BACKGROUND Chronic pain is a common condition in children with juvenile idiopathic arthritis (JIA), affecting their ability to participate in physical activity, a necessary and integral part of a child’s growth and maturation. Resistance training specifically displays a paucity of research in children with JIA, and could potentially be a beneficial form of exercise training for this population. The purpose of this study was to determine the safety, feasibility, and effects of a six week resistance training program on pain in children with JIA. METHODS Seven JIA patients (8-18 years) participated in a home-based, three days per week exercise training program. Pain was measured using an electronic pain diary (PinGo©) for Android tablets. Participants answered questions initially a week prior to training, once a day on non-exercise days and three times a day (before exercise, after exercise, and end of day) on exercise days for a total of seven weeks. Secondary outcome measures included muscle size, muscle strength, and functional ability, measured at baseline and following the 6 week exercise program. Statistical analyses included attaining the average number of exercise sessions completed, pain changes over the seven weeks (averaged over the initial week and then biweekly) via repeated measures ANOVA, dependent t tests between before and after exercise pain intensity and affect, and dependent t tests between secondary outcomes. RESULTS Seven participants completed an average of 13.0 ± 3.6 exercise sessions out of a possible 18. The repeated measures ANOVA revealed no significant differences between pain scores over the seven weeks within each individual (p>0.05). When all participants were pooled dependent t tests before and after exercise showed no differences in pain intensity or pain affect (p>0.05). Secondary measures revealed a significant difference between vastus lateralis thickness before compared to after training (p<0.05). CONCLUSIONS The results of this study suggest that a 6 week home-based resistance training program was tolerable in children with JIA and did not cause a clinically significant increase in pain or any other adverse events. The uniqueness of this exercise program was that it was home-based, allowing children to undertake this emerging form of healthcare within their home environment. As well, the training program was able to significantly improve aspects of fitness in this population. Further research of resistance training in children with JIA is necessary to attain definitive results of its effects and optimal levels of resistance exercise in this population.

L’arthrite juvénile idiopathique (AJI) est un groupe hétérogène de rhumatismes inflammatoires chroniques affectant les enfants de moins de 16 ans. Cette atteinte inflammatoire d’origine inconnue est caractérisée par une arthrite persistant plus de 6 semaines en l’absence de traitements.Afin de mettre en évidence des mécanismes impliqués dans la physiopathologie de l’AJI, une inclusion de patients atteints d’une autre forme d’arthrite juvénile, à savoir l’arthrite septique, a été effectuée. En parallèle, des études comparatives entre le sang périphérique (SP) et le liquide synovial (LS) des patients atteints d’AJI ont été réalisées afin de rechercher des mécanismes spécifiques aux perturbations articulaires. Un intérêt particulier a été porté sur les sous-populations de monocytes et de cellules dendritiques (DCs) ainsi que les profils d’expression des microARNs (miARNs) dans le sang périphérique et le LS des patients. Ces différents marqueurs biologiques ont été choisis car ils jouent un rôle majeur à la fois dans la régulation de l’inflammation et la pathogénèse des maladies inflammatoires.L’analyse de l’expression des miARNs par une approche de séquençage à haut débit suivie d’une validation par RT-qPCR a mis en évidence des miARNs dérégulés de façon spécifique dans l’AJI par rapport à l’AS. De plus, la caractérisation phénotypique des sous-populations de cellyles myéloïdes a montré une accumulation et une activation cellulaire propre à l’AJI. Dans l’ensemble, ce projet m’a permis d’identifier différents acteurs cellulaires et moléculaires pouvant être impliqués dans la physiopathologie de l’AJI. / Juvenile idiopathic arthritis (JIA) is a heterogeneous group of chronic inflammatory rheumatism affecting children under 16 years of age. This inflammatory disorder of unknown origin is characterized by arthritis lasting more than 6 weeks in the absence of treatments.In order to highlight mechanisms involved in the pathophysiology of JIA, an inclusion of patients suffering from septic arthritis, another form of juvenile arthritis, was performed. In parallel, comparative studies between the peripheral blood (PB) and the synovial fluid (SF) of patients with JIA were carried out in order to search for mechanisms specific of joint disturbances.We focused on monocytes and dendritic cells (DCs) subsets as well as the expression patterns of microRNAs (miRNAs) in the PB and SF of patients. These different biological markers are known to play a major role both in the regulation of inflammation and the pathogenesis of inflammatory diseases.Analysis of miRNA expression by a high-throughput sequencing approach followed by RT-qPCR validation revealed specifically deregulated miRNAs in JIA compared to AS. In addition, the phenotypic characterization of myeloid cell subpopulations showed an accumulation and activation profile specific of JIA cells. Overall, this project allowed me to identify different cellular and molecular actors that might be involved in the pathophysiology of JIA.

