Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes

The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 ± 3.0% for global cartilage and -5.5 ± 4.3% for the medial compartment at 12 months, and -5.7 ± 4.4% and -8.3 ± 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression

The challenge of indication extrapolation for infliximab biosimilars

AbstractA biosimilar is intended to be highly similar to a reference biologic such that any differences in quality attributes (i.e., molecular characteristics) do not affect safety or efficacy. Achieving this benchmark for biologics, especially large glycoproteins such as monoclonal antibodies, is challenging given their complex structure and manufacturing. Regulatory guidance on biosimilars issued by the U.S. Food and Drug Administration, Health Canada and European Medicines Agency indicates that, in addition to a demonstration of a high degree of similarity in quality attributes, a reduced number of nonclinical and clinical comparative studies can be sufficient for approval. Following a tiered approach, clinical studies are required to address concerns about possible clinically significant differences that remain after laboratory and nonclinical evaluations. Consequently, a critical question arises: can clinical studies that satisfy concerns regarding safety and efficacy in one condition support “indication extrapolation” to other conditions? This question will be addressed by reviewing the case of a biosimilar to infliximab that was approved recently in South Korea, Europe, and Canada for multiple indications through extrapolation. The principles discussed should also apply to biosimilars of other monoclonal antibodies that are approved to treat multiple distinct conditions

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration

Background JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. Methods In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. Results We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. Conclusion The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.Peer reviewe

Évaluation quantitative de la composition minéralogique de l'amiante chrysotile par thermogravimétrie

L'investigation de l'utilisation de l'analyse thermogravimétrique (ATG-DTG) comme méthode routinière de la détermination de la composition minéralogique de l'amiante chrysotile a été effectuée sur 9 grades d'origines diverses. À partir des résultats de l'analyse chimique et de l'utilisation adéquate des paramètres expérimentaux (masse, taux de chauffe, type de creuset et atmosphère de balayage}, il a été possible d'identifier et de quantifier la brucite Mg(OH)2, la calcite Caco3 et le chrysotile Mg3Si2O5(0H)4. Cependant, les recherches les plus approfondies n'ont pu permettre une caractérisation valable de la magnésite MgC03. Les raisons de ces difficultés ont été mises en évidence par l'analyse des gaz d'évolution (EGA) qui a confirmé la décomposition simultanée de ce carbonate et du chrysotile. Enfin, une banque de données et un logiciel d'analyse thermique (acquisition, traitement graphique et mise en mémoire des courbes expérimentales)ont été créés dans le but d'améliorer la reproductibilité des analyses et de faciliter l’interprétation des observations

Évaluation quantitative de la composition minéralogique de l'amiante chrysotile par thermogravimétrie

L'investigation de l'utilisation de l'analyse thermogravimétrique (ATG-DTG) comme méthode routinière de la détermination de la composition minéralogique de l'amiante chrysotile a été effectuée sur 9 grades d'origines diverses. À partir des résultats de l'analyse chimique et de l'utilisation adéquate des paramètres expérimentaux (masse, taux de chauffe, type de creuset et atmosphère de balayage}, il a été possible d'identifier et de quantifier la brucite Mg(OH)2, la calcite Caco3 et le chrysotile Mg3Si2O5(0H)4. Cependant, les recherches les plus approfondies n'ont pu permettre une caractérisation valable de la magnésite MgC03. Les raisons de ces difficultés ont été mises en évidence par l'analyse des gaz d'évolution (EGA) qui a confirmé la décomposition simultanée de ce carbonate et du chrysotile. Enfin, une banque de données et un logiciel d'analyse thermique (acquisition, traitement graphique et mise en mémoire des courbes expérimentales)ont été créés dans le but d'améliorer la reproductibilité des analyses et de faciliter l’interprétation des observations

Stress and Fatigue on Educators in Residential Treatment Centres: How does this impact restraint & seclusion?

Les mesures de contention et d’isolement (MCI) en centre de réadaptation pour jeunes en difficultés sont controversées et employées sur une base régulière. Bien que l’utilisation des MCI soit balisée par des lois, le stress ou la fatigue de l’éducateur est susceptible de teinter le processus décisionnel menant à leur application. Considérant les effets iatrogènes physiques et psychologiques pour le jeune et l’intervenant liés à cette pratique, il est pertinent d’approfondir la recherche à ce sujet. L’objectif de cette étude longitudinale prospective est d’examiner les liens associatifs entre le niveau de stress perçu, de fatigue aiguë, de fatigue chronique ainsi que la récupération des éducateurs et leurs recours aux contentions et isolements. Les 155 éducateurs composant l’échantillon final ont rempli des questionnaires à huit reprises sur une base hebdomadaire. Les données ont fait l’objet d’analyses en décalage croisé. Aucune des hypothèses n’a été confirmée. Les résultats ont toutefois révélé que le stress de l’éducateur était associé négativement aux MCI au temps subséquent. De plus, l’utilisation de MCI était associée positivement avec la fatigue aigüe, négativement avec la récupération et positivement à une utilisation de MCI dans les semaines suivantes.Restraints and seclusions (R&S) in youth residential treatment centers (RTCs) are used regularly even though their use is controversial. Although R&S are meant to be used within a legal framework, their application in the day-to-day operations can be influenced by the caregiver’s stress and fatigue. Considering the physical and psychological iatrogenic effects of R&S for both youth and educators, it is highly relevant to widen the current knowledge on the matter. Our objective was to examine, via a prospective longitudinal design, the associative links between the level of perceived stress, acute fatigue, chronic fatigue and intershift recovery on the use of R&S in youth RTCs. Our sample of 155 educators working in RTCs completed eight weekly diaries and cross-lagged analyses were conducted. None of the hypothesis were confirmed. However, results showed that the educator’s stress was negatively associated with R&S at a later time. Moreover, the use of R&S was positively associated with acute fatigue, negatively with recovery and positively with a subsequent use of R&S