Eine Erkrankung gilt dann als selten, wenn weniger als eine von 2.000 Personen betroffen ist. Diese durch geringe Prävalenz und meist multisystemische Morbidität gekennzeichneten Krankheiten schränken die Lebensqualität der Betroffenen ein und führen oftmals zu frühzeitiger Mortalität. Chronisch und häufig nicht heilbar, stellen diese Erkrankungen die Versorgung im deutschen Gesundheitswesen vor vielfältige Herausforderungen. Aufgrund der geringen Patientenzahl pro seltener Erkrankung erhielten bisher nur 240 seltene Krankheiten eine eigenständige Diagnosis Related Groups-Ziffer (DRG) und somit eine leistungsorientierte Vergütung. Von den bis zu 8.000 seltenen Erkrankungen werden die meisten in Überkategorien subsumiert. Spezialisierte Diagnostik, eine erhöhte Anzahl an Facharztkonsultationen sowie intensivere und multiprofessionelle Betreuung bedingen jedoch einen Mehraufwand, welcher sich kostenseitig niederschlägt. Um gegenüber den Kostenträgern argumentieren zu können, fehlten bisher umfassende Erhebungen. Die Prävalenzen beruhen auf Schätzungen und ausgehend von DRG-Kodierungen können die meisten seltenen Diagnosen nicht einwandfrei identifiziert werden. Der Nationale Aktionsplan für Menschen mit Seltenen Erkrankungen benennt zahlreiche Maßnahmen, welche Menschen mit seltenen Erkrankungen zugutekommen sollen, unter anderem eine verbesserte Kodierung und Sichtbarkeit in Abrechnungssystemen. Besonders die Maximalversorger kommen diesen Maßnahmen mit der Gründung von Zentren für Seltene Erkrankungen nach. Als solches hat das UniversitätsCentrum für Seltene Erkrankungen am Universitätsklinikum Carl Gustav Carus es sich zur Aufgabe gemacht, erstmals eine lokale Erhebung der behandelten seltenen Erkrankungen durchzuführen.

Rasmussen’s encephalitis is a rare neurological disease first described in 1958 that is characterized by medico-refractory seizures, focal unilateral cerebral inflammation, and deficits such as hemiparesis. While we still do not have a full understanding of this disease, proposed theories behind its etiology include auto-immune manifestations, immune attack by T cells, and malfunctional alterations in genetic expression. It is classically considered a rare childhood malady with a median age of onset of six years, and cases in adolescents and adults are even rarer, representing up to 10% of all cases to date. In this report, we would like to share a rare case of Rasmussen's encephalitis that occurred in an adolescent. Our 17-year-old male patient presented with signs and symptoms beginning at age 14 and was initially diagnosed with cerebral palsy only to later present with additional symptoms and characteristic EEG and MRI findings that ultimately led to a diagnosis of Rasmussen’s encephalitis. Thus, with this case report, our intent is twofold: to shed light on an atypical presentation of an already rare disease, even rarer in adolescents and adults, and to underscore the importance of keeping a broad differential when it comes to evaluating a patient with seizures.

