Made available in DSpace on 2016-06-02T20:19:20Z (GMT). No. of bitstreams: 1 4902.pdf: 1687901 bytes, checksum: 884057c536a8157ba6c0445defdeb8bb (MD5) Previous issue date: 2013-02-19 / Financiadora de Estudos e Projetos / Postural variations are common in childhood / adolescence and are corrected spontaneously. When maintained can cause overload. The objective of the first study was to evaluate the prevalence of postural variations in children / adolescents and to identify factors that explain these variations among age, gender, manual preference, body mass index (BMI) and physical activity, through multiple logistic regression analysis. 288 students were evaluated through postural observation. They were 59.4% female, mean age 10.6 (2.4) years, body mass 38.6 (12.7) kg and height 1.5 (0.1) m. Results show high prevalence of postural changes and their association with factors: age (forward head posture, shoulders and iliac crests asymmetry winged scapula), sex (winged scapula), BMI (forward head, iliac crest asymmetry, valgus knees and winged scapula) and not perform physical activity (valgus knees). Among the factors evaluated, obesity is a modifiable factor. Therefore, its association with the changes must be explored to facilitate the planning of preventive measures and more effective treatment. So, the objectives of the second study were to describe the prevalence of overweight in adolescents and identify differences in posture, (evaluated qualitatively and quantitatively) and the reporting of musculoskeletal pain (assessed by an adaptation of the Nordic Questionnaire) among normal weight and overweight in a large sample of students. 420 students were evaluated, 60% female, with mean age 11.1 (2.3) years, height 1.5 (0.1) m. body mass 44.5 (14.1) kg. Findings indicate that the prevalence of overweight was 36.2%. There was a higher prevalence of thoracic kyphosis, lumbar hyperlordosis and valgus knees with overweight students. There was no association between the presence of pain and weight excess. In childhood and adolescence, the posture lies in the development process. Therefore, any functional change to poor posture will reflect negatively in the future. So, the objective of the third study was to evaluate the effects of an exercise program of stretching and strengthening exercises in relation to posture, mobility of the spine and musculoskeletal pain in primary school children. Qualitative and quantitative postural evaluation of the trunk, pain and spine mobility (Whistance method) were collected before and after the intervention. The subjects were randomly assigned to groups. The exercise program was applied in groups, at school, twice weekly for eight weeks, for 50 minutes. The analysis included 78 subjects in the intervention group and 93 in the control, with mean age 11.6 (1.7) years, 1.5 (0.1) meters of height, 46.3 (14.1) kg of mass. It was also comprised of 67.3% female. The control group showed greater worsening percentage than intervention group to the posture of the shoulders. For the pain, the intervention group showed greater improvement percentage. These results show that the exercise program as described is effective in pain and posture of the shoulders. For other variables, adjustments in the duration of the program and individualized care may be recommended. / Variações posturais são frequentes na infância/adolescência e são corrigidas espontaneamente. Quando mantidas podem causar sobrecarga. O objetivo do primeiro estudo foi avaliar a prevalência de variações posturais em crianças/adolescentes e identificar fatores explicativos para estas variações, dentre: idade, sexo, dominância manual, índice de massa corporal (IMC) e atividade física, por meio da análise de regressão logística múltipla. Foram avaliados por meio de observação postural 288 escolares, sendo 59,4% do sexo feminino; idade média de 10,6 (2,4) anos, massa corporal 38,6 (12,7) kg e altura 1,5 (0,1) metros. Os resultados mostram altas prevalências de alterações posturais e sua associação com os fatores avaliados: idade (anteriorização da cabeça, assimetria entre os ombros e cristas ilíacas e escápulas aladas), sexo (escápulas aladas), IMC (anteriorização da cabeça, elevação da crista, joelhos valgos e escápulas aladas) e não realização de atividade física (joelhos valgos). Dentre os fatores avaliados, a obesidade é um fator modificável. Portanto, sua associação com as alterações deve ser explorada para propiciar o planejamento de medidas preventivas e de tratamento mais eficazes. Nesse sentido, os objetivos do segundo estudo foram: descrever a prevalência de excesso de peso em escolares, e identificar diferenças na postura, avaliada de forma qualitativa e quantitativa, e no relato de dor musculoesquelética (avaliada por uma adaptação do Questionário Nórdico) entre sujeitos eutróficos e com excesso de peso em uma ampla amostra de escolares. Foram avaliados 420 escolares, sendo 60% do sexo feminino, com médias de idade 11,1(2,3) anos; altura 1,5(0,1) metros e massa corporal 44,5(14,1) kg. A prevalência de excesso de peso foi 36,2%. Houve maior prevalência de hipercifose torácica, hiperlordose lombar e joelhos valgos entre os estudantes com excesso de peso. Não houve associação entre a presença de dor e o excesso de peso. Como na infância e adolescência a postura encontra-se em processo de desenvolvimento, qualquer alteração funcional conseguinte à má postura irá repercutir negativamente no futuro. Portanto, o objetivo do terceiro estudo foi avaliar os efeitos de um programa de exercícios de alongamento e fortalecimento muscular em relação à postura do tronco, mobilidade da coluna vertebral e dor musculoesquelética em estudantes do ensino fundamental. Avaliação postural qualitativa e quantitativa (SAPo), dor e mobilidade da coluna (método de Whistance) foram coletados antes e após a intervenção. Os sujeitos foram aleatoriamente alocados nos grupos. O programa de exercícios foi aplicado em grupo, no ambiente escolar, duas vezes por semana por oito semanas, durante 50 minutos. A análise contou com 78 sujeitos no grupo intervenção e 93 no controle, com médias de idade 11,6(1,7) anos, 1,5(0,1) metros de altura, 46,3(14,1) quilogramas de massa. Era também constituída de 67,3% do sexo feminino. O grupo controle apresentou porcentagem de piora maior que o grupo intervenção para a postura dos ombros. Para a presença de dor, o grupo intervenção apresentou maior porcentagem de melhora. Esses resultados mostram que o programa de exercícios como descrito tem efeito na a dor e na postura dos ombros. Para as outras variáveis, ajustes na duração do programa e atendimento individualizado podem ser recomendados.

