Impacto orçamentário da incorporação da tomografia de emissão de pósitrons (PET scan) no estadiamento do câncer de pulmão na perspectiva do Sistema Único de Saúde

O aumento exponencial dos gastos em saúde demanda estudos econômicos que subsidiem as decisões de agentes públicos ou privados quanto à incorporação de novas tecnologias aos sistemas de saúde. A tomografia de emissão de pósitrons (PET) é uma tecnologia de imagem da área de medicina nuclear, de alto custo e difusão ainda recente no país. O nível de evidência científica acumulada em relação a seu uso no câncer pulmonar de células não pequenas (CPCNP) é significativo, com a tecnologia mostrando acurácia superior às técnicas de imagem convencionais no estadiamento mediastinal e à distância. Avaliação econômica realizada em 2013 aponta para seu custo-efetividade no estadiamento do CPCNP em comparação à estratégia atual de manejo baseada no uso da tomografia computadorizada, na perspectiva do SUS. Sua incorporação ao rol de procedimentos disponibilizados pelo SUS pelo Ministério da Saúde (MS) ocorreu em abril de 2014, mas ainda se desconhecem os impactos econômico-financeiros decorrentes desta decisão. Este estudo buscou estimar o impacto orçamentário (IO) da incorporação da tecnologia PET no estadiamento do CPCNP para os anos de 2014 a 2018, a partir da perspectiva do SUS como financiador da assistência à saúde. As estimativas foram calculadas pelo método epidemiológico e usaram como base modelo de decisão do estudo de custo-efetividade previamente realizado. Foram utilizados dados nacionais de incidência; de distribuição de doença e acurácia das tecnologias procedentes da literatura e de custos, de estudo de microcustos e das bases de dados do SUS. Duas estratégias de uso da nova tecnologia foram analisadas: (a) oferta da PET-TC a todos os pacientes; e (b) oferta restrita àqueles que apresentem resultados de TC prévia negativos. Adicionalmente, foram realizadas análises de sensibilidade univariadas e por cenários extremos, para avaliar a influência nos resultados de possíveis fontes de incertezas nos parâmetros utilizados. A incorporação da PET-TC ao SUS implicaria a necessidade de recursos adicionais de R$ 158,1 (oferta restrita) a 202,7 milhões (oferta abrangente) em cinco anos, e a diferença entre as duas estratégias de oferta é de R$ 44,6 milhões no período. Em termos absolutos, o IO total seria de R$ 555 milhões (PET-TC para TC negativa) e R$ 600 milhões (PET-TC para todos) no período. O custo do procedimento PET-TC foi o parâmetro de maior influência sobre as estimativas de gastos relacionados à nova tecnologia, seguido da proporção de pacientes submetidos à mediastinoscopia. No cenário por extremos mais otimista, os IOs incrementais reduzir-se-iam para R$ 86,9 (PET-TC para TC negativa) e R$ 103,9 milhões (PET-TC para todos), enquanto no mais pessimista os mesmos aumentariam para R$ 194,0 e R$ 242,2 milhões, respectivamente. Resultados sobre IO, aliados às evidências de custo-efetividade da tecnologia, conferem maior racionalidade às decisões finais dos gestores. A incorporação da PET no estadiamento clínico do CPCNP parece ser financeiramente factível frente à magnitude do orçamento do MS, e potencial redução no número de cirurgias desnecessárias pode levar à maior eficiência na alocação dos recursos disponíveis e melhores desfechos para os pacientes com estratégias terapêuticas mais bem indicadas.

Indicateurs de durabilité urbaine selon une approche épidémiologique : la ville de Maringá, au Brésil

Les analyses spatiales et statistiques ont été réalisées avec les logiciels ArcView et SPSS

Uso do protocolo no serviço de psicologia e avaliação psicodinâmica em candidatos à cirurgia bariátrica

A clínica da Obesidade Mórbida e a Cirurgia Bariátrica exige estudos e acompanhamentos do paciente. Os benefícios e riscos do emagrecimento por tratamento cirúrgico devem servir como ponto de alerta aos profissionais da saúde. O uso do questionário no serviço de psicologia é norteado pela escuta psicológica. Objetivos: 1) Descrever o perfil sócio-demográfico candidatos à cirurgia bariátrica. 2) Analisar a percepção dos pacientes sobre características de personalidade associadas à obesidade e transtornos alimentares. 3) Descrever os conteúdos psicodinâmicos da narrativa do sujeito e avaliar o sistema tensional inconsciente de dois pacientes por meio do Teste das Relações Objetais de Phillipson (TRO). Método: O delineamento metodológico com análise de dados pelo método epidemiológico e estudo de caso clínico, orientação psicanalítica. Na primeira etapa foram consultados 300 questionários do serviço de psicologia e na segunda dois pacientes com ganho de peso após 24 meses. São pacientes que procuraram tratamento em clínica especializada, em uma metrópole do sudeste brasileiro, sob consentimento pós-informado. Os questionários foram preenchidos por 227 mulheres e 73 homens; com média de idade igual a 36 anos; escolaridade ensino médio e superior, 53%; maioria casados; IMC entre grave e super mórbido (94,3%). Técnicas cirúrgicas indicadas Capella Bypass e Fobi-Capella (67%). Resultados: características psicológicas referidas pelos pacientes, a ansiedade apontou em 93,7% das respostas, seguidas por impulsividade, depressão, tolerância à frustração, baixa auto-estima, resolvedor de problemas dos outros (mais de 50%). No histórico familiar da obesidade está em mais de 70% depressão e uso do álcool em 30%; realização de psicoterapia (30%) e medicamentos para depressão e ansiedade (10%). Na segunda etapa, foi realizado o diagnóstico psicodinâmico, por meio do Teste das Relações Objetais