Role of malnutrition and parasite infections in the spatial variation in children’s anaemia risk in northern Angola

Anaemia is known to have an impact on child development and mortality and is a severe public health problem in most countries in sub-Saharan Africa. We investigated the consistency between ecological and individual-level approaches to anaemia mapping by building spatial anaemia models for children aged ≤15 years using different modelling approaches. We aimed to (i) quantify the role of malnutrition, malaria, Schistosoma haematobium and soil-transmitted helminths (STHs) in anaemia endemicity; and (ii) develop a high resolution predictive risk map of anaemia for the municipality of Dande in northern Angola. We used parasitological survey data for children aged ≤15 years to build Bayesian geostatistical models of malaria (PfPR≤15), S. haematobium, Ascaris lumbricoides and Trichuris trichiura and predict small-scale spatial variations in these infections. Malnutrition, PfPR≤15, and S. haematobium infections were significantly associated with anaemia risk. An estimated 12.5%, 15.6% and 9.8% of anaemia cases could be averted by treating malnutrition, malaria and S. haematobium, respectively. Spatial clusters of high risk of anaemia (>86%) were identified. Using an individual-level approach to anaemia mapping at a small spatial scale, we found that anaemia in children aged ≤15 years is highly heterogeneous and that malnutrition and parasitic infections are important contributors to the spatial variation in anaemia risk. The results presented in this study can help inform the integration of the current provincial malaria control programme with ancillary micronutrient supplementation and control of neglected tropical diseases such as urogenital schistosomiasis and STH infections.

Caffeine effect on mortality and oviposition in successive generations of Aedes aegypti

OBJECTIVE: Previous experiments showed that caffeine blocks the development of Aedes aegypti (Diptera, Culicidae) in the larval stage, consequently inhibiting the production of adults. This study aimed at obtaining data suggestive of caffeine resistance by these mosquitoes. METHODS: Experiments were carried out in successive generations to assess adult production from eggs laid in previous generation and oviposition rate in every generation using 200 and 500 µg/mL caffeine. Tap water was used as control. Experiments were conducted in the city of São José do Rio Preto, Southeastern Brazil between 2002 and 2005. Statistical tests consisted of exploratory data analysis and smoothing algorithms. RESULTS: Increasing reduction in productivity of adults occurred among generations at both caffeine concentrations but the differences were only significant at 200µg/mL caffeine. As for the oviposition rate, there was a decrease in the mean number of eggs per female over generations at both caffeine concentrations. CONCLUSIONS: There was no evidence of caffeine resistance over generations. The study results corroborate caffeine as an alternative as an important Ae. Aegypti control agent to avoid resistance.

Risk-factors for antepartum fetal deaths in the city of São Paulo, Brazil

OBJECTIVE: To assess risk factors for antepartum fetal deaths. METHODS: A population-based case-control study was carried out in the city of São Paulo from August 2000 to January 2001. Subjects were selected from a birth cohort from a linked birth and death certificate database. Cases were 164 antepartum fetal deaths and controls were drawn from a random sample of 313 births surviving at least 28 days. Information was collected from birth and death certificates, hospital records and home interviews. A hierarchical conceptual framework guided the logistic regression analysis. RESULTS: Statistically significant factors associated with antepartum fetal death were: mother without or recent marital union; mother's education under four years; mothers with previous low birth weight infant; mothers with hypertension, diabetes, bleeding during pregnancy; no or inadequate prenatal care; congenital malformation and intrauterine growth restriction. The highest population attributable fractions were for inadequacy of prenatal care (40%), hypertension (27%), intrauterine growth restriction (30%) and absence of a long-standing union (26%). CONCLUSIONS: Proximal biological risk factors are most important in antepartum fetal deaths. However, distal factors - mother's low education and marital status - are also significant. Improving access to and quality of prenatal care could have a large impact on fetal mortality.

Risk factors for cesarean section by category of health service

OBJECTIVE: To analyze the rate of cesarean section and differences in risk factors by category of health service, either public or private. METHODS: A cross-sectional study was carried out including all pregnant women in labor admitted to hospitals in the city of Rio Grande, Southern Brazil, between January 1 and December 31, 2007. A pre-coded and pre-tested questionnaire was used to collect on social, demographic, obstetric and newborn care information. Two regression models were constructed: one for public users and the other one for private ones. Poisson regression was used in each model in the multivariate analysis. Prevalence rates and 95% confidence intervals were calculated for each adjusted factor. RESULTS: The rate of cesarean section was 43% and 86% among public and private users. Sociodemographic factors and twin births have a more significant impact among public users as well as number of pregnancies (25% vs. 13% reduction in public and private users, respectively) and previous cesarean section (86% vs. 24% increase in public and private users, respectively). Prenatal care visits and hospital admissions affected the outcome only in women users of public services. CONCLUSIONS: Cesarean section rates were high in both groups studied, but it was twice as high among women cared in the private sector. Associated factors differ in magnitude by category of service used.

Risk Assessment of Chronic Exposure to Magnetic Fields near Electrical Apparatus

Conferência: 9th International Symposium on Occupational Safety and Hygiene (SHO) Guimaraes, Portugal - FEB 14-15, 2013

Disparities in cervical and breast cancer mortality in Brazil

OBJECTIVE To analyze cervical and breast cancer mortality in Brazil according to socioeconomic and welfare indicators. METHODS Data on breast and cervical cancer mortality covering a 30-year period (1980-2010) were analyzed. The data were obtained from the National Mortality Database, population data from the Brazilian Institute of Geography and Statistics database, and socioeconomic and welfare information from the Institute of Applied Economic Research. Moving averages were calculated, disaggregated by capital city and municipality. The annual percent change in mortality rates was estimated by segmented linear regression using the joinpoint method. Pearson’s correlation coefficients were conducted between average mortality rate at the end of the three-year period and selected indicators in the state capital and each Brazilian state. RESULTS There was a decline in cervical cancer mortality rates throughout the period studied, except in municipalities outside of the capitals in the North and Northeast. There was a decrease in breast cancer mortality in the capitals from the end of the 1990s onwards. Favorable socioeconomic indicators were inversely correlated with cervical cancer mortality. A strong direct correlation was found with favorable indicators and an inverse correlation with fertility rate and breast cancer mortality in inner cities. CONCLUSIONS There is an ongoing dynamic process of increased risk of cervical and breast cancer and attenuation of mortality because of increased, albeit unequal, access to and provision of screening, diagnosis and treatment. 