A dor crônica musculoesquelética é um importante problema de saúde pública, pois, além de ter alta prevalência, suas consequências são nefastas à condição física, psicológica e comportamental, levando ao afastamento do trabalho e aposentadoria precoce. Considerando que quadros de dor crônica são relacionados a alterações biológicas em importantes sistemas endógenos, a busca de biomarcadores sistêmicos interrelacionados com este processo podeser útil para o entendimento dos possíveis efeitos terapêuticos e adversos de técnicas de neuromodulacão, tanto centrais quanto periféricas. Baseado nisto, o objetivo principal deste estudo foi avaliar o efeito dos tratamentos com estimulação magnética transcraniana repetitiva (rTMS) e eletroestimulação intramuscular (DIMST) na intensidade da dor e em parâmetros bioquímicos e neurofisiológicos em pacientes com dor crônica musculoesquelética,e, secundariamente, buscar possíveis biomarcadores em quadros de dor crônica musculoesquelética. Este estudo foi dividido em dois experimentos. No experimento 1, comparou-se o efeito das técnicas de neuromodulação periférica (DIMST) e central (rTMS) sobre os parâmetros de excitabilidade cortical e níveis séricos de BDNF, S100β, citocinas e parâmetros de estresse oxidativo em pacientes com SDM. Foram recrutadas 46 mulheres, com idade entre 19 e 75 anos e diagnóstico de síndrome dolorosa miofascial (SDM). Trata-se de um ensaio clínico randomizado, cego, em paralelo, controlado com placebo-sham. As pacientes foram randomizadas em 4 grupos: (1) rTMS+DIMST, (2) rTMS +sham-DIMST, (3) sham-rTMS+DIMST e (4) sham-rTMS + sham-DIMST. No experimento 2, avaliou-se parâmetros neurofisiológicos de excitabilidade cortical e níveis séricos de BDNF como marcadores de dor crônica musculoesquelética. Foram recrutadas 72 mulheres, com idade entre 19 e 75 anos e diagnóstico de osteoartrite (OA) e SDM. Os parâmetros mensurados foram: dor pela escala análogo-visual (EAV), limiar de dor por algometria (PPT) e excitabilidade cortical pelo TMS. No experimento 1, as pacientes mostrarem-se iguais entre os grupos no basal. Houve uma redução na dor mensurada pela EAV nos grupos 1, 2 e 3 em relação ao grupo 4. O parâmetro de excitabilidade, potencial evocado motor (MEP), apresentou um aumento de amplitude ao final da intervenção 2. Não foram observadas mudanças nos parâmetros bioquímicos analisados durante e ao final das intervenções, seja entre as intervenções e dentro das intervenções. No experimento 2, observou-se que o PPT apresenta uma correlação positiva com inibição intracortical (ICI) e negativa com a facilitação intracortical (ICF). As pacientes com SDM apresentam o período silente (CSP) mais longo que pacientes com OA. O BDNF e estradiol apresentam relação positiva com PPT; no entanto, quando foi avaliada a interação destes fatores, o efeito sobre o PPT foi em direção oposta. Em resumo, os tratamentos ativos, central e/ou periférico, mostraram-se eficazes no alívio da dor, porém, dentre os parâmetros bioquímicos analisados, não se observouum biomarcador responsivo a estas técnicas. Sugere-se uma relação entre dor crônica musculoesquelética e alterações na excitabilidade cortical do córtex motor. Além disto, é importante ressaltar que estes tratamentos não alteraram nenhum dos parâmetros de avaliação de dano celular, como, por exemplo, o aumento de proteína glial (S100β), sugerindo que são técnicas seguras no que se refere aos parâmetros avaliados nesta tese. Posteriores estudos são necessários buscando novos biomarcadores que permitam um melhor diagnóstico, prognóstico e avaliação da resposta ao tratamento com técnicas de neuromodulação na dor crônica musculoesquelética. / Chronic musculoskeletal pain is a major public health problem with high prevalence, because, besides its high prevalences, its consequences are harmful to the physical, psychological and behavioral condition, leading to absence from work and early retirement. Taking into account that chronic pain processes are related to biological changes in endogenous systems, searching systemic biomarkers interconnected with this process can be useful to understand the potential therapeutic and adverse effects of the neuromodulation techniques, both central and peripheral. Based on that, the aim of this study was to evaluate the effect of treatment with repetitive transcranial magnetic stimulation (rTMS) and intramuscular electrical stimulation (DIMST) on pain intensity, biochemical and neurophysiological parameters in chronic musculoskeletal pain patients. Secondly, the aim was to find possible biomarkers in chronic musculoskeletal pain conditions. This study was divided into two protocols. Protocol 1, it was compared the effect of central (rTMS) and peripheral (DIMST) neuromodulation techniques on pain intensity, cortical excitability parameters and serum levels of BDNF, S100β, cytokines and oxidative stress parameters in patients with myofascial pain syndrome (MPS.) Fourty women, aged between 19 and 75 years, MPS diagnosis were recruited. This is a randomized, blind, parallel, placebo - sham clinical trial. The patients were randomized into four groups: (1) rTMS + DIMST, (2) rTMS + sham-DIMST, (3) sham-rTMS + DIMST, and (4) sham-rTMS + sham-DIMST. Protocol 2, we assessed the neurophysiological parameters of cortical excitability and BDNF serum levels as markers of chronic musculoskeletal pain. Seventy-two women, aged between 19 and 75 years diagnosed with osteoarthritis (OA) and MPS were recruited. The measured parameters were: pain intensity by visual analogue scale (VAS), pain pressure threshold (PPT) and cortical excitability by TMS. In protocol 1, the patients presented similarities in the baseline between the four groups. The patients presented a reduction in painintensity measured by VAS in the groups 1, 2 and 3 in relation to group 4. After rTMS intervention, there was an increase in the MEP amplitude. There were no changes in biochemical parameters analyzed during and after the interventions. In protocol 2, it was observed that PPT has a positive correlation with intracortical inhibition (ICI) and negative correlation with intracortical facilitation (ICF). Patients with MPS exhibit longer silent period (CSP) than OA patients. BDNF and estradiol serum levels presented a positive correlation with PPT; however, when their interaction was assessed, the effect on the PPT was in the opposite direction. In summary, the active, central and/ or peripheral treatments were effective in relieving the pain; however, among the biochemical parameters analyzed, there was no biomarker responsive to these techniques. It is suggested a relationship between chronic musculoskeletal pain and changes in cortical excitability of the motor cortex. Furthermore, it is important to note that these treatments did not alter any of the parameters of cellular damage assessment, such as the increase of glial protein (S100β), suggesting that they are safe as to the parameters evaluated in these techniques. Further studies are needed to find new biomarkers that allow better diagnosis, prognosis and assessment of treatment response with neuromodulation techniques in chronic musculoskeletal pain.

A dor crônica musculoesquelética é um importante problema de saúde pública, pois, além de ter alta prevalência, suas consequências são nefastas à condição física, psicológica e comportamental, levando ao afastamento do trabalho e aposentadoria precoce. Considerando que quadros de dor crônica são relacionados a alterações biológicas em importantes sistemas endógenos, a busca de biomarcadores sistêmicos interrelacionados com este processo podeser útil para o entendimento dos possíveis efeitos terapêuticos e adversos de técnicas de neuromodulacão, tanto centrais quanto periféricas. Baseado nisto, o objetivo principal deste estudo foi avaliar o efeito dos tratamentos com estimulação magnética transcraniana repetitiva (rTMS) e eletroestimulação intramuscular (DIMST) na intensidade da dor e em parâmetros bioquímicos e neurofisiológicos em pacientes com dor crônica musculoesquelética,e, secundariamente, buscar possíveis biomarcadores em quadros de dor crônica musculoesquelética. Este estudo foi dividido em dois experimentos. No experimento 1, comparou-se o efeito das técnicas de neuromodulação periférica (DIMST) e central (rTMS) sobre os parâmetros de excitabilidade cortical e níveis séricos de BDNF, S100β, citocinas e parâmetros de estresse oxidativo em pacientes com SDM. Foram recrutadas 46 mulheres, com idade entre 19 e 75 anos e diagnóstico de síndrome dolorosa miofascial (SDM). Trata-se de um ensaio clínico randomizado, cego, em paralelo, controlado com placebo-sham. As pacientes foram randomizadas em 4 grupos: (1) rTMS+DIMST, (2) rTMS +sham-DIMST, (3) sham-rTMS+DIMST e (4) sham-rTMS + sham-DIMST. No experimento 2, avaliou-se parâmetros neurofisiológicos de excitabilidade cortical e níveis séricos de BDNF como marcadores de dor crônica musculoesquelética. Foram recrutadas 72 mulheres, com idade entre 19 e 75 anos e diagnóstico de osteoartrite (OA) e SDM. Os parâmetros mensurados foram: dor pela escala análogo-visual (EAV), limiar de dor por algometria (PPT) e excitabilidade cortical pelo TMS. No experimento 1, as pacientes mostrarem-se iguais entre os grupos no basal. Houve uma redução na dor mensurada pela EAV nos grupos 1, 2 e 3 em relação ao grupo 4. O parâmetro de excitabilidade, potencial evocado motor (MEP), apresentou um aumento de amplitude ao final da intervenção 2. Não foram observadas mudanças nos parâmetros bioquímicos analisados durante e ao final das intervenções, seja entre as intervenções e dentro das intervenções. No experimento 2, observou-se que o PPT apresenta uma correlação positiva com inibição intracortical (ICI) e negativa com a facilitação intracortical (ICF). As pacientes com SDM apresentam o período silente (CSP) mais longo que pacientes com OA. O BDNF e estradiol apresentam relação positiva com PPT; no entanto, quando foi avaliada a interação destes fatores, o efeito sobre o PPT foi em direção oposta. Em resumo, os tratamentos ativos, central e/ou periférico, mostraram-se eficazes no alívio da dor, porém, dentre os parâmetros bioquímicos analisados, não se observouum biomarcador responsivo a estas técnicas. Sugere-se uma relação entre dor crônica musculoesquelética e alterações na excitabilidade cortical do córtex motor. Além disto, é importante ressaltar que estes tratamentos não alteraram nenhum dos parâmetros de avaliação de dano celular, como, por exemplo, o aumento de proteína glial (S100β), sugerindo que são técnicas seguras no que se refere aos parâmetros avaliados nesta tese. Posteriores estudos são necessários buscando novos biomarcadores que permitam um melhor diagnóstico, prognóstico e avaliação da resposta ao tratamento com técnicas de neuromodulação na dor crônica musculoesquelética. / Chronic musculoskeletal pain is a major public health problem with high prevalence, because, besides its high prevalences, its consequences are harmful to the physical, psychological and behavioral condition, leading to absence from work and early retirement. Taking into account that chronic pain processes are related to biological changes in endogenous systems, searching systemic biomarkers interconnected with this process can be useful to understand the potential therapeutic and adverse effects of the neuromodulation techniques, both central and peripheral. Based on that, the aim of this study was to evaluate the effect of treatment with repetitive transcranial magnetic stimulation (rTMS) and intramuscular electrical stimulation (DIMST) on pain intensity, biochemical and neurophysiological parameters in chronic musculoskeletal pain patients. Secondly, the aim was to find possible biomarkers in chronic musculoskeletal pain conditions. This study was divided into two protocols. Protocol 1, it was compared the effect of central (rTMS) and peripheral (DIMST) neuromodulation techniques on pain intensity, cortical excitability parameters and serum levels of BDNF, S100β, cytokines and oxidative stress parameters in patients with myofascial pain syndrome (MPS.) Fourty women, aged between 19 and 75 years, MPS diagnosis were recruited. This is a randomized, blind, parallel, placebo - sham clinical trial. The patients were randomized into four groups: (1) rTMS + DIMST, (2) rTMS + sham-DIMST, (3) sham-rTMS + DIMST, and (4) sham-rTMS + sham-DIMST. Protocol 2, we assessed the neurophysiological parameters of cortical excitability and BDNF serum levels as markers of chronic musculoskeletal pain. Seventy-two women, aged between 19 and 75 years diagnosed with osteoarthritis (OA) and MPS were recruited. The measured parameters were: pain intensity by visual analogue scale (VAS), pain pressure threshold (PPT) and cortical excitability by TMS. In protocol 1, the patients presented similarities in the baseline between the four groups. The patients presented a reduction in painintensity measured by VAS in the groups 1, 2 and 3 in relation to group 4. After rTMS intervention, there was an increase in the MEP amplitude. There were no changes in biochemical parameters analyzed during and after the interventions. In protocol 2, it was observed that PPT has a positive correlation with intracortical inhibition (ICI) and negative correlation with intracortical facilitation (ICF). Patients with MPS exhibit longer silent period (CSP) than OA patients. BDNF and estradiol serum levels presented a positive correlation with PPT; however, when their interaction was assessed, the effect on the PPT was in the opposite direction. In summary, the active, central and/ or peripheral treatments were effective in relieving the pain; however, among the biochemical parameters analyzed, there was no biomarker responsive to these techniques. It is suggested a relationship between chronic musculoskeletal pain and changes in cortical excitability of the motor cortex. Furthermore, it is important to note that these treatments did not alter any of the parameters of cellular damage assessment, such as the increase of glial protein (S100β), suggesting that they are safe as to the parameters evaluated in these techniques. Further studies are needed to find new biomarkers that allow better diagnosis, prognosis and assessment of treatment response with neuromodulation techniques in chronic musculoskeletal pain.

Background: Work-related stress (WRS) is associated with musculoskeletal pain (MSP), changes in the autonomic nervous system (ANS) and anxiety. Objective: To determine the feasibility of a follow-up study and treatment efficacy of the Reaset Approach on MSP, ANS and State-Trait anxiety. Methods: 15 subjects with WRS and MSP were assigned into 3 groups (Body, Head-Neck, Head-Neck-Body). Each group received a single 25 minute ‘Reaset Approach’ intervention. Heart rate variability (HRV), electro-dermal activity (EDA), State Trait Anxiety (STAI) and MSP were measured. Results: HRV parameters: SDNN increased in 13 of 15 subjects while SD1 and SD2 increased in 12 of 15 subjects. EDA reduced in 10 of 14 subjects. State Anxiety reduced in all subjects and Trait Anxiety reduced in 14 of 15 subjects. MSP reduced in all subjects after the intervention and were still lower three days afterwards. Conclusions: This pilot study determined that a follow-up study can ensue provided minor modifications are implemented and that the ‘Reaset Approach’ has an influence on the ANS, anxiety and MSP. Results do differ between groups. The intervention groups including the head and neck modalities demonstrated better results. / Hintergrund: Arbeitsbedingter Stress (ABS) ist verbunden mit muskelschmerzen, Veränderungen im autonomen Nervensystem (ANS) und Angst. Ziel: Machbarkeit einer Follow-up-Studie und Wirksamkeit der Behandlung des Reaset Ansatzes auf ANS, Muskelschmerzen und State und Trait- Angst bestimmen. Methoden: 15 Patienten mit ABS und Muskelschmerzen wurden in 3 Gruppen eingeteilt (Körper, Kopf-Hals, Kopf-Hals-Körper). Jede Gruppe erhielt eine einzige 25 Minuten dauernde 'Reaset Approach’-Behandlung. Herzfrequenzvariabilität (HRV), elektro-dermale Aktivität (EDA), State-Trait-Angstsinventar (STAI) und Muskelschmerzen (SF-MPQ) wurden gemessen. Ergebnisse: Die HRV-wert: SDNN ist bei 13 von 15 Probanden erhöht, während SD1 und SD2 bei 12 von 15 Probanden zugenommen hat. EDA war bei 10 von 14 Probanden reduziert. Die State-Angst hat bei allen Probanden und die Trait-Angst bei 14 der 15 Probanden abgenommen. Muskelschmerzen waren bei alle Probanden anschließend an und drei Tage nach der Intervention reduziert. Schlussfolgerung: Diese Pilotstudie hat gezeigt, dass eine Follow-up-Studie fortgesetzt werden kann, sofern kleinere Änderungen durchgeführt werden. Die 'Reaset Approach’ hat einen günstigen Einfluss auf die ANS, State-Trait-Angst und Muskelschmerzen. Ergebnisse zwischen den Gruppen sind unterschiedlich. Die Interventionsgruppen mit einschließlich der Kopf-Hals-Modalitäten zeigten bessere Ergebnisse..

