Comparative efficacy and safety of alternative glucocorticoids regimens in patients with ANCA-associated vasculitis: a systematic review.

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

Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: a systematic review of non-randomised studies.

OBJECTIVE: To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, PsycINFO and CENTRAL from inception to 1 April 2020. STUDY SELECTION: Non-randomised studies reporting on harms of medical cannabis or cannabinoids in adults or children living with chronic pain with ≥4 weeks of follow-up. DATA EXTRACTION AND SYNTHESIS: A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data and assessed risk of bias. We used random-effects models for all meta-analyses and the Grades of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence. RESULTS: We identified 39 eligible studies that enrolled 12 143 adult patients with chronic pain. Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2% to 41.2%) among users of medical cannabis for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6% to 30.6%). Very low certainty evidence, however, indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are less common and each typically occur in fewer than 1 in 20 patients. We compared studies with <24 weeks and ≥24 weeks of cannabis use and found more adverse events reported among studies with longer follow-up (test for interaction p<0.01). Palmitoylethanolamide was usually associated with few to no adverse events. We found insufficient evidence addressing the harms of medical cannabis compared with other pain management options, such as opioids. CONCLUSIONS: There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events

Factors Associated with the Magnitude Of acUpuncture treatment effectS (FAMOUS): a meta-epidemiological study of acupuncture randomised controlled trials

Objective To identify factors and assess to what extent they impact the magnitude of the treatment effect of acupuncture therapies across therapeutic areas.Data source Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc, between 2015 and 2019.Study selection The inclusion criteria were trials with a total number of randomised patients larger than 100, at least one patient-important outcome and one of two sets of comparisons.Data analysis The potential independent variables were identified by reviewing relevant literature and consulting with experts. We conducted meta-regression analyses with standardised mean difference (SMD) as effect estimate for the dependent variable. The analyses included univariable meta-regression and multivariable meta-regression using a three-level robust mixed model.Results 1304 effect estimates from 584 acupuncture randomised controlled trials (RCTs) were analysed. The multivariable analyses contained 15 independent variables . In the multivariable analysis, the following produced larger treatment effects of large magnitude (&gt;0.4): quality of life (difference of adjusted SMDs 0.51, 95% CI 0.24 to 0.77), or pain (0.48, 95% CI 0.27 to 0.69), or function (0.41, 95% CI 0.21 to 0.61) vs major events. The following produced larger treatment effects of moderate magnitude (0.2–0.4): single-centred vs multicentred RCTs (0.38, 95% CI 0.10 to 0.66); penetration acupuncture vs non-penetration types of acupuncture (0.34, 95% CI 0.15 to 0.53); non-pain symptoms vs major events (0.32, 95% CI 0.12 to 0.52). The following produced larger treatment effects of small magnitude (&lt;0.2): high vs low frequency treatment sessions (0.19, 95% CI 0.03 to 0.35); pain vs non-pain symptoms (0.16, 95% CI 0.04 to 0.27); unreported vs reported funding (0.12, 95% CI 0 to 0.25).Conclusion Patients, clinicians and policy-makers should consider penetrating over non-penetrating acupuncture and more frequent treatment sessions when feasible and acceptable. When designing future acupuncture RCTs, trialists should consider factors that impact acupuncture treatment effects