Isolated and synergistic effects of PM10 and average temperature on cardiovascular and respiratory mortality

OBJECTIVE To analyze the effect of air pollution and temperature on mortality due to cardiovascular and respiratory diseases. METHODS We evaluated the isolated and synergistic effects of temperature and particulate matter with aerodynamic diameter < 10 µm (PM10) on the mortality of individuals > 40 years old due to cardiovascular disease and that of individuals > 60 years old due to respiratory diseases in Sao Paulo, SP, Southeastern Brazil, between 1998 and 2008. Three methodologies were used to evaluate the isolated association: time-series analysis using Poisson regression model, bidirectional case-crossover analysis matched by period, and case-crossover analysis matched by the confounding factor, i.e., average temperature or pollutant concentration. The graphical representation of the response surface, generated by the interaction term between these factors added to the Poisson regression model, was interpreted to evaluate the synergistic effect of the risk factors. RESULTS No differences were observed between the results of the case-crossover and time-series analyses. The percentage change in the relative risk of cardiovascular and respiratory mortality was 0.85% (0.45;1.25) and 1.60% (0.74;2.46), respectively, due to an increase of 10 μg/m3 in the PM10 concentration. The pattern of correlation of the temperature with cardiovascular mortality was U-shaped and that with respiratory mortality was J-shaped, indicating an increased relative risk at high temperatures. The values for the interaction term indicated a higher relative risk for cardiovascular and respiratory mortalities at low temperatures and high temperatures, respectively, when the pollution levels reached approximately 60 μg/m3. CONCLUSIONS The positive association standardized in the Poisson regression model for pollutant concentration is not confounded by temperature, and the effect of temperature is not confounded by the pollutant levels in the time-series analysis. The simultaneous exposure to different levels of environmental factors can create synergistic effects that are as disturbing as those caused by extreme concentrations.

Past and present: conditions of life during childhood and mortality of older adults

ABSTRACT OBJECTIVE: To analyze whether socioeconomic and health conditions during childhood are associated with mortality during old age. METHODS: Data were extracted from the SABE Study (Saúde, Bem-estar e Envelhecimento – Health, Welfare and Aging), which were performed in 2000 and 2006. The sample consisted of 2004 (1,355 living and 649 dead) older adults. The statistical analysis was performed based on Poisson regression models, taking into account the time variation of risk observed. Older adults’ demographic characteristics and life conditions were evaluated, as were the socioeconomic and lifestyle conditions they acquired during their adult life. RESULTS: Only the area of residence during childhood (rural or urban) remained as a factor associated with mortality at advanced ages. However, this association lost significance when the variables acquired during adulthood were added to the model. CONCLUSIONS: Despite the information regarding the conditions during childhood being limited and perhaps not accurately measure the socioeconomic status and health in the first years of life, the findings of this study suggest that improving the environmental conditions of children and creating opportunities during early adulthood may contribute to greater survival rates for those of more advanced years.

Contributo para o estudo da influência do stress na resposta imunitária à vacina contra a gripe em profissionais de saúde

