Thesis (M.CM)--Hong Kong Baptist University, 2006. / Dissertation submitted to the School of Chinese Medicine. Includes bibliographical references (leaf 22).

Orientador: Arlete Maria Valente Coimbra / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T18:16:14Z (GMT). No. of bitstreams: 1 Falsarella_GlauciaRegina_M.pdf: 1971232 bytes, checksum: d2166302be1edbdaaa70b45429e1b7e5 (MD5) Previous issue date: 2010 / Resumo: As doenças reumáticas representam condição multifatorial, responsável pela limitação funcional, pelo alto custo para o paciente e sociedade, o que compromete a Qualidade de Vida Relacionada à Saúde (QVRS), tendo, portanto, grande relevância para a saúde pública. O presente estudo, na área da saúde e qualidade de vida na velhice, tem em sua composição dois artigos, que apresentam como objetivo determinar a prevalência e os fatores associados às doenças reumáticas e aos sintomas articulares crônicos, bem como suas repercussões sobre a QVRS. Este estudo transversal, com caráter epidemiológico envolveu 2209 idosos (?60 anos) do município de Amparo-SP. Foram avaliados os dados sociodemográficos, as doenças reumáticas, os sintomas articulares, as condições de saúde, os sintomas depressivos pela GDS-15 e a qualidade de vida pelo SF-36. Para investigar a associação entre doenças reumáticas/sintomas articulares e fatores de risco foram utilizadas a regressão logística univariada e a multivariada. Para determinar a relação entre as condições reumáticas e a QVRS empregou-se tanto a Análise de Variância Multivariada (MANOVA) como a Análise de Variância Univariada (ANOVA). As doenças reumáticas atingiram 22.7% dos idosos e associaram-se significativamente com: sexo feminino (Odds Ratio - OR 1.91), renda familiar 3-9.9 salários mínimos (SM) (OR 1.29), ?10 SM (OR 2.34), doença cardiovascular (OR 1.42), catarata (OR 1.39), glicocorticóides (OR 5.24), outros anti-inflamatórios (OR 2.24), dor (OR 0.983). Após ajuste para glicocorticóides e diabetes identificou-se OR=1.42 para catarata. Os sintomas articulares acometeram 45.6% da amostra e apresentaram a seguinte relação: mulheres (OR 1.40), Índice de Massa Corporal (IMC) 18.5-24.9 kg/m² (OR 2.29), 25.0-29.9 kg/m² (OR 2.55), ?30.0 kg/m² (OR 3.31), capacidade funcional (OR 0.990), estado geral de saúde (OR 0.993) e dor (OR 0.981). Após ajuste para glicocorticóides e diabetes identificou-se OR=1.30 para catarata. Ao investigar o impacto das doenças reumáticas sobre a QVRS verificou-se o comprometimento relativo da: capacidade funcional (F=10.9) e dor (F=34.77). Os sintomas articulares repercutiram: capacidade funcional (F=10.9); aspectos físicos (F=72.61); dor (F=164.29); estado geral de saúde (F=71.95); vitalidade (F=55.78); aspectos sociais (F=73.14); aspectos emocionais (F=49.09); saúde mental (F=44.72). A identificação destas características possibilita determinar o impacto das alterações osteoarticulares nos diversos domínios da saúde, maior entendimento dos processos fisiopatológicos, além de auxiliar nas medidas preventivas precoces e eficientes. / Abstract: Rheumatic diseases represent a multifactorial condition responsible for functional limitations and high cost to the patient and society, undermining health-related quality of life (HRQOL). The present study considered two articles on health and quality of life in old age, aiming to determine prevalence and risk factors associated with rheumatic diseases and chronic joint symptoms, as well as their impact on HRQOL. The following questionnaires were applied in this cross-sectional study comprising 2,209 elderly (?60 years): self-reported medical diagnosis of rheumatism and chronic joint symptoms, sociodemographic, health status, ADL, IAVD, GDS-15 and SF-36. Univariate and multivariate analyses were used to investigate association between rheumatic diseases/chronic arthritis symptoms and selected factors. To determine the relationship between rheumatism conditions and HRQOL was employed MANOVA e ANOVA, with p?0.05. The prevalence of arthritis was 22.7%. Multivariate analysis showed significant arthritis: female sex (OR 1.91); family income ?10 minimum wages (mw) (OR 2.34); cardiovascular disease (OR 1.42); cataract (OR 1:39); glucocorticoids (OR 5.24); pain (OR 0.983). A significant association between cataract and arthritis was detected even after adjusting for use of glucocorticoids and diabetes (OR 1.42). The prevalence of chronic joint symptoms was 45.6%. Multivariate regression results for joint symptoms included: female gender (OR 1.40); BMI ?30.0 kg/m² (OR 3.31); functional capacity (OR 0.990); general health (OR 0.993) and pain (OR 0.981). A significant association between cataract and joint pain was detected after adjusting for the use of glucocorticoids and diabetes (OR 1.42). It was found impairment when investigating the impact of rheumatic diseases on HRQOL: physical functioning (F = 10.9) and pain (F = 34.77). The joint symptoms caused the following problems: functional (F=10.9), physical problems (F=72.61), pain (F=164.29), general health (F=71.95), vitality (F=55.78), social (F=73.14), emotional (F= 49.09), mental health (F= 44.72). The identification of these characteristics will allow determining the impact of osteoarticular changes on the various health fields, providing a better understanding of pathophysiological processes, as well as contributing to early and effective preventive measures. / Mestrado / Gerontologia / Mestre em Gerontologia

A series of five individual studies explored: (1) Whether a treatment focus emphasizing active anger expression would alter the subject's awareness of and ability to express anger and (2) Whether such a treatment focus would alter the subject's experience of illness in the form of her report of pain and stiffness as "better", "the same", or "worse" than yesterday's experience. The treatment strategy utilized general Gestalt principles and was further focused on specific techniques of Anger Therapy as an agent of change. Evaluation of outcome in this time-lagged multiple baseline design viewed the overall process from the beginning of a baseline observation period through a maximum of one week following the conclusion of the last six weekly treatment sessions; daily measurement of the process of change during treatment; and clinical description of the subjects and of the treatment process itself. The overall process was formally assessed in pre and post treatment testing which included the Novaco Anger Inventory, Buss-Durkee Hostility Inventory, Marlowe-Crowne Social Desirability Scale, and FIRO-B. Daily telephone interview measured the frequency of anger awareness, anger expression; and ratings of anger intensity, overall daily mood, pain, and stiffness. Information from the treatment process was integrated with that obtained from other sources in discussing the outcome for each subject. It was concluded that intense anger expression appeared to effect temporary or transitory improvement in pain; that there was a relationship between each subject's perceived daily anger intensity and pain which appeared consistent for all subjects studied; and that issues of need for approval and control appeared related to anger awareness and expression as measured by the psychometrics utilized. These were recommended as potentially fruitful areas of future investigation. Background data revealed striking similarities in birth order and parenting practices which seemed worthy of further study as well.

This project was carried out under a broad theme of Maori health and investigates the genetics of rheumatoid arthritis (RA) and gout within two Maori case-control cohorts. In addition, it reports on the developmental stages of a whanau project focussing on the compilation of our whakapapa and collation of information relating to type 2 diabetes within the Parata whanau, which I whakapapa to. My conducting this research in light of me being Maori is also considered: much of the prevailing literature on Maori and science describes science as the handmaid of colonisation, and singles out genetic research as being "neo-colonial". I reject those that would label me a "sell-out" and show how my research is shaped by, and consistent with, the history of my immediate tipuna, and my iwi more generally, since European contact. RA is an autoimmune disease of the joints and affects approximately 1% of the general population. There is currently very little data available on its prevalence in New Zealand although it is thought that it is similar to those of the rest of the world. Gout is the most common form of inflammatory arthritis in Caucasian males and recent data suggests a worldwide increase in prevalence in many populations. Gout is characterised by the deposition of monosodium urate or uric acid crystals in the joints, which produces an inflammatory response. In New Zealand, the prevalence of gout is estimated to be 3% in Caucasians and twice this in Maori. Both RA and gout are complex arthritic diseases and are influenced by a combination of genetic and environmental factors. It is likely that numerous genetic susceptibility loci are responsible for the genetic components of these diseases. This project tests various genetic regions for susceptibility to or protection against both RA and gout in two separate Maori case cohorts and a common control cohort. To do this, the confounding factor of population stratification, resulting from population admixture, was overcome via developing a method specific for these Maori cohorts. This tool utilised genotype data from a set of unlinked genome-wide markers and the structure and STRAT software packages, allowing valid case-control studies to be carried out in the presence of population stratification. These data showed that four sub-populations exist in the Maori RA case-control cohort and three in the Maori gout case-control cohort. A number of studies have confirmed the HLA region as the major genetic determinant of autoimmunity and recently, PTPN22 and CTLA-4 variants have been shown to be common to the onset of a number of autoimmune phenotypes. The IDDM6 region on chromosome 18 has also been implicated in type 1 diabetes, RA and autoimmune thyroiditis and contains a number of candidate genes for a role in RA, many of which were investigated in this thesis. Polymorphisms within the PTPN22, CTLA-4, BCL2, SMAD4, DCC, TNFRSF11A, PADI4, CCR5 and CCL3L1 genes were tested for association with RA in the Maori cohort (98 cases and 109 controls) with some significant association results obtained. The HLA-DRB1*02 and HLA-DRB1*08 loci were associated with the protection against and susceptibility for RA, respectively (P = 0.004 and 0.017). The deviation of CCL3L1 copy-number from the cohort mean (two copies) was also associated with the RA development. Copy-number <2 indicated association with protection against RA (P = 0.012) and copy-number >2 indicated association with susceptibility to RA (P = 0.002). However, it must be stressed that these results were obtained without accounting for the presence of population stratification. The organic anion transporter (OAT) and the urate transporter 1 (URAT1) genes, involved in the regulation of blood urate levels, are members of the solute carrier transporter (SLC) family and provide good candidates for a role in gout. A number of polymorphisms within the OAT, URAT1 and the SLC5A8 genes were tested for association with gout in the Maori cohort (72 cases and 109 controls) with some success. The SLC5A8 rs1709189 SNP was significantly associated with gout in this cohort (P = 0.004). Polymorphisms within two alcohol dehydrogenase (ADH) genes were also tested for association due to their role in alcohol metabolism and the association between alcohol consumption and gout. The ADH2 rs1229984 SNP was also significantly associated with gout in this cohort (P = 0.012). These significant results were obtained after population stratification was taken into account. The data presented in this thesis confirm the presence of population stratification in the two Maori case-control cohorts and demonstrate some association of the HLA-DRB1 region and CCL3L1 with RA and the SLC5A8 and ADH2 genes with gout. An extensive whakapapa of our whanau has also been compiled and associated type 2 diabetes information collected. However, this is by no means a completed task and work will continue on this project under the guidance of the Parata whanau.

En la presente tesis doctoral se estudian las características de los pacientes aquejados de reumatismos psicógenos en función de cuatro parámetros: clínico, psicométrico, farmacológico y psico-fisiológico. A partir de este planteamiento se propone una hipótesis explicativa del trastorno interpretable desde una perspectiva cortico-visceral.

A fim de avaliar o resultado da gestação em pacientes cardíacas foram considerados dois grupos controle: o grupo \"I\" ou clínico e o grupo \"II\" ou cirúrgico. Foram considerados para este estudo todas as pacientes reumáticas matriculadas no Programa de Assistência à Gestante Cardíaca, no período de 01/06/15 a 30/10/79, tomando-se por base a gravidez e a doença reumática como ponto comum a todas as pacientes. Os resultados obtidos nestas gestações estão baseados nos parâmetros a seguir relacionados: idade da paciente no início da gestação, número de gestações, paridade, diagnóstico clínico-cardiológico, tipo funcional segundo a \"New York Heart Association\", idade gestacional, eletrocardiograma, tipo de parto, peso do recém-nascido ao nascer e suas condições de saúde. As pacientes do grupo \"II\" ou cirúrgico foram divididas em três subgrupos a saber: cirúrgico \"1\" (submetidas a comissurotomia valvar); cirúrgico \"2\" (submetidas a implante de prótese valvar-metálica tipo Starr-Edwards; e cirúrgico \"3\" (submetida a implante de prótese biológica de dura-máter). Os filhos das gestantes do grupo \"II\" ou cirúrgico têm peso significativamente menor que os filhos das gestantes do grupo \"I\" ou clínico. Entre as pacientes dos subgrupos cirúrgicos os filhos das pacientes com prótese de Starr-Edwards têm peso menor do que os filhos das gestantes dos outros subgrupos cirúrgicos, o que pode, pelo menos em parte, ser explicado pela ação dos anticoagulantes orais. Em relação ao tipo funcional, as pacientes cardíacas reumáticas clínicas podem engravidar se estiverem classificadas nos tipos funcionais I e II da \"New York Heart Association\", enquanto que as do grupo cirúrgico, com qualquer tipo de procedimento cirúrgico anterior, só poderão engravidar se pertencerem ao tipo funcional I, sem história de descompensação cardíaca anterior. As pacientes com prótese de Starr-Edwards na vigência de anticoagulação oral, devem ser bem orientadas em relação aos riscos do uso de tal medicação e entrarem para o programa especial de acompanhamento, com emprego de heparina subcutânea, principalmente durante a organogênese e ao controle rigoroso do tempo de protrombina, para prevenir o aparecimento de fenômenos trómboembólicos e do síndrome warfarínico fetal. As pacientes com prótese de dura-máter aórtica devem ser desencorajadas a engravidar. O período ideal para uma gravidez em pacientes cardíacas reumáticas, após qualquer tipo de cirurgia cardíaca, é com duração superior a 1 ano e inferior a 6 anos de pós-operatório. O maior número de cesáreas foi uma constante em todos os grupos estudados e realizadas por indicação obstétrica. No cirúrgico \"2\" (ou com prótese de Starr-Edwards) há indicação relativa de parto programado devido ao uso de anticoagulantes orais. Os procedimentos cirúrgicos devem ser realizados preferentemente antes ou apÓs a gestação. Durante o período gestacional,a época teoricamente \"ideal\" é entre a 18a. e 24a. semanas de gestação, ou em qualquer fase da gestação quando este for um procedimento de urgência. A cardioversão elétrica, processo inócuo durante a gravidez pode ser realizado em qualquer período gestacional para reversão da fibrilação atrial a ritmo sinusal. A taxa de óbitos maternos nas 301 gestações estudadas foi de 1,66 por cento , sendo que houve diferença significativa entre as proporções de óbitos nos dois grupos \"I\" e \"II\". As perdas do produto conceptual foram significativamente menores no grupo \"I\" ou clínico (4,48 por cento ) do que no grupo \"II\" ou cirúrgico (12,39 por cento ). Os resultados obtidos permitiram melhor avaliação dos riscos cardiológico e gravídico, bem como possibilitaram a caracterização de diferentes parâmetros que, considerados em conjunto, serão fundamentais para a avaliação do prognóstico destas mulheres com cardiopatia reumática. / With a view to assessing the consequences of pregnancy in rheumatic heart patients this study considered two control groups: the clinical group (I) and the surgical group (II). All the rheumatic patients enrolled, during the period from June 1, 1975 to October 3 O, 1979, in the \"Programme of Assistance to the Cardiac pregnant Woman\" were included in this study. Pregnancy and rheumatic disease were the common factors in all the cases studied. The results obtained during these pregnancies are based on the following parameters: age of the patient at the beginning of pregnancy, number of pregnancies, parity, cardiological clinical diagnosis, functional type according to the \"New York Heart Association\", gestational age, electrocardiogram, type of birth, birth-weight and state of health of the babies. The patients of Group \"II\" (Surgical) were divided into three sub-groups, namely: Surgical \"1\" (composed of those who had undergone Valvotomy); Surgical \"2\" (who had undergone implant of the Starr-Edwards heart valve prosthesis) and Surgical \"3\" (who had undergone implant of the \"dura-mater\" allograft prosthesis). The children of the mothers of group II (Surgical) were found to be of considerably lower weight than the children of mothers of group I (Clinical). With regard to the patients of the surgical sub-groups, the children of those with Starr-Edwards prosthesis are of lower weight than the children of the patients of the other surgical sub-groups which can be accounted for, at least in some measure, as a result of the use of oral anticoagulants. With regard to the functional type, theclinical rheumatic heart patients may become pregnant if classified as of the functional types I and II of the \"New York Heart Association\", while those of the surgical group, with any kind of earlier surgical treatment, may only become pregnant if they belong to the functional type I, with no previous history of cardiac insufficiency. The patients with Starr-Edwards prosthesis must be fully advised about the risks of using oral anticoagulants and must be put onto a special assistance programme, with employment of intradermic heparin, especially during organogenesis. They must also be advised about the necessary rigorous control of the prothrombine time to guard against the appearance of thromboembolic problems and Warfarin embryopathy. Patients with aortic \"dura-mater\" prosthesis should be discouraged from becoming pregnant. The most favorable period for pregnancy in rheumatic heart patients with any kind of cardiac surgical history is that lasting from a minimum of one year to a maximum of six years after operation. A majority of births by ceasarean section was a constant in all groups studied these were carried out on the basis of the obstetrician\'s recommendation. In the surgical sub-group \"2\" (those with Starr-Edwards prosthesis) there is a relatively high probability of programm~d births due to the use of oral anticoagulants. Surgery ought to be carried out, preferably, either before of after pregnancy. During the period of pregnancy the theoretically ideal occasion for surgery is between the 18th and 24th. weeks of pregnancy or, at any time during the pregnancy in urgent cases. Electrical cardioversion is a harmless procedure for the expectant mother and may be carried out at any time during the pregnancy for the reversal of the atrial fibrilation to the sinus rhythm. The maternal death rate for the 301 pregnancies studied was of 1.66 per cent , though there was a significant difference between the proportion of deaths occuring in groups I and II. The loss of the conceptual product was significantly less in Group I (clinical) 4.48 per cent than in Group II (surgical) 12.39 per cent . The result obtained permitted a better assessment of the cardiological and pregnancy risks, as well as making possible the characterization of the different parameters which, considered as a group, will be fundamental to the assessment of the prognosis of women with rheumatic heart disease.

