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.

Nonparametric estimation of the survival function for ordered multivariate failure time data: a comparative study

In longitudinal studies of disease, patients may experience several events through a follow-up period. In these studies, the sequentially ordered events are often of interest and lead to problems that have received much attention recently. Issues of interest include the estimation of bivariate survival, marginal distributions and the conditional distribution of gap times. In this work we consider the estimation of the survival function conditional to a previous event. Different nonparametric approaches will be considered for estimating these quantities, all based on the Kaplan-Meier estimator of the survival function. We explore the finite sample behavior of the estimators through simulations. The different methods proposed in this article are applied to a data set from a German Breast Cancer Study. The methods are used to obtain predictors for the conditional survival probabilities as well as to study the influence of recurrence in overall survival.

Paving the way for predictive diagnostics and personalized treatment of invasive aspergillosis

Invasive aspergillosis (IA) is a life-threatening fungal disease commonly diagnosed among individuals with immunological deficits, namely hematological patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation. Vaccines are not available, and despite the improved diagnosis and antifungal therapy, the treatment of IA is associated with a poor outcome. Importantly, the risk of infection and its clinical outcome vary significantly even among patients with similar predisposing clinical factors and microbiological exposure. Recent insights into antifungal immunity have further highlighted the complexity of host-fungus interactions and the multiple pathogen-sensing systems activated to control infection. How to decode this information into clinical practice remains however, a challenging issue in medical mycology. Here, we address recent advances in our understanding of the host-fungus interaction and discuss the application of this knowledge in potential strategies with the aim of moving toward personalized diagnostics and treatment (theranostics) in immunocompromised patients. Ultimately, the integration of individual traits into a clinically applicable process to predict the risk and progression of disease, and the efficacy of antifungal prophylaxis and therapy, holds the promise of a pioneering innovation benefiting patients at risk of IA.

Impact of an educational hands-on project on the antimicrobial, antitumor and anti-inflammatory properties of plants on Portuguese students' awareness, knowledge, and competences

Promoting environmental and health education is crucial to allow students to make conscious decisions based on scientific criteria. The study is based on the outcomes of an Educational Project implemented with Portuguese students and consisted of several activities, exploring pre-existent Scientific Gardens at the School, aiming to investigate the antibacterial, antitumor and anti-inflammatory properties of plant extracts, with posterior incorporation in soaps and creams. A logo and a webpage were also created. The effectiveness of the project was assessed via the application of a questionnaire (pre- and post-test) and observations of the participants in terms of engagement and interaction with all individuals involved in the project. This project increased the knowledge about autochthonous plants and the potential medical properties of the corresponding plant extracts and increased the awareness about the correct design of scientific experiments and the importance of the use of experimental models of disease. The students regarded their experiences as exciting and valuable and believed that the project helped to improve their understanding and increase their interest in these subjects and in science in general. This study emphasizes the importance of raising students’ awareness on the valorization of autochthonous plants and exploitation of their medicinal properties.

Relation between oral health and socioeconomic variables among schoolchildren aged 12 in the City of Manaus - AM

Studies have shown that the age of 12 was determined as the age of global monitoring of caries for international comparisons and monitoring of disease trends. The aimed was to evaluate the prevalence of dental caries, fluorosis and periodontal condition and their relation with socioeconomic factors among schoolchildren aged twelve in the city of Manaus, AM. This study with a probabilistic sample of 661 children was conducted, 609 from public and 52 from private schools, in 2008. Dental caries, periodontal condition and dental fluorosis were evaluated. In order to obtain the socioeconomic classification of each child (high, upper middle, middle, lower middle, low and lower low socioeconomic classes), the guardians were given a questionnaire. The mean decayed teeth, missing teeth, and filled teeth (DMFT) found at age twelve was 1.89. It was observed that the presence of dental calculus was the most severe periodontal condition detected in 39.48%. In relation to dental fluorosis, there was a low prevalence in the children examined, i.e., the more pronounced lines of opacity only occasionally merge, forming small white areas. The study showed a significant association of 5% among social class with dental caries and periodontal condition. In schoolchildren of Manaus there are low mean of DMFT and fluorosis, but a high occurrence of gingival bleeding.

Joint modelling of longitudinal and survival data on breast cancer

Tese de Doutoramento em Ciências (Especialidade em Matemática)

Assessment of prognosis in patients with stage II colon cancer

Assessment of prognosis of patients with stage II colon cancer.