INTRODUÇÃO: A infecção pelo vírus C é um grande problema de saúde pública e tem se tornado a principal indicação de transplante de fígado. Com uma distribuição universal, é a segunda doença crônica viral mais frequente no mundo. No entanto, a hepatite C crônica é mais que uma doença hepática. Pacientes com infecção crônica pelo HCV podem desenvolver um grande número de manifestações extra-hepáticas independentemente da gravidade da doença hepática. Há muitas doenças reumatológicas associadas à infecção pelo HCV, incluindo artralgia, mialgia e artrite. MÉTODOS: Um estudo transversal desenvolvido entre os pacientes atendidos no Ambulatório de Hepatites da Divisão de Clínica de Moléstias Infeciosas e Parasitárias do HCFMUSP, na cidade de São Paulo, no período de 2004 a 2008, selecionou 243 pacientes que preencheram os critérios de inclusão e assinaram o termo de consentimento após esclarecimentos sobre a pesquisa. Foi realizada uma entrevista com os pacientes, em que foram coletadas informações demográficas, epidemiológicas e clinico-laboratoriais. Foram realizados exames laboratoriais, bioquímicos, hematológicos, imunológicos, PCR, HCV, RNA quantitativo e genotipagem do HCV. A avaliação das características da infecção pelo HCV (epidemiológica, histológica, virológica), associada às manifestações extra-hepáticas clínicas reumatológicas (aquelas com prevalência > 10%) e laboratoriais (com prevalência > 5%), foi realizada utilizando-se as análises univariada e multivariada (regressão logística). Odds ratios (OR) ajustados e intervalos de confiança de 95% (IC 95%) foram derivados do coeficiente do modelo logístico multivariado final. Todas as análises foram realizadas com o pacote estatístico SPSS. RESULTADOS: Dos 243 pacientes estudados, pudemos determinar a provável forma de infecção em 147 (60,49%). Dos 147 pacientes, 93 (38,27%) sofreram transfusão sanguínea prévia, 10 (4,11%) tinham histórico de uso droga injetável há mais de 1 ano, 15 (6,17%) tinham antecedente de uso do droga inalatória há mais de 1 ano, 11 (4,52%) eram profissionais da saúde com histórico de acidente com material perfuro-cortante, 10 (4,11%) realizaram tatuagem e 8 (3,29%) tinham parceiro portador de hepatite C crônica. Nessa análise, 148 (60,9%) dos pacientes com hepatite C crônica apresentaram queixa de artralgia, 145 (59,7%) apresentaram queixa de mialgia, 144 (59,3%), de cansaço. A artrite esteve presente em 50 (20,57%) dos pacientes avaliados nesse estudo. Dentre estes pacientes, o envolvimento foi predominantemente poliarticular em 36 (72%) deles, acometendo grandes e pequenas articulações, simultaneamente, em 29 (58%). Idade maior que 50 anos, dor nas costas e crepitação em articulações mostraram-se fatores associados à artrite. Observou-se que sexo feminino, tabagismo importante e fibrose hepática avançada (F3 e F4) foram fatores associados à artralgia. Sexo feminino e tabagismo importante foram fatores associados à mialgia. CONCLUSÃO: Foi encontrada elevada prevalência de manifestações musculoesqueléticas entre os pacientes portadores de hepatite C crônica deste serviço. Os fatores de risco mais frequentes para a presença das manifestações extra-hepáticas foram sexo feminino e idade maior que 50 anos. Os autoanticorpos, embora freqüentes, não mostraram significância estatística com relação às principais manifestações musculoesqueléticas analisadas. Infiltrado inflamatório hepático e nível de transaminases também não apresentaram significância estatística / INTRODUCTION: C virus infection is a major public health problem and has become the leading indication for liver transplantation. With a worldwide distribution, is the second most common chronic viral worldwide. However, chronic hepatitis C is more than a liver disease. Patients with chronic HCV infection may develop a large number of extra hepatic manifestations regardless of the severity of liver disease. There are many rheumatic diseases associated with HCV infection including arthralgia, myalgia and arthritis. METHODS: A cross-sectional study carried out among patients treated in outpatient Hepatitis Clinical Division of Infectious and Parasitic Diseases of the HC-USP, in São Paulo, in the period from 2004 to 2008, selected 243 patients who met the inclusion criteria and signed the consent form after clarification of the research. An interview was conducted with patients which were collected demographic, epidemiological and clinical-laboratory. Laboratory tests were carried, biochemical, hematological, immunological, quantitative PCR HCV RNA and HCV genotyping. The evaluation of the characteristics of HCV infection (epidemiological, histological, virological) associated with extrahepatic manifestations rheumatology clinics (those with prevalence > 10%) and laboratory (with prevalence > 5%) were performed using univariate and multivariate analysis (regression logistics). Odds ratios (OR) and adjusted confidence intervals of 95% (95% CI) were derived from the ratio of the final multivariate logistic model. All analyzes were performed with the SPSS statistical package. RESULTS: Of the 243 patients studied were able to determine the likely form of infection in 147 (60.49%). Of the 147 patients, 93 (38.27%) had previous blood transfusion, 10 (4.11%) had a history of injection drug use for more than 1 years, 15 (6.17%) had prior use of the drug is inhaled over 1 year, 11 (4.52%) were health professionals with a history of accidents with sharp objects, 10 (4.11%) underwent tattooing and 8 (3.29%) had a partner with hepatitis C chronic. In this analysis, 148 (60.9%) of patients with chronic hepatitis C complained of arthralgia, 145 (59.7%) complained of myalgia, 144 (59.3%) of fatigue. Arthritis was present in 50 (20.57%) of the patients evaluated in this study. Among patients with arthritis of this study, involvement was predominantly polyarticular in 36 (72%) of them, affecting large and small joints simultaneously in 29 (58%). Age greater than 50 years, back pain and crepitus in the joints proved to be factors associated with arthritis. We observed that female smoking important and advanced liver fibrosis (F3 and F4) were associated with arthralgia. Female gender and smoking were important factors associated with myalgia. CONCLUSION: We found a high prevalence of musculoskeletal manifestations among patients with chronic hepatitis C of this service. The most common risk factors for the presence of extra hepatic manifestations were female and older than 50 years. The autoantibodies, although frequently not statistically significant compared with the major musculoskeletal manifestations analyzed. Inflammatory infiltrate and liver transaminase levels did not show statistical significance