A fim de avaliar o resultado da gestação em pacientes cardíacas foram considerados dois grupos controle: o grupo \"I\" ou clínico e o grupo \"II\" ou cirúrgico. Foram considerados para este estudo todas as pacientes reumáticas matriculadas no Programa de Assistência à Gestante Cardíaca, no período de 01/06/15 a 30/10/79, tomando-se por base a gravidez e a doença reumática como ponto comum a todas as pacientes. Os resultados obtidos nestas gestações estão baseados nos parâmetros a seguir relacionados: idade da paciente no início da gestação, número de gestações, paridade, diagnóstico clínico-cardiológico, tipo funcional segundo a \"New York Heart Association\", idade gestacional, eletrocardiograma, tipo de parto, peso do recém-nascido ao nascer e suas condições de saúde. As pacientes do grupo \"II\" ou cirúrgico foram divididas em três subgrupos a saber: cirúrgico \"1\" (submetidas a comissurotomia valvar); cirúrgico \"2\" (submetidas a implante de prótese valvar-metálica tipo Starr-Edwards; e cirúrgico \"3\" (submetida a implante de prótese biológica de dura-máter). Os filhos das gestantes do grupo \"II\" ou cirúrgico têm peso significativamente menor que os filhos das gestantes do grupo \"I\" ou clínico. Entre as pacientes dos subgrupos cirúrgicos os filhos das pacientes com prótese de Starr-Edwards têm peso menor do que os filhos das gestantes dos outros subgrupos cirúrgicos, o que pode, pelo menos em parte, ser explicado pela ação dos anticoagulantes orais. Em relação ao tipo funcional, as pacientes cardíacas reumáticas clínicas podem engravidar se estiverem classificadas nos tipos funcionais I e II da \"New York Heart Association\", enquanto que as do grupo cirúrgico, com qualquer tipo de procedimento cirúrgico anterior, só poderão engravidar se pertencerem ao tipo funcional I, sem história de descompensação cardíaca anterior. As pacientes com prótese de Starr-Edwards na vigência de anticoagulação oral, devem ser bem orientadas em relação aos riscos do uso de tal medicação e entrarem para o programa especial de acompanhamento, com emprego de heparina subcutânea, principalmente durante a organogênese e ao controle rigoroso do tempo de protrombina, para prevenir o aparecimento de fenômenos trómboembólicos e do síndrome warfarínico fetal. As pacientes com prótese de dura-máter aórtica devem ser desencorajadas a engravidar. O período ideal para uma gravidez em pacientes cardíacas reumáticas, após qualquer tipo de cirurgia cardíaca, é com duração superior a 1 ano e inferior a 6 anos de pós-operatório. O maior número de cesáreas foi uma constante em todos os grupos estudados e realizadas por indicação obstétrica. No cirúrgico \"2\" (ou com prótese de Starr-Edwards) há indicação relativa de parto programado devido ao uso de anticoagulantes orais. Os procedimentos cirúrgicos devem ser realizados preferentemente antes ou apÓs a gestação. Durante o período gestacional,a época teoricamente \"ideal\" é entre a 18a. e 24a. semanas de gestação, ou em qualquer fase da gestação quando este for um procedimento de urgência. A cardioversão elétrica, processo inócuo durante a gravidez pode ser realizado em qualquer período gestacional para reversão da fibrilação atrial a ritmo sinusal. A taxa de óbitos maternos nas 301 gestações estudadas foi de 1,66 por cento , sendo que houve diferença significativa entre as proporções de óbitos nos dois grupos \"I\" e \"II\". As perdas do produto conceptual foram significativamente menores no grupo \"I\" ou clínico (4,48 por cento ) do que no grupo \"II\" ou cirúrgico (12,39 por cento ). Os resultados obtidos permitiram melhor avaliação dos riscos cardiológico e gravídico, bem como possibilitaram a caracterização de diferentes parâmetros que, considerados em conjunto, serão fundamentais para a avaliação do prognóstico destas mulheres com cardiopatia reumática. / With a view to assessing the consequences of pregnancy in rheumatic heart patients this study considered two control groups: the clinical group (I) and the surgical group (II). All the rheumatic patients enrolled, during the period from June 1, 1975 to October 3 O, 1979, in the \"Programme of Assistance to the Cardiac pregnant Woman\" were included in this study. Pregnancy and rheumatic disease were the common factors in all the cases studied. The results obtained during these pregnancies are based on the following parameters: age of the patient at the beginning of pregnancy, number of pregnancies, parity, cardiological clinical diagnosis, functional type according to the \"New York Heart Association\", gestational age, electrocardiogram, type of birth, birth-weight and state of health of the babies. The patients of Group \"II\" (Surgical) were divided into three sub-groups, namely: Surgical \"1\" (composed of those who had undergone Valvotomy); Surgical \"2\" (who had undergone implant of the Starr-Edwards heart valve prosthesis) and Surgical \"3\" (who had undergone implant of the \"dura-mater\" allograft prosthesis). The children of the mothers of group II (Surgical) were found to be of considerably lower weight than the children of mothers of group I (Clinical). With regard to the patients of the surgical sub-groups, the children of those with Starr-Edwards prosthesis are of lower weight than the children of the patients of the other surgical sub-groups which can be accounted for, at least in some measure, as a result of the use of oral anticoagulants. With regard to the functional type, theclinical rheumatic heart patients may become pregnant if classified as of the functional types I and II of the \"New York Heart Association\", while those of the surgical group, with any kind of earlier surgical treatment, may only become pregnant if they belong to the functional type I, with no previous history of cardiac insufficiency. The patients with Starr-Edwards prosthesis must be fully advised about the risks of using oral anticoagulants and must be put onto a special assistance programme, with employment of intradermic heparin, especially during organogenesis. They must also be advised about the necessary rigorous control of the prothrombine time to guard against the appearance of thromboembolic problems and Warfarin embryopathy. Patients with aortic \"dura-mater\" prosthesis should be discouraged from becoming pregnant. The most favorable period for pregnancy in rheumatic heart patients with any kind of cardiac surgical history is that lasting from a minimum of one year to a maximum of six years after operation. A majority of births by ceasarean section was a constant in all groups studied these were carried out on the basis of the obstetrician\'s recommendation. In the surgical sub-group \"2\" (those with Starr-Edwards prosthesis) there is a relatively high probability of programm~d births due to the use of oral anticoagulants. Surgery ought to be carried out, preferably, either before of after pregnancy. During the period of pregnancy the theoretically ideal occasion for surgery is between the 18th and 24th. weeks of pregnancy or, at any time during the pregnancy in urgent cases. Electrical cardioversion is a harmless procedure for the expectant mother and may be carried out at any time during the pregnancy for the reversal of the atrial fibrilation to the sinus rhythm. The maternal death rate for the 301 pregnancies studied was of 1.66 per cent , though there was a significant difference between the proportion of deaths occuring in groups I and II. The loss of the conceptual product was significantly less in Group I (clinical) 4.48 per cent than in Group II (surgical) 12.39 per cent . The result obtained permitted a better assessment of the cardiological and pregnancy risks, as well as making possible the characterization of the different parameters which, considered as a group, will be fundamental to the assessment of the prognosis of women with rheumatic heart disease.

