Long-Term Lamivudine Treatment of Children with Chronic Hepatitis B: Durability of Therapeutic Responses and Safety

Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fifty-one children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children.

Development and Characterization of bioactive, edible whey protein films and coatings to improve quality and safety of Food products

Dissertação para a obtenção de grau de doutor em Ciências da Engenharia e Tecnologia

The influence of the regional basic diet from northeast Brazil on health and nutritional conditions of mice infected with Schistosoma mansoni

Protein nutritionalstatus indicators were studied in weanling albino Swiss mice infected with S. mansoni andfed the Regional Basic Diet (RBD)from Northeast Brazil, a multideficient diet of low-protein content. Each mouse was infected percutaneously with 80 cercariae. The experiment lasted 63 days. The growth curve, food consumption, protein intake, weight gain, Protein Efficiency Ratio (PER) and Net Protein Ratio (NPR) were the parameters investigated. RBD-fed mice showed a marked weight loss, a lower food and protein intake, a slower body weight gain and lower rates of food protein utilization when compared to casein-fed animals. Differences between infected and non-infected mice were not consistent. The present results suggest that the effects of RBD-induced malnutrition on health and nutritional conditions of the mice are more severe than those of Manson's schistosomiasis, in the initial phase of the disease.

Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T) Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age

Vaccination of infants with conjugated Haemophilus influenzae type b (Hib) vaccines has been proven to reduce Hib meningitis by 95% and pneumoniae by 20%. The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI (Expanded Plan of Immunization). The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib (diphtheria-tetanus-whole cell pertussis) combination, using the technology of two Brazilian manufacturers, against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2, 4 and 6 months according to the local national schedule. The Brazilian combination was highly immunogenic with Hib seroprotection rates (anti-PRP > 0.15 mg /ml of 98% after 2 doses and 100% after 3). Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart, except the diphtheria seroprotection rates and titers were lower. There was also no clinically relevant difference in reactogenicity. If these feasibility results are confirmed, the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil.

Infeção por Mycobacterium Tuberculosis em profissionais de saúde : metodologia de avaliação do risco e sua aplicação num hospital central

RESUMO - A Tuberculose surge, de acordo com o último relatório da Organização Mundial da Saúde, como a segunda principal causa de morte em todo o mundo, de entre as doenças infeciosas. Em 2012, 1.3 milhões de pessoas morreram devido a esta patologia e surgiram 8.6 milhões de novos casos. De entre os grupos de risco de infeção, surgem os profissionais de saúde. A dificuldade no diagnóstico da Tuberculose, o contacto próximo com os pacientes, as medidas de controlo de infeção por vezes inadequadas são algumas das razões que explicam o risco mais elevado de contrair Tuberculose no local de trabalho. Esta Dissertação de Mestrado pretende estabelecer uma nova classificação de risco de infeção por M. tuberculosis em estabelecimentos de saúde, com vista a promover a saúde destes profissionais, inovadora nos critérios de avaliação das medidas de controlo de infeção e de análise dos casos de exposição não protegida a Tuberculose ativa. Esta metodologia de avaliação foi o resultado de uma revisão bibliográfica sobre a temática, tendo sido aplicada num hospital para verificar a sua adequabilidade e mais-valia.

Mental health and the crisis: Evidence from share

Mental health constitutes a significant share of the global burden of disease. It is shaped to a great extent by socioeconomic factors and is vulnerable to external shocks. The recent financial crisis brought about stressors prone to trigger and aggravate mental illnesses. This project presents a micro analysis of the effect of the economic crisis on mental health in eleven European countries, through the estimation of individual health production functions accounting for socioeconomic controls and macroeconomic indicators. We find that mental health has deteriorated since 2007, even though the development of depression episodes is unchanged. Additionally, his variation can be partially attributed to economic recession and budgetary cuts in health spending.

