The EULAR–OMERACT rheumatoid arthritis MRI reference image atlas: the metacarpophalangeal joints

This paper presents the metacarpophalangeal (MCP) joint magnetic resonance images of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas. The illustrations include synovitis in the MCP joints (OMERACT RA magnetic resonance imaging scoring system (RAMRIS), grades 0–3), bone oedema in the metacarpal head and the phalangeal base (grades 0–3), and bone erosion in the metacarpal head and the phalangeal base (grades 0–3, and examples of higher grades). The presented reference images can be used to guide scoring of MCP joints according to the OMERACT RA MRI scoring system

An introduction to the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas

This article gives a short overview of the development and characteristics of the OMERACT rheumatoid arthritis MRI scoring system (RAMRIS), followed by an introduction to the use of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas. With this atlas, MRIs of wrist and metacarpophalangeal joints of patients with rheumatoid arthritis can be scored for synovitis, bone oedema, and bone erosion, guided by standard reference images

The development of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas

Based on a previously developed rheumatoid arthritis MRI scoring system (OMERACT 2002 RAMRIS), the development team agreed which joints, MRI features, MRI sequences, and image planes would best illustrate the scoring system in an atlas. After collecting representative examples for all grades for each abnormality (synovitis, bone oedema, and bone erosion), the team met for a three day period to review the images and choose by consensus the most illustrative set for each feature, site, and grade. A predefined subset of images (for example, for erosion—all coronal slices through the bone) was extracted. These images were then re-read by the group at a different time point to confirm the scores originally assigned. Finally, all selected images were photographed and formatted by one centre and distributed to all readers for final approval

Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis

Objectives: Obesity has been proposed as a risk factor for refractory rheumatoid arthritis (RA). We evaluated the impact of obesity on achieving clinical and imaging definitions of low disease activity. Methods: This study evaluated 470 patients with RA from GO-BEFORE and GO-FORWARD randomised clinical trials. Included patients had blinded clinical disease activity measures and MRI at baseline, 24 and 52 weeks. Synovitis, osteitis and total inflammation scores were determined using the RA MRI scoring system. Multivariable logistic regression analyses compared odds of achieving Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) remission, low component measures, or low MRI inflammation measures at 24 weeks in patients with obesity versus no obesity. Results: At 24 weeks, patients with obesity were significantly less likely to achieve DAS28(CRP) remission (OR 0.47; 95% CI 0.24 to 0.92, p=0.03). In contrast, patients with obesity had similar odds of achieving low synovitis (OR 0.94; 95% CI 0.51 to 1.72, p=0.84) and inflammation scores (OR 1.16; 95% CI 0.61 to 2.22, p=0.64) and greater odds of achieving low osteitis scores (OR 2.06; 95% CI 1.10 to 3.84, p=0.02) versus normal weight patients. Conclusions: Patients with RA and obesity have lower rates of DAS28 remission but similar rates of low MRI activity compared with patients without obesity, suggesting that obesity and its associated comorbidities can bias clinical disease activity measures. Trial registration number: NCT00361335 and NCT00264550; Post-results

Automated Decision-Support System for Prediction of Treatment Responders in Acute Ischemic Stroke

MRI is widely used in the assessment of acute ischemic stroke. In particular, it identifies the mismatch between hypoperfused and the permanently damaged tissue, the PWI-DWI mismatch volume. It is used to help triage patients into active or supportive treatment pathways. COMBAT Stroke is an automated software tool for estimating the mismatch volume and ratio based on MRI. Herein, we validate the decision made by the software with actual clinical decision rendered. Furthermore, we evaluate the association between treatment decisions (both automated and actual) and outcomes. COMBAT Stroke was used to determine PWI-DWI mismatch volume and ratio in 228 patients from two European multi-center stroke databases. We performed confusion matrix analysis to summarize the agreement between the automated selection and the clinical decision. Finally, we evaluated the clinical and imaging outcomes of the patients in the four entries of the confusion matrix (true positive, true negative, false negative, and false positive). About 186 of 228 patients with acute stroke underwent thrombolytic treatment, with the remaining 42 receiving supportive treatment only. Selection based on radiographic criteria using COMBAT Stroke classified 142 patients as potential candidates for thrombolytic treatment and 86 for supportive treatment; 60% sensitivity and 29% specificity. The patients deemed eligible for thrombolytic treatment by COMBAT Stroke demonstrated significantly higher rates of compromised tissue salvage, less neurological deficit, and were more likely to experience thrombus dissolving and reestablishment of normal blood flow at 24 h follow-up compared to those who were treated without substantial PWI-DWI mismatch. These results provide evidence that COMBAT Stroke, in addition to clinical assessment, may offer an optimal framework for a fast, efficient, and standardized clinical support tool to select patients for thrombolysis in acute ischemic stroke

Biopharmaceutical implications of excipient variability on drug dissolution from immediate release products