Stage at presentation of breast cancer in Luanda, Angola - a retrospective study

Background: It is expected that, by 2020, 15 million new cases of cancer will occur every year in the world, one million of them in Africa. Knowledge of cancer trends in African countries is far from adequate, and improvements in cancer prevention efforts are urgently needed. The aim of this study was to characterize breast cancer clinically and pathologically at presentation in Luanda, Angola; we additionally provide quality information that will be useful for breast cancer care planning in the country. Methods: Data on breast cancer cases were retrieved from the Angolan Institute of Cancer Control, from 2006 to 2014. For women diagnosed in 2009 (5-years of follow-up), demographic, clinical and pathological information, at presentation, was collected, namely age at diagnosis, parity, methods used for pathological diagnoses, tumor pathological characteristics, stage of disease and treatment. Descriptive statistics were performed. Results: The median age of women diagnosed with breast cancer in 2009 was 47 years old (range 25–89). The most frequent clinical presentation was breast swelling with axillary lymph nodes metastasis (44.9 %), followed by a mass larger than 5 cm (14.2 %) and lump (12.9 %). Invasive ductal carcinoma was the main histologic type (81.8 %). Only 10.1 % of cancer cases had a well differentiated histological grade. Cancers were diagnosed mostly at advanced stages (66.7 % in stage III and 11.1 % in stage IV). Discussion: In this study, breast cancer was diagnosed at a very advanced stage. Although it reports data from a single cancer center in Luanda, Angola it reinforces the need for early diagnosis and increasing awareness. According to the main challenges related to breast cancer diagnosis and treatment herein presented, we propose a realistic framework that would allow for the implementation of a breast cancer care program, built under a strong network based on cooperation, teaching, audit, good practices and the organization of health services. Conclusion: Angola needs urgently a program for early diagnosis of breast cancer.

Lipids under stress - a lipidomic approach for the study of mood disorders

The emerging field of lipidomics has identified lipids as key players in disease physiology. Their physicochemical diversity allows precise control of cell structure and signaling events through modulation of membrane prop- erties and trafficking of proteins. As such, lipids are important regulators of brain function and have been implicated in neurodegenerative and mood disorders. Importantly, environmental chronic stress has been associated with anxiety and depression and its exposure in rodents has been extensively used as a model to study these diseases. With the accessibility to modern mass- spectrometry lipidomic platforms, it is now possible to snapshot the extensively interconnected lipid network. Here, we review the fundamentals of lipid biology and outline a framework for the interpretation of lipidomic studies as a new approach to study brain pathophysiology. Thus, lipid profiling provides an exciting avenue for the identification of disease signatures with important implications for diagnosis and treatment of mood disorders.

Ontological representation of tumor-node-metastasis classification and an ontology-driven classifier: a study on colorectal cancer

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Informática Médica)

Diversity of non-clinical Acinetobacter species in a sub-saharan Africa region: evidence of carbapenem-hydrolysing class D-β-lactamase producers

[Excerpt] Although Acinetobacter baumannii has been the main agent for healthcare infections, recent reports suggest that some Acinetobacter environmental species should be considered as a potential cause of disease. In Angola, there are no previous data on its environmental reservoirs and resistance features. We aimed to unveil the occurrence and diversity of Acinetobacter species and the presence of resistance mechanisms in different non-clinical settings in Angola.

Characteristics associated with the dropout of hypertensive patients followed up in an outpatient referral clinic

OBJECTIVE: To determine the characteristics associated with the dropout of patients followed up in a Brazilian out patient clinic specializing in hypertension. METHODS: Planned prospective cohort study of patients who were prescribed an antihypertensive treatment after an extensive initial evaluation. The following parameters were analyzed: sex, age, educational level, duration of disease, pressure level used for classifying the patient, previous treatment, physical activity, smoking, alcohol consumption, familial history of hypertension, and lesion in a target organ. RESULTS: We studied 945 hypertensive patients, 533 (56%) of whom dropped out of the follow-up. The mean age was 52.3±12.9 years. The highest probabilities of dropout of the follow-up were associated with current smoking, relative risk of 1.46 (1.04-2.06); educational level equal to or below 5 years of schooling, relative risk of 1.52 (1.11-2.08); and hypertension duration below 5 years, relative risk of 1.78 (1.28-2.48). Age increase was associated with a higher probability of follow-up with a relative risk of 0.98 (0.97-0.99). CONCLUSION: We identified a group at risk for dropping out the follow-up, which comprised patients with a lower educational level, a recent diagnosis of hypertension, and who were smokers. We think that measures assuring adherence to treatment should be directed to this group of patients.

Pre-clinical trials for Machado-Joseph Disease: Hypothesis-based and hypothesis-free therapeutic approaches

Tese de Doutoramento em Ciências da Saúde

Serological evidence of rotavirus infection in guinea pig colony

Antibodies reacting with simian rotavirus SAII were detected by enzyme immunoassay (EIA) and Western blot assay (WBA) in sera from guinea pigs bred for experimental use at the Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. The proportion of antibody-positive animals and the antibody titres rose sharply in 1985, were maintained at a high levels in 1986 and declined in 1987. There were no obvious signs of disease coinciding with serological evidence of infection. Results of WBA suggest that the virus involved belongs to subgroup 1 of group A rotaviruses.