L’identification des mutations génétiques impliquées dans les maladies rares est un prérequis pour mieux les comprendre, les traiter et accompagner les patients. Pour se faire, des modèles animaux présentant des maladies spontanées homologues aux maladies humaines sont très prometteurs. Le chien développe spontanément des maladies génétiques, rares chez l’Homme, mais fréquentes dans certaines races de chiens, ce qui simplifie les analyses génétiques. Ma thèse a porté sur deux maladies neurologiques : l’épilepsie et la neuropathie. Pour l’épilepsie, l’objectif était d’identifier des variants génétiques à partir de données de génotypage et de séquençage de génomes complets de deux races canines prédisposées. Un locus lié à la maladie a été identifié dans une race et des variants ponctuels et structuraux candidats ont été identifiés dans les deux races et sont en cours de validation par séquençage ciblé. Pour la neuropathie, l’équipe avait identifié une mutation en amont du gène GDNF, responsable d’une neuropathie sensitive chez des chiens de chasse. J’ai participé à la validation fonctionnelle de cette mutation. De plus, GDNF étant un excellent gène candidat pour les neuropathies humaines, j’ai séquencé ce gène chez 111 patients et extrait les variants de GDNF d’une base de données d’exomes et de génomes de plus de 600 patients. J’ai ainsi identifié 21 variants rares ou inconnus et les ai priorisé selon leurs impacts prédits in silico. Ces deux projets, alliant analyses génétiques, génomiques et fonctionnelles, chez l’homme et le chien, montrent le potentiel du chien pour l’identification de gènes candidats dans des maladies rares et/ou complexes chez l’Homme. / The identification of genetic mutations involved in rare diseases is a prerequisite for a better understanding, therapies and care to patients. To this aim, animal models declaring spontaneous diseases, homologous to human diseases are very promising. Dogs spontaneously develop genetic diseases, rare in humans, but frequent in some dog breeds, which simplifies the genetic analyzes. My thesis focused on two neurological diseases: epilepsy and neuropathy. For epilepsy, the goal was to identify genetic variants from genotyping data and sequencing of whole genome of dogs from two predisposed breeds. A disease-related locus has been identified in one breed and candidate point mutations and structural variants were identified in the two breeds and are being validated by targeted sequencing. For neuropathy, the team previously identified a mutation upstream of the GDNF gene, responsible for sensory neuropathy in hunting dogs. I participated to the functional validation of this mutation. In addition, GDNF being an excellent candidate gene for human neuropathies, I sequenced this gene in 111 patients and extracted GDNF variants from a database of exomes and genomes from more than 600 patients. I identified 21 rare or unknown variants and prioritized them according to their in silico predicted impacts. These two projects, combining genetics, genomics and functional analyses, in humans and dogs, show the dog's potential for identifying candidate genes in rare and / or complex diseases in humans.

Rare diseases represent a heterogeneous group of more than ~7000 different diseases, affecting 3,5-5,9% of the global population. Most rare diseases are genetic, but causal genes are known only in some of them. Many patients with rare diseases remain without a diagnosis, which is crucial for genetic counseling, prevention, and treatment. With the development of new methods of genome analysis, decreasing cost of sequencing, and increasing knowledge of the human genome, a new concept for identifying disease-causing genes was established. It is based on comparing the patient's genetic variability with the genetic variability of the general population. This dissertation describes next-generation sequencing technologies (NGS), bioinformatic analysis of acquired data and their applications in the elucidation of molecular underpinnings of rare genetic diseases. These procedures have led to the identification and characterization of causal genes and gene mutations in autosomal dominant tubulointerstitial kidney disease (SEC61A1, MUC1), autosomal dominant neuronal ceroid lipofuscinosis (CLN6, DNAJC5), neurodegenerative disease of unknown etiology (VPS15), Acadian variant of Fanconi syndrome (NDUFAF6) and spinal muscular atrophy (SMN1). The application of novel genome analysis techniques increased the...

The diploma thesis is focused on the topic of Living with patients with rare diseases - Epidermolysis bullosa in the Czech Republic is focused on identifying the role of individual actors involved in financing support for patients and evaluating the significance of their roles. Patients suffering from rare diseases have a very specific situation in terms of financial contributions from the public budget, as their situation is not common. The diploma thesis is focused on the role of public sector actors, the non-profit sector (the role of Debra) and patient families in financing treatment and necessary care. It examines and compares the share of funding support for these individual actors, especially focusing on the share of funding from the public sector and the non-profit sector, where the majority is occupied by Debra, which focuses on supporting patients with butterfly wing disease. The thesis examines whether the role of the public sector in financing is sufficient and how significantly its role is complemented by the non-profit sector. Subsequently, the quality of life and social construction of patients in the Czech Republic is evaluated, as well as the provision of care and financial assistance for their illness. The situation of patients will be compared with the situation in other European...

