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.

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.

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.

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.

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 ).

GRADE Guidance 39: Using GRADE-ADOLOPMENT to adopt, adapt or create contextualized recommendations from source guidelines and evidence syntheses.

INTRODUCTION: The GRADE-ADOLOPMENT methodology has been widely used to adopt, adapt or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. This guidance refines the operationalization for applying GRADE-ADOLOPMENT. METHODS: Through iterative discussions, online meetings and email communications, the GRADE-ADOLOPMENT Project Group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned Adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE Working Group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people) and twice in September 2023 (approximately 60 and 90 people) for approval. RESULTS: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing EtDs when available or developing new EtDs if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others. CONCLUSION: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over six years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources.