The aim of this study is to provide updated guidance on when The Grading of Recommendations Assessment, Development and Evaluation (GRADE) users should consider rating down more than one level for imprecision using a minimally contextualized approach. Based on the first GRADE guidance addressing imprecision rating in 2011, a project group within the GRADE Working Group conducted iterative discussions and presentations at GRADE Working Group meetings to produce this guidance. GRADE suggests aligning imprecision criterion for systematic reviews and guidelines using the approach that relies on thresholds and confidence intervals (CI) of absolute effects as a primary criterion for imprecision rating (i.e., CI approach). Based on the CI approach, when a CI appreciably crosses the threshold(s) of interest, one should consider rating down two or three levels. When the CI does not cross the threshold(s) and the relative effect is large, one should implement the optimal information size (OIS) approach. If the sample size of the meta-analysis is far less than the OIS, one should consider rating down more than one level for imprecision. GRADE provides updated guidance for imprecision rating in a minimally contextualized approach, with a focus on the circumstances in which one should seriously consider rating down two or three levels for imprecision.

To provide practical principles and examples to help GRADE users make optimal choices regarding their ratings of certainty of evidence using a minimally or partially contextualized approach. Based on the GRADE clarification of certainty of evidence in 2017, a project group within the GRADE Working Group conducted iterative discussions and presentations at GRADE Working Group meetings to refine this construct and produce practical guidance. Systematic review and health technology assessment authors need to clarify what it is in which they are rating their certainty of evidence (i.e., the target of their certainty rating). The decision depends on the degree of contextualization (partially or minimally contextualized), thresholds (null, small, moderate or large effect threshold), and where the point estimate lies in relation to the chosen threshold(s). When the 95% confidence interval crosses multiple possible thresholds (i.e., including both large benefit and large harm), it is not worthwhile for authors to determine the target of certainty rating. GRADE provides practical principles to help systematic review and health technology assessment authors specify the target of their certainty of evidence rating.

Objective To explore values and preferences towards medical cannabis among people living with chronic pain. Design Mixed-methods systematic review. Data sources We searched MEDLINE, EMBASE and PsycINFO from inception to 17 March 2020. Study selection Pairs of reviewers independently screened search results and included quantitative, qualitative and mixed-methods studies reporting values and preferences towards medical cannabis among people living with chronic pain. Review methods We analysed data using meta-narrative synthesis (quantitative findings were qualitised) and tabulated review findings according to identified themes. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess certainty of evidence. Results Of 1838 initial records, 15 studies proved eligible for review. High to moderate certainty evidence showed that patient’s use of medical cannabis for chronic pain was influenced by both positive (eg, support from friends and family) and negative social factors (eg, stigma surrounding cannabis use). Most patients using medical cannabis favoured products with balanced ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD), or high levels of CBD, but not high THC preparations. Many valued the effectiveness of medical cannabis for symptom management even when experiencing adverse events related to concentration, memory or fatigue. Reducing use of prescription medication was a motivating factor for use of medical cannabis, and concerns regarding addiction, losing control or acting strangely were disincentives. Out-of-pocket costs were a barrier, whereas legalisation of medical cannabis improved access and incentivised use. Low to very low certainty evidence suggested highly variable values towards medical cannabis among people living with chronic pain. Individuals with pain related to life-limiting disease were more willing to use medical cannabis, and preferred oral over inhaled administration. Conclusions Our findings highlight factors that clinicians should consider when discussing medical cannabis. The variability of patients’ values and preferences emphasise the need for shared decision making when considering medical cannabis for chronic pain.

Universally acknowledged standards for trustworthy guidelines include the necessity to ground recommendations in patient values and preferences. When information is limited - which is typically the case - guideline panels often find it difficult to explicitly integrate patient values and preferences into their recommendations. Our objective was to develop and evaluate a framework for systematically navigating guideline panels in incorporating patient values and preferences in making recommendations. In the context of developing a guideline for colorectal cancer screening, we generated an initial framework for creating panel surveys to elicit guideline panelists' views of patient values and preferences and to inform panel discussions on recommendations. With further applications in guidelines of diverse topic areas, we dynamically refined the framework through iterative discussions and consensus. The finial framework consists five steps for creating and implementing panel surveys. The surveys can serve three objectives following from the quantitative information regarding patient values and preferences that guideline panels usually require. An accompanying video provides detailed instructions of the survery. The framework for creating and implementing panel surveys offers explicit guidance for guideline panels considering transparently and systematically incorporating patient values and preferences into guideline recommendations.

Purpose: To evaluate the toxicity of azithromycin in neonates, infants, and children. Methods: A systematic review was performed for relevant studies using Medline (Ovid), PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and International Pharmaceutical Abstracts. We calculated the pooled incidence of adverse drug reactions (ADRs) associated with azithromycin based on prospective studies (RCTs and prospective cohort studies) and analyzed the risk difference (RD) of ADRs between azithromycin and placebo or other antibiotics using meta-analysis of RCTs. Results: We included 133 studies with 4243 ADRs reported in 197,675 neonates, infants, and children who received azithromycin. The safety of azithromycin as MDA in pediatrics was poorly monitored. The main ADRs were diarrhea and vomiting. In prospective non-MDA studies, the most common toxicity was gastrointestinal ADRs (938/1967; 47.7%). The most serious toxicities were cardiac (prolonged QT or irregular heart beat) and idiopathic hypertrophic pyloric stenosis (IHPS). Compared with placebo, azithromycin did not show increased risk ADRs based on RCTs (risk difference − 0.17 to 0.07). The incidence of QT prolonged was higher in the medium-dosage group (10–30 mg/kg/day) than that of low-dosage group (≤ 10 mg/kg/day) (82.0% vs 1.2%). Conclusion: The safety of azithromycin as MDA needs further evaluation. The most common ADRs are diarrhea and vomiting. The risk of the most serious uncommon ADRs (cardiac-prolonged QT and IHPS) is unknown.

Objective To compare the efficacy and safety of alternative glucocorticoids (GCs) regimens as induction therapy for patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. Design Systematic review of randomised controlled trials (RCTs). Data sources Medline, Embase, Clinicaltrials.gov and Cochrane Central Register of Controlled Trials up to 10 April 2020. Study selection and review methods RCTs comparing two (or more) different dose regimens of GC in ANCA-associated vasculitis during induction of remission, regardless of other therapies. Pairs of reviewers independently screened records, extracted data and assessed risk of bias. Two reviewers rated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results Of 3912 records identified, the full texts of two records met the eligibility criteria. Due to the heterogeneity of population and dose regimen of GCs between the two trials, we descriptively presented the two trials and did not combine the results using meta-analysis. Compared with the standard-dose regimen, the reduced-dose regimen of GC may reduce death risk difference (RD): from −1.7% to −2.1%, low certainty), while not increasing end-stage kidney disease (ESKD) (RD: from −1.5% to 0.4%, moderate certainty). The reduced-dose regimen probably has an important reduction in serious infections at 1 year (RD: from −12.8% to −5.9%, moderate certainty). Reduced-dose regimen of GCs probably has trivial or no effect in disease remission, relapse or health-related quality of life (moderate to high certainty). Conclusions The reduced-dose regimen of GC may reduce death at the follow-up of 6 months to longer than 1 year and serious infections while not increasing ESKD. PROSPERO registration number CRD42020179087.