INTRODUÇÃO: A infecção pelo vírus C é um grande problema de saúde pública e tem se tornado a principal indicação de transplante de fígado. Com uma distribuição universal, é a segunda doença crônica viral mais frequente no mundo. No entanto, a hepatite C crônica é mais que uma doença hepática. Pacientes com infecção crônica pelo HCV podem desenvolver um grande número de manifestações extra-hepáticas independentemente da gravidade da doença hepática. Há muitas doenças reumatológicas associadas à infecção pelo HCV, incluindo artralgia, mialgia e artrite. MÉTODOS: Um estudo transversal desenvolvido entre os pacientes atendidos no Ambulatório de Hepatites da Divisão de Clínica de Moléstias Infeciosas e Parasitárias do HCFMUSP, na cidade de São Paulo, no período de 2004 a 2008, selecionou 243 pacientes que preencheram os critérios de inclusão e assinaram o termo de consentimento após esclarecimentos sobre a pesquisa. Foi realizada uma entrevista com os pacientes, em que foram coletadas informações demográficas, epidemiológicas e clinico-laboratoriais. Foram realizados exames laboratoriais, bioquímicos, hematológicos, imunológicos, PCR, HCV, RNA quantitativo e genotipagem do HCV. A avaliação das características da infecção pelo HCV (epidemiológica, histológica, virológica), associada às manifestações extra-hepáticas clínicas reumatológicas (aquelas com prevalência > 10%) e laboratoriais (com prevalência > 5%), foi realizada utilizando-se as análises univariada e multivariada (regressão logística). Odds ratios (OR) ajustados e intervalos de confiança de 95% (IC 95%) foram derivados do coeficiente do modelo logístico multivariado final. Todas as análises foram realizadas com o pacote estatístico SPSS. RESULTADOS: Dos 243 pacientes estudados, pudemos determinar a provável forma de infecção em 147 (60,49%). Dos 147 pacientes, 93 (38,27%) sofreram transfusão sanguínea prévia, 10 (4,11%) tinham histórico de uso droga injetável há mais de 1 ano, 15 (6,17%) tinham antecedente de uso do droga inalatória há mais de 1 ano, 11 (4,52%) eram profissionais da saúde com histórico de acidente com material perfuro-cortante, 10 (4,11%) realizaram tatuagem e 8 (3,29%) tinham parceiro portador de hepatite C crônica. Nessa análise, 148 (60,9%) dos pacientes com hepatite C crônica apresentaram queixa de artralgia, 145 (59,7%) apresentaram queixa de mialgia, 144 (59,3%), de cansaço. A artrite esteve presente em 50 (20,57%) dos pacientes avaliados nesse estudo. Dentre estes pacientes, o envolvimento foi predominantemente poliarticular em 36 (72%) deles, acometendo grandes e pequenas articulações, simultaneamente, em 29 (58%). Idade maior que 50 anos, dor nas costas e crepitação em articulações mostraram-se fatores associados à artrite. Observou-se que sexo feminino, tabagismo importante e fibrose hepática avançada (F3 e F4) foram fatores associados à artralgia. Sexo feminino e tabagismo importante foram fatores associados à mialgia. CONCLUSÃO: Foi encontrada elevada prevalência de manifestações musculoesqueléticas entre os pacientes portadores de hepatite C crônica deste serviço. Os fatores de risco mais frequentes para a presença das manifestações extra-hepáticas foram sexo feminino e idade maior que 50 anos. Os autoanticorpos, embora freqüentes, não mostraram significância estatística com relação às principais manifestações musculoesqueléticas analisadas. Infiltrado inflamatório hepático e nível de transaminases também não apresentaram significância estatística / INTRODUCTION: C virus infection is a major public health problem and has become the leading indication for liver transplantation. With a worldwide distribution, is the second most common chronic viral worldwide. However, chronic hepatitis C is more than a liver disease. Patients with chronic HCV infection may develop a large number of extra hepatic manifestations regardless of the severity of liver disease. There are many rheumatic diseases associated with HCV infection including arthralgia, myalgia and arthritis. METHODS: A cross-sectional study carried out among patients treated in outpatient Hepatitis Clinical Division of Infectious and Parasitic Diseases of the HC-USP, in São Paulo, in the period from 2004 to 2008, selected 243 patients who met the inclusion criteria and signed the consent form after clarification of the research. An interview was conducted with patients which were collected demographic, epidemiological and clinical-laboratory. Laboratory tests were carried, biochemical, hematological, immunological, quantitative PCR HCV RNA and HCV genotyping. The evaluation of the characteristics of HCV infection (epidemiological, histological, virological) associated with extrahepatic manifestations rheumatology clinics (those with prevalence > 10%) and laboratory (with prevalence > 5%) were performed using univariate and multivariate analysis (regression logistics). Odds ratios (OR) and adjusted confidence intervals of 95% (95% CI) were derived from the ratio of the final multivariate logistic model. All analyzes were performed with the SPSS statistical package. RESULTS: Of the 243 patients studied were able to determine the likely form of infection in 147 (60.49%). Of the 147 patients, 93 (38.27%) had previous blood transfusion, 10 (4.11%) had a history of injection drug use for more than 1 years, 15 (6.17%) had prior use of the drug is inhaled over 1 year, 11 (4.52%) were health professionals with a history of accidents with sharp objects, 10 (4.11%) underwent tattooing and 8 (3.29%) had a partner with hepatitis C chronic. In this analysis, 148 (60.9%) of patients with chronic hepatitis C complained of arthralgia, 145 (59.7%) complained of myalgia, 144 (59.3%) of fatigue. Arthritis was present in 50 (20.57%) of the patients evaluated in this study. Among patients with arthritis of this study, involvement was predominantly polyarticular in 36 (72%) of them, affecting large and small joints simultaneously in 29 (58%). Age greater than 50 years, back pain and crepitus in the joints proved to be factors associated with arthritis. We observed that female smoking important and advanced liver fibrosis (F3 and F4) were associated with arthralgia. Female gender and smoking were important factors associated with myalgia. CONCLUSION: We found a high prevalence of musculoskeletal manifestations among patients with chronic hepatitis C of this service. The most common risk factors for the presence of extra hepatic manifestations were female and older than 50 years. The autoantibodies, although frequently not statistically significant compared with the major musculoskeletal manifestations analyzed. Inflammatory infiltrate and liver transaminase levels did not show statistical significance

Long-term musculoskeletal pain is a large public health problem with serious consequences for both the individual and society. Psychosocial factors have been shown to be good predictors of long-term disability and play an important role in the transition from acute to chronic pain. Early identification and intervention of those that run the risk of developing long-term disability would offer a great opportunity for reducing costs and personal suffering. The overall aim of this thesis was to assess a biopsychosocial approach to the assessment and management of musculoskeletal pain patients in primary health care. To this end, biopsychosocial assessment and treatment methods were tested in two different populations of primary care patients suffering pain. Results indicated that improvements in quality of life and work capacity one year after early multimodal rehabilitation were basically maintained after five years. The most salient prognostic factors determining return to work were educational level and the individual’s perceived health (Study I). Psychosocial factors as measured by the Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) were related to disability and perceived health three years after treatment for non-acute pain problems (Study II). The experimental group in the controlled multimodal pain rehabilitation programme had lower health care utilization and a reduced risk of using large amounts of medication after three years compared with the participants in the control group. However, there were no significant differences between the groups on variables such as work capacity, function, catastrophizing and pain (Study III). Distinct profiles of catastrophizing, fear-avoidance beliefs, and distress were extracted and meaningfully related to future sick leave and dysfunction (Study IV). Our findings provide support for the biopsychosocial model and highlight the importance of psychosocial factors in long-term outcome. The results underscore the need for early identification of patients at risk. Further, multimodal treatment that covers not only biological but also psychosocial factors seems to be a key to successful treatment, and ideally this intervention should be matched to the patients' needs.