Le diagnostic des rétinopathies pigmentaires pose différents problèmes, au niveau clinique comme au niveau moléculaire. En premier lieu, il s'agit de maladies rares, la faible prévalence de chaque pathologie à l'échelle de la population mondiale rend difficile leur étude. En second lieu, la caractérisation phénotypique de ces maladies est délicate car les symptômes qui en découlent s'avèrent très similaires. De manière liée, l'œil et le processus de la vision s'avèrent complexes et impliquent les produits d'expression de nombreux gènes. Ainsi, bien que les rétinopathies soient majoritairement monogénique et respectent le modèle d'hérédité mendélienne, les causes génétiques des maladies sont variées. Sur la base de ce double constat, nous proposons deux approches méthodologiques complémentaires menant à une meilleure compréhension de ce groupe de pathologies. Une première approche a pour finalité l'acquisition du jeu exhaustif des gènes impliqués. Les travaux portent sur l'exploitation des puces de génotypage. Nous effectuons une étude de liaison génétique entre les variations ponctuelles et les pathologies. Une seconde approche porte sur la représentation des connaissances associées aux phénotypes cliniques. Un composant ontologique est construit afin d'expliciter les savoirs nécessaires au diagnostic. Les données collectées sur le long terme par les experts sont étiquetées au travers de termes organisés au sein d'un thésaurus dédié. Les profils cliniques des patients et des maladies sont manipulés sous forme de collections de caractéristiques et comparés au moyen d'une mesure de similarité adaptée. L'objectif est alors de proposer un système d'aide au diagnostic. / Diagnosis of retinitis pigmentosa could be difficult regarding both to clinics or molecular issues. Firstly, there are rare diseases, so the prevalence of each pathology in the world population is very low. Secondly, the symptoms of diseases are very similar, so their phenotypic characterization is hard. Moreover, the eye and the visual process are complex and numerous genes' products are implicated. Although retinopathies are mainly monogenic and mendelian inherited diseases, the polymorphisms involved in these diseases are very diverse.These both observations lead us to develop two complementary methodological approaches in a view to better understand the retinopathies.The first approach aims to identify all the genes involved in the diseases using genotyping chips. For this purpose, we studied genetic linkage between single nucleotide variations and pathologies. The second approach leads to the representation of clinical knowledge. An ontological compound was built to make explicit the knowledge involved in the process of diagnosis. The data previously collected by experts were labeled by terms that were organized in a specific thesaurus. The clinic profiles of the patients and diseases were handled as features collections and were compared by similarity calculations. The goal of this work is to build a knowledge-based system for diagnosis.

Made available in DSpace on 2016-04-29T13:31:15Z (GMT). No. of bitstreams: 1 Camila Claudiano Quina Pereira.pdf: 4102802 bytes, checksum: ba4ab62f6be485d3857e0d190e6ddb46 (MD5) Previous issue date: 2015-03-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this research was to understand how lay people, collectively organized, take part in the construction of knowledge about health problems affecting them. We have chosen a case study: how associations for people with rare diseases take part in the construction of the National Policy of Comprehensive Care for People with Rare Diseases in the Unified Health System (SUS). We started from the assumption that biological dimension enables new identities and expressions of citizenship, which have been reviewed with the advancement of biotechnology, like expressed in the human genome research. New socialities, based on political action and driven by hope in new treatments and medicines, have also been produced. Our hypothesis is: these collectives will organize forums when grey areas of knowledge appear or when new research horizons cease to exist. To achieve our purpose, our methodological strategy was to use multiple sources of information, such as analysis of public domain documents, interviews, participation in events and conversations with patients association s representatives. The study showed how new identities emerged by an organic design (biossocialities) and how they were rewritten in citizenship projects (biocitizenship) which claim for public policies that meet patients desires, including diagnosis, treatment and access to medicines / O objetivo desta pesquisa foi entender a participação de leigos, organizados em coletivos, na construção do conhecimento sobre os problemas de saúde que os acometem. Para isso, escolhemos como estudo de caso a participação das