This research was inspired by a need to discover more refined technologies for imaging growing joints to facilitate research in childhood arthritis, which is among the most common chronic conditions of childhood. The objective of this project was to develop and test a new technology for imaging growing joints using diffraction enhanced imaging (DEI) combined with computed tomography (CT) using a synchrotron radiation source. DEI is a modality that derives contrast from x-ray refraction, extinction (an extreme form of scatter rejection), and absorption (as in conventional radiography). The ability to add to an image’s contrast from the refraction of x-rays, rather than that solely from absorption, generates more detailed visualization of soft tissue and of interfaces between tissues. Additionally, refraction-based imaging allows reduction of absorbed radiation dose by the sample tissue. For this research, stifle joints from four-week piglet joints were imaged by DEI-CT using the BioMedical Imaging and Therapy (BMIT) beamline at the Canadian Light Source (CLS) synchrotron facility. This new modality for imaging growing joints incorporated a novel feedback control to maintain precise alignment of the analyzer crystal, which is used to re- diffract the beam that passes through the object, throughout the scanning procedure. Results showed that high-resolution DEI-CT provided three-dimensional images of the bone and soft tissue of growing joints at a resolution on the order of microns. Fine detail within and between all joint structures and tissues, including striking detail of cartilage vasculature, a iii characteristic of growing but not mature joints, was demonstrated. This report documents for the first time that DEI combined with CT and using a synchrotron radiation source can generate more detailed images of intact, growing joints than is currently available from conventional imaging modalities. The development of this high resolution imaging system, which provides excellent contrast for both hard and soft tissues, fills an important gap in the suite of imaging modalities available for joint research, particularly during growth.

L'arthrite juvénile idiopathique (AJI) est une des maladies chroniques les plus prévalentes chez les adolescents au Canada (Levy & Twilt, 2017). Son diagnostic repose en grande partie sur l'examen musculosquelettique pédiatrique (MSQp). Or, il semble exister un besoin de développer de nouvelles stratégies pour son enseignement (Foster & Rapley, 2010), comme en démontre d’une part la faible confiance de plusieurs médecins de première ligne en leurs capacités à la réaliser (Jandial, Myers, Wise, & Foster, 2009), et d’autre part le fait que l’enseignement de cet examen est bien souvent absent du curriculum de base des facultés de médecine (Jandial, Rapley, & Foster, 2009). Chez les adultes, plusieurs programmes engageant des patients formateurs avec arthrite chronique ont été développés et ont démontré des bénéfices tant pour les apprenants que pour les patients eux-mêmes (Hassell, 2012). À notre connaissance, ce type de programme n'existe pas actuellement pour la population adolescente avec arthrite juvénile ou autre maladie chronique. Nous proposons de développer un programme de patients formateurs engageant des adolescents avec AJI pour permettre 1) de répondre à un besoin de formation spécifique et 2) d’inclure la perspective d’un groupe de patients sous-représentés en éducation médicale. Nous avons donc comme objectif principal d'explorer les facteurs et processus à prendre en considération dans la création, la mise en oeuvre éventuelle et l'évaluation de ce futur programme. En vue de répondre à cet objectif, nous avons adopté une méthodologie qualitative. Des entrevues semi-structurées ont été effectuées avec 19 adolescents atteints d'arthrite juvénile provenant de deux centres tertiaires pédiatriques canadiens. Le premier des trois articles composant cette thèse s'attarde à explorer les perceptions des adolescents avec arthrite juvénile sur leurs habiletés à enseigner en tant que patient formateur. Il apparaît que les adolescents se sentent habiletés à réaliser ce rôle essentiellement parce qu’ils reconnaissent avoir acquis un savoir expérientiel du fait de vivre avec leur maladie. Ces derniers souhaitent par ailleurs aller au-delà de l'enseignement de l'examen MSQp et désirent incorporer l'enseignement de leur expérience de la maladie ainsi que des aspects de la communication. L'importance d'intégrer ces messages éducatifs au futur programme afin qu'il reflète la vision des adolescents est discutée. Une fois la question de savoir « comment » les adolescents avec arthrite juvénile souhaitent s'engager