Mental health and neuroscience. A perspective from the magazine market

Mental health awareness has been rising worldwide, motivated by its social and economic costs. Despite the investment in research in neuroscience in the recent years, little is known about the underlying mechanisms in the brain that are correlated with psychiatric conditions. This project, through two feature articles suitable to be published in magazines, provides perspectives onto mental health research. First it presents an example where psychiatry joins forces with neuroscience and computer science in an interdisciplinary effort to improve the life of those affected by mental disorders. The second article gathers opinions which claim that mental health research priorities should be set by patients themselves, or even that people with lived experience of mental health issues should have an active role in that research. This project was planned and researched while I was an Erasmus student at Nottingham Trent University, in the United Kingdom.

Breastfeeding: making the difference in the development, health and nutrition of term and preterm newborns

Breastfeeding is the natural and safe way of feeding small infants, providing nutritional, immunological, psychological and economic recognized and unquestionable advantages. These qualities are especially important in premature infants, because of their vulnerability. Despite highly desirable, there is, in general, little success in breastfeeding preterm infants, especially in special care neonatal units. There are evidences that a high supportive hospital environment, with an interdisciplinary team, makes possible to these infants to be breastfed. In this article, the authors present an up-to-date review about the components of human milk and its unique characteristics, as well as describes aspects that make the breast milk particularly suitable for feeding the premature newborn.

Políticas integradas de protecção e promoção da saúde e segurança do trabalho nas empresas portuguesas

RESUMO - Foi construída uma tipologia com cinco grupos principais de políticas, programas e actividades: A (Higiene & Segurança no Trabalho/Melhoria do ambiente físico de trabalho); B (Avaliação de saúde/Vigilância médica/Prestação de cuidados de saúde); C (Prevenção de comportamentos de risco/ Promoção de estilos de vida saudáveis); D (Intervenções a nível organizacional/Melhoria do ambiente psicossocial de trabalho); E (Actividades e programas sociais e de bem-estar). Foi concebido e desenhado, para ser autoadministrado, um questionário sobre Política de Saúde no Local de Trabalho. Foram efectuados dois mailings, e um follow-up telefónico. O trabalho de campo decorreu entre a Primavera de 1997 e o Verão de 1998. A amostra (n = 259) é considerada representativa das duas mil maiores empresas do país. Uma em cada quatro era uma multinacional. A taxa de sindicalização rondava os 30% da população trabalhadora, mas apenas 16% dos respondentes assinalou a existência de representantes dos trabalhadores eleitos para a S&ST (abreviadamente, Saúde & Segurança do Trabalho). É o sistema de gestão integrado de S&ST, e não o tamanho da empresa ou outra característica sociodemográfica ou técnicoorganizacional, que permite predizer a existência de empresas, mais activas e inovadoras no domínio da protecção e promoção da saúde no trabalho.

Decision methods applied to solve a safety problem on a waste treatment facility

To solve a health and safety problem on a waste treatment facility, different multicriteria decision methods were used, including the PROV Exponential decision method. Four alternatives and ten attributes were considered. We found a congruent solution, validated by the different methods. The AHP and the PROV Exponential decision method led us to the same options ordering, but the last method reinforced one of the options as being the best performing one, and detached the least performing option. Also, the ELECTRE I method results led to the same ordering which allowed to point the best solution with reasonable confidence. This paper demonstrates the potential of using multicriteria decision methods to support decision making on complex problems such as risk control and accidents prevention.

