Identifying subgroups of osteoarthritis: implications for prognosis and treatment

Osteoarthritis (OA) is one of the most prevalent and disabling chronic diseases worldwide. As yet, no therapies have been approved for structural modification or proven to be highly effective for symptomatic relief. There is an extraordinary interpatient variability in OA, which may be associated with the difficulties to identify “one-size-fits-all” treatments. The aim of this thesis was to elucidate diverse aspects related to OA heterogeneity with a focus on prognosis and treatment. In Chapter two, we systematically reviewed the literature and identified the key phenotypic characteristics that may be relevant for OA phenotyping for use in future studies. In Chapter three, we used a data-driven statistical approach to investigate heterogeneity in the rate of knee cartilage thickness loss over two years and found three subgroups: stable cartilage thickness, moderate and substantial cartilage loss. There was a strong association of the subgroups with clinical outcomes. A prediction model was developed to identify those in the cartilage loss subgroups. The study in Chapter four investigated MRI-based subgroups in early radiographic knee OA. We found four subgroups with potential differences in the contribution of each joint tissue to OA initiation and with differences in OA risk factors. The subsequent two chapters examined heterogeneity in thumb base OA. Chapter five showed that concomitant presence of interphalangeal joint pain (digital or thumb) and/or erosive OA were associated with worse hand function in persons with thumb base OA. Chapter six was a pre-planned subgroup analysis of a thumb base OA trial. In this analysis, lower joint subluxation was associated with greater efficacy of a combined conservative intervention compared to control on pain and patient global assessment. This thesis provides new insights into the importance of better phenotyping OA patients. The findings in this thesis may be used in future research to: 1) define a comprehensive classification of knee OA phenotypes; 2) identify individuals at higher risk of progression for inclusion in clinical trials 24 investigating disease-modifying therapies; 3) personalize treatment for individuals with thumb base OA and greater joint subluxation; 4) better understand knee OA populations that would be suitable for targeted therapies

Alterações eletrocardiográficas em dermatomiosite e polimiosite

ResumoIntroduçãoAcometimento cardíaco nas miopatias inflamatórias é frequente. Eletrocardiograma (ECG) pode mostrar indícios desse acometimento e suas alterações devem ser bem conhecidas e descritas.ObjetivosDevido à escassez de trabalhos na literatura, analisamos as alterações de ECG em pacientes com dermatomiosite (DM) e polimiosite (PM) e as comparamos com um grupo controle.MétodosEste estudo transversal comparou ECGs de 86 indivíduos sem doenças reumatológicas (controles) com 112 pacientes (78 DM e 34 PM), de 2010 a 2013. Também comparamos os ECGs entre DM e PM.ResultadosCaracterísticas demográficas, comorbidades e alterações de ECG foram semelhantes entre controles e pacientes (p>0,05), exceto pela maior frequência de sobrecarga de ventrículo esquerdo (SVE) nos pacientes (10,7% vs. 1,2%; p=0,008). Características demográficas, comorbidades, manifestações clínicas e laboratoriais também foram semelhantes entre os grupos PM e DM, exceto por lesões cutâneas apenas em pacientes com DM. Um terço dos pacientes apresentou alterações de ECG, que foram mais prevalentes em PM do que em DM (50% vs. 24,4%, p=0,008). Sobrecarga de câmaras esquerdas (SCE), distúrbios do ritmo e da condução foram mais encontrados em PM do que em DM (p<0,05 para todos), sobretudo o bloqueio divisional do ramo anterossuperior.ConclusõesEncontramos alterações distintas de ECG entre PM e DM e frequência aumentada de SVE em pacientes quando comparados com controles. Investigação do acometimento cardíaco nessas doenças deve ser considerada mesmo em pacientes assintomáticos, especialmente em se tratando de PM. Mais estudos são necessários para correlacionar os achados de ECG com outros exames complementares, manifestações clínicas, atividade das miopatias e evolução para outras doenças cardíacas.AbstractIntroductionCardiac involvement is frequent in inflammatory myopathies. Electrocardiogram (ECG) may show evidence of this involvement and its changes should be well‐known and described.ObjectivesDue to the lack of studies in the literature, we conducted an analysis of the ECG findings in patients with dermatomyositis (DM) and polymyositis (PM), comparing them with a control group.MethodsThis cross‐sectional study compared the ECG of 86 individuals with no rheumatic disorders (controls) with 112 patients (78 DM and 34 PM), during 2010 to 2013. The ECG findings between DM and PM were also compared.ResultsDemographic characteristics, comorbidities and ECG abnormalities were similar between controls and patients (p>0.05), except for a higher frequency of left ventricular hypertrophy (LVH) in patients (10.7% vs. 1.2%, p=0.008). Demographic characteristics, comorbidities, clinical and laboratory manifestations, were also similar between the groups PM and DM, except for the presence of cutaneous lesions only in DM. One third of the patients had ECG abnormalities, which were more prevalent in PM than DM (50% vs. 24.4%, p=0.008). LVH, left atrial enlargement, rhythm and conduction abnormalities were more frequent in PM than DM (p<0.05 for all), especially the left anterior fascicular block.ConclusionsWe showed distinct ECG changes between DM and PM and a higher frequency of LVH in patients compared to controls. Investigation of cardiac involvement should be considered even in asymptomatic patients, especially PM. Further studies are necessary in order to determine the correlation of ECG findings with other complementary tests, clinical manifestations, disease activity and progression to other cardiac diseases

Electrocardiographic changes in dermatomyositis and polymyositis

ABSTRACT Introduction: Cardiac involvement is frequent in inflammatory myopathies. Electrocardiogram (ECG) may show evidence of this involvement and its changes should be well-known and described. Objectives: Due to the lack of studies in the literature, we conducted an analysis of the ECG findings in patients with dermatomyositis (DM) and polymyositis (PM), comparing them with a control group. Methods: This cross-sectional study compared the ECG of 86 individuals with no rheumatic disorders (controls) with 112 patients (78 DM and 34 PM), during 2010 to 2013. The ECG findings between DM and PM were also compared. Results: Demographic characteristics, comorbidities and ECG abnormalities were similar between controls and patients (p > 0.05), except for a higher frequency of left ventricular hypertrophy (LVH) in patients (10.7% vs. 1.2%, p = 0.008). Demographic characteristics, comorbidities, clinical and laboratory manifestations, were also similar between the groups PM and DM, except for the presence of cutaneous lesions only in DM. One third of the patients had ECG abnormalities, which were more prevalent in PM than DM (50% vs. 24.4%, p = 0.008). LVH, left atrial enlargement, rhythm and conduction abnormalities were more frequent in PM than DM (p < 0.05 for all), especially the left anterior fascicular block. Conclusions: We showed distinct ECG changes between DM and PM and a higher frequency of LVH in patients compared to controls. Investigation of cardiac involvement should be considered even in asymptomatic patients, especially PM. Further studies are necessary in order to determine the correlation of ECG findings with other complementary tests, clinical manifestations, disease activity and progression to other cardiac diseases