Alterations in lipid transfer to High-Density Lipoprotein (HDL) and activity of paraoxonase-1 in HIV+ patients

HIV+ patients often develop alterations of the plasma lipids that may implicate in development of premature coronary artery disease. High-density lipoprotein (HDL) has an important role in preventing atherogenesis and the aim of this study was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n = 48) and healthy control subjects (n = 45) of both sexes with similar age were studied. Twenty-five were not being treated with antiretroviral agents, 13 were under reverse transcriptase inhibitor nucleosidic and non-nucleosidic (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment. Paraoxonase 1 (PON1) activity and the transfer of free and esterified cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL were analyzed. In comparison with healthy controls, HIV+ patients presented low PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In contrast, phospholipid transfer was increased in those patients, whereas the transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller antioxidant properties, as shown by lower PON-1 activity, and the transfer of lipids to this lipoprotein fraction is also altered, suggesting that HDL function is defective in those patients.

Prostatic Artery Embolization in the Treatment of Benign Prostatic Hyperplasia: Short and Medium Follow-Up

To evaluate the short and mid-term results of prostatic artery embolization in patients with benign prostatic embolization. Retrospective study between March 2009 and June 2011 with 103 patients (mean age 66.8 years, 50-85) that met our inclusion criteria with symptomatic benign prostatic hyperplasia. The clinical outcome was evaluated by the International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function, prostate volume (PV), prostate-specific antigen (PSA), peak urinary flow (Q(max)), and post-void residual volume (PVR) measurements at 3 and 6 months, 1 year, 18 months, and 2 years after PAE and comparison with baseline values was made. Technical and clinical successes, as well as poor clinical outcome definitions, were previously defined. In this review, we evaluate the short and mid-term clinical outcomes and morbidity of patients treated only with non-spherical polyvinyl alcohol. Six months after the procedure, the PV decreased about 23%, IPSS changed to a mean value of 11.95 (almost 50% reduction), the QoL improved slightly more than 2 points, the Q(max) changed to a mean value of 12.63mL/s, the PVR underwent a change of almost half of the baseline value, and the PSA decreased about 2.3ng/mL. In the mid-term follow-up and comparing to the baseline values, we still assisted to a reduction in PV, IPSS, QoL, PVR, and PSA, and an increase in Q(max). Prostatic Artery Embolization is a safe procedure with low morbidity that shows good short- and mid-term clinical outcome in our institution.

Ankylosing spondylitis: genomic and functional characterization of candidate genes and their repercussion in clinical practice

RESUMO: Introdução: A espondilite anquilosante (EA) é uma doença inflamatória crónica caracterizada pela inflamação das articulações sacroilíacas e da coluna. A anquilose progressiva motiva uma deterioração gradual da função física e da qualidade de vida. O diagnóstico e o tratamento precoces podem contribuir para um melhor prognóstico. Neste contexto, a identificação de biomarcadores, assume-se como sendo muito útil para a prática clínica e representa hoje um grande desafio para a comunidade científica. Objetivos: Este estudo teve como objetivos: 1 - caracterizar a EA em Portugal; 2 - investigar possíveis associações entre genes, MHC e não-MHC, com a suscetibilidade e as características fenotípicas da EA; 3 - identificar genes candidatos associados a EA através da tecnologia de microarray. Material e Métodos: Foram recrutados doentes com EA, de acordo com os critérios modificados de Nova Iorque, nas consultas de Reumatologia dos diferentes hospitais participantes. Colecionaram-se dados demográficos, clínicos e radiológicos e colhidas amostras de sangue periférico. Selecionaram-se de forma aleatória, doentes HLA-B27 positivos, os quais foram tipados em termos de HLA classe I e II por PCR-rSSOP. Os haplótipos HLA estendidos foram estimados pelo algoritmo Expectation Maximization com recurso ao software Arlequin v3.11. As variantes alélicas dos genes IL23R, ERAP1 e ANKH foram estudadas através de ensaios de discriminação alélica TaqMan. A análise de associação foi realizada utilizando testes da Cochrane-Armitage e de regressão linear, tal como implementado pelo PLINK, para variáveis qualitativas e quantitativas, respetivamente. O estudo de expressão génica foi realizado por Illumina HT-12 Whole-Genome Expression BeadChips. Os genes candidatos foram validados usando qPCR-based TaqMan Low Density Arrays (TLDAs). Resultados: Foram incluídos 369 doentes (62,3% do sexo masculino, com idade média de 45,4 ± 13,2 anos, duração média da doença de 11,4 ± 10,5 anos). No momento da avaliação, 49,9% tinham doença axial, 2,4% periférica, 40,9% mista e 7,1% entesopática. A uveíte anterior aguda (33,6%) foi a manifestação extra-articular mais comum. Foram positivos para o HLA-B27, 80,3% dos doentes. Os haplótipo A*02/B*27/Cw*02/DRB1*01/DQB1*05 parece conferir suscetibilidade para a EA, e o A*02/B*27/Cw*01/DRB1*08/DQB1*04 parece conferir proteção em termos de atividade, repercussão funcional e radiológica da doença. Três variantes (2 para IL23R e 1 para ERAP1) mostraram significativa associação com a doença, confirmando a associação destes genes com a EA na população Portuguesa. O mesmo não se verificou com as variantes estudadas do ANKH. Não se verificou associação entre as variantes génicas não-MHC e as manifestações clínicas da EA. Foi identificado um perfil de expressão génica para a EA, tendo sido validados catorze genes - alguns têm um papel bem documentado em termos de inflamação, outros no metabolismo da cartilagem e do osso. Conclusões: Foi estabelecido um perfil demográfico e clínico dos doentes com EA em Portugal. A identificação de variantes génicas e de um perfil de expressão contribuem para uma melhor compreensão da sua fisiopatologia e podem ser úteis para estabelecer modelos com relevância em termos de diagnóstico, prognóstico e orientação terapêutica dos doentes. -----------ABSTRACT: Background: Ankylosing Spondylitis (AS) is a chronic inflammatory disorder characterized by inflammation in the spine and sacroiliac joints leading to progressive joint ankylosis and in progressive deterioration of physical function and quality of life. An early diagnosis and early therapy may contribute to a better prognosis. The identification of biomarkers would be helpful and represents a great challenge for the scientific community. Objectives: The present study had the following aims: 1- to characterize the pattern of AS in Portuguese patients; 2- to investigate MHC and non-MHC gene associations with susceptibility and phenotypic features of AS and; 3- to identify candidate genes associated with AS by means of whole-genome microarray. Material and Methods: AS was defined in accordance to the modified New York criteria and AS cases were recruited from hospital outcares patient clinics. Demographic and clinical data were recorded and blood samples collected. A random group of HLA-B27 positive patients and controls were selected and typed for HLA class I and II by PCR-rSSOP. The extended HLA haplotypes were estimated by Expectation Maximization Algorithm using Arlequin v3.11 software. Genotyping of IL23R, ERAP1 and ANKH allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests as implemented in PLINK, for dichotomous and quantitative variables, respectively. Gene expression profile was carried out using Illumina HT-12 Whole-Genome Expression BeadChips and candidate genes were validated using qPCR-based TaqMan Low Density Arrays (TLDAs). Results: A total of 369 patients (62.3% male; mean age 45.4±13.2 years; mean disease duration 11.4±10.5 years), were included. Regarding clinical disease pattern, at the time of assessment, 49.9% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopathic disease. Acute anterior uveitis (33.6%) was the most common extra-articular manifestation. 80.3% of AS patients were HLA-B27 positive. The haplotype A*02/B*27/Cw*02/DRB1*01/DQB1*05 seems to confer susceptibility to AS, whereas A*02/B*27/Cw*01/DRB1*08/DQB1*04 seems to provide protection in terms of disease activity, functional and radiological repercussion. Three markers (two for IL23R and one for ERAP1) showed significant single-locus disease associations. Association of these genes with AS in the Portuguese population was confirmed, whereas ANKH markers studied did not show an association with AS. No association was seen between non-MHC genes and clinical manifestations of AS. A gene expression signature for AS was established; among the fourteen validated genes, a number of them have a well-documented inflammatory role or in modulation of cartilage and bone metabolism. Conclusions: A demographic and clinical profile of patients with AS in Portugal was established. Identification of genetic variants of target genes as well as gene expression signatures could provide a better understanding of AS pathophysiology and could be useful to establish models with relevance in terms of susceptibility, prognosis, and potential therapeutic guidance.