Resumo: Os profissionais de saúde podem estar expostos a vários factores indutores de stress crónico nomeadamente de natureza profissional destacando-se, entre os seus possíveis efeitos, a diminuição da resposta de anticorpos após administração de vacinas, entre as quais, a vacina contra a gripe. Uma vez que os trabalhadores da saúde estão expostos a factores indutores de stress e, simultaneamente, a agentes biológicos cujos efeitos poderão ser prevenidos pela vacinação, é pertinente estudar a influência do stress na resposta imunitária à vacina contra a gripe em enfermeiros. Constituíram objectivos deste trabalho: (1) estudar a associação entre a presença de stress crónico em enfermeiros hospitalares e a “insuficiente” resposta imunitária à vacina contra a gripe, avaliada um mês após a vacinação (T1); (2) estudar a associação entre a presença de stress crónico em enfermeiros hospitalares e a redução dos títulos de anticorpos dirigidos às hemaglutininas seis meses após a vacinação (T6) e (3) identificar algumas características das unidades de internamento e do trabalho dos participantes que possam estar associadas à presença de stress crónico e estudar a sua possível associação com a resposta imunitária à vacina contra a gripe. Realizou-se um estudo caso-controlo incorporado num estudo de coortes e a amostra em estudo foi constituída por 136 enfermeiros saudáveis (83,8% sexo feminino; média de idades de 33anos) de um hospital universitário. Realizaram-se entrevistas individuais e aplicaram-se as versões portuguesas dos questionários The General Health Questionnaire (GHQ12) e Maslach Burnout Inventory – Human Services Survey (MBI-HSS) para determinação da presença de stress crónico pelo método da triangulação, no início do estudo (T0) e realizou-se a recolha de dados relativos à caracterização de elementos de trabalho nas unidades de internamento. Foi administrada a vacina contra a gripe e determinou-se os títulos de anticorpos dirigidos às hemaglutininas de cada estirpe componentes da vacina contra a gripe utilizada em 2007, antes da vacinação, um mês e seis meses após a vacinação. Não se encontrou associação, ao nível de significância de 5%, entre a presença de stress e a “insuficiente” resposta à vacina contra a gripe, avaliada pela taxa de indivíduos que apresentaram um aumento, ao fim de um mês, inferior a quatro vezes os títulos de anticorpos antes da vacinação. No entanto, encontrou-se uma maior proporção de indivíduos com stress no grupo de participantes em que ocorreu uma diminuição do título de anticorpos dirigidos à hemaglutinina AH1 (ac AH1) em T6, quando comparado com o respectivo grupo controlo. A diferença entre grupos foi estatisticamente significativa, quando se avaliou a presença de stress pelo método da triangulação usando a entrevista (p=0,006), pelo método da triangulação usando o GHQ12 (p=0,045) e ainda usando a combinação dos três critérios (p=0,001). Após análise multivariada, verificou-se que a associação entre a presença de XXVI stress e a redução dos ac AH1 em T6 manteve significado estatístico (respectivamente, p= 0,010, p= 0,042 e p=0,002) e apresentou odds ratio ajustados, em função de cada um dos métodos de avaliação da presença de stress, de 3,643, de 2,733 e de 5,223. A quantidade de trabalho percepcionada como sobrecarga constituiu o factor indutor de stress mais vezes referido (58,8% da amostra e 61,8% dos enfermeiros de unidades de internamento), seguida dos conflitos entre profissionais. O contacto com o sofrimento e a morte de doentes foram identificados em quarto lugar pela amostra, mas em segundo pelos enfermeiros de unidades de internamento. Nesses, verificou-se uma associação positiva entre trabalhar em Serviços onde o número de doentes falecidos foi muito elevado e a presença de stress, medido pelo método da triangulação usando a entrevista (p=0,039), usando o GHQ12 (p=0,019), usando a escala de exaustão emocional do MBI-HSS (p=0,012) e pela combinação dos três métodos (p=0,014). Verificou-se também uma associação positiva entre a presença de stress, identificada pelo método da triangulação usando a escala de exaustão emocional do MBI-HSS, e o trabalho em serviços de internamento onde a percentagem de doentes idosos (p=0,025) e a taxa de letalidade (p=0,036) foram elevadas. Contudo, não se encontrou associação entre a exposição muito frequente ao sofrimento e à morte de doentes e a redução do título de ac AH1 em T6. Possivelmente, a exposição a esse factor indutor de stress, apesar de estar relacionada com a presença de stress nos enfermeiros de serviços de internamento, não foi suficientemente intenso para, por si só, estar associada à redução do título de ac AH1 em T6. A associação encontrada entre a presença de stress crónico e a redução do título de anticorpos AH1 em T6 vem apoiar a resposta à questão de investigação inicialmente colocada de que o stress poderá influenciar negativamente a manutenção dos títulos de anticorpos, mesmo em indivíduos adultos não idosos. Assim, o risco de um enfermeiro com stress apresentar redução do título de anticorpos dirigidos à hemaglutinina da estirpe AH1N1 – A/Solomon Islands/3/2006 ao fim dos seis meses do estudo, foi 3,6, 2,7 ou 5,2 vezes superior ao de um enfermeiro sem stress, consoante o critério de stress ter sido determinado, respectivamente, pelo método da triangulação usando a entrevista, pelo método da triangulação utilizando o GHQ12 ou pela combinação dos três critérios. Summary: Health workers may be exposed to various factors causing chronic stress namely those related directly to their activity, in particular the decrease in the capacity of the response of antibodies after the administration of the vaccines, amongst others the Influenza vaccine. Since health workers are exposed to factors causing stress and at the same time biological agents, whose effects may be prevented through vaccination, it is important to study the influence of stress in the immunity response to the Influenza vaccine on nurses. The aims of this study are: (1) to examine the relation between chronic stress in hospital nurses and the “insufficient” immunity response to the Influenza vaccine, assessed at one month after vaccination (T1); (2) to examine the relation between chronic stress in hospital nurses and the decrease of the hemagglutinin titles of antibodies six months after vaccination (T6); (3) to identify some characteristics of internment units and the work of the participants that may be related to the presence of chronic stress and to study its possible relation with the immunity response to the Influenza vaccine. A control-case study, integrated in a coortes study, was carried out and the sample under analysis consisted of 136 healthy nurses (83,8% female; average age 33 years old) from a university hospital. Several individual interviews were conducted and the portuguese versions of General Health Questionnaire (GHQ12) and Maslach Burnout Inventory – Human Services Survey (MBI-HSS) was applied in order to determine the presence of chronic stress, using the triangulation method at the beginning of the study (T0). Data concerning the particular features of the internment units was collected. The Influenza vaccine was administered and the titles of hemagglutinin antibodies of each strain composing the Influenza vaccine used in 2007, before vaccination, and a month and six months after vaccination, were determined. There was no statistically relevant (5%) relation between stress and the “insufficient” immune response to the Influenza vaccine, according to the rate of individuals that showed, after a month, a level of antibodies concentration lower than four times the level prior to the vaccination. Nevertheless, there was a greater number of individuals with stress in the group of participants in which there was a decrease of the hemagglutinin titles of antibodies AH1 (ac AH1) in T6, when compared to the control group under study. The difference between groups was statistically relevant when assessing the presence of stress by triangulation method using the interview (p=0,006), by triangulation method using the GHQ12 (p=0,045) and by the combination of the three criteria (p=0,001). After multivariate analysis, it was verified that the XXVIII relation between the presence of stress and the reduction of the ac AH1 in T6 was statistically relevant (respectively, p= 0,010, p= 0,042 and p=0,002) and the odds ratio were, according to each of the methods used to assess the presence of stress, 3,643, 2,733 and 5,223. Overwork was the most emphasised stress-causing factor (58,8% of the sample and 61,8% of the nurses working in the Internment Units), followed by conflicts arousing among co-workers. Witnessing the suffering and death of patients was ranked as the fourth cause of stress, but the second by the nurses of the internment units. The former revealed a positive connection between working in the services, where there was a high rate of deaths, and the presence of stress, when assessing the presence of stress by triangulation method using the interview (p=0,039), the GHQ12 (p=0,019), the MBI-HSS emotional exhaustion scale (p=0,012) and by the combination of the three criteria (p=0,014).There was also a connection between the presence of stress, identified by the method of triangulation using the MBI-HSS emotional exhaustion scale, and working in the internment units, where the percentage of elderly people (p=0,025) and the mortality rate (p=0,036) were high. However, there was no connection between frequent exposure to suffering and death in patients and the reduction of ac AH1 titles, in T6. Although one can establish a connection between stress in nurses working in the internment units and the aforementioned stress-causing factor, the exposure to that factor was not, per se, intense enough to reduce the ac AH1 title in T6. The relation found between the presence of chronic stress and the reduction of AH1 antibodies titles in T6, corroborates the hypothesis that stress can negatively influence the title of antibodies, even in non-elderly adults. Thus, and according to the criteria used to define stress, by the triangulation method using the interview, by the triangulation method using the GHQ12 or the combination of the three criteria respectively, the risk of a nurse suffering from stress showing a reduction in the title of hemagglutinin antibodies for the strain AH1N1 – A/Solomon Islands/3/2006 six-month after Influenza vaccine was 3,6, 2,7 or 5,2 times greater than on a nurse suffering from no stress at all. Résumé: Les professionnels de la santé peuvent être exposés à différents facteurs inducteurs de stress chronique de nature professionnelle. On remarque, parmi les effets possibles, une baisse de la réponse des anticorps après l´administration de vaccins, comme en particulier, le vaccin de la grippe. Lorsque les professionnels de la santé ont été exposés à des facteurs inducteurs de stress, et de manière simultanée, à des agents biologiques dont les effets pourront être prévenus par la vaccination, il est pertinent d´étudier l´influence du stress dans la réponse immunitaire au vaccin de la grippe chez les infirmiers. Ils ont constitué des objectifs d´études et de discussion : (1) étudier l´association entre la présence de stress chronique chez les infirmiers, en milieu hospitalier, et la “insuffisant” réponse immunitaire au vaccin de la grippe, vérifiée à un mois après la vaccination (T1); (2) étudier l´association entre la présence de stress chronique chez les infirmiers, en milieu hospitalier, et la réduction de la teneur des anticorps dirigé à la hémaglutinina six mois après la vaccination (T6) (3) identifier certaines caractéristiques des unités d´internement, et étudier les aspects du travail des participants, qui puissent être associée à la présence de stress chronique et étudier sa possible association avec la réponse immunitaire au vaccin de la grippe. Une étude cas-contrôle incorporée dans une étude de groupe a été réalisée et un échantillon, pour étude, a été constitué par 136 infirmiers sains (83,8% de sexe féminin, âge moyen 33 ans) travaillant dans un hôpital universitaire. Des entretiens individuels ont été réalisés et les versions portugaises des questionnaires de General Health Questionnaire (GHQ12) et Maslach Burnout Inventory- Human Service Survey (MBI-HSS) ont été utilisés pour déterminer la présence de stress chronique grâce à la méthode de triangulation, au début de l´étude (T0) et un relevé de données relatives à la caractérisation d´éléments de travail dans les unités d´internement a été fait. Le vaccin de la grippe a été administré et les teneurs en anticorps dirigés aux hémaglutininas de chaque composant du vaccin de la grippe pour 2007 ont été déterminés, avant la vaccination et un mois et six mois après. On n´a pas trouvé d´association, à un niveau significatif de au moins 5%, entre la présence de stress et la “insuffisant” réponse au vaccin de la grippe, évaluée par le taux d´individus qui ont présenté une augmentation, à la fin du mois, inférieur à quatre fois la teneur des anticorps par rapport à avant la vaccination. Cependant , on a trouvé une plus grande proportion d´individus victimes de stress dans le groupe des participants où il y a eu une baisse de la teneur des anticorps dirigé à la hémaglutinina AH1 (ac AH1) en T6, après comparaison avec le respectif groupe de contrôle. La différence entre les groupes a été statistiquement significative lorsqu´on a vérifié la présence de stress grâce à la méthode de triangulation, en utilisant l´entretien (p=0,006), par la méthode de triangulation en utilisant le GHQ12 (p=0,045) et en utilisant aussi la combinaison des trois critères (p=0,001). Après une analyse XXX multivariée, on a vérifié que l´association entre la présence de stress et la réduction des ac AH1 en T6 a conservé un signifié statistique (respectivement, p=0,010, p=0,042 et p=0,002) et a présenté des odds ratio ajustés, en fonction de chacune des méthodes de vérification de la présence de stress de 3,643, de 2,733 et de 5,223. La quantité de travail perçue comme une surcharge constitue le facteur inducteur de stress le plus souvent cité (58,8% de l´échantillon et 61,8% des infirmiers des unités d´internement), suivi par les conflits entre professionnels. Le contact avec la souffrance et la mort des patients a été placé en quatrième position par l´échantillon, mais en deuxième position par les infirmiers des unités d´internement. Dans ces cas, on a vérifié une association évidente entre le fait de travailler dans des services où le nombre de patients décédés a été très élevé et la présence de stress, identifiée par la méthode de triangulation, en utilisant l´entretien (p=0,039), le GHQ12 (p=0,019), l´échelle de fatigue émotionnelle du MBI-HSS (p=0,012) et en utilisant aussi la combinaison des trois critères (p=0,014). On a aussi vérifié une association positive entre la présence de stress, identifiée par la méthode de triangulation, en utilisant l´échelle de fatigue émotionnelle du MBI-HSS et le travail dans des services d´internement où le pourcentage de malade âgés (p=0,025) et le taux de mortalité ont été élevés (p=0,036). Malgré tout, on n´a pas trouvé d´association entre l´exposition très fréquente à la souffrance et à la mort des patients et la réduction de la teneur de ac AH1 en T6. Probablement l´exposition à ce facteur inducteur de stress, bien qu´elle soit liée à la présence de stress chez les infirmiers des services d´internement, n´a pas été suffisamment intense pour, en elle-même, être associée à la réduction de la teneur ac AH1 enT6. L´association trouvée entre la présence de stress chronique et la réduction de la teneur des anticorps AH1 en T6 vient renforcer l´hypothèse que le stress pourra influencer négativement la manutention des teneurs en anticorps même chez les individus adultes jeunes. Donc le risque qu´un infirmier stressé présente une réduction de la teneur en anticorps dirigés à la hémaglutinina de le composant AH1N1-A/Solomon Island/3/2006 à la fin des six mois d´études a été 3,6, 2,7 ou 5,2 fois supérieure à celui d´un infirmier sans stress, après avoir déterminé le critère de stress, respectivement par la méthode de triangulation utilisant l´entretien, par la méthode de triangulation utilisant le GHQ12 ou par la combinaison des trois critères.

