1.79, 95% CI 1.47 to 2.17; studies = five; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence), perinatal mortality (average OR 0.74, 95% CI 0.57 to 0.95; studies = five; Heterogeneity: Tau² = 0.06; I² = 83%; moderate quality evidence) and low birthweight (average OR 0.61, 95% CI 0.46 to 0.80; studies = two; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). Meta-analyses for both ANC coverage four or more visits and perinatal mortality had substantial statistical heterogeneity. Combined interventions improved the proportion of women who had tetanus protection (average OR 1.48, 95% CI 1.18 to 1.87; studies = 3; Heterogeneity: Tau² = 0.01; I² = 33%). No trial in this comparison reported on intermittent prophylactic treatment for malaria. Comparison 3: Two interventions compared head to head. No trials found. Comparison 4: One intervention versus a combination of interventionsThere was no difference in ANC coverage (four or more visits and at least one visit), pregnancy-related deaths, deliveries in a health facility or perinatal mortality. No trials in this comparison reported on low birthweight orintermittent prophylactic treatment of malaria. AUTHORS' CONCLUSIONS: Implications for practice - Single interventions may improve ANC coverage (at least one visit and four or more visits) and deliveries in health facilities. Combined interventions may improve ANC coverage (at least one visit), reduce perinatal mortality and reduce the occurrence of low birthweight. The effects of the interventions are unrelated to whether they are community or health system interventions. Implications for research - More details should be provided in reporting numbers of events, group totals and the ICCs used to adjust for cluster effects. Outcomes should be reported uniformly so that they are comparable to commonly-used population indicators. We recommend further cluster-RCTs of pregnant women and women in their reproductive years, using combinations of interventions and looking at outcomes that are important to pregnant women, such as maternal and perinatal morbidity and mortality, alongside the explanatory outcomes along the pathway of care: ANC coverage, the services provided during ANC and deliveries in health facilities.

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.

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.

GRADE concept paper 8: judging the certainty of discrimination performance estimates of prognostic models in a body of validation studies.

BACKGROUND: Prognostic models incorporate multiple prognostic factors to estimate the likelihood of future events for individual patients based on their prognostic factor values. Evaluating these models crucially involves conducting studies to assess their predictive performance, like discrimination. Systematic reviews and meta-analyses of these validation studies play an essential role in selecting models for clinical practice. METHODS: In this paper, we outline 3 thresholds to determine the target for certainty rating in the discrimination of prognostic models, as observed across a body of validation studies. RESULTS AND CONCLUSION: We propose 3 thresholds when rating the certainty of evidence about a prognostic model's discrimination. The first threshold amounts to rating certainty in the model's ability to classify better than random chance. The other 2 approaches involve setting thresholds informed by other mechanisms for classification: clinician intuition or an alternative prognostic model developed for the same disease area and outcome. The choice of threshold will vary based on the context. Instead of relying on arbitrary discrimination cut-offs, our approach positions the observed discrimination within an informed spectrum, potentially aiding decisions about a prognostic model's practical utility.

Considering planetary health in health guidelines and health technology assessments: a scoping review protocol.

BACKGROUND: This protocol outlines a scoping review with the objective of identifying and exploring planetary health considerations within existing health guidelines and health technology assessments (HTA). The insights gained from this review will serve as a basis for shaping future Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidance on planetary health. METHODS: We will adhere to the JBI methodology for scoping reviews. We will conduct a comprehensive search and screening of results in all languages across various databases including MEDLINE, EMBASE, CINAHL, Global Health, Health Systems Evidence, Greenfile, and Environmental Issues. Additionally, we will supplement this search with resources such as the GIN library, BIGG database, Epistemonikos, GRADE guidelines repository, GRADEpro Guideline Development Tool Database, MAGICapp, NICE website, WHO websites, and a manual exploration of unpublished relevant documents using Google incognito mode. Two independent reviewers will screen and assess the full texts of identified documents according to the eligibility criteria. The following information from each full text will be extracted: document title; first author's name; publication year; language; document type; document as a guideline or HTA; the topic/discipline; document purpose/study objective; developing/sponsoring organization; the country in which the study/guideline/HTA report was conducted; definition of planetary health or related concept provided; types of planetary health experts engaged; study methods; suggested methods to assess planetary health; use of secondary data on planetary health outcomes; description for use of life cycle assessment; description for assessing the quality of life cycle; population/intended audience; interventions; category; applicable planetary health boundaries; consideration of social justice/global equity; phase of intervention in life cycle related to planetary health addressed; the measure of planetary health impact; impact on biodiversity/land use; one health/animal welfare mention; funding; and conflict of interest. Data analysis will involve a combination of descriptive statistics and directed content analysis, with results presented in a narrative format and displayed in tables and graphs. DISCUSSION: The final review results will be submitted to open-access peer-reviewed journals for publication when they become available. The research findings will also be disseminated at relevant planetary health conferences and workshops. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( https://osf.io/3jmsa ).

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.