Embolisation of Prostatic Arteries as Treatment of Moderate to Severe Lower Urinary Symptoms (LUTS) Secondary to Benign Hyperplasia: Results of Short- and Mid-Term Follow-Up

OBJECTIVES: To evaluate the short- and medium-term results of prostatic arterial embolisation (PAE) for benign prostatic hyperplasia (BPH). METHODS: This was a prospective non-randomised study including 255 patients diagnosed with BPH and moderate to severe lower urinary tract symptoms after failure of medical treatment for at least 6 months. The patients underwent PAE between March 2009 and April 2012. Technical success is when selective prostatic arterial embolisation is completed in at least one pelvic side. Clinical success was defined as improving symptoms and quality of life. Evaluation was performed before PAE and at 1, 3, 6 and every 6 months thereafter with the International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF), uroflowmetry, prostatic specific antigen (PSA) and volume. Non-spherical polyvinyl alcohol particles were used. RESULTS: PAE was technically successful in 250 patients (97.9 %). Mean follow-up, in 238 patients, was 10 months (range 1-36). Cumulative rates of clinical success were 81.9 %, 80.7 %, 77.9 %, 75.2 %, 72.0 %, 72.0 %, 72.0 % and 72.0 % at 1, 3, 6, 12, 18, 24, 30 and 36 months, respectively. There was one major complication. CONCLUSIONS: PAE is a procedure with good results for BPH patients with moderate to severe LUTS after failure of medical therapy. KEY POINTS: • Prostatic artery embolisation offers minimally invasive therapy for benign prostatic hyperplasia. • Prostatic artery embolisation is a challenging procedure because of vascular anatomical variations. • PAE is a promising new technique that has shown good results.

Spatial analysis and investigation of fire events occurrences in the Valencian Community, Spain

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Chronic Calcified Subdural Hematoma: Case Report and Review of the Literature

Background: Calcified chronic subdural hematoma is a rare but known entity, estimated to represent 0.3-2.7% of chronic subdural hematomas. Although surgical treatment is unanimous for chronic subdural hematomas, therein lies some doubt on it being applied to calcified chronic subdural hematomas. Case Description: We report a case of a 73‑year‑old male, presenting with deterioration of motor function in his right limbs since 18 months, with computed tomography (CT) scans and magnetic resonance imaging (MRI) documenting a large subdural collection of the left hemisphere, with calcified inner membrane, which was successfully and completely removed, with progressive clinical and radiological improvement. Conclusions: We report a case where this type of rare lesion was removed with a progressive and complete resolution of the patient’s symptoms, restoring his previous neurological condition. From the cases described in the literature and our own experience with this case, we think surgical treatment in these patients, when symptomatic, is necessary and viable, frequently resulting in the patient’s improvement.

Compositional and functional analysis of polycomb target chromatin

Dissertation presented to obtain the Ph.D degree in Molecular Biology

Effect of Efavirenz on High-Density Lipoprotein Antioxidant Properties in HIV-Infected Patients