Anemia de células falciformes na idade pediátrica : contribuição para o estudo das suas principais complicações e indicadores de prognóstico

RESMO: Introdução: A anemia de células falciformes doença hereditária, com repercussão multi-orgânica, tem grande variabilidade na sua expressão clínica. Daí o interesse do estudo de indicadores de prognóstico. A investigação realizada foi precedida de um resumo histórico incidindo sobre a compreensão de aspectos fundamentais da doença ao longo dos tempos. Na primeira parte do estudo e após revisão bibliográfica, foram referidos dados da fisiopatologia como base para os estudos que integram a presente dissertação. Abordou-se o estado da arte relativamente às complicações, aos indicadores de prognóstico e à terapêutica utilizada. Objectivos: Constituíram objectivos deste estudo realizado numa amostra populacional representativa: identificar as lesões a nível dos sistemas cardio-respiratório e nervoso central, avaliando-se as respectivas repercussões; avaliar a presença de indicadores de prognóstico entre as variáveis seleccionadas; estudar a eficácia e toxicidade da HU nos doentes com as formas graves da ACF. Para a prossecução destes objectivos foram delineados para além do estudo global três estudos específicos: Estudo 1- repercussão no sistema cardio-respiratório; Estudo 2- repercussão no sistema nervoso central; Estudo 3- terapêutica com hidroxiureia. Doentes e métodos: Procedeu-se a um estudo prospectivo e multi-institucional durante um período de três anos tendo-se seleccionado para a amostra, e de acordo com critérios pré-definidos, 30 doentes com ACF na fase estável da doença, com idades compreendidas entre os sete e os 18 anos, todos de origem africana à excepção de um caucasiano. O diagnóstico baseou-se em técnicas de electroforese e estudo molecular que definiu o genotipo da doença e a presença da delecção da -talassémia assim como os haplotipos da amostra populacional. Foram utilizadas diferentes metodologias para avaliar a existência de lesão pulmonar e cerebral. Através do estudo estatístico foram seleccionadas diversas variáveis como hipotéticos indicadores de prognóstico. Estudo 1. Para determinar a existência de lesão a nível pulmonar usaram-se duas metodologias diferentes, a avaliação da função pulmonar com estudo da saturação da Hb em O2 no sangue arterial e a tomografia computadorizada de alta resolução. Estudou-se também a possível disfunção cardíaca como repercussão da lesão pulmonar, através do ecocardiograma, e os indicadores de prognóstico com significado estatístico para a lesão encontrada. Estudo 2. O desenho deste estudo foi sobreponível ao anterior, mas com metodologia adequada para o SNC. Procedeu-se ao estudo das lesões cerebrais por meio de exames imagiológicos, (RMN-CE e DTC) e de testes psicológicos. Correlacionaram-se as três metodologias utilizadas e a importância de cada uma para a decisão de atitudes terapêuticas preventivas. Estudo 3. Consistiu num estudo aberto prospectivo não controlado com nove crianças e adolescentes com formas graves de ACF, com o objectivo de avaliar a eficácia da terapêutica com hidroxiureia, durante um período de 24 meses. Todos os doentes completaram no mínimo 15 meses de terapêutica, com uma dose final média de 194 mg/K/dia. Resultados globais: Durante o período anterior à investigação caracterizou-se a amostra populacional estudada quanto ao fenotipo genético, clínico e hematológico de acordo com os critérios utilizados por outros investigadores. Verificou-se: predomínio do haplotipo Bantu na forma homozigótica em 53% dos doentes; número total de EVO ≥3/ano em 87,5% dos doentes; crises de sequestração em 18,75%; dactilites no primeiro ano de vida em 31,2%; quadro de sépsis grave apenas num doente; crises de hiper-hemólise em 50%; e STA em 59,38% dos doentes. Quanto ao fenotipo hematológico evidenciaram-se como factores de risco reticulocitose (13,1x103/l) e hiperbilirrubinémia (2,5 mg/dl) e como factores de bom prognóstico a presença de delecção de um gene da -talassémia em 46,9% dos doentes e valor médio de Hb 8,1 g/dl. Resultados dos estudos parcelares: Estudo 1. Deste estudo infere-se que a DPR ligeira foi diagnosticada em 70% dos doentes, uma vez que as alterações da difusão não foram estatisticamente significativas, o estudo dos gases no sangue não evidenciaram resultados anormais e a TCAR evidenciou alterações em 43,3% dos doentes. Apenas num doente se verificou doença pulmonar obstrutiva relacionada com maior número da STA.O estudo da disfunção cardíaca encontrada em 86,7% dos doentes não reflecte a repercussão da DPR a nível cardíaco, podendo estar associada às alterações fisiopatológicas da própria anemia crónica. Encontraram-se indicadores de prognóstico hematológicos e clínicos. Entre os primeiros, valores de Hb ≥8,5 g/dl e de HbF ≥13% foram considerados indicadores de bom prognóstico para a lesão pulmonar. Em relação aos parâmetros clínicos, as STA não foram consideradas indicadoras de prognóstico para a DPR ao contrário do que se verificou com o número de EVO. Pela análise dos parâmetros genéticos e socio-económicos provou-se a ausência de relação estatisticamente significativa com lesão pulmonar. Estudo 2. Pela RMN-CE foram diagnosticados ES em 33,3% com uma localização preferencial na substância branca profunda em 26,6% dos doentes. Relativamente aos parâmetros hematológicos seleccionados, o valor médio da HbF 8,6% constituíu um indicador de bom prognóstico para o aparecimento de ES, enquanto o valor médio de leucócitos 12.39x103/μl foi considerado um indicador de mau prognóstico. No estudo do DTC apenas um doente apresentou aumento da velocidade do fluxo cerebral na ACM igual a 196 cm/segundos, associado a vasculopatia grave. Os testes psicológicos alterados em 80% dos doentes mostraram ser o método mais sensível para detectar alterações do neurodesenvolvimento, mas sem correlação com os ES em 10% dos doentes. Realça-se a baixa percentagem de DTC patológicos encontrados neste estudo em relação ao número elevado de ES e de testes psicológicos alterados, não se verificando concordância entre os três exames. Dos indicadores de prognóstico estudados a -talassémia foi considerada um factor de protecção para o coeficiente de inteligência da escala de Wechsler. Em relação a parâmetros clínicos estudados os doentes com maior número de EVO, tem em média valores inferiores nos testes psicológicos. Estudo 3. Neste estudo verificou-se que o valor médio da HbF aumentou significativamente de 7,0±4% para 13,7±5,3% (p=0,028) ao fim de 15 meses de terapêutica com hidroxiureia. Clinicamente todos os doentes responderam significativamente com uma redução de 80% no número de EVO, 69% no número de internamentos, 76% no número de dias de hospitalização e 67% no número de transfusões. Deste modo comprovou-se não só a eficácia desta terapêutica neste grupo pediátrico como também a falta de efeitos secundários significativos. Considera-se a necessidade de estudos mais prolongados e em grande séries, para com segurança se usar a HU antes que a lesão orgânica se estabeleça, portanto logo nos primeiros anos de vida. Conclusão: Na amostra populacional estudada foram evidenciadas lesões pulmonares e cerebrais na grande maioria dos doentes que condicionaram a sua qualidade de vida. Foram identificados indicadores de prognóstico que poderão eventualmente ditar medidas terapêuticas precoces com o objectivo de diminuir a morbilidade e a mortalidade neste grupo etário. Demonstrou-se que a terapêutica com a HU foi eficaz e bem tolerada----------ABSTRACT: Background: Sickle cell anemia (SCA), a hereditary disease characterized by pain and lifetime multi-organic lesion, is a challenge for all that work with carriers of this disease. The clinical expression variability of SCA is a constant reality and a problem to be solved in the current world of investigation, for which the knowledge of prognostic indicators responsible for the different aspects of