comme patient formateur, nous nous intéressons à savoir « pourquoi » ils désireraient faire partie d'un tel programme. Notre deuxième article explore donc les diverses sources de motivation des adolescents à s'engager comme patient formateur à travers la lentille du cadre conceptuel d'auto-détermination (Ryan & Deci, 2000). Des thèmes associés à la motivation intrinsèque (s'aider soi-même, vivre une expérience de socialisation) et extrinsèque à régulation intégrée (défendre la cause, aider les autres) sont identifiés. Des facilitateurs et obstacles à l'engagement des adolescents sont aussi explorés. La pertinence d'incorporer ces divers éléments dans le développement du programme afin de s'assurer d'un bon niveau d'engagement des participants est discuté. Dans notre troisième et dernier article, nous proposons un cadre générique de développement et d'évaluation des programmes en sciences de la santé basé sur une revue de différents modèles dans la discipline plus large de l'évaluation de programme. Nous discutons par la suite de l'application de ce cadre spécifiquement au programme proposé de patients formateurs avec arthrite juvénile, et délimitons des facteurs et processus à prendre en compte lors de sa création, sa mise en oeuvre et son évaluation future, en lien avec les résultats obtenus. Nous concluons par une discussion sur les implications éducatives de cette étude doctorale et élaborons des pistes de recherche futures. / Juvenile idiopathic arthritis (JIA) is one of the most prevalent chronic diseases among adolescents in Canada (Levy & Twilt, 2017). Its diagnosis is largely based on the pediatric musculoskeletal examination (pMSK). However, there seems to be a need to develop new strategies for the pMSQ exam teaching (Foster & Rapley, 2010). In adults, several programs involving patient educators with chronic arthritis have been developed and have shown benefits for both learners and patients themselves (Hassell, 2012). To our knowledge, this type of program does not currently exist for the adolescent population with juvenile arthritis, or with other chronic illness. Therefore, we propose to develop a patient educator program engaging adolescents with JIA with the aims to 1) respond to a specific identified training need and 2) include the perspective of a group of underrepresented patients in medical education. Our main objective is to explore factors and processes that need to be considered in the creation, eventual implementation and evaluation of this future program. In order to meet this objective, we adopted a qualitative methodology. Semi-structured interviews were conducted with 19 adolescents with juvenile arthritis from two Canadian pediatric tertiary centers. The first article of this thesis focuses on exploring adolescents with JIA perceptions of their ability to teach as a patient educator. It appears that adolescents feel empowered to perform this role primarily because they recognize that they have acquired experiential knowledge by living with their illness. Teens also want to go beyond the MSQp exam teaching and incorporate teaching of their experience of the disease as well as aspects of communication. The importance of integrating these educational messages into the future curriculum to reflect adolescents' visions is discussed. Following the question of 'how' adolescents with juvenile arthritis envisage to be actively involved as patient educators, we then explore in more details 'why' they would 6 like to be part of such a program. Our second article therefore explores the various sources of motivation for adolescents to engage as patient educators through the lens of the self-determination conceptual framework (Ryan & Deci, 2000). Themes associated with intrinsic motivation (helping oneself, experiencing socialization) and extrinsic motivation (advocating for the cause, helping others) are identified. Facilitators and barriers to adolescents' engagement are also explored. The relevance of incorporating these various elements in the program development to ensure an adequate level of participants' commitment is discussed. In our third and final article, we propose a generic framework for curriculum development and evaluation in health sciences based on a review of different models in the broader discipline of program evaluation. We then discuss the application of this framework specifically to the proposed adolescents with juvenile arthritis patient educator program and delineate factors and processes that need to be considered in its creation, implementation, and future evaluation. We conclude with a discussion of this doctoral study's educational implications and development of future lines of research.