Grading Of Recommendations Assessment, Development And Evaluation Approach Research Articles

The effects of resveratrol supplementation in patients with type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease: an umbrella review of meta-analyses of randomized controlled trials

Uncertainty remains about the estimates of the effects for resveratrol supplementation, including the certainty of the evidence for each estimate and the magnitude of the observed impact based on the minimal important difference. We aimed to provide an overview of the effects of resveratrol supplementation, in comparison to control groups, for the management of cardiometabolic risk factors in patients with type 2 diabetes (T2D), metabolic syndrome (MetS), and nonalcoholic fatty liver disease (NAFLD). PubMed, Scopus, and ISI Web of Science were searched from inception to May 2021. For each meta-analysis, the mean difference and its 95% CI were recalculated using a random-effects model. The certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. We identified 11 meta-analyses corresponding to 29 outcomes in 1476 individuals with T2D, 17 meta-analyses reporting 26 outcomes in 727 participants with the MetS, and 10 meta-analyses reporting 24 outcomes in 271 patients with NAFLD. Resveratrol supplementation had beneficial effects on some outcomes such as blood pressure, lipid profile, glycemic control, and insulin resistance in T2D, waist circumference in MetS, and body-weight and inflammation markers in NAFLD; however, for almost all outcomes, the magnitude of the effect was trivial, the certainty of evidence was very low to low, or the number of trials was too few. In the case of glycated hemoglobin (HbA1c), there was evidence that resveratrol can exert favorable and clinically important effects in the short term (<12 wk; mean difference: -1.05%, 95% CI: -2.09%, -0.02%; n=6; GRADE=moderate). Current evidence does not support supplementation with resveratrol for the management of cardiometabolic risk factors in patients with T2D, MetS, and NAFLD. In the case of HbA1c, subject to the limitations such as short-term follow-up and small sample size, there was a clinically important effect. The protocol of the present systematic review was registered in Open Science Framework (https://osf.io/ake85; registration doi: 10.17605/OSF.IO/AKE85).

The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section

BackgroundThe rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). MethodsThe SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. ResultsThe SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. ConclusionThe SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

Should we really avoid fat in diet? The beneficial effects of low carbohydrate diet versus low fat diet on cardiovascular health: a systematic review and meta-analysis

Abstract Background European Society of Cardiology and the American College of cardiology recommend a diet that is considerably low in fat (&amp;lt;35%) and high in carbohydrates (45–55%) for cardiovascular disease (CVD) prevention. However, recent evidence suggests that low-carbohydrate diets (LCD) can provide similar, if not, better CVD protection. Design Systematic review and meta-analysis Methods 3 databases were screened until 17th of August 2020 for randomized controlled trials (RCTs). Two investigators selected studies, extracted data, and assessed risk of bias. Certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Weighted mean differences and 95% confidence intervals were calculated. Results 25 trials with a total of 2438 patients were included. LCD resulted in greater reductions in body weight (WMD −1.93 (95% CI −2.69, −1.16) kg; p&amp;lt;0.0001), triglycerides (WMD −26.13 (95% CI −23.45, −14.29) mg/dL; p&amp;lt;0.0001), TNF-alpha (WMD −0.5 (95% CI −0.82, −0.17) pg/mL; p=0.003) and IL-6 (95% CI −2.29, −0.59) pg/mL; p=0.0009) with a greater increase in HDL-C (WMD 3.73 (95% CI 2.92, 4.54) mg/dL; p&amp;lt;0.ehab724.24271) and LDL-C (WMD 5.07 (95% 1.9, 8.23) mg/dL; p=0.002) compared to low fat diet (LFD). There was no statistical difference in systolic (WMD 0.5 (95% CI −1.06, 2.05) mmHg; p=0.53) and diastolic blood pressure reduction (WMD −0.22 (95% CI −1.35, 0.91) mmHg; p=0.70). Conclusions Obese patients with other cardiovascular risk factors assigned to an LCD achieved greater reductions in weight loss and triglycerides levels with a greater increase in HDL-C levels and a more pronounced anti-inflammatory state than patients assigned to an LFD. Hence, low carbohydrate diets could be an alternative tool for cardiovascular protection in selected patients. Funding Acknowledgement Type of funding sources: None.

