Best practices for MRI systematic reviews and metaâ analyses

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149543/1/jmri26198.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149543/2/jmri26198_am.pd

A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial)

To assess the efficacy of the interleukin 1 receptor antagonist anakinra in systemic-onset juvenile idiopathic arthritis (SJIA).status: publishe

Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn's Disease: A Post Hoc Analysis From the CALM Study

Abstract Background CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) <4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP <5 mg/L or ≥5 mg/L and FC <250 μg/g or ≥250 μg/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using χ 2 test. Results The proportion of patients who achieved the primary end point CDEIS <4 and no deep ulcers was significantly greater for those with FC <250 µg/g (74%; P < 0.001), with an additive effect for CRP <5 mg/L. The association of FC <250 µg/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin <250 µg/g, CRP <5 mg/L, and CDAI <150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS <4 and no deep ulcers 48 weeks after randomization. Conclusion This post hoc analysis of CALM demonstrated that a cutoff of FC <250 µg/g is a useful surrogate marker for mucosal healing in CD

I-CARE, a European prospective cohort study assessing safety and effectiveness of biologics in inflammatory bowel disease

There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with for anti-tumor necrosis factor and other biologics monotherapy as well as in combination with immunomodulators.I-CARE was designed as a European prospective longitudinal observational multicenter cohort study, to include patients with a diagnosis of Crohn's disease, ulcerative colitis or IBD unclassified established at least 3 months prior to enrollment.A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6,169 (60.4%) patients with Crohn's disease, 3,853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving AZA/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one quarter of patients (26.8%) underwent prior IBD related surgery. Sixty-six % of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion, and 1.1% had a history of colonic, esophageal or uterine cervix high-grade dysplasia.I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients

Immunodeficiency, auto-inflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency

We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic auto-inflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1, a component the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin-1β (IL-1β) was compromised in the patients’ fibroblasts. By contrast, the patients’ mononuclear leukocytes, particularly monocytes, were hyperresponsive to IL-1β. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1β responses thus differed between cell types, consistent with the unique association of auto-inflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB-dependent IL-1β responses differently in different cell types

Preferred reporting items for journal and conference abstracts of systematic reviews and meta-analyses of diagnostic test accuracy studies (PRISMA-DTA for Abstracts):checklist, explanation, and elaboration

For many users of the biomedical literature, abstracts may be the only source of information about a study. Hence, abstracts should allow readers to evaluate the objectives, key design features, and main results of the study. Several evaluations have shown deficiencies in the reporting of journal and conference abstracts across study designs and research fields, including systematic reviews of diagnostic test accuracy studies. Incomplete reporting compromises the value of research to key stakeholders. The authors of this article have developed a 12 item checklist of preferred reporting items for journal and conference abstracts of systematic reviews and meta-analyses of diagnostic test accuracy studies (PRISMA-DTA for Abstracts). This article presents the checklist, examples of complete reporting, and explanations for each item of PRISMA-DTA for Abstracts

Belgian rare diseases plan in clinical pathology : identification of key biochemical diagnostic tests and establishment of reference laboratories and financing conditions

BackgroundOne objective of the Belgian Rare Diseases plan is to improve patients' management using phenotypic tests and, more specifically, the access to those tests by identifying the biochemical analyses used for rare diseases, developing new financing conditions and establishing reference laboratories.MethodsA feasibility study was performed from May 2015 until August 2016 in order to select the financeable biochemical analyses, and, among them, those that should be performed by reference laboratories. This selection was based on an inventory of analyses used for rare diseases and a survey addressed to the Belgian laboratories of clinical pathology (investigating the annual analytical costs, volumes, turnaround times and the tests unavailable in Belgium and outsourced abroad). A proposal of financeable analyses, financing modalities, reference laboratories' scope and budget estimation was developed and submitted to the Belgian healthcare authorities. After its approval in December 2016, the implementation phase took place from January 2017 until December 2019.ResultsIn 2019, new reimbursement conditions have been published for 46 analyses and eighteen reference laboratories have been recognized. Collaborations have also been developed with 5 foreign laboratories in order to organize the outsourcing and financing of 9 analyses unavailable in Belgium.ConclusionsIn the context of clinical pathology and rare diseases, this initiative enabled to identify unreimbursed analyses and to meet the most crucial financial needs. It also contributed to improve patients' management by establishing Belgian reference laboratories and foreign referral laboratories for highly-specific analyses and a permanent surveillance, quality and financing framework for those tests