clinical evolution diversity wiil be an added value. The study is preceded by a historical summary of the most important factors in the evolution of SCA, which are in themselves, an incentive for future research. In the first part of the study, after an extensive bibliographical revision, physiopathology data is referred to in general and specifically regarding the target organs, that constituted the base for the studies presented in the dissertation. The state of the art for the complications to be studied, the choice of prognostic indicators and the therapeutics application, were approached for the renewed interest in the theme. Aims: In regard to the investigation, the objective was to study the lesions in the most affected organs of a chosen pediatric group, to investigate prognostic indicators for lung and cerebral lesions and to evaluate the protective effect of hydroxyurea in children with severe outcomes. Patients and methods: A prospective and multi-institutional study was carried out during a three-year period, February 1998 to March 2001, with children and adolescents followed up at a Immunohematology Outpatient Clinic of Dona Estefânia's Hospital, Lisbon. Based in predefined criteria, 30 children with SCA were selected in a stable phase of the disease, aged from seven to 18 years old, all of whom were of African origin with exception of one who was Caucasian. The diagnosis was based on electrophoresis techniques and molecular study that allowed to define the genotype, the presence of deletional alpha-thalassemia as well as haplotypes in the population. Different methodologies were used to evaluate the existence of lung and cerebral lesion. Statistical study of the different variables selected the prognostic indicators. In Study 1, to determine the existence of lung lesion two different methodologies were used: pulmonar function study with arterial blood gases determination; and high resolution computerized tomography. Heart dysfunction as a repercussion of lung lesion was also studied through echocardiography, and prognostic indicators were statistically significant for lesions found. The design of Study 2 was similar to Study 1, but with the appropriate methodology for CNS. After neurological examination, which was normal in all patients (control group), cerebral lesions were studied with imagiologic exams (MRN-CE and TCD) and psychological tests. These three methodologies were correlated and the importance of each one in the decision of the therapeutic profilactic attitudes. Study 3 consisted of a controlled prospective open study in children with severe forms of SCA, with the aim of the evaluating therapeutic effectiveness of hydroxyurea, during a period of 24 months. Results: In the global overall study preceding the Studies 1,2 and 3, there were a prevalence of haplotype Bantu (53%) and other risk factors, namely the number of VOC (87,5%), sequestration crisis (18,75%), dactilytis in first year of life(31,2%), hyperhemolysis crisis (50%) and ATC in more than half of the patients (59,38%). This group of bad prognostic indicators, associated with the population of the lower class according to the Graffar scale, demonstrates the importance of primary health care services, information provided to the children and their relatives, as well as the interest in prophylactic therapeutics, specific screening and prenatal diagnosis. Study 1. It was evident from this study that slight RPD was diagnosed in 70% of the patients, because alterations of the diffusion had no statistical significance and arterial blood gases determinations were normal. Only one patient had restrictive lung disease related with numerous ACS. However ACS was not considered a prognostic indicator for RPD, contrary to the number of EVO. HRTC revealed discreet fibrotic lines that could be related with slight RPD, but the lack of correlation of these two exams (33%) supports the value of lung function tests for precocious diagnosis of RPD. Heart dysfunction was found in 86,7% of patients, does not reflect the repercussion of RPD, but with the physiopathology of chronic anemia. Hematologic and clinical prognostic indicators were found. Good prognostic indicators for the non-evolution of RPD with average Hb values of ≥ 8,5 g/dl and average HbF values of ≥13%, respectively. The genetic and social-economic factors had no statistical significance; nevertheless, they were more prevalent among Bantu haplotype (53,3%) in patients with RPD. Study 2. RMN-CE detected SI in 33,3% of the patients, with preferential location in deep white substance in 26,6% and in front lobe in 20%. This distribution can be related to structural aspects of the brain and with the high sensibility of this organ to hypoxia. From the hematological parameters selected, average HbF value 8,6% and average leucocyte count 12.39x103/μl were prognostic indicators with different meaning to SI. The increase in the total bilirubin related to hyperhemolysis clinically explains the genesis of SI In the TCD study, only one patient had increased cerebral flow speed >196 cm/sec in CMA, which corresponded to serious vasculopathy in AngioMR. This patient never present previously neurological symptoms and had several hyperhemolysis crisis and VOC as risk factors. Low percentage of pathological TCD in this study, in relation to the high number of SI and altered tests, although without correlation among the three exams, is probably attributed to factors related to the methodology, aspects of cerebral physiopathology or perhaps a sign of good prognostic if the duration of study had not been so short. TCD should be used as a screening method in the age groups with higher risk of AVC and should never be considered separately in prophylactic therapeutics indication. Psychological tests were the most sensitive method to detect neurodevelopment impairment; in 80% of patients the neuropsychologics tests were altered, but without correlation with SI (10%). Since SI can become evident during the first two years of life and develop with time, the first psychological tests should be carried out between 3 and 5 years of age to timely be referred to special education and stimulation programs. Prognostic indicators to psychological tests were also found: alpha-thalassemia was found to be a protection factor of the IQ, just as other hematologic factors (hematocrit, MGCV and erythrocytes count). In relation to clinical parameters, although without statistical significance, patients with larger number of VOC had average lower scores versus the average in tests, except in TP. Results from different studies were conclusive as to the type of lesion found and the importance of prognostic indicators. Study 3. All the patients completed a minimum of 15 months therapeutic treatment with the final average daily dose of 19±4 mg/kg/day. The average value of the fetal hemoglobin increased significantly from 7,0±3,9% to 13,7±5,3% (p=0.028). The HbF average values increased from 6% to 15% after 15 months of therapeutic treatment. Clinically there was a reduction of 80% in the number of VOE , 69% in the number of hospitalization, 76% in the number of days of hospitalization and 67% in the number of transfusions. Once again the effectiveness of this treatment in this pediatric group, as well as the lack of any significant secondary effects, was evident. The study confirms the need for further detailed research in order to safely effect the appropriate treatment prior to the development of organic lesions, which ideally should be in the first year of life. Conclusions: These results allow us to clarify the importance of either pulmonary lesions or either nervous central system impairment among patients, children and adolescents, with sickle cell anemia. These lesions were demonstrated in most of the patients studied compromising their quality of life and the mortality. The treatment with HU is proved to be effective and having low toxicity.