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * In previous work, we showed a long-term and concentration-dependent beneficial effect of the non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) on high-density lipoproteins (HDL) in human immunodeficiency virus (HIV)-infected patients. * Furthermore, it has been suggested that instead of the current practice of only measuring HDL-chelesterol values, the evaluation of HDL function, namely its antioxidant properties, might be an improved tool for identifying subjects at increased risk for cardiovascular events. * Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is responsible for HDL antioxidant function. WHAT THIS STUDY ADDS: * In the present work, we studied the effect of EFV on the activity of PON-1 and showed, for the first time, that EFV-based antiretroviral therapy is associated with a better antioxidant function, i.e. with a higher PON-1 activity. AIMS: A long-term and concentration-dependent beneficial effect of efavirenz (EFV) on cholesterol associated with high-density lipoprotein (HDL-c) in human immunodeficiency virus (HIV)-infected patients has been documented. Furthermore, it has been suggested that, instead of the current practice of only measuring HDL-c values, the evaluation of HDL quality might be an improved tool for identifying subjects at increased risk of cardiovascular events. Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is involved in the onset of cardiovascular disease and responsible for HDL antioxidant function. The aim of the present study was to investigate the effect of EFV on the circulating activity of PON-1 in HIV-infected patients. METHODS: The patients included were adults with a documented HIV-1 infection, nontreated or treated with antiretroviral regimens including EFV 600 mg once daily as first therapeutic regimen for at least 3 months. The influence of treatment with EFV, HDL-c and CD4 cell count on PON-1 activity was analysed. RESULTS: HIV-infected White patients treated with EFV had higher PON-1 activity [77.35 U l(-1) (65.66, 89.04)] (P < 0.05) and higher PON-1 activity : HDL-c ratio [1.88 (1.49, 2.28)] (P < 0.01) than untreated patients. PON-1 activity was higher in Black patients (P < 0.001) and in patients with a CD4 cell count >500 cells ml(-1) (P= 0.0120). CONCLUSIONS: EFV-based antiretroviral regimens are associated with HDL particles with a better antioxidant function, i.e. with a higher PON-1 activity. The PON-1 activity of Black patients is higher than that found in Whites regardless of treatment. Ethnicity should be taken into consideration when studying drug effects on PON-1 activity.

Triple Regimen with Rituximab, Plasmapheresis and Intravenous Immunoglobulin in the Treatment of Dialysis Dependent Acute Humoral-Mediated Rejection in Kidney Grafts

Introduction: The clinical importance of humoral-mediated acute rejection has been progressively recognised. Early recognition and treatment with plasmapheresis and intravenous immunoglobulin have recently improved short term prognosis. Case report: In this report we describe the clinical features of three 2nd transplant patients developing severe acute humoral rejection during the first week post-transplant while on anti-thymocyte globulin therapy. Treatment with plasmapheresis/ intravenous immunoglobulin/rituximab resulted in rapid reversal of oliguria,and recovery of renal function within the 1st week of treatment in 2/3 patients. Diagnosis was confirmed by graft biopsies revealing peritubular neutrophiles and C4d deposits. Sequential graft biopsies in all three patients revealed complete histological recovery within two weeks. One patient never recovered renal function, and one patient lost his graft at three months following hemorrhagic shock. After 2 years follow up, the remaining patient maintains a serum creatinine of 1.1mg/dl. Conclusion: The regimen using plasmapheresis plus intravenous immunoglobulin and rituximab was effective in rapidly reversing severe acute humoral rejection.

Absence of clinical abnormalities suggesting renal involvement during the long-term course of visceral Leishmaniasis

Abnormalities of renal function have been demonstrated inpatients with visceral leishmaniasis; although there was a trend toward normalization following antiparasitic therapy, some abnormalities persisted. With thepurpose of studying the long- term clinical course of renal involvement in visceral leishmaniasis, 32 patients with a diagnosis of this parasitic disease were evaluated in the endemic area and at least 6 months after the clinical cure of the disease and compared with a control group of 28 individuals. No patient had a history or clinical findings suggestive of renal disease and all were normotensive. Laboratory evaluation was normal in all except 3 patients with abnormal urinalysis. Mild proteinuria and microscopic hematuria were seen in a single urinalysis in one patient (although three other urinalysis were normal), and leucocyturia in two female patients. It was concluded that the renal involvement in visceral leishmaniasis is mild and transient, with normal renal function observed on long-term follow-up after cure of the parasitic infection.

Synchronization properties of multi-oscillator circadian systems

Dissertation presented to obtain the Ph.D degree in Computational Biology

Is autonomic function associated with left ventricular systolic function in Chagas heart disease patients undergoing treatment for heart failure?

Introduction The association between cardiac autonomic and left ventricular (LV) dysfunction in Chagas disease (ChD) is controversial. Methods A standardized protocol that includes the Valsalva maneuver, a respiratory sinus arrhythmia (RSA) test, and an echocardiographic examination was used. Spearman correlation coefficients (rho) were used to investigate associations. Results The study population consisted of 118 ChD patients undergoing current medical treatment, with an average LV ejection fraction of 51.4±2.6%. The LV ejection fraction and diastolic dimension were correlated with the Valsalva index (rho=0.358, p<0.001 and rho=-0.266, p=0.004, respectively) and the RSA (rho=0.391, p<0.001 and rho=-0.311, p<0.001, respectively). Conclusions The impairment of LV function is directly associated with a reduction of cardiac autonomic modulation in ChD.

Surgical treatment of type I neuritis in a teenage boy with borderline tuberculoid leprosy

Exacerbation of the immune response against Mycobacterium leprae can lead to neuritis, which is commonly treated via immunosuppression with corticosteroids. Early neurolysis may be performed concurrently, especially in young patients with a risk of functional sequelae. We report the case of a young patient experienced intense pain in the left elbow one year after the treatment of tuberculoid-tuberculoid leprosy. The pain was associated with paresthesias in the ulnar edge and left ulnar claw. After evaluation, the diagnosis was changed to borderline tuberculoid leprosy accompanied with neuritis of the left ulnar nerve. Early neurolysis resulted in rapid reduction of the pain and recovery of motor function.

Usefulness of zebrafish model to assess glomerular and tubular alterations induced by tenofovir

Tenofovir (TFV) is one of the most used antiretroviral drugs. However, it is associated with tubular damage with mitochondria as a possible target. Tubulopathy precedes glomerular dysfunction, thus classic markers of renal function like the glomerular filtration rate (GFR) do not detect early TFV damage. Prediction and management of drug induced renal injury (DIRI) rely on the mechanisms of the drug insult and in optimal animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI, since the pronephros is structurally very similar to its human counterpart and is fully developed at 3.5 days postfertilization. The main aim of the present work was to evaluate the effects of TFV, as well as its pro-drug, tenofovir disoproxil fumarate (TDF), on the GFR and in mitochondria morphology in tubular cells of zebrafish larvae. Lethality curves were performed to understand the relationship between drug concentration and lethality. LC10 was selected to explore the renal function using the FITC-inulin assay and to analyze the mitochondrial toxicity by electron microscopy on larvae exposed to TDF, TFV, paracetamol and gentamicin (positive controls) or water (negative control). Lethality curves showed that gentamicin was the most lethal drug, followed by TDF, TFV and paracetamol. Gentamicin and paracetamol decreased the GFR, but no differences were found for either TDF or TFV, when compared to controls (%FITC Control = 33±8; %FITC TDF = 35±10; %FITC TFV = 30±10; %FITC Gentamicin = 46±17; %FITC Paracetamol = 83±14). Tubular mitochondria from treated larvae were notably different from non-treated larvae, showing swelling, irregular shapes, decreased mitochondria network, cristae disruption and loss of matrix granules. These results are in agreement with the effects of these drugs in humans and thus, demonstrate that zebrafish larvae can be a good model to assess the functional and structural damage associated with DIRI.

The burden of chronic low back pain in the adult Portuguese population : an epidemiological population-based study under the scope of Epireumapt