Technology interventions to support adherence to oral oncolytic agents: A systematic review and meta-analysis.

320 Background: The increase in patients receiving oral oncolytics requires oncology health care professionals to have processes and interventions that support patient adherence. Because adherence to oral oncolytics is a priority for achieving optimal outcomes, the ASCO QOPI Standards emphasize the need to assess for adherence at meaningful intervals as well as implement interventions to promote adherence. Technology-based interventions have the potential to assess and support adherence. The objective of this review is to evaluate the overall effect of any technology-based intervention, as well as compare the use of interactive technology rather than non-interactive technology to improve oral oncolytic adherence. This review will serve as the evidence base for a clinical practice guideline on oral oncolytic adherence. Methods: A medical librarian searched EMBASE, PubMed, and CINAHL for comparative studies published in English from January 2000 to May 2021. Two reviewers screened titles and abstracts, and eligible full text articles independently and in duplicate using Covidence. When possible, quantitative findings were pooled in a meta-analysis. Risk of bias assessment for randomized controlled trials was done using the Cochrane Collaboration risk-of-bias 2.0 tool and for observational studies, the ROBINS-I instrument was used. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Results: Out of 663 studies, we identified 14 as eligible for analysis. Of the six RCTs (n = 737) that compared any technological intervention to no intervention, there was some heterogeneity across interventions (e.g., text messaging, mobile app, computer program) and reported outcome measures for adherence, including adherence rates, relative dose intensity (RDI), and number of weeks adherent. Patients using any technology rather than no technology may have higher adherence rates (MD: 8.81; 95% CI: 3.82, 13.81); however, there may be little effect on RDI (MD: -0.01; 95% CI: -0.04, 0.02) and number of weeks adherent (MD: -0.70; 95% CI: -1.96, 0.56), respectively. One RCT (n = 444) reported on adolescents receiving interactive and non-interactive interventions. There may be little effect on adherence rates among patients receiving interactive technology interventions rather than non-interactive education intervention (MD: 1.5; 95% CI, −0.2, 3.2). Conclusions: Better systems of oral oncolytic care are needed to support patients and their caregivers. Technology-based interventions may improve medication adherence in cancer patients on oral oncolytics; however, we are uncertain about the impact on other measure of adherence or the superiority of interactive rather than non-interactive technology interventions. Due to inconsistency in the evidence, additional research in this area is recommended.

A few panel members dominated guideline development meeting discussions: Social network analysis

ObjectivesTo identify patterns of interactions that may influence guideline panels’ decision-making. Study Design and SettingSocial network analysis (SNA) to describe the conversation network in a guideline development meeting in United States. ResultsWe analyzed one two-day guideline panel meeting that included 20 members who developed a guideline using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The conversation pattern of the guideline panel indicated a well-connected network (density=0.59, clustering coefficient=0.82). GRADE topics on quality of evidence and benefits versus harms accounted for 46%; non-GRADE factors accounted for 30% of discussion. The chair, co-chair and methodologist initiated 53% and received 60% of all communications in the meeting; 42% of their communications occurred among themselves. SNA metrics (eigenvector, betweenness and closeness) indicated that these individuals also exerted highest influence on discussion, controlled information flow and were at the center of all communications. Members were more likely to continue previous discussion with the same individuals after both morning breaks (r=0.54, P<0.005; r=0.17, P=0.04), and after the last break on day 2 (r=0.44, P=0.015). ConclusionNon-GRADE factors such as breaks, and the members’ roles, affect guideline development more than previously recognized. Collectively, the chair, co-chair and methodologist dominated the discussion.

Pharmacological Treatments for Borderline Personality Disorder: A Systematic Review and Meta-Analysis.

BackgroundBorderline personality disorder (BPD) is a debilitating psychiatric disorder that affects 0.4–3.9% of the population in Western countries. Currently, no medications have been approved by regulatory agencies for the treatment of BPD. Nevertheless, up to 96% of patients with BPD receive at least one psychotropic medication.ObjectivesThe objective of this systematic review was to assess the general efficacy and the comparative effectiveness of different pharmacological treatments for BPD patients.MethodsWe conducted systematic literature searches limited to English language in MEDLINE, EMBASE, the Cochrane Library, and PsycINFO up to April 6, 2021, and searched reference lists of pertinent articles and reviews. Inclusion criteria were (i) patients 13 years or older with a diagnosis of BPD, (ii) treatment with anticonvulsive medications, antidepressants, antipsychotic medications, benzodiazepines, melatonin, opioid agonists or antagonists, or sedative or hypnotic medications for at least 8 weeks, (iii) comparison with placebo or an eligible medication, (iv) assessment of health-relevant outcomes, (v) randomized or non-randomized trials or controlled observational studies. Two investigators independently screened abstracts and full-text articles and graded the certainty of evidence based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. For meta-analyses, we used restricted maximum likelihood random effects models to estimate pooled effects.ResultsOf 12,062 unique records, we included 21 randomized controlled trials (RCTs) with data on 1768 participants. Nineteen RCTs compared pharmacotherapies with placebo; two RCTs assessed active treatments head-to-head. Out of 87 medications in use in clinical practice, we found studies on just nine. Overall, the evidence indicates that the efficacy of pharmacotherapies for the treatment of BPD is limited. Second-generation antipsychotics, anticonvulsants, and antidepressants were not able to consistently reduce the severity of BPD. Low-certainty evidence indicates that anticonvulsants can improve specific symptoms associated with BPD such as anger, aggression, and affective lability but the evidence is mostly limited to single studies. Second-generation antipsychotics had little effect on the severity of specific BPD symptoms, but they improved general psychiatric symptoms in patients with BPD.ConclusionsDespite the common use of pharmacotherapies for patients with BPD, the available evidence does not support the efficacy of pharmacotherapies alone to reduce the severity of BPD.RegistrationPROSPERO registration number, CRD42020194098.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-021-00855-4.

Peritoneal Dialysis Guidelines 2019 Part 2: Main Text (Position paper of the\xa0Japanese Society for Dialysis Therapy)

BackgroundThis article is a duplicated publication from the Japanese version of “2019 JSDT Guidelines for Peritoneal Dialysis” with permission from the Japanese Society for Dialysis Therapy (JSDT). This clinical practice guideline (CPG) was developed primarily by the Working Group on Revision of Peritoneal Dialysis (PD) Guidelines of the Japanese Society for Dialysis Therapy. Recently, the definition and creation process for CPGs have become far more rigorous; traditional methods and formats no longer adhere to current standards. To improve the reliability of international transmission of our findings, CPGs are created in compliance with the methodologies developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group. Part 2 of this PD guideline is the first CPG developed by our society that conforms to the GRADE approach.MethodsDetailed processes were created in accordance with the Cochrane handbook and the GRADE approach developed by the GRADE working group.ResultsClinical question (CQ)1: Is the use of renin-angiotensin system inhibitors (RAS inhibitors), such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), effective in PD patients?Recommendation: We suggest the usage of RAS inhibitors (ACEI and ARB) in PD patients (GRADE 2C).CQ2: Icodextrin or glucose solution: which is more useful as a dialysate among patients with PD?Recommendation: We suggest using icodextrin when managing body fluids in PD patients (GRADE 2C).CQ3: Is it better to apply or not apply mupirocin/gentamicin ointment to the exit site?Recommendation: We suggest not applying mupirocin/gentamicin ointment to the exit sites of PD patients (GRADE 2C).CQ4: Which surgical approach is more desirable when a PD catheter is placed, open surgery or laparoscopic surgery?No recommendation.CQ5: Which administration route of antibiotics is better in PD patients with peritonitis, intravenous or intraperitoneal?Recommendation: We suggest intraperitoneal administration of antibiotics in PD patients with peritonitis (GRADE 2C).Note: The National Insurance does not currently cover intraperitoneal administration.CQ6: Is peritoneal dialysis or hemodialysis better as the first renal replacement therapy in diabetic patients?No recommendation.ConclusionsIn the future, we suggest that society members construct their own evidence to answer CQs not brought up in this guideline, and thereby show the achievements of Japan worldwide.