associações de apoio às pessoas com doenças raras na construção da Política Nacional de Atenção Integral às Pessoas com Doenças Raras no SUS. Partimos do pressuposto de que a dimensão biológica possibilita novas identidades e expressões de cidadania, que são reconfiguradas com o avanço da biotecnologia, a exemplo do que ocorre com as pesquisas sobre o genoma humano. São também construídas novas socialidades pautadas por uma ação política, movida pela esperança de novos tratamentos e medicamentos. Nossa hipótese é que esses coletivos passem a se organizar em fóruns, quando houver zonas cinzentas de conhecimento ou quando cessarem de existir novos horizontes de pesquisa. Para cumprir com os objetivos propostos, nossa estratégia metodológica foi utilizar múltiplas fontes de informação, como análise de documentos de domínio público, realização de entrevistas, participação em eventos e diálogos com representantes de associações de pacientes. O estudo das associações de apoio às pessoas com doenças raras nos permitiu entender não só como emergem novas identidades em torno de uma concepção biológica (biossocialidades), mas também como são reconfiguradas em projetos de cidadania (biocidadania), ao reivindicarem políticas públicas para atender à demanda dos pacientes, incluindo o diagnóstico, o tratamento e o acesso aos medicamentos

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-06-20T12:21:13Z No. of bitstreams: 1 Ana Catarina dos Santos Holtz.pdf: 26567764 bytes, checksum: a64dbe08b35339d1978a3394c0a08985 (MD5) / Made available in DSpace on 2017-06-20T12:21:13Z (GMT). No. of bitstreams: 1 Ana Catarina dos Santos Holtz.pdf: 26567764 bytes, checksum: a64dbe08b35339d1978a3394c0a08985 (MD5) Previous issue date: 2017-06-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The research seeks to analyze how the pharmaceutical industry builds the discourse on rare diseases and their patients. Taking the Orphan Drug Act, which guarantees benefits for medicines for such diseases, also called orphan drugs, the first chapter seeks to understand the creation of this market and to base the concepts of power, life, speech and governmentality, based on a documental and bibliographical research. The second chapter aims to reflect on the biopolitical strategies that operate in the discursive construction of the concepts of health and patient in the contemporary neoliberal scenario, while the third analyze the discourse of pharmaceutical company Novartis, the sales leader of the orphan drug segment, to understand how the laboratory establishes its institutional and commercial communication regarding rare diseases and their patients. The laboratory discourse exposes the vulnerability of the untreated patient and seeks to create a model of behavior for their rare disease patients. The theoretical foundation is formed by: Michel Foucault; Nikolas Rose; Giorgio Agamben; Didier Fassin; Peter Miller; Carlos Novas; Adriana Petryna; Paul Rabinow; Adele Clarke; Aidar Prado; Peter Pàl Pelbart; Paulo Vaz; Kátia Lerner; Paula Sibilia and Rogério da Costa / A pesquisa busca analisar de que maneira a indústria farmacêutica constrói o discurso sobre as doenças raras e os seus portadores. Tendo como ponto de partida o decreto norte-americano Orphan Drug Act, que garante benefícios para os medicamentos destinados a tais doenças, também denominados medicamentos órfãos, o primeiro capítulo procura compreender a criação deste mercado e fundamentar os conceitos de poder, vida, discurso e governamentalidade, a partir de uma pesquisa documental e bibliográfica. O segundo capítulo tem como objetivo refletir sobre as estratégias biopolíticas que operam na construção discursiva dos conceitos de saúde e paciente diante do cenário neoliberal contemporâneo, enquanto o terceiro consiste em analisar o discurso do laboratório farmacêutico Novartis, líder de vendas do segmento de medicamentos órfãos, para entender como o laboratório estabelece a sua comunicação institucional e comercial em relação às doenças raras e seus portadores. O discurso do laboratório expõe a vulnerabilidade do paciente sem tratamento e procura criar um modelo de conduta para os seus pacientes de doenças raras. A fundamentação teórica é formada por: Michel Foucault; Nikolas Rose; Giorgio Agamben; Didier Fassin; Peter Miller; Carlos Novas; Adriana Petryna; Paul Rabinow; Adele Clarke; Aidar Prado; Peter Pàl Pelbart; Paulo Vaz; Kátia Lerner; Paula Sibilia e Rogério da Costa