Risk of Surgery for Congenital Heart Disease in the Adult: a Multicentered European Study

BACKGROUND: Surgery for congenital heart disease (CHD) has changed considerably during the last three decades. The results of primary repair have steadily improved, to allow treating almost all patients within the pediatric age; nonetheless an increasing population of adult patients requires surgical treatment. The objective of this study is to present the early surgical results of patients who require surgery for CHD in the adult population within a multicentered European study population. METHODS: Data relative to the hospital course of 2,012 adult patients (age > or = 18 years) who required surgical treatment for CHD from January 1, 1997 through December 31, 2004 were reviewed. Nineteen cardiothoracic centers from 13 European countries contributed to the data collection. RESULTS: Mean age at surgery was 34.4 +/- 14.53 years. Most of the operations were corrective procedures (1,509 patients, 75%), followed by reoperations (464 patients, 23.1%) and palliative procedures (39 patients, 1.9%). Six hundred forty-nine patients (32.2%) required surgical closure of an isolated ostium secundum atrial septal defect. Overall hospital mortality was 2%. Preoperative cyanosis, arrhythmias, and NYHA class III-IV, proved significant risk factors for hospital mortality. Follow-up data were available in 1,342 of 1,972 patients (68%) who were discharged home. Late deaths occurred in 6 patients (0.5%). Overall survival probability was 97% at 60 months, which is higher for corrective procedures (98.2%) if compared with reoperations (94.1%) and palliations (86.1%). CONCLUSIONS: Surgical treatment of CHD in adult patients, in specialized cardiac units, proved quite safe, beneficial, and low-risk.