European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment.

The optimal management of post-stroke cognitive impairment remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making around prevention, diagnosis, treatment and prognosis. These guidelines were developed according to ESO standard operating procedure and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and, where possible, meta-analyses of the literature, assessed the quality of the available evidence and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. There was limited randomised controlled trial evidence regarding single or multicomponent interventions to prevent post-stroke cognitive decline. Interventions to improve lifestyle and treat vascular risk factors may have many health benefits but a beneficial effect on cognition is not proven. We found no evidence around routine cognitive screening following stroke but recognise the importance of targeted cognitive assessment. We described the accuracy of various cognitive screening tests but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine nootropics or cognitive rehabilitation. There was limited evidence on the use of prediction tools for post-stroke cognitive syndromes (cognitive impairment, dementia and delirium). The association between post-stroke cognitive impairment and most acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on acute MRI brain may help predict cognitive outcomes. These guidelines have highlighted fundamental areas where robust evidence is lacking. Further, definitive randomised controlled trials are needed, and we suggest priority areas for future research.

"Closing the chasm" - guidelines bridge the gap from evidence to implementation.

"Closing the chasm" - guidelines bridge the gap from evidence to implementation.

European Stroke Organisation and European Society for Swallowing Disorders guideline for the diagnosis and treatment of post-stroke dysphagia.

Post-stroke dysphagia (PSD) is present in more than 50% of acute stroke patients, increases the risk of complications, in particular aspiration pneumonia, malnutrition and dehydration, and is linked to poor outcome and mortality. The aim of this guideline is to assist all members of the multidisciplinary team in their management of patients with PSD. These guidelines were developed based on the European Stroke Organisation (ESO) standard operating procedure and followed the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. An interdisciplinary working group identified 20 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence and wrote evidence-based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found moderate quality of evidence to recommend dysphagia screening in all stroke patients to prevent post-stroke pneumonia and to early mortality and low quality of evidence to suggest dysphagia assessment in stroke patients having been identified at being at risk of PSD. We found low to moderate quality of evidence for a variety of treatment options to improve swallowing physiology and swallowing safety. These options include dietary interventions, behavioural swallowing treatment including acupuncture, nutritional interventions, oral health care, different pharmacological agents and different types of neurostimulation treatment. Some of the studied interventions also had an impact on other clinical endpoints such as feedings status or pneumonia. Overall, further randomized trials are needed to improve the quality of evidence for the treatment of PSD.

Management of children and adolescents with bronchiectasis: summary of the ERS clinical practice guideline.

Bronchiectasis, characterised by chronic wet/productive cough with recurrent respiratory exacerbations and abnormal bronchial dilatation on computed tomography scans, remains an increasingly recognised but often neglected chronic pulmonary disorder in children and adolescents. An early diagnosis combined with optimal management offers the prospect, at least in some patients, of curing a condition previously considered irreversible. However, unlike in adults, until now no international paediatric guidelines existed. The recently published European Respiratory Society clinical practice guidelines for the management of children and adolescents with bronchiectasis attempts to address this clinical information gap. The guidelines were formulated by panel members comprised of experts from several relevant health fields, the European Lung Foundation and parents of children with bronchiectasis. Systematic reviews and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach guided the nature and strength of recommendations. The recommendations are grouped into clinically relevant topics: diagnosis, evaluating for underlying causes, defining exacerbations, management, systematic care, monitoring, reversibility and prevention. The guidelines seek to achieve: 1) optimal lung growth, 2) preserved lung function, 3) enhanced quality of life, 4) minimal exacerbations, 5) few or no complications, and 6) if possible, reversal of lung injury for each child/adolescent with bronchiectasis. This review presents example cases that highlight the recommendations of the clinical practice guidelines.Educational aimsThis article is intended for those involved in caring for children/adolescents with bronchiectasis. It aims to inform:Clinicians of the European Respiratory Society recommendations for the diagnosis and management of children/adolescents with bronchiectasis.Adolescents and parents of children/adolescents with bronchiectasis of these recommendations, so as to assist discussions with healthcare teams and help facilitate access to appropriate care.

Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics.

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

GRACE-recurrent low-risk chest pain: A user's guide.

GRACE-recurrent low-risk chest pain: A user's guide.

Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice Guideline.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 clinical practice guideline for the management of blood pressure (BP) in patients with chronic kidney disease (CKD) not receiving dialysis is an update of the KDIGO 2012 guideline on the same topic and reflects new evidence on the risks and benefits of BP-lowering therapy among patients with CKD. It is intended to support shared decision making by health care professionals working with patients with CKD worldwide. This article is a synopsis of the full guideline. The KDIGO leadership commissioned 2 co-chairs to convene an international Work Group of researchers and clinicians. After a Controversies Conference in September 2017, the Work Group defined the scope of the evidence review, which was undertaken by an evidence review team between October 2017 and April 2020. Evidence reviews were done according to the Cochrane Handbook. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to guide the development of the recommendations and rate the strength and quality of the evidence. Practice points were included to provide guidance when evidence was insufficient to make a graded recommendation. The guideline was revised after public consultation between January and March 2020. The updated guideline comprises 11 recommendations and 20 practice points. This synopsis summarizes key recommendations pertinent to the diagnosis and management of high BP in adults with CKD, excluding those receiving kidney replacement therapy. In particular, the synopsis focuses on recommendations for standardized BP measurement and a target systolic BP of less than 120 mm Hg, because these recommendations differ from some other guidelines.

Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including metaanalyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force’s questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations:• suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes;• suggest using a blood eosinophil cut-point ≥150 μL−1 to guide anti-IL-5 initiation in adult patients with severe asthma;• suggest considering specific eosinophil (≥260 μL−1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy;• suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4 – 5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies;• suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype;• suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels.These recommendations should be reconsidered as new evidence becomes available.

The GRADE approach, Part 2: Evidence to decision frameworksoutlining decision-making in health.

The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology provides a framework for assessing the certainty of the evidence and making recommendations. The Evidence to Decision Framework (EtD) is a transparent and structured system for formulating health recommendations. Once the problem is identified and the certainty of the evidence is assessed, EtD provides several criteria for formulating a recommendation. These criteria include the trade-off between benefits and harms, patients values and preferences, acceptability, feasibility, resource use, and impact on equity. The resulting recommendations may differ in strength (strong or weak) and direction (for or against). The process is transparent, allowing other users to adjust the framework of recommendations by modifying the criteria to fit the desired context through an adaptation-adoption process. Given the extensive information available on EtD and the GRADE methodology in general, this narrative review seeks to explain the main concepts involved in decision-making in health by using simplified and friendly descriptions, accompanied by practical examples, thus facilitating its understanding by inexperienced readers.

Canadian Rheumatology Association Recommendation for the Use of COVID-19 Vaccination for Patients With Autoimmune Rheumatic Diseases.

To develop guidance on the use of coronavirus disease 2019 (COVID-19) vaccines in patients with autoimmune rheumatic diseases (ARD). The Canadian Rheumatology Association (CRA) formed a multidisciplinary panel including rheumatologists, researchers, methodologists, vaccine experts, and patients. The panel used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Outcomes were prioritized according to their importance for patients and clinicians. Evidence from the COVID-19 clinical trials was summarized. Indirect evidence for non-COVID-19 vaccines in ARD was also considered. The GRADE evidence-to-decision (EtD) framework was used to develop a recommendation for the use of the 4 COVID-19 vaccines approved in Canada as of March 25, 2021 (BNT162b2, mRNA-1273, ChAdOx1, and Ad26.COV2.S), over 4 virtual panel meetings. The CRA guideline panel suggests using COVID-19 vaccination in persons with ARD. The panel unanimously agreed that for the majority of patients, the potential health benefits of vaccination outweigh the potential harms in people with ARDs. The recommendation was graded as conditional because of low or very low certainty of the evidence on the effects in the population of interest, primarily due to indirectness and imprecise effect estimates. The panel felt strongly that persons with autoimmune rheumatic diseases who meet local eligibility should not be required to take additional steps compared to people without ARDs to obtain their vaccination. Guidance on medications, implementation, monitoring of vaccine uptake, and research priorities are also provided. This recommendation will be updated over time as new evidence emerges, with the latest recommendation, evidence summaries, and EtD available on the CRA website.