Retosios ligos (RL) – tai ypač mažai paplitusios ligos (gyvybei pavojų keliančios arba lėtai sekinančios ligos), kuriomis Europos Sąjungoje (ES) serga ne daugiau kaip 5 iš 10 000 asmenų. Pirmą kartą terminą „retosios ligos“ 1978 metais pavartojo Neilas A. Holtzmanas. Kiekviena RL ES serga apie 246 000 žmonių. Iš viso RL, kurių žinoma 5 000 – 8 000, kokiu nors gyvenimo etapu suserga apie 6% ES gyventojų ir tai yra 29 – 36 mln. ligonių. Lietuvoje sergančių RL galėtų būti apie 200 000 žmonių. Dauguma RL yra genetinės ligos (jos sudaro 80%), o likusios – kitų kategorijų retos vėžio formos, autoimuninės ligos, įgimtos raidos anomalijos, toksinės ir infekcinės ligos. Habilitacijos procedūrai teikiamų mokslo darbų apžvalgoje nagrinėtos 22 mokslinės publikacijos. Istoriniai šaltiniai apie RL gali būti anatominių preparatų muziejai, antikvarinės knygos medicinine tematika, tautosaka. Apžvalgoje nagrinėta Vilniaus universiteto Medicinos fakulteto anatominių preparatų kolekcija, kurioje nustatytas unikalus žmogaus anotocefalijos atvejis ir 11 kitų nozologinių RL (įgimtų anomalijų) vienetų. Pagrindinės priemonės žinioms apie RL turtinti ir klinikiniams moksliniams tyrimams plėtoti yra registrai ir duomenų bazės. Tai vienintelis būdas kaupti duomenis, kad būtų galima gauti pakankamo dydžio imtis epidemiologiniams ir (arba) klinikiniams tyrimams. Apžvalgoje nagrinėtos autopsijų ir Lietuvos paveldimų ligų ir įgimtų anomalijų (LIRECA) duomenų bazės, kurių analizės metu taikyti statistiniai... [toliau žr. visą tekstą] / Rare diseases (RD) – life menacing or slowly emaciating diseases of extremely low incidence (less than 5 cases in 10,000 EU inhabitants). The term was launched by Neil A. Holtzman in 1978. There are about 5,000 – 8,000 RD, each manifesting itself in some life stage of about 6% of EU population, that amounts from 29 to 36 million people. In Lithuania that would make about 200,000 people. The majority of RD are genetic (80%), the remaining consist of rare cancer forms, autoimmune diseases, inborn developmental anomalies, toxic or contagious illnesses. The author presented an analytical review of 22 publications on RD. Historical indications about RD could be found in anatomical museums, ancient medical books, and folk art. In the collection of anatomical specimens of Medical Faculty of Vilnius University the author has discovered a unique case of human anotocephaly and eleven more nosological entities of RD (congenital anomalies). The main sources for information on RD are registers and data bases. This is the only way to obtain sufficient samples for epidemiologic and/or clinical research. Lithuanian Register of Congenital Anomalies (LIRECA) and autopsies data base were reviewed by the author and analyzed by statistical research models applicable in registration of RD, in particular Poisson linear model and logistic (binomic) regression. Analysis of standardized remainders confirmed their adequacy and suitability. Biological asymmetry was evaluated by analysis of... [to full text]

Esta dissertação é composta por dois ensaios sobre economia da saúde. O primeiro ensaio tem como objetivo analisar o ambiente regulatório no mercado de medicamentos para doenças raras. Essas doenças são caracterizadas por afetar um pequeno número de indivíduos em uma determinada população e por serem crônicas, progressivas, degenerativas, 80% são de origem genética, 50% afetam as crianças, das quais 30% morrem antes dos 5 anos de idade. Elas representam risco de morte e um custo socioeconômico alto para o paciente e sua família. Devido à raridade, a indústria farmacêutica tem não demonstra interesse em desenvolver novos medicamentos órfãos. Apesar de individualmente raras, estima-se que o número de casos de alcançar 420 a 560 milhões de pessoas. Para a referida análise foi utilizado o modelo econômico desenvolvido por DeBrock (1985), que consiste na determinação simultânea de esforço de inovação e extensão de patentes, estabelecendo a trajetória ótima de proteção como resultado de um jogo não cooperativo entre o regulador e a empresa inovadora. Foram identificados individualmente os principais incentivos e instrumentos de regulação econômica. Eles são compostos por assistência à protocolos, procedimento centralizado de análise, reduções de taxas, o acesso de pesquisa financiado e exclusividade de mercado. Conclui-se que o instrumento regulatório mais importante foi a exclusividade de mercado, pois garante lucros extraordinários para a empresa inovadora, tornando o desenvolvimento de novas drogas tornou-se economicamente viável. No entanto, ressalta-se que todos os mecanismos tem um papel importante no sistema de incentivos e que cada um deles deve ser considerado para o desenvolvimento de políticas públicas para doenças raras. O segundo ensaio tem como objetivo medir o impacto do Diabete Melito nos rendimentos dos trabalhadores brasileiros no ano de 2008. Essa doença é caracterizada pelo elevado nível de glicose no sangue, problema que pode desencadear desencadeia má cicatrização, ataque cardíaco, acidente vascular cerebral, insuficiência renal, problemas de visão e amputação de membros. Dados do Ministério da Saúde indicam que, no Brasil, em 2010, havia cerca de 10 milhões de casos da doença, sendo a quarta principal causa de morte no país. Dados da WHO estimam