RESUMO: Nos países desenvolvidos a lombalgia é a condição músculo-­‐esquelética mais prevalente. Quando evolui para um quadro crónico é responsável por um encargo económico bastante considerável, não só em relação aos indivíduos, mas também para a sociedade. A lombalgia crónica é por isso uma das principais causas de perda de produtividade e de perda de independência económica, nomeadamente através do absenteísmo (ausência do trabalho), do presenteísmo (perda de produtividade no trabalho, devido à capacidade diminuída provocada pela lombalgia) e da incapacidade para trabalhar (invalidez permanente, total ou parcial). Até à data, em Portugal, a prevalência e carga social da lombalgia crónica eram desconhecidas. Até agora não existiam estudos populacionais de grande dimensão sobre este tema. O objetivo principal desta tese foi determinar a prevalência de lombalgia crónica, e também avaliar a carga social que esta tem na população adulta Portuguesa. O trabalho de investigação foi desenvolvido no âmbito do Estudo Epidemiológico de Doenças Reumáticas em Portugal (EpiReumaPt). Este foi o primeiro estudo de larga escala e de base populacional, que determinou a prevalência de doenças reumáticas e músculo-­‐ esqueléticas na população adulta portuguesa. Foi realizado numa amostra aleatória e representativa, de 10.661 indivíduos do Continente, da Região Autónoma dos Açores e da Região Autónoma da Madeira, entre Setembro de 2011 e Dezembro de 2013. Esta tese foi dividida em duas secções. A primeira secção incluiu o detalhe das questões relativas ao desenvolvimento e gestão do EpiReumaPt, constituindo-­‐se como um guia prático sobre como realizar um estudo de base populacional de larga escala, em Portugal. A metodologia detalhada do EpiReumaPt foi também descrita nesta secção e incluiu os objectivos, o desenho do estudo, as características de recrutamento e a preparação de dados para análise. Nesta secção foram ainda descritos os principais resultados do EpiReumaPt. Estes evidenciaram que a lombalgia foi a condição músculo-­‐esquelética com maior prevalência na população adulta portuguesa.A segunda secção desta tese estimou a prevalência da lombalgia crónica ativa na população adulta Portuguesa, e avaliou a carga social esta condição. A lombalgia ativa foi definida com base na dor auto-­‐relatada no dia da entrevista e que persistia há pelo menos 90 dias (independentemente da causa). A lombalgia foi definida como dor na área definida entre a margem inferior das décimas segundas costelas até às pregas glúteas inferiores, com ou sem dor nos membros inferiores. A carga social foi medida tendo em conta os seguintes parâmetros: qualidade de vida, função, consumo de recursos de saúde, consumo de analgésicos e outros fármacos usados no alívio da dor, sintomas de ansiedade e sintomas de depressão. Os resultados mostraram que o consumo de recursos em saúde e a carga social da lombalgia crónica na população adulta Português é significativa. Também a incapacidade causada pela lombalgia crónica,nos indivíduos com idade ativa, é responsável por elevadas taxas de absenteísmo e má qualidade de vida, aos quais acresce o consequente ónus socioeconómico. Esta tese também concluiu que o consumo de analgésicos e outros medicamentos para alívio da dor, na população adulta portuguesa com lombalgia crónica ativa, é relativamente baixa. A maioria destes indivíduos não tomava nenhum medicamento analgésico, independentemente da intensidade da dor. Mesmo os indivíduos que reportaram dor intensa, apenas 4.0% estavam no primeiro degrau da escada analgésica da Organização Mundial de Saúde; 2.3% usavam opióides fracos e 0.03% usavam opióides fortes para controlar a dor (segundo e terceiro degrau da escada analgésica da Organização Mundial da Saúde). O trabalho de investigação também confirmou que a prevalência de sintomas de ansiedade e depressão entre os indivíduos adultos portugueses com lombalgia crónica ativa é elevada. Nestes indivíduos, registou-­‐se um consumo mais elevado de analgésicos e outros medicamentos para alívio da dor, quando comparados com os indivíduos com lombalgia crónica activa sem esses sintomas psicológicos. Os grupos terapêuticos mais utilizados foram os ansiolíticos, sedativos e hipnóticos, os antidepressivos e os anti-­‐inflamatórios não esteróides. A intensidade média da dor reportada foi também maior entre os indivíduos com lombalgia ativa e sintomas de ansiedade e/ou depressão. Também nestes, foi reportada pior função e pior estado de saúde. Em relação ao consumo de recursos de saúde foram encontradas diferenças significativas entre as duas populações: os indivíduos com lombalgia ativa e sintomas psicológicos concomitantes registaram maior número de consultas de psiquiatria de outras especialidades médicas, assim como precisaram de mais apoio domiciliário nos 12 meses prévios à entrevista do EpiReumaPt. Foram também identificados os fatores associados a sintomas isolados de ansiedade, a sintomas isolados de depressão e a sintomas de ansiedade e depressão. Resumindo,esta tese permitiu concluir que a lombalgia crónica é um problema de saúde comum na população adulta portuguesa, contribuindo para um elevado grau de incapacidade e que consequentemente afeta o desempenho laboral e o bem-­‐estar dos indivíduos. A lombalgia crónica é também responsável por um consumo considerável de recursos de saúde. Acresce ainda que os sintomas de ansiedade e depressão são comuns, entre os indivíduos com lombalgia crónica, contribuindo com uma carga social adicional.