Systematic reviews on interventions for COVID-19 have rarely graded the certainty of the evidence.

Numerous systematic reviews on coronavirus disease-19 (COVID-19) treatment have been developed to provide syntheses of the large volume of primary studies. However, the methodological quality of most of these reviews is questionable and the results provided may therefore present bias. To investigate how many systematic reviews on the therapeutic or preventive options for COVID-19 assessed the certainty of the evidence through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We conducted a sensitive search in MEDLINE (via PubMed) and included all systematic reviews that assessed any intervention for COVID-19. The systematic reviews included were examined to identify any planned and/or actual assessment using the GRADE approach (or absence thereof) regarding the certainty of the evidence. We included 177 systematic reviews and found that only 37 (21%; 37/177) assessed and reported the certainty of the evidence using the GRADE approach. This number reduced to 27 (16.2%; 27/167) when Cochrane reviews (n = 10), in which an evaluation using GRADE is mandatory, were excluded. Most of the systematic reviews on interventions relating to COVID-19 omitted assessment of the certainty of the evidence. This is a critical methodological omission that must not be overlooked in further research, so as to improve the impact and usefulness of syntheses relating to COVID-19.

Janus Kinase Inhibitors and Risk of Venous Thromboembolism: A Systematic Review and Meta-analysis

ObjectiveTo assess the risk of venous thromboembolism (VTE) in patients treated with Janus kinase (JAK) inhibitors in clinical trials. Patients and MethodsWe performed a literature search of Ovid MEDLINE and ePub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily; Ovid EMBASE; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus, from inception to December 4, 2019, for randomized, placebo-controlled trials with JAK inhibitors as an intervention and reported adverse events. Odds ratio with 95% CI was calculated to estimate the VTE risk using a random effects model. Two independent reviewers screened and extracted data. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess certainty in estimated VTE risk. ResultsWe included 29 trials (13,910 patients). No statistically significant association was found between use of JAK inhibitors and risk of VTE (odds ratio, 0.91; 95% CI, 0.57 to 1.47; P=.70; I2=0; low certainty because of serious imprecision). Results using Bayesian analysis were consistent with those of the primary analysis. Results of stratified and meta-regression analyses suggested no interaction by dose of drug, indication for treatment, or length of follow-up. ConclusionWe found insufficient evidence to support an increased risk of JAK inhibitor–associated VTE based on currently available data.

The GRADE approach, Part 1: how to assess the certainty of the evidence.

The certainty of the evidence for interventions is the certainty or confidence that the true effect is within a particular range or relative to a threshold. In the new pyramid of evidence, systematic reviews represent the magnifying glass through which this certainty is evaluated. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach arises in response to the existence of multiple evidence classification systems, and it offers a transparent and structured process to develop and present summaries of evidence considering its certainty and, in a second step, the strength of the recommendations that they inform. The GRADE process begins with an explicit question that includes all important and critical outcomes explicitly. The main domains used to assess the certainty of the evidence are risk of bias, inconsistency, indirectness of evidence, imprecision, and publication bias. The factors that can increase the certainty of the evidence are dose-response gradient, large magnitude of an effect, and effect of plausible residual confounding. Finally, the Summary of Findings tables summarize the process in a simplified way and with controlled language. This narrative reviews purpose is to address the GRADE approachs theoretical and practical underlying concepts in a simplified way and with practical examples.