Development of a clinical practice guideline for orthodontically induced external apical root resorption

Objectives: To develop a clinical practice guideline on orthodontically induced external apical root resorption (EARR), with evidence-based and, when needed, consensus-based recommendations concerning diagnosis, risk factors, management during treatment, and after-treatment care. Materials and methods: The Appraisal of Guidelines for Research and Evaluation II instrument and the Dutch Method for Evidence-Based Guideline Development were used to develop the guideline. Based on a survey of all Dutch orthodontists, we formulated four clinical questions regarding EARR. To address these questions, we conducted systematic literature searches in MEDLINE and Embase, and we performed a systematic literature review. The quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. After discussing the evidence, a Task Force formulated considerations and recommendations. The drafted guideline was sent for comments to all relevant stakeholders. Results: Eight studies were included. The quality of evidence (GRADE) was rated as low or very low. Only the patient-related risk factors, 'gender' and 'age', showed a moderate quality of evidence. The Task Force formulated 13 final recommendations concerning the detection of EARR, risk factors, EARR management during treatment, and after-treatment care when EARR has occurred. Stakeholder consultation resulted in 51 comments on the drafted guideline. After processing the comments, the final guideline was authorized by the Dutch Association of Orthodontists. The entire process took 3 years. Limitations: The quality of the available evidence was mainly low, and patient-reported outcome measures were lacking. Conclusions/implications: This clinical practice guideline allows clinicians to respond to EARR based on current knowledge, although the recommendations are weak due to low-quality evidence. It may reduce variation between practices and aid in providing patients appropriate information

Relationship between the type I interferon signature and the response to rituximab in rheumatoid arthritis patients

To analyze the relationship between the type I interferon (IFN) signature and clinical response to rituximab in rheumatoid arthritis (RA) patients. Twenty RA patients were treated with rituximab (cohort 1). Clinical response was defined as a decrease in the Disease Activity Score evaluated in 28 joints (DAS28) and as a response according to the European League Against Rheumatism (EULAR) criteria at week 12 and week 24. The presence of an IFN signature was analyzed in peripheral blood mononuclear cells by measuring the expression levels of 3 IFN response genes by quantitative polymerase chain reaction analysis. After comparison with the findings in healthy controls, patients were classified as having an IFN high or an IFN low signature. The data were confirmed in a second independent cohort (n = 31). Serum IFNα bioactivity was analyzed using a reporter assay. In cohort 1, there was a better clinical response to rituximab in the IFN low signature group. Consistent with these findings, patients with an IFN low signature had a significantly greater reduction in the DAS28 and more often achieved a EULAR response at weeks 12 and 24 as compared with the patients with an IFN high signature in cohort 2 versus cohort 1. The pooled data showed a significantly stronger decrease in the DAS28 in IFN low signature patients at weeks 12 and 24 as compared with the IFN high signature group and a more frequent EULAR response at week 12. Accordingly, serum IFNα bioactivity at baseline was inversely associated with the clinical response, although this result did not reach statistical significance. The type I IFN signature negatively predicts the clinical response to rituximab treatment in patients with RA. This finding supports the notion that IFN signaling plays a role in the immunopathology of R