Impacto da Obesidade nos Resultados após Angioplastia Primária em Doentes com Enfarte Agudo do Miocárdio com Elevação do Segmento ST

INTRODUCTION: Obesity is an important risk factor for the development of diabetes, hypertension, coronary disease, left ventricular dysfunction, stroke and cardiac arrhythmias. Paradoxically, previous studies in patients undergoing elective coronary angioplasty showed a reduction in hospital and long-term mortality in obese patients. The relation with body mass index (BMI) has been less studied in the context of primary angioplasty. OBJECTIVES: To evaluate the impact of obesity on the results of ST-segment elevation acute myocardial infarction treated by primary angioplasty. METHODS: This was a study of 464 consecutive patients with ST-segment elevation acute myocardial infarction undergoing primary angioplasty, 78% male, mean age 61 +/- 13 years. We assessed in-hospital, 30-day and one-year mortality according to BMI. Patients were divided into three groups according to BMI: normal--18-24.9 kg/m2 (n = 171); overweight--25-29.9 kg/m2 (n = 204); and obese-- > 30 kg/m2 (n = 89). RESULTS: Obese patients were younger (ANOVA, p < 0.001) and more frequently male (p = 0.014), with more hypertension (p = 0.001) and dyslipidemia (p = 0.006). There were no differences in the prevalence of diabetes, previous cardiac history, heart failure on admission, anterior location, multivessel disease, peak total CK or medication prescribed, except that obese patients received more beta-blockers (p = 0.049). In-hospital mortality was 9.9% for patients with normal BMI, 3.4% for overweight patients and 6.7% for obese patients (p = 0.038). Mortality at 30 days was 11 4.4% and 7.8% (p = 0.032) and at one year 12.9%, 4.9% and 9% (p = 0.023), respectively. On univariate analysis, overweight was the only BMI category with a protective effect; however, after multivariate logistic regression analysis, adjusted for confounding variables, none of the BMI categories could independently predict outcome. CONCLUSIONS: Overweight patients had a better prognosis after primary angioplasty for ST-segment elevation acute myocardial infarction compared with other BMI categories, but this was dependent on other potentially confounding variables.

Clinical guideline for diagnosis and management of melioidosis

Melioidosis is an emerging infection in Brazil and neighbouring South American countries. The wide range of clinical presentations include severe community-acquired pneumonia, septicaemia, central nervous system infection and less severe soft tissue infection. Diagnosis depends heavily on the clinical microbiology laboratory for culture. Burkholderia pseudomallei, the bacterial cause of melioidosis, is easily cultured from blood, sputum and other clinical samples. However, B. pseudomallei can be difficult to identify reliably, and can be confused with closely related bacteria, some of which may be dismissed as insignificant culture contaminants. Serological tests can help to support a diagnosis of melioidosis, but by themselves do not provide a definitive diagnosis. The use of a laboratory discovery pathway can help reduce the risk of missing atypical B. pseudomallei isolates. Recommended antibiotic treatment for severe infection is either intravenous Ceftazidime or Meropenem for several weeks, followed by up to 20 weeks oral treatment with a combination of trimethoprim-sulphamethoxazole and doxycycline. Consistent use of diagnostic microbiology to confirm the diagnosis, and rigorous treatment of severe infection with the correct antibiotics in two stages; acute and eradication, will contribute to a reduction in mortality from melioidosis.

HTLV- I infection is not associated with a higher risk of death in peruvian HIV-infected patients

Limited and contradictory information exists regarding the prognosis of HIV/HTLV-I co-infection. Our goal was to estimate the effect of HTLV-I infection on mortality in HIV-infected patients at a HIV reference center in Peru. We studied a retrospective cohort of HIV-infected patients, who were exposed or unexposed to HTLV-I. Exposed patients were Western Blot (WB) positive for both retroviruses. Unexposed patients were WB positive for HIV, and had least one negative EIA for HTLV-I. These were selected among patients who entered our Program immediately before and after each exposed patient, between January 1990 and June 2004. Survival time was considered between the diagnosis of exposure to HTLV-I and death or censoring. Confounding variables were age, gender, baseline HIV clinical stage, baseline CD4+ T cell count, and antiretroviral therapy. We studied 50 exposed, and 100 unexposed patients. Exposed patients had a shorter survival compared to unexposed patients [median survival: 47 months (95% CI: 17-77) vs. 85 months (95% CI: 70-100), unadjusted p = 0.06]. Exposed patients had a higher rate of mortality compared to unexposed patients (HIV/HTLV-I (24/50 [48%]) vs. HIV only (37/100 [37%]), univariable p = 0.2]. HTLV-I exposure was not associated to a higher risk of death in the adjusted analysis: HR: 1.2 (0.4-3.5). AIDS clinical stage and lack of antiretroviral therapy were associated to a higher risk of dying. In conclusions, HTLV-I infection was not associated with a higher risk of death in Peruvian HIV-infected patients. Advanced HIV infection and lack of antiretroviral therapy may explain the excess of mortality in this population.

Sepsis Mortality Prediction Based on Predisposition, Infection and Response

OBJECTIVE: To empirically test, based on a large multicenter, multinational database, whether a modified PIRO (predisposition, insult, response, and organ dysfunction) concept could be applied to predict mortality in patients with infection and sepsis. DESIGN: Substudy of a multicenter multinational cohort study (SAPS 3). PATIENTS: A total of 2,628 patients with signs of infection or sepsis who stayed in the ICU for >48 h. Three boxes of variables were defined, according to the PIRO concept. Box 1 (Predisposition) contained information about the patient's condition before ICU admission. Box 2 (Injury) contained information about the infection at ICU admission. Box 3 (Response) was defined as the response to the infection, expressed as a Sequential Organ Failure Assessment score after 48 h. INTERVENTIONS: None. MAIN MEASUREMENTS AND RESULTS: Most of the infections were community acquired (59.6%); 32.5% were hospital acquired. The median age of the patients was 65 (50-75) years, and 41.1% were female. About 22% (n=576) of the patients presented with infection only, 36.3% (n=953) with signs of sepsis, 23.6% (n=619) with severe sepsis, and 18.3% (n=480) with septic shock. Hospital mortality was 40.6% overall, greater in those with septic shock (52.5%) than in those with infection (34.7%). Several factors related to predisposition, infection and response were associated with hospital mortality. CONCLUSION: The proposed three-level system, by using objectively defined criteria for risk of mortality in sepsis, could be used by physicians to stratify patients at ICU admission or shortly thereafter, contributing to a better selection of management according to the risk of death.