Background: Work-related stress (WRS) is associated with musculoskeletal pain (MSP), changes in the autonomic nervous system (ANS) and anxiety. Objective: To determine the feasibility of a follow-up study and treatment efficacy of the Reaset Approach on MSP, ANS and State-Trait anxiety. Methods: 15 subjects with WRS and MSP were assigned into 3 groups (Body, Head-Neck, Head-Neck-Body). Each group received a single 25 minute ‘Reaset Approach’ intervention. Heart rate variability (HRV), electro-dermal activity (EDA), State Trait Anxiety (STAI) and MSP were measured. Results: HRV parameters: SDNN increased in 13 of 15 subjects while SD1 and SD2 increased in 12 of 15 subjects. EDA reduced in 10 of 14 subjects. State Anxiety reduced in all subjects and Trait Anxiety reduced in 14 of 15 subjects. MSP reduced in all subjects after the intervention and were still lower three days afterwards. Conclusions: This pilot study determined that a follow-up study can ensue provided minor modifications are implemented and that the ‘Reaset Approach’ has an influence on the ANS, anxiety and MSP. Results do differ between groups. The intervention groups including the head and neck modalities demonstrated better results.:I. Abstract (En) III II. Abstract (De) IV III. Table of Contents V IV. Index of figures VIII V. Index of tables IX VI. Index of abbreviations X 1 Introduction 1 2 Background 2 2.1 Work-related musculoskeletal pain 2 2.2 Work-related stress 3 2.3 Osteopathy and the autonomic nervous system 3 2.4 Stress, pain and osteopathy 4 3 Questions 6 3.1 Feasibility 6 3.2 Treatment effect 6 4 Methods 7 4.1 Study design 7 4.2 Participants 8 4.2.1 Inclusion criteria 8 4.2.2 Exclusion criteria 8 4.2.3 Recruitment 8 4.2.4 Randomization 10 4.3 Parameters 11 4.3.1 Heart rate variability 11 4.3.2 Electro-dermal activity 11 4.3.3 State anxiety 11 4.3.4 Trait anxiety 12 4.3.5 Perceived pain 12 4.4 Measuring Instruments 13 4.4.1 Heart rate variability 13 4.4.2 Electro-dermal Activity 13 4.4.3 State-Trait Anxiety Inventory 13 4.4.4 Short-Form McGill Pain Questionnaire 13 4.5 Interventions 14 4.5.1 Intervention ‘B’: Body 14 4.5.2 Intervention ‘HN’: Head and Neck 16 4.5.3 Intervention ‘HNB’: Head, Neck and Body 16 4.6 Study flow 18 4.7 Statistics 20 5 Results 21 5.1 Autonomic nervous system: Heart rate variability 21 5.1.1 SDNN 22 5.1.2 SD1 25 5.1.3 SD2 28 5.2 Autonomic Nervous System: Electro-dermal activity 31 5.3 Anxiety 34 5.3.1 State anxiety 34 5.3.2 Trait anxiety 37 5.4 Musculoskeletal pain 39 5.4.1 Visual analogue scale 40 5.4.2 Total Short-Form McGill Pain Questionnaire 43 6 Discussion 46 6.1 Discussion of the method 46 6.2 Discussion of the results 50 6.2.1 Autonomic nervous system 50 6.2.1.1 Heart rate variability 50 6.2.1.2 Electro-dermal activity 51 6.2.2 Anxiety 51 6.2.2.1 State anxiety 51 6.2.2.2 Trait Anxiety 52 6.2.3 Musculoskeletal pain 52 6.3 Suggestions for future research 53 7 Conclusion 54 8 Literature 55 9 Addendum 63 9.1 Table: SF-MPQ with Sensory, Affective and Evaluative dimension 63 9.2 Patient Information Sheet 64 9.3 Structured telephone interview 70 9.4 Structured pre-treatment interview 72 9.5 SF-MPQ permission 73 9.6 SF-MPQ 74 9.7 STAI License 76 9.8 STAI forms Y-1 and Y-2 77 / Hintergrund: Arbeitsbedingter Stress (ABS) ist verbunden mit muskelschmerzen, Veränderungen im autonomen Nervensystem (ANS) und Angst. Ziel: Machbarkeit einer Follow-up-Studie und Wirksamkeit der Behandlung des Reaset Ansatzes auf ANS, Muskelschmerzen und State und Trait- Angst bestimmen. Methoden: 15 Patienten mit ABS und Muskelschmerzen wurden in 3 Gruppen eingeteilt (Körper, Kopf-Hals, Kopf-Hals-Körper). Jede Gruppe erhielt eine einzige 25 Minuten dauernde 'Reaset Approach’-Behandlung. Herzfrequenzvariabilität (HRV), elektro-dermale Aktivität (EDA), State-Trait-Angstsinventar (STAI) und Muskelschmerzen (SF-MPQ) wurden gemessen. Ergebnisse: Die HRV-wert: SDNN ist bei 13 von 15 Probanden erhöht, während SD1 und SD2 bei 12 von 15 Probanden zugenommen hat. EDA war bei 10 von 14 Probanden reduziert. Die State-Angst hat bei allen Probanden und die Trait-Angst bei 14 der 15 Probanden abgenommen. Muskelschmerzen waren bei alle Probanden anschließend an und drei Tage nach der Intervention reduziert. Schlussfolgerung: Diese Pilotstudie hat gezeigt, dass eine Follow-up-Studie fortgesetzt werden kann, sofern kleinere Änderungen durchgeführt werden. Die 'Reaset Approach’ hat einen günstigen Einfluss auf die ANS, State-Trait-Angst und Muskelschmerzen. Ergebnisse zwischen den Gruppen sind unterschiedlich. Die Interventionsgruppen mit einschließlich der Kopf-Hals-Modalitäten zeigten bessere Ergebnisse..:I. Abstract (En) III II. Abstract (De) IV III. Table of Contents V IV. Index of figures VIII V. Index of tables IX VI. Index of abbreviations X 1 Introduction 1 2 Background 2 2.1 Work-related musculoskeletal pain 2 2.2 Work-related stress 3 2.3 Osteopathy and the autonomic nervous system 3 2.4 Stress, pain and osteopathy 4 3 Questions 6 3.1 Feasibility 6 3.2 Treatment effect 6 4 Methods 7 4.1 Study design 7 4.2 Participants 8 4.2.1 Inclusion criteria 8 4.2.2 Exclusion criteria 8 4.2.3 Recruitment 8 4.2.4 Randomization 10 4.3 Parameters 11 4.3.1 Heart rate variability 11 4.3.2 Electro-dermal activity 11 4.3.3 State anxiety 11 4.3.4 Trait anxiety 12 4.3.5 Perceived pain 12 4.4 Measuring Instruments 13 4.4.1 Heart rate variability 13 4.4.2 Electro-dermal Activity 13 4.4.3 State-Trait Anxiety