Elucidating the impact of excipient variability on oral product performance in a biopharmaceutical perspective would be beneficial and allow excipient implementation on Quality by Design (QbD) approaches. The current study investigated the impact of varying viscosity of binders (hypromellose (HPMC)) and superdisintegrants (sodium starch glycolate (SSG)) and particle size distribution of lubricants (magnesium stearate (MgSt)) on the in vitro dissolution of a highly and a poorly soluble drug from immediate release formulations. Compendial (pharmacopoeia buffers) and biorelevant (media simulating the gastrointestinal fluids) media and the USP 2 and USP 4 apparatuses were used to assess the exerted excipient effects on drug dissolution. Real-time dissolution UV imaging provided mechanistic insights into disintegration and dissolution of the immediate release formulations. Varying the viscosity type of HPMC or SSG did not significantly affect drug dissolution irrespective of the compound used. Faster drug dissolution was observed when decreasing the particle size of MgSt for the highly soluble drug. The use of real-time dissolution UV Imaging revealed the influential role of excipient variability on tablet disintegration, as for the highly soluble drug, tablets containing high viscosity HPMC or low particle size MgSt disintegrated faster as compared to the control tablets while for the poorly soluble drug, slower tablet disintegration was observed when increasing the viscosity of the HPMC as compared to the control tablets. Changes in drug dissolution when varying excipients may be anticipated if the excipient change has previously affected drug solubility. The use of multivariate data analysis revealed the influential biopharmaceutical factors such as critical excipient types/properties, drug aqueous solubility, medium/hydrodynamic characteristics affecting the impact of excipient variability on in vitro drug dissolution.</p

Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis

Objectives: Obesity has been proposed as a risk factor for refractory rheumatoid arthritis (RA). We evaluated the impact of obesity on achieving clinical and imaging definitions of low disease activity. Methods: This study evaluated 470 patients with RA from GO-BEFORE and GO-FORWARD randomised clinical trials. Included patients had blinded clinical disease activity measures and MRI at baseline, 24 and 52 weeks. Synovitis, osteitis and total inflammation scores were determined using the RA MRI scoring system. Multivariable logistic regression analyses compared odds of achieving Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) remission, low component measures, or low MRI inflammation measures at 24 weeks in patients with obesity versus no obesity. Results: At 24 weeks, patients with obesity were significantly less likely to achieve DAS28(CRP) remission (OR 0.47; 95% CI 0.24 to 0.92, p=0.03). In contrast, patients with obesity had similar odds of achieving low synovitis (OR 0.94; 95% CI 0.51 to 1.72, p=0.84) and inflammation scores (OR 1.16; 95% CI 0.61 to 2.22, p=0.64) and greater odds of achieving low osteitis scores (OR 2.06; 95% CI 1.10 to 3.84, p=0.02) versus normal weight patients. Conclusions: Patients with RA and obesity have lower rates of DAS28 remission but similar rates of low MRI activity compared with patients without obesity, suggesting that obesity and its associated comorbidities can bias clinical disease activity measures. Trial registration number: NCT00361335 and NCT00264550; Post-results

Smart Demand for Improving Short-term Voltage Control on Distribution Networks

Smart grids must involve active roles from end users in order to be truly smart. The energy consumption has to be done in a flexible and intelligent manner, in accordance with the current conditions of the power system. Moreover, with the advent of dispersed and renewable generation, increasing customer integration to aid power system performance is almost inevitable. This study introduces a new type of smart demand side technology, denoted demand as voltage controlled reserve (DVR), to improve short-term voltage control, where customers are expected to play a more dynamic role to improve voltage control. The technology can be provided by thermostatically controlled loads as well as other types of load. This technology is proven to be effective in case of distribution systems with a large composition of induction motors, where the voltage presents a slow recovery characteristic due to deceleration of the motors during faults. This study presents detailed models, discussion and simulation tests to demonstrate the technical viability and effectiveness of the DVR technology for short-term voltage control.3872473

Baseline Objective Inflammation by Magnetic Resonance Imaging as a Predictor of Therapeutic Benefit in Early Rheumatoid Arthritis With Poor Prognosis

Objective: High magnetic resonance imaging (MRI )–detected inflammation is associated with greater progression and poorer outcomes in rheumatoid arthritis (RA ). This analysis aimed to determine if baseline MRI inflammation was related to clinical response and remission in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT ) study. Methods: AVERT was a phase III b, randomized, controlled trial with a 12‐month, double‐blind treatment period enrolling patients with early (≤2 years' duration), anti‐citrullinated peptide–positive methotrexate (MTX )‐naive RA . In this post hoc analysis, patients in the abatacept plus MTX (n = 114) and MTX (n = 111) arms with available MRI results were stratified into low and high baseline MRI inflammation groups based on previously developed cutoffs of synovitis and osteitis on unilateral hand–wrist contrast‐enhanced MRI . Simplified Disease Activity Index (SDAI ) remission (≤3.3), Clinical Disease Activity Index (CDAI ) remission (≤2.8), Boolean remission, and Disease Activity Score in 28 joints using the C‐reactive protein level (<2.6) were assessed. Results: Overall, 100 of 225 patients (44.4%) had high baseline MRI inflammation. In patients with high baseline MRI inflammation, a significantly greater proportion achieved remission at 12 months with abatacept plus MTX versus MTX across SDAI (45.1% versus 16.3%; P = 0.0022), CDAI (47.1% versus 20.4%; P = 0.0065), and Boolean indices (39.2% versus 16.3%; P = 0.0156). In patients with low baseline MRI inflammation, remission rates were not significantly different with abatacept plus MTX versus MTX (SDAI : 39.7% versus 32.3%; P = 0.4961). Conclusion: In seropositive, MTX ‐naive patients with early RA and presence of objectively measured high inflammation by MRI , indicating poor prognosis, remission rates were higher with abatacept plus MTX treatment versus MTX