Workplace ergonomics in lean production environments: A literature review

BACKGROUND: Lean Production Systems (LPS) have become very popular among manufacturing industries, services and large commercial areas. A LPS must develop and consider a set of work features to bring compatibility with workplace ergonomics, namely at a muscular, cognitive and emotional demands level. OBJECTIVE: Identify the most relevant impacts of the adoption of LPS from the ergonomics point of view and summarizes some possible drawbacks for workplace ergonomics due to a flawed application of the LPS. The impacts identified are focused in four dimensions: work pace, intensity and load; worker motivation, satisfaction and stress; autonomy and participation; and health outcome. This paper also discusses the influence that the work organization model has on workplace ergonomics and on the waste elimination previewed by LPS. METHODS: Literature review focused LPS and its impact on occupational ergonomics conditions, as well as on the Health and Safety of workers. The main focus of this research is on LPS implementations in industrial environments and mainly in manufacturing industry workplaces. This is followed by a discussion including the authors’ experience (and previous research). RESULTS: From the reviewed literature it seems that there is no consensus on how Lean principles affect the workplace ergonomics since most authors found positive (advantages) and negative (disadvantages) impacts. CONCLUSIONS: The negative impacts or disadvantages of LPS implementations reviewed may result from the misunderstanding of the Lean principles. Possibly, they also happen due to partial Lean implementations (when only one or two tools were implemented) that may be effective in a specific work context but not suitable to all possible situations as the principles of LPS should not lead, by definition, to any of the reported drawbacks in terms of workplace ergonomics.

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.

Prevalence of excessive daytime sleepiness in Brazilian community-dwelling older adults with very low levels of schooling, and its association with sociodemographic characteristics and lifestyle: the Bambuí Health and Ageing Study (BHAS)

OBJECTIVE: Population-based studies on excessive daytime sleepiness (EDS) in older adults living in less developed countries are scarce. The purpose of this paper was to estimate the prevalence of EDS and its association with sociodemographic characteristics and lifestyle factors in Brazilian community-dwelling older adults. METHODS: The study was carried out in Bambuí, a city in the state of Minas Gerais, Brazil. EDS was defined as the presence of sleepiness in the last month occurring three or more times per week, with any interference in usual activities. The exploratory variables were: gender, age, skin color, marital status, schooling level, current employment status, religion, recent migration, smoking, binge drinking and physical activities during leisure time. RESULTS: Of 1,742 residents aged > 60 years, 1,514 (86.9%) participated. The prevalence of EDS was 13%. After adjustment for confounders, female gender and low schooling level remained positively and independently associated with EDS. CONCLUSIONS: The prevalence of EDS in the study population was within the range observed in studies carried out in developed countries. The most impressive finding was the association of EDS with schooling, indicating that even in a population with low levels of schooling, this was an important factor to explain the distribution of EDS.

The role of IFNγ in higher brain function: in health and under chronic stress

Tese de Doutoramento em Ciências da Saúde

Myocardial perfusion by contrast echocardiography. Establishment of normal pattern of intracoronary injection and safety in humans

OBJECTIVE: To establish the normal pattern and safety of echocardiographic contrast in patients with no significant obstruction of epicardial coronary arteries. METHODS: 67 patients with normal coronary arteries or obstructions < 50% were selected from 277 patients who underwent coronary angiography (CA). Mean age was 56 ± 11years and 36 were males. At the end CA, echocardiographic contrast was selectively injected into each coronary artery. The parasternal short axis of the left ventricle (LV) was divided into six segments: anterior (A), antero-lateral (AL), postero-lateral (PL), posterior (P), infero-septal (IS) and antero-septal (AS). Anterolateral (ALPM) and posteromedial papillary muscles (PMPM) were also considered. The pattern and intensity of the appearance of the myocardial contrast was visually analyzed. RESULTS: The right coronary artery (RCA) was dominant in 60 patients. Contrast appearance was sudden and simultaneous in the 3 muscle layers. All segments could be contrasted after the injection in both coronary arteries. 100% of the AS, A and AL segments, 97% of the PL and 98% of the ALPM were perfused by the left coronary artery (LCA). P and IS segments were perfused by the RCA in 85% and 82%, respectively, and by a dominant LCA in 71% of the cases. The PMPM was perfused by a dominant RCA in 77% and by a dominant LCA in 86%. There were no symptoms. CONCLUSION: Intracoronary injection of the sonicated solution is a safe procedure that allows for an excellent opacification of the myocardium and can potentially be used during routine CA.