que a prevalência da doença no Brasil é de 10,2% da população, cerca de 20 milhões de pessoas. A hipótese a ser testada é que o estado de saúde interfere nos rendimentos por meio de três mecanismos distintos: (i) na decisão de participar no mercado de trabalho, mensurado por meio de um Probit binário, (ii) na quantidade de horas trabalhadas e (iii) a produtividade por hora, ambos mensurados por meio do método de dois estágios de Heckman. Cada modelo é estimado separadamente para indivíduos com e sem doenças, sendo tomada a diferença do valor esperado de ambos para capturar o efeito contrafactual. Os resultados obtidos indicaram a existência de perdas progressivas, que incidem com maior intensidade entre a população feminina e que, no agregado, podem chegar ao valor de R$ 8.064.408.441.99 (USD 3.450.709.518,02 e EUR 2.490.436.905,56), correspondendo a cerca de 0,54% dos rendimentos totais e 0,20% do PIB do referido ano. Concluiu-se que o Diabete Melito gera perdas significativas na renda dos trabalhadores brasileiros, especialmente em relação à sua participação no mercado de trabalho. Os resultados indicam que as políticas públicas devem ser direcionadas para a prevenção da doença, uma vez que o desenvolvimento de comorbidades amplifica o efeito de perdas. Por fim, visando a manter a inter-relação entre os temas e a estabelecer a unidade do trabalho, foram abordadas na última seção as conclusões a respeito da dissertação. / This dissertation consists of two essays on health economics. The aim of the first essay is to analyze the regulatory environment for medicinal products for rare diseases. These diseases are characterized by to affect a small number of individuals in a given population and to be chronic, progressive, degenerative, 80% are genetic in origin, 50% affect children, of which 30% die before the age of 5. They represent death risk and a high socioeconomic cost to the patient and his family. Due to the rarity, pharmaceutical industry has not shown interest in developing new orphan drugs. Although individually rare, estimatives show that the number of cases to reach 420 million to 560 million people. For this analysis the economic model developed by DeBrock (1985), which consists of the simultaneous determination of innovation effort and extension of patents, establishing the optimal path protection as a result of a non-cooperative game between the regulator and the innovator was used. The main incentives and instruments of economic regulation were individually identified. They are protocols assistance, centralized analysis procedure, fee reductions, access to funded research and market exclusivity. We conclude that the most important regulatory tool was market exclusivity, because it ensures extraordinary profits for the innovator, making the development of new drugs become economically viable. However, it is noteworthy that all the mechanisms have an important role in the incentive system and that each of them should be considered for the development of public policies for rare diseases. The second essay aims to measure the impact of diabetes mellitus on the income of Brazilian workers in 2008. The main disease characteristic is high blood glucose, a problem that can trigger scarring troubles, heart attack, stroke, failure kidney, vision problems and limbs amputation. Ministry of Health data indicate that, in Brazil, in 2010, there were about 10 million cases of the disease, making it the fourth leading cause of death in the country. WHO data estimate that the disease prevalence is 10.2% of the Brazilian population, about 20 million people. The hypothesis to be tested is that the health status interfere in worker income through three distinct mechanisms: (i) in the decision to participate in the labor market, measured by means of a binary Probit, (ii) in the amount of hours worked and (iii) in the productivity per hour, both measured by the Heckman two-stage method. Each model is estimated separately for individuals with and without disease, and taking the difference of the expected value of both to capture the counterfactual effect. The results indicated the existence of progressive losses, which focus more strongly among women and that, in the aggregate, may reach R$ 8.064.408.441.99 (3,450,709,518.02 USD and EUR 2,490,436,905, 56), corresponding to about 0.54% of the total income and 0.20% of GDP in that year. It was concluded that diabetes mellitus causes significant losses in Brazilian workers income, especially in relation to their participation in the labor market. The results indicate that public policies should be directed to the prevention of disease, since the development of comorbidities amplifies the losses effect. Finally, to keep the inter-relationship between the issues and to establish the unity of the work, have been addressed in the last section the conclusions regarding the dissertation.