Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial.

Background: Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis.

Translating IL-6 biology into effective treatments.

In 1973, IL-6 was identified as a soluble factor that is secreted by T cells and is important for antibody production by B cells. Since its discovery more than 40 years ago, the IL-6 pathway has emerged as a pivotal pathway involved in immune regulation in health and dysregulation in many diseases. Targeting of the IL-6 pathway has led to innovative therapeutic approaches for various rheumatic diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still's disease, giant cell arteritis and Takayasu arteritis, as well as other conditions such as Castleman disease and cytokine release syndrome.

Comparative effectiveness of TNF inhibitors and tocilizumab with and without conventional synthetic disease-modifying antirheumatic drugs in a pan-European observational cohort of bio-naïve patients with rheumatoid arthritis.

Objectives: To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs).

Methods: Patients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan-Meier and Cox models, and CDAI over time by mixed models.

From Early Radiographic Knee Osteoarthritis to Joint Arthroplasty: Determinants of Structural Progression and Symptoms.

Objective: To assess structural progression in knees with no/mild radiographic osteoarthritis (OA) (i.e., Kellgren/Lawrence [K/L] grades 0-2) that will undergo knee replacement during a 5-year period; to assess differences in structural damage on magnetic resonance imaging (MRI) in knees with no/mild radiographic OA versus those with severe radiographic OA (i.

Comparison of radiographic joint space width and magnetic resonance imaging for prediction of knee replacement: A longitudinal case-control study from the Osteoarthritis Initiative.

Objective: To evaluate whether change in fixed-location measures of radiographic joint space width (JSW) and cartilage thickness by MRI predict knee replacement.

Methods: Knees replaced between 36 and 60 months' follow-up in the Osteoarthritis Initiative were each matched with one control by age, sex and radiographic status. Radiographic JSW was determined from fixed flexion radiographs and subregional femorotibial cartilage thickness from 3 T MRI.

Application of the OMERACT filter to measures of core outcome domains in recent clinical studies of acute gout.

Objective: To determine the extent to which instruments that measure core outcome domains in acute gout fulfill the Outcome Measures in Rheumatology (OMERACT) filter requirements of truth, discrimination, and feasibility.

Methods: Patient-level data from 4 randomized controlled trials of agents designed to treat acute gout and 1 observational study of acute gout were analyzed. For each available measure, construct validity, test-retest reliability, within-group change using effect size, between-group change using the Kruskall-Wallis statistic, and repeated measures generalized estimating equations were assessed.

Quantitative MRI measures of cartilage predict knee replacement: a case-control study from the Osteoarthritis Initiative.

Objective: Knee osteoarthritis commonly requires joint replacement, substantially reduces quality of life and increases healthcare utilisation and costs. This study aimed to identify whether quantitative measures of articular cartilage structure predict knee replacement, and to establish their utility as outcomes in clinical trials of disease-modifying therapy.

Methods: A nested case-control study was performed in Osteoarthritis Initiative participants, a multicentre observational cohort of 4796 participants with or at risk of knee osteoarthritis.

The single dose pharmacokinetic profile of a novel oral human parathyroid hormone formulation in healthy postmenopausal women.

Parathyroid hormone (PTH), currently the only marketed anabolic treatment for osteoporosis, is available as the full-length hormone, human PTH1-84, or as the human PTH1-34 fragment (teriparatide). Both must be administered as a daily subcutaneous (sc) injection. A new oral formulation of human PTH1-34 (PTH134) is being developed as a more convenient option for patients.

Greater rates of cartilage loss in painful knees than in pain-free knees after adjustment for radiographic disease stage: data from the osteoarthritis initiative.

Objective: To investigate whether rates of cartilage loss differ in knees with frequent baseline pain versus those without pain, after adjustment for radiographic osteoarthritis (OA) stage.

Methods: One knee in each of 718 Osteoarthritis Initiative participants was examined: 310 with calculated Kellgren/Lawrence (K/L) grade 2, 299 with calculated K/L grade 3, and 109 with calculated K/L grade 4. Twelve-month change in (subregional) cartilage thickness was assessed by magnetic resonance imaging.

1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: a novel series of potent calcium-sensing receptor antagonists.

Parathyroid hormone (PTH) is an effective bone anabolic agent. However, only when administered by daily sc injections exposure of short duration is achieved, a prerequisite for an anabolic response. Instead of applying exogenous PTH, mobilization of endogenous stores of the hormone can be envisaged.

Rapid and robust response of biochemical markers of bone formation to teriparatide therapy.

Teriparatide, a parathyroid hormone analogue, is a potent anabolic treatment for postmenopausal osteoporosis. Studies have shown that teriparatide induces large increases in biochemical markers of bone formation after 1 month of therapy followed by a delayed increase in bone resorption markers. The aims of this study were to (1) describe changes in bone turnover markers during 28 days of treatment with teriparatide; (2) identify the earliest time point by which most subjects showed a biochemical response to teriparatide; (3) identify potential biomarkers of positive bone response; (4) describe changes in bone turnover markers 4 weeks after stopping teriparatide.

Retentive memory of bacteria: Long-term regulation of dehalorespiration in Sulfurospirillum multivorans.

The gram-negative, strictly anaerobic epsilonproteobacterium Sulfurospirillum multivorans is able to gain energy from dehalorespiration with tetrachloroethene (perchloroethylene [PCE]) as a terminal electron acceptor. The organism can also utilize fumarate as an electron acceptor. Prolonged subcultivation of S.

Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice.

Objectives: Models for the development of new treatment options in vestibular schwannoma (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice.

Study Design And Methods: Both rat malignant schwannoma cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice.