Thesis (M.S.)--University of Michigan, 1985.

Thesis (M.S.)--University of Michigan, 1977.

Thesis (Ph. D.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains ix, 226 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 204-212).

Introdução: A estratégia de tratamento baseado em metas tem sido extensamente estudada em pacientes com AR inicial. No entanto, estudos sobre os benefícios de longo prazo do controle de atividade de doença em pacientes com AR estabelecida ainda são escassos. Objetivo: Avaliar a efetividade de longo prazo da estratégia de tratamento baseado em metas em pacientes com artrite reumatoide estabelecida na prática diária. Métodos: Pacientes com AR, previamente tratados de forma convencional, iniciaram estratégia de tratamento baseado em metas, sendo incluídos de março de 2005 a fevereiro de 2007 e acompanhados até dezembro de 2014. Os pacientes eram avaliados a cada 3 meses até remissão ou baixa atividade de doença serem alcançadas, e após a cada 6 meses. O tratamento seguiu um escalonamento de acordo com as recomendações vigentes. A atividade de doença foi mensurada através do DAS28 e do CDAI e a capacidade funcional, através do HAQ-DI. As informações foram extraídas pela revisão de formulários e de tabelas padronizadas. Variações na atividade de doença e na capacidade funcional foram comparadas pelo teste de Wilcoxon e Equações de Estimativas Generalizadas (GEE) A mortalidade foi avaliada através da curva de Kaplan-Meier. Resultados: Duzentos e vinte e nove pacientes foram incluídos, com duração média de doença 10,6±7,4 anos. Dentre os pacientes em moderada e alta atividade de doença no início da coorte, houve significativa redução do DAS28 (4,6±0,1 vs. 3,1±0,1; p<0,001) e do CDAI (21,2±1,0 vs. 7,9±0,7; p<0,001). Também houve redução do HAQ-DI (1,3±0,05 vs 1,0±0,1; p<0,001). A proporção de pacientes em remissão ou em baixa atividade de doença aumentou de 20% para 62% pelo DAS28. Com a estratégia de tratamento baseado em metas, houve um aumento na proporção de pacientes em uso de biológico para 30%. A taxa de mortalidade foi de 24,2 por 1000 pacientes-ano, discretamente superior à descrita na literatura. Conclusão: A estratégia de tratamento baseado em metas com objetivo de remissão e de baixa atividade de doença é efetivo em pacientes com AR estabelecida. / Introduction: Treating RA to a target has become a landmark strategy to be pursued in every patient. Nonetheless, few studies have addressed the true long-term impact of a T2T strategy in a real-world setting with established RA patients. Objective. To examine the long-term effectiveness of a treat-to-target (T2T) strategy in patients with established rheumatoid arthritis (RA) in daily practice. Methods. Patients with RA who were previously given the standard of care were started on a T2T strategy between March 2005 and February 2007 and followed through December 2014. Participants were seen every 3 months until remission/low disease activity was achieved and every 6 months thereafter. Treatment escalation followed a step-up strategy, according to national recommendations. Disease activity was measured by the DAS28 score and Clinical Disease Activity Index (CDAI), and physical function by the Health Assessment Questionnaire (HAQ). Data were extracted with standardized forms and a chart review. Changes in disease activity and physical function were compared using Wilcoxon’s test and generalized estimating equations. Mortality was analyzed using a Kaplan–Meier survival curve. Results. Two hundred and twenty-nine patients were included, with a mean (S.D.) disease duration of 10.6 (7.4) years. Significant reductions were observed in DAS28 (4.6±0.1 vs. 3.1±0.1; p<0.001), CDAI (21.2±1.0 vs. 7.9±0.7; p<0.001), and HAQ (1.3±0.05 vs 1.0±0.1; p<0.001) scores. The proportion of participants in remission/with low disease activity according to DAS28 increased from 20% to 62%. During implementation of the T2T strategy, a gradual increase in the proportion of participants using biologics was observed, to nearly 30%. The mortality rate was 24.2 per 1000 patient-years, slightly higher than that reported in other cohorts. Conclusion. A treat-to-target strategy aiming for remission or low disease activity is effective in patients with established RA.

Thesis (MTech (Medical Technology))--Cape Technikon, 1996. / Intensive investigations in many different populations over the last decade, have indicated a failure to understand the inheritance of rheumatoid arthritis (RA). It was hoped that genes within the class II region of the major histocompatibility complex (MHC) could shed some light on the inheritance of this autoimmune disease and which are now known without doubt, to confer susceptibility to the disease. Genetic studies of RA have concentrated primarily on its autoimmune nature and several investigations of MHC class II molecules, have demonstrated an association between specific HLA alleles and susceptibility to RA, in particular the DRB1 *04 and DRB1 *01 alleles. The HLA system is known to be associated with many diseases involving an immune aetiology. The structural features of specific DR and DQ genes give clues to the molecular mechanisms by which these alleles are associated with RA. It has been found by many investigators that there is more than one susceptibility allele for RA at the DRB1 locus. Questions arise whether the DRB1 molecule itself directly contributes to the pathogenesis of RA and why some DRB1 genes carrying DRBI *04 alleles, are not associated with RA.

Introdução: A estratégia de tratamento baseado em metas tem sido extensamente estudada em pacientes com AR inicial. No entanto, estudos sobre os benefícios de longo prazo do controle de atividade de doença em pacientes com AR estabelecida ainda são escassos. Objetivo: Avaliar a efetividade de longo prazo da estratégia de tratamento baseado em metas em pacientes com artrite reumatoide estabelecida na prática diária. Métodos: Pacientes com AR, previamente tratados de forma convencional, iniciaram estratégia de tratamento baseado em metas, sendo incluídos de março de 2005 a fevereiro de 2007 e acompanhados até dezembro de 2014. Os pacientes eram avaliados a cada 3 meses até remissão ou baixa atividade de doença serem alcançadas, e após a cada 6 meses. O tratamento seguiu um escalonamento de acordo com as recomendações vigentes. A atividade de doença foi mensurada através do DAS28 e do CDAI e a capacidade funcional, através do HAQ-DI. As informações foram extraídas pela revisão de formulários e de tabelas padronizadas. Variações na atividade de doença e na capacidade funcional foram comparadas pelo teste de Wilcoxon e Equações de Estimativas Generalizadas (GEE) A mortalidade foi avaliada através da curva de Kaplan-Meier. Resultados: Duzentos e vinte e nove pacientes foram incluídos, com duração média de doença 10,6±7,4 anos. Dentre os pacientes em moderada e alta atividade de doença no início da coorte, houve significativa redução do DAS28 (4,6±0,1 vs. 3,1±0,1; p<0,001) e do CDAI (21,2±1,0 vs. 7,9±0,7; p<0,001). Também houve redução do HAQ-DI (1,3±0,05 vs 1,0±0,1; p<0,001). A proporção de pacientes em remissão ou em baixa atividade de doença aumentou de 20% para 62% pelo DAS28. Com a estratégia de tratamento baseado em metas, houve um aumento na proporção de pacientes em uso de biológico para 30%. A taxa de mortalidade foi de 24,2 por 1000 pacientes-ano, discretamente superior à descrita na literatura. Conclusão: A estratégia de tratamento baseado em metas com objetivo de remissão e de baixa atividade de doença é efetivo em pacientes com AR estabelecida. / Introduction: Treating RA to a target has become a landmark strategy to be pursued in every patient. Nonetheless, few studies have addressed the true long-term impact of a T2T strategy in a real-world setting with established RA patients. Objective. To examine the long-term effectiveness of a treat-to-target (T2T) strategy in patients with established rheumatoid arthritis (RA) in daily practice. Methods. Patients with RA who were previously given the standard of care were started on a T2T strategy between March 2005 and February 2007 and followed through December 2014. Participants were seen every 3 months until remission/low disease activity was achieved and every 6 months thereafter. Treatment escalation followed a step-up strategy, according to national recommendations. Disease activity was measured by the DAS28 score and Clinical Disease Activity Index (CDAI), and physical function by the Health Assessment Questionnaire (HAQ). Data were extracted with standardized forms and a chart review. Changes in disease activity and physical function were compared using Wilcoxon’s test and generalized estimating equations. Mortality was analyzed using a Kaplan–Meier survival curve. Results. Two hundred and twenty-nine patients were included, with a mean (S.D.) disease duration of 10.6 (7.4) years. Significant reductions were observed in DAS28 (4.6±0.1 vs. 3.1±0.1; p<0.001), CDAI (21.2±1.0 vs. 7.9±0.7; p<0.001), and HAQ (1.3±0.05 vs 1.0±0.1; p<0.001) scores. The proportion of participants in remission/with low disease activity according to DAS28 increased from 20% to 62%. During implementation of the T2T strategy, a gradual increase in the proportion of participants using biologics was observed, to nearly 30%. The mortality rate was 24.2 per 1000 patient-years, slightly higher than that reported in other cohorts. Conclusion. A treat-to-target strategy aiming for remission or low disease activity is effective in patients with established RA.

Orientadores: Manoel Barros Bértolo, Lilian Tereza Lavras Costallat / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T07:51:21Z (GMT). No. of bitstreams: 1 Yazbek_MichelAlexandre_D.pdf: 3193834 bytes, checksum: 4155cea9577385c29405700add4864ef (MD5) Previous issue date: 2014 / Resumo: A etiopatogenia da Artrite Reumatoide (AR) envolve fatores genéticos, imunológicos e ambientais que interagem entre si. Os principais fatores de risco estudados são a presença dos alelos do epítopo compartilhado (shared epitope- SE), dos anticorpos anti-peptídeos cíclicos citrulinados (anti-CCP) e do tabagismo. Há evidências que o Epstein-Barr vírus (EBV), ao interagir com esses fatores de risco, possa causar uma resposta imune anômala em indivíduos susceptíveis. Essas interações também podem contribuir para o desenvolvimento da AR. O objetivo principal desse estudo é estabelecer se há uma associação entre o EBV com os alelos do SE, os anticorpos anti-CCP e o tabagismo em pacientes brasileiros com AR. Os objetivos secundários são: avaliar a correlação entre os alelos do SE, os anticorpos anti-CCP e o tabagismo; detectar a exposição ao EBV e quantificar sua carga viral e estimar o risco de cada fator estudado para o desenvolvimento da AR nessa casuística. Nesse estudo caso-controle, incluímos 140 pacientes brasileiros com AR e 143 controles saudáveis; pareados por idade, sexo e etnia. Foi feita uma caracterização clínico-laboratorial da casuística. Foram realizadas a genotipagem para identificar os alelos do SE, a determinação dos anticorpos anti-CCP pelo método de ELISA e coletada a história de tabagismo de todos os sujeitos da pesquisa. Para avaliar a exposição ao EBV, realizamos a dosagem dos anticorpos anti-Epstein-Barr Nuclear Antigen 1 (anti-EBNA1). Para quantificar a carga viral do EBV, realizamos o método quantitativo da reação em cadeia polimerase em tempo real ou real-time PCR. A análise comparativa entre os grupos mostrou uma positividade significativamente maior para os alelos do SE, anticorpos anti-CCP e tabagismo no grupo de pacientes. A análise dos anticorpos anti-EBNA1 mostrou uma positividade alta, tanto em pacientes como em controles, sem diferença significativa. Entretanto, a quantificação da carga viral pela PCR em tempo real mostrou-se muito maior em pacientes do que em controles (p<0.001). As análises associativas dos anticorpos anti-EBNA1 com os outros fatores estudados não se mostraram significativas; assim como as análises associativas da carga viral do EBV pela PCR em tempo real. A positividade do anti-CCP foi maior em pacientes com os alelos do SE que são tabagistas ou ex-tabagistas (p=0.038). Nas análises de regressão logística, a variável com maior risco para o desenvolvimento da AR foi a positividade dos anticorpos anti-CCP. Apesar dos pacientes com AR apresentarem uma carga viral do EBV aumentada, esse estudo não conseguiu associá-la aos demais fatores de risco estudados. Sugerimos que esses achados possam ocorrer devido a um controle deficitário do EBV em pacientes com AR, mas que não está relacionado aos fatores de risco mais conhecidos da doença. A imunidade celular defeituosa dos pacientes com AR dificulta o controle de uma infecção latente do vírus. Portanto, não é possível estabelecer uma relação causal direta entre o EBV e a AR / Abstract: The pathogenesis of rheumatoid arthritis (RA) involves genetic, immunological and environmental factors. The main risk factors are the presence of the shared epitope alleles (shared epitope- SE), anti-cyclic citrullinated peptide antibodies (Anti-CCP) and smoking. There is evidence that the Epstein-Barr virus (EBV), when interacts with these risk factors, may cause an abnormal immune response in susceptible individuals. These interactions may contribute to the development of RA. The main objective of this study is to establish whether there is an association between EBV and alleles of SE, anti-CCP antibodies and smoking in Brazilian patients with RA. Secondary objectives are the assessment of the correlation between alleles of SE, anti-CCP antibodies and smoking; the detection of EBV; the quantification of EBV viral load and the estimation of the likelihood of each analyzed factor for the development of RA in this sample. In this case-control study, we included 140 Brazilian patients with RA and 143 healthy controls; matched for age, sex and ethnicity. We performed a clinical and laboratory characterization of the sample. Genotyping was performed to identify SE alleles, anti-CCP antibodies were examined by ELISA and smoking information was collected from all subjects. To assess the exposure to EBV, we examined anti-Epstein-Barr Nuclear Antigen 1 (anti-EBNA1) antibodies. To quantify the viral load of EBV, we performed the quantitative method of polymerase chain reaction in real time or real-time PCR. The comparative analysis between groups showed a significantly higher positivity for the alleles of SE, anti-CCP antibodies and smoking in patients. The analysis of anti-EBNA1 antibodies showed a high positivity, both in patients and in controls, with no significant difference. However, the quantification of viral load by real-time PCR proved to be much higher in patients than in controls (p <0.001). Associative analysis of anti-EBNA1 antibodies with other factors studied were not significant; as well as the association analyzes of the EBV viral load by PCR in real time. The positivity of anti-CCP antibodies was higher in patients with SE alleles which are smoker or ex-smoker (p = 0.038). In logistic regression analyzes, the variable with higher risk for RA was the positivity of anti-CCP antibodies. Although patients with RA present an increased EBV viral load, this study did not link EBV to the other risk factors studied. We suggest that these findings may be due to a deficient control of EBV in RA patients, which is unrelated to the better-known disease risk factors. Defective cellular immunity of patients with RA complicates the control of latent virus infection. Therefore it is not possible to establish a direct causal relationship between EBV and RA / Doutorado / Clinica Medica / Doutor em Clínica Médica

Having identified the need to provide services to elderly, homebound people with arthritis, the Social Work Department at the Vancouver Arthritis Centre initiated an Arthritis Telephone Contact Program in Autumn, 1989. The purpose of this study was to investigate whether or not a weekly telephone call from volunteers would impact positively on subjects' physical and psychological functioning, level of pain and perceived level of social support. The 11 subjects in this study were elderly, Caucasian women identified by health care professionals as being socially isolated due, in part, to the limits placed on them by either osteoarthritis or rheumatoid arthritis. The one-group pretest-posttest research design was employed for this study. Quantitative measures used were the Arthritis Impact Measurement Scales (AIMS) and the Perceived Social Support From Friends and From Family Scale (PSS-Fr & Fa). Interviews of subjects were conducted in order to describe the efficacy of the Telephone Contact Program from more than one perspective. Over 16 weeks, paired t-test found that the physical functioning of subjects had improved significantly. It was noted that there was a trend towards improved health status for the experimental group in that seven out of the eight subscales of AIMS measured improvement, while one subscale showed no change. Contrary to prediction, perception of social support from family members decreased significantly, as measured by the PSS-Fa scale. Pearson correlation coefficients found no association between changes in perception of social support and changes in health status. Interview data suggests that callers were perceived as sources of social support. Specifically, callers seemed to provide participants with emotional support, informational support, and positive social interaction. Overall, the data suggested that the Telephone Contact Program had the capability to evoke small, but clinically meaningfully improvements in the health status of elderly women with arthritis. Further investigation into the use of telephone contact programs as a minimal intervention is advised. / Arts, Faculty of / Social Work, School of / Graduate

The aim of this study was to establish whether a splint programme is effective in preventing the deterioration of already evident swan neck and boutonniere deformities in rheumatoid arthritis (RA). A randomised clinical trial was done on 34 RA patients with swan neck and 34 RA patients with boutonniere deformities. The literature revealed that several factors such as age, gender, socio-economic status, time after onset of the illness and lifestyle could influence results. Care was taken to allocate, as far as possible equal numbers of patients with these attributes to the experimental and control groups. It became clear from the literature that swan neck and boutonniere deformities could manifest themselves in different forms and stages or grades of deterioration. Various splints to halt the downward spiral of the deformity were recommended, without proper scientific verification, by the authors. No specifications as to which splint was recommended for which form or grade of deformity or instructions for wearing of the splints were included. For the study the PIP hyperextension splint and the three-point-PIP extension splint was chosen for the swan neck and boutonniere deformities respectively. Patients were followed up for one year. Results were marginally positive for the prevent ion of swan neck deformities by the hyperextension splint programme, but results for the three-point PIP extension splint programmes were negative for grade I boutonniere deformities. Loss of flexor muscle strength was evident in almost all the groups (experimental and control) but more so for grade I swan neck and grade I boutonniere deformities. The variability of measurements were found to be large. Many possible sources of variation were identified, which included biological differences between people, different courses the illness could take and a weak test-retest reliability of some goniometer measurements. This fact and the relatively small sample subgroups caused some results to be not significant on the 5% level. From the significant findings, and other not significant tendencies that were too persistent to ignore, linked to the different manifestations and grades of swan neck and boutonniere deformities, recommendations were made. These suggestions will have to be tested by experimentation.

Eine Dysregulation neuro-immunologischer Interaktionen und eine veränderte Stressantwort werden als Teil der Pathogenese der Rheumatoiden Arthrtitis (RA) diskutiert. Dabei könnte eine autonome Dysfunktion eine wichtige Rolle spielen. Um dem nachzugehen, wurde an Patienten mit unterschiedlicher Krankheitsaktivität die Aktivität des autonomen Nervensystems in Ruhe und in Reaktion auf minor Stress sowie erstmals deren Assoziation zu Gen-Polymorphismen β2- adrenerger Rezeptoren (β2ARs), welche sich u.a. auf Immunzellen befinden, untersucht. Zur Bestimmung autonomer Aktivität wurde an 112 RA- und 48 Osteoarthrose-Patienten die sympathische Hautantwort (SSR) sowie die Herzratenvariabilität (HRV) getestet. Standardisierte Stresstests kamen zur Anwendung. Eine Allel-spezifische Polymerase-Ketten-Reaktion diente zur Ermittlung der Varianten des β2ARs an Aminosäureposition 16, 27 und 164. Es konnte gezeigt werden, dass die autonome Aktivität bei RA in Ruhe durch eine signifikant erhöhte Herzfrequenz, ein Überwiegen des Sympathikus im Verhältnis zum Parasympathikus sowie eine signifikant erniedrigte Parasympathikusaktivität gekennzeichnet ist. Die Stressantwort bei RA war signifikant häufiger pathologisch als bei der Kontrollgruppe und durch signifikante Hypoaktivität und Hyporeaktivität des Parasympathikus sowie eine signifikant erniedrigte HRV charakterisiert. Das Zusammenspiel beider Schenkel des ANS erschien gestört. Die SSR-Werte befanden sich im Normbereich. Schlechtere Werte waren jedoch signifikant mit hohem CRP assoziiert. Desweiteren war Heterozygotie an allen Gen-Positionen der β2ARs signifikant mit RA assoziiert. Gln27Gln (signifikant häufiger für Gesunde) ging mit signifikant niedrigerer Krankheitsaktivität einher. Starkes Überwiegen des SNS in Ruhe sowie niedrige parasympathische Aktivität (HRV-Daten) waren signifikant mit hoher Krankheitsaktivität assoziiert. Zusammenfassend weist die vorliegende Arbeit auf eine autonome Dysregulation bei Patienten mit RA hin, was mit klinischen Parametern der RA assoziiert war. Weiterhin unterstreicht die Studie die Assoziation von β2AR Polymorphismen mit einer RA und liefert einen weiteren Beitrag zum Verständnis der Pathogenese dieser Erkrankung.