M.A. (Psychology) / Numerous amounts ofliterature has confirmed the positive correlation that exists between exercise and psychological well-being. With the increased interest in the associated psychological factors ofpain, the present study was undertaken to investigate the effects of chronic pain on rheumatoid arthritic and osteoarthritic patients, with the overall aim of reducing, and alleviating these factors. The psychological factors studied were depression, effects ofthe impact ofarthritis, for example, on the independent, physical and psychosocial aspects oftheir lives, as well as coping. It was hypothesized that by engaging in an aquatic exercise program there would be a reduction/alleviation ofpain, which in tum would demonstrate a reduction in the psychological components ofpain. Evidence was found to support the hypothesis, due to the fact that, after exposure to the aquatic therapy program, subjects demonstrated a reduction in pain followed by a reduction in depression, slight improvement in coping with their arthritis, and the impact of arthritis was partially alleviated. The need for a larger sample group, as well a longer period of investigation will be needed for future research.

Afin de modéliser l'évolution de l’infection par le chikungunya (CHIK), son impact, et les facteurs pronostiques de chronicité, nous avons travaillé en trois parties. L'impact à long terme de l’épidémie de CHIK en 2005-2006 à la Réunion a été estimé en calculant la proportion de patients en phase chronique au cours du temps et la charge globale de morbidité du CHIK par la méthode des années de vie ajustées sur l'invalidité (méthode DALY de l’OMS, qui prend en compte les années de vie perdues en raison de la mortalité prématurée et des années de vie vécues avec une incapacité). Ainsi entre 51,2 et 65,3% des patients étaient estimés symptomatiques après 1 an et 0% à15,2% après 5 ans. Le total d’années de vie en bonne santé perdues à la Réunion a été estimé à 65-73/1000 personnes, 55,5% des pertes concernant la population active (les 20 à 60 ans), et 86% étant dues à la persistance de rhumatismes post-CHIK (phase chronique). Les facteurs pronostiques de la persistance de rhumatismes et de l’altération de la qualité de vie (QdV) à long terme (30 mois) ont été étudiés dans une cohorte des gendarmes dont 25% étaient infectés (CHIK+). Etre CHIK+, avoir des comorbidités et un moral déprimé pendant la phase aiguë étaient prédictifs de la persistance d’arthrite comme d’arthralgies. De plus, la présence d’arthralgies ou arthrite à six mois était très prédictive de la persistance des mêmes rhumatismes à 30 mois. / To model the evolution of chikungunya virus (CHIK) infection, its impact and the prognostic factors of post-CHIK rheumatism and quality of life, we worked in three parts. The long-term impact of the 2005-2006 CHIK outbreaks in Reunion Island was estimated by calculating the proportion of chronic patients over time and the global burden of CHIK using the Disability Adjusted Life Years (DALY) method. This method sums the years of life lost due to premature mortality and the years lived with disability. Between 51.2 and 65.3% of patients were estimated chronic after 1 year and 0%-15.2% after 5 years. The global disease burden of CHIK was estimated 65-73 DALYs/1000 persons, 55.5% concerning the active population (20-60 years old), and 86% due to persistence of post-CHIK rheumatisms. Prognostic factors of the long-term (30 months) rheumatisms and impaired quality of life (QoL) were studied in a cohort of French army policemen (25% CHIK infected: CHIK+). Being CHIK+, suffering of comorbidity and having depressed mood during the acute stage were predictive for both persistent arthritis and arthralgias at 30 months. In addition, suffering of either arthralgias or arthritis at six months was predictive of the same symptoms at 30 months. Determinants of impaired QoL were CHIK infection and comorbidity, in addition to older age, work-stoppage during the acute infection and arthritis at 6 months for the QoL physical component, and depressed mood at 6 months for the mental health component.Association between the severity of initial CHIK-stages and recovery were studied using multiple correspondence analysis (MCA).

Diese Arbeit untersucht die Wirksamkeit des monoklonalen Antikörpers Belimumab bei Patient*innen mit systemischem Lupus erythematodes in einer monozentrischen Routinekohorte. Besonderes Augenmerk lag auf der Betrachtung des Ansprechens einzelner Organmanifestationen. Es sollten Subgruppen mit hoher oder niedriger Wahrscheinlichkeit für ein Ansprechen identifiziert werden. Es erfolgte eine retrospektive Auswertung von regelmäßig und standardisiert erhobenen Patient*innendaten. Betrachtet wurden dokumentierte Symptome, Laborparameter und daraus abgeleitete klinische Scores. Betrachtet wurden 4 Zeitpunkte in den ersten 12 Monaten der Therapie und ein weiterer Last visit-Zeitpunkt zur Evaluation des Langzeiterfolges. Bei Patient*innen, deren Therapie vorzeitig beendet wurde, wurden die Werte der letzten Beobachtung unter Therapie übernommen. Es erfolgte eine Auswertung in Untergruppen, abhängig vom Nachweis von Organmanifestationen zu Therapiebeginn. Untersucht wurde ein aussagekräftiges Studienkollektiv mit eher niedriger Krankheitsaktivität. Die Therapie mit Belimumab am UKD wurde für die meisten Patient*innen als erfolgreich bewertet; von 27 Therapien wurden 21 (78 %) von den behandelnden Ärzt*innen als erfolgreich eingeschätzt, was auf eine gute Wirksamkeit in der Population hinweist. Die Zahl symptomfreier Personen stieg innerhalb von 12 Monaten von 1 auf 7 und im weiteren Therapieverlauf auf 10. Es zeigten sich signifikante Änderungen von klinischen Scores und Komplementproteinen; so fiel der mediane SLEDAI von 6 auf 4 Punkte und das mediane C4 stieg von 0,09 g/l innerhalb von 12 Monaten auf normwertige 0,10 g/l sowie im weiteren Verlauf auf 0,16 g/l. Die mittlere Prednisolondosierung wurde innerhalb von 12 Monaten von 5,8 mg/d auf 5,0 mg/d und langfristig auf 3,3 mg/d gesenkt. Belimumab zeigte sich bei 6 von 6 Patient*innen mit Exanthem und 4 von 6 Patient*innen mit Arthritis mit fast vollständigem Symptomrückgang sehr gut wirksam. Von 10 Patient*innen mit einem initialem Prednisolonbedarf von ≥ 7,5mg/d konnten 6 ihre Prednisolondosis um mindestens 25 % senken. Das Symptom Fatigue wurde bei 6 von 18 Patient*innen nach 12 Monaten nicht mehr dokumentiert. Von 11 Patient*innen mit Raynaud-Symptomatik wurde ebendiese nach 12 Monaten nur noch von 7 dokumentiert. Es zeigten sich keine Hinweise auf eine Wirksamkeit auf Leuko- oder Thrombopenie. In weiteren Studien könnte die Wirksamkeit von Belimumab bei Patient*innen mit Lupusnephritis, Raynaud-Symptomatik, Fatigue, hämatologischer Beteiligung und niedriger Krankheitsaktivität weiter untersucht werden.:INHALTSVERZEICHNIS III ABKÜRZUNGSVERZEICHNIS VIII 1 EINLEITUNG 10 1.1 Systemischer Lupus erythematodes (SLE) 10 1.1.1 Geschichte 10 1.1.2 Epidemiologie 11 1.1.3 Ätiologie und Pathogenese 11 1.1.4 Symptome 12 1.1.4.1 Konstitutionell 14 1.1.4.2 Hämatologisch 14 1.1.4.3 Neuropsychiatrisch 14 1.1.4.4 Mukokutan 14 1.1.4.5 Serositis 15 1.1.4.6 Muskuloskelettal 15 1.1.4.7 Renal 15 1.1.4.8 weitere Symptome 15 1.1.5 Diagnostik 16 1.1.5.1 Anamnese 16 1.1.5.2 Klinische Untersuchung 16 1.1.5.3 Labordiagnostik 16 1.1.6 Aktivitätsmessung 17 1.1.7 Letalität 17 1.1.8 Sozioökonomische Belastung und QOL-Einschränkung 18 1.1.9 Klassifikationskriterien 19 1.1.10 Aktivitätsscores 20 1.1.11 Therapie 20 1.1.11.1 Basismaßnahmen 21 1.1.11.2 Glukokortikoide 21 1.1.11.3 DMARDs (disease-modifying anti-rheumatic drugs) 21 1.1.11.4 Cyclophosphamid 22 1.2 Belimumab 23 1.2.1 Wirkmechanismus 23 1.2.2 Zulassungsstudien 23 1.2.2.1 Studienpopulation 24 1.2.2.2 nachgewiesene Effekte 24 Unerwünschte Arzneimittelwirkungen (UAW) in den Zulassungsstudien 25 1.2.2.3 Zulassung 26 1.2.3 Belimumab in der klinischen Anwendung 26 2 FRAGESTELLUNG 27 3 MATERIAL UND METHODEN 28 3.1 Studienkollektiv 28 3.2 Ethik 28 3.3 Erhobene Daten 28 3.3.1 Charakterisierung des Studienkollektivs 29 3.3.2 Datumsangaben 29 3.3.3 Zeitpunkte 29 3.3.4 Zeitpunktabhängige Parameter 30 3.3.5 Erhobene, nicht aussagekräftige Daten 32 3.3.6 Organmanifestationen 32 3.4 Quellen 33 3.4.1 Patient*innenakte 34 3.4.2 Ärztliche Verlaufsdokumentation 34 3.4.3 Medikamente 35 3.4.4 SLE-Bogen 35 3.4.5 Laborwerte 36 3.4.6 Berechnung von klinischen Scores 37 3.4.7 Therapieerfolg 37 3.4.8 Dokumentationsungenauigkeiten 37 3.5 Statistische Verfahren 38 3.5.1 Normalverteilung 38 3.5.2 Signifikanztests 39 4 ERGEBNISSE 41 4.1 Studienkollektiv 41 4.1.1 Allgemeine Zusammensetzung 41 4.1.2 Erfüllung der EULAR/ACR2019-Kriterien 43 4.1.3 Antikörperstatus 44 4.1.4 Charakterisierung der einzelnen Patient*innen 45 4.2 Zeitpunktübergreifende Ergebnisse 49 4.2.1 Auswertungszeitraum 49 4.2.2 Therapiedauer 50 4.2.3 Zeitpunkte und beendete Therapien 50 4.2.4 Therapieerfolg 51 4.2.5 Krankheitsschübe und Prednisolonstoßtherapien 52 4.2.6 weitere Medikamente 53 4.2.7 Unerwünschte Arzneimittelwirkungen 53 4.3 Zeitpunktabhängige Ergebnisse 55 4.3.1 Datumsdifferenzen 55 4.3.2 Prednisolonbasistherapie 56 4.3.3 Symptome 56 4.3.4 Paraklinik 58 4.3.5 Scores 58 4.3.6 Angaben auf der visuellen Analogskala 59 4.4 Auswertung nach Patient*innengruppen 61 4.4.1 Indikationsrelevante Organbeteiligungen 61 4.4.2 Patient*innen mit Arthritis 62 4.4.3 Patient*innen mit Fatigue 64 4.4.4 Patient*innen mit Exanthem 67 4.4.5 Patient*innen mit Raynaud-Symptomatik 68 4.4.6 Patient*innen mit hämatologischer Beteiligung 70 4.4.7 Patient*innen mit hohem Prednisolonbedarf 74 4.4.8 Patient*innen mit aktiver Lupusnephritis 76 5 DISKUSSION 78 5.1 Stärken und Schwächen der Studie 78 5.1.1 Anzahl der Patient*innen 78 5.1.2 Definition des Therapieerfolgs 78 5.1.3 Schubförmiger Verlauf der Erkrankung 79 5.1.4 Systematischer Fehler der Scores 79 5.1.5 Fortführung der letzten Beobachtung bei Patient*innen mit beendeter Therapie 80 5.1.6 Last visit-Zeitpunkt 80 5.1.7 Auswertung nach Patient*innengruppen 80 5.2 Studienkollektiv 82 5.2.1 Allgemeine Zusammensetzung 82 5.2.2 Erfüllung der EULAR/ACR2019-Kriterien 84 5.2.3 Antikörperstatus 86 5.3 Zeitpunktübergreifende Ergebnisse 87 5.3.1 Therapieerfolg 87 5.3.2 Krankheitsschübe und Prednisolonstoßtherapien 87 5.3.3 weitere Medikamente 87 5.3.4 Unerwünschte Arzneimittelwirkungen 87 5.4 Zeitpunktabhängige Ergebnisse 89 5.4.1 Datumsdifferenzen 89 5.4.2 Prednisolonbasistherapie 89 5.4.3 Symptome 89 5.4.4 Paraklinik 89 5.4.5 Scores 90 5.4.6 Angaben auf der visuellen Analogskala 91 5.5 Auswertung nach Patient*innengruppen 92 5.5.1 Indikationsrelevante Organbeteiligungen 92 5.5.2 Patient*innen mit Arthritis 93 5.5.3 Patient*innen mit Fatigue 93 5.5.4 Patient*innen mit Exanthem 93 5.5.5 Patient*innen mit Raynaud-Symptomatik 94 5.5.6 Patient*innen mit hämatologischer Beteiligung 94 5.5.7 Patient*innen mit hohem Prednisolonbedarf 94 5.5.8 Patient*innen mit aktiver Lupusnephritis 95 5.6 Relevanteste Ergebnisse 96 5.7 Ausblick 97 6 ZUSAMMENFASSUNG 98 7 SUMMARY 99 LITERATURVERZEICHNIS 106 ANHANG 123 DANKSAGUNG 124 ANLAGE 1: ERKLÄRUNG ZUR ERÖFFNUNG DES PROMOTIONSVERFAHRENS 125 ANLAGE 2: ERKLÄRUNG ZUR EINHALTUNG AKTUELLER GESETZLICHER VORGABEN 126