---------------------------------- ABSTRACT:Low Back Pain(LBP) is the most prevalent of musculoskeletal condition in developed countries.When it becomes chronic, LBP causesan enormous economic burden on individuals and society -­‐ it is one of the leading causes of loss of productivity and economic independence through absenteeism (time off work), presenteeism (lost productivity because of diminished capacity while at work) and work disability (permanent, partial or complete disablement for work purposes). In Portugal the prevalence and burden of LBP and chronic LBP (CLBP) were poorly defined. Until now no large population-­‐based studies have focused on this. The main aim of this thesis was to determine the prevalence of LBP and CLBP, and also to assess the burden of CLBP in the adult rtuguese population. The research work was developed under the scope of EpiReumaPt (the Portuguese Epidemiologic Study of Rheumatic Diseases). EpiReumaPt was the first national large population-­‐based and prevalence study of rheumatic and musculoskeletal diseases (RMD). It was performed among a randomized and representative sample of 10,661 adult Portuguese subjects recruited in Mainland, Azores and Madeira Islands, from September 2011 to December 2013. The first section of this thesis included detailed issues regarding the development and management of EpiReumaPt, and provided a practical guide on how to set-­‐up a large population-­‐based study in Portugal. The detailed methodology of EpiReumaPt, including its objectives,study design,recruitment features,and data preparation for analyses were also described. The main results from EpiReumaPt study were provided in this section and showed that LBP was the musculoskeletal condition with highest prevalence among Portuguese population. The second section of this thesis estimated the prevalence of active CLBP among adult Portuguese population, and assessed the social burden of this condition. Active CLBP was defined based on self-­‐reported pain on the day of the interview, and for most of the time for at least 90 days (independently from cause). LBP was defined as pain in the back area from the lower margin of the twelfth ribs to he lower gluteal folds, with or without pain referred to the lower limbs. Social burden was measured taking into account the following outcomes: quality of life, function, healthcare resources consumption, analgesic and other pain relief drugs intake, anxiety and depression symptoms. Results showed that the healthcare consumption and social burden of CLBP among adult Portuguese population were enormous, and the disability caused by CLBP among subjects in a working age provides high rates of absenteeism (work loss) and poor quality of life, with a consequent socioeconomic burden. This thesis also concluded that analgesic and other pain relief drugs untake among adult Portuguese population with active CLBP was very low. Most of the subjects with active CLBP did not take any analgesic drug regardless pain severity. Even when subjects self-­‐reported severe pain, only 24.0% were in the 1st step of the analgesic ladder,2.3% used weak analgesic opioids and 0.03% used strong opioids (2nd and 3rd step of WHO analgesic ladder, respectively) to control pain . The research work also confirmed that the prevalence of anxiety and depression symptoms among adult Portuguese subjects with active CLBP was high. Regarding pharmacological therapy, the intake of analgesic and other pain relief drugs was higher among subjects with anxiety and/or depression symptoms, when compared with subjects without these psychological symptoms. Anxiolytics, sedatives and hypnotics, antidepressants and NSAIDs intake had higher usage rates among these subjects. The pain severity mean was also higher among this subjects and function and health status was worse. Regarding healthcare resources consumption,significant differences between the two populations were found. Subjects with ctive CLBP and concomitant psychological symptoms had a higher number of psychiatrist and other physician visits. They also needed more home care in the previous 12 months. Factors associated with isolated symptoms of anxiety, depression,and concomitant anxiety and depression symptoms were also identified. Summarizing, we concluded that CLBP is a common health problem among adult Portuguese population contributing to disability and affecting labor performance, and the well being of subjects. it is also responsible for considerable healthcare resource consumption. Anxiety and depression symptoms are common among subjects with CLBP and provided an additional burden among them.