Inventory 13 4.4.4 Short-Form McGill Pain Questionnaire 13 4.5 Interventions 14 4.5.1 Intervention ‘B’: Body 14 4.5.2 Intervention ‘HN’: Head and Neck 16 4.5.3 Intervention ‘HNB’: Head, Neck and Body 16 4.6 Study flow 18 4.7 Statistics 20 5 Results 21 5.1 Autonomic nervous system: Heart rate variability 21 5.1.1 SDNN 22 5.1.2 SD1 25 5.1.3 SD2 28 5.2 Autonomic Nervous System: Electro-dermal activity 31 5.3 Anxiety 34 5.3.1 State anxiety 34 5.3.2 Trait anxiety 37 5.4 Musculoskeletal pain 39 5.4.1 Visual analogue scale 40 5.4.2 Total Short-Form McGill Pain Questionnaire 43 6 Discussion 46 6.1 Discussion of the method 46 6.2 Discussion of the results 50 6.2.1 Autonomic nervous system 50 6.2.1.1 Heart rate variability 50 6.2.1.2 Electro-dermal activity 51 6.2.2 Anxiety 51 6.2.2.1 State anxiety 51 6.2.2.2 Trait Anxiety 52 6.2.3 Musculoskeletal pain 52 6.3 Suggestions for future research 53 7 Conclusion 54 8 Literature 55 9 Addendum 63 9.1 Table: SF-MPQ with Sensory, Affective and Evaluative dimension 63 9.2 Patient Information Sheet 64 9.3 Structured telephone interview 70 9.4 Structured pre-treatment interview 72 9.5 SF-MPQ permission 73 9.6 SF-MPQ 74 9.7 STAI License 76 9.8 STAI forms Y-1 and Y-2 77

Indiana University-Purdue University Indianapolis (IUPUI) / Aromatase inhibitors (AIs) are the current standard of care for the treatment of hormone receptor positive breast cancer in postmenopausal women. Nearly one-half of patients receiving AI therapy develop musculoskeletal toxicity that is characterized by joint and/or muscle pain and approximately one-fourth of patients discontinue their therapy as a result of musculoskeletal pain. Since there are no effective strategies for prevention or treatment, insight into the mechanisms of AI-induced pain is critical to improve treatment. However, there are few studies of AI effects in animal models of nociception. To determine whether AIs produce hypersensitivity in animal models of pain, I examined the effects of AI administration on mechanical, thermal, and chemical sensitivity in rats. The results demonstrate that (1) repeated injection of 5 mg/kg letrozole in male rats produces mechanical, but not thermal, hypersensitivity that extinguishes when drug dosing is stopped; (2) administering a single dose of 1 or 5 mg/kg letrozole in ovariectomized (OVX) rats also induces mechanical hypersensitivity, without altering thermal sensitivity and (3) a single dose of 5 mg/kg letrozole or daily dosing of letrozole or exemestane in male rats augments flinching behavior induced by intraplantar ATP injection. To determine whether the effects of AIs on nociceptive behaviors are mediated by activation or sensitization of peptidergic sensory neurons, I determined whether letrozole exposure alters release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons and from sensory nerve endings in rat spinal cord slices. No changes in basal, capsaicin-evoked or high extracellular potassium-evoked CGRP release were observed in sensory neuronal cultures acutely or chronically exposed to letrozole. Furthermore, letrozole exposure did not alter the ability of ATP to augment CGRP release from sensory neurons in culture. Finally, chronic letrozole treatment did not augment neuropeptide release from spinal cord slices. Taken together, these results do not support altered release of this neuropeptide into the spinal cord as mediator of letrozole-induced mechanical hypersensitivity and suggest the involvement of other mechanisms. Results from this dissertation provide a new experimental model for AI-induced hypersensitivity that could be beneficial in delineating mechanisms mediating pain during AI therapy.

Indiana University-Purdue University Indianapolis (IUPUI) / Symptoms of post-traumatic stress disorder (PTSD) are a common comorbidity in veterans seeking treatment of chronic musculoskeletal pain (CMP). However, little is known regarding the mutual influence of PTSD and CMP in this population. Using cross-sectional and longitudinal data from a randomized clinical trial evaluating a stepped care intervention for CMP in Iraq/Afghanistan veterans (ESCAPE), this dissertation examined the relationships between PTSD and CMP along with other factors including depression, anxiety, catastrophizing and health-related quality of life. The Classification and Regression Tree (CART) analysis was conducted to identify key factors associated with baseline PTSD besides CMP severity. A series of statistical analyses including logistical regression analysis, mixed model repeated measure analysis, confirmatory factor analysis and cross-lagged panel analysis via structural equation modeling were conducted to test five competing models of PTSD symptom clusters, and to examine the mutual influences of PTSD symptom clusters and CMP outcomes. Results showed baseline pain intensity and pain disability predicted PTSD at 9 months. And baseline PTSD predicted improvement of pain disability at 9 months. Moreover, direct relationships were found between PTSD and the disability component of CMP, and indirect relationships were found between PTSD, CMP and CMP components (intensity and disability) mediated by depression, anxiety and pain catastrophizing. Finally, the coexistence of PTSD and more severe pain was associated with worse SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Together these findings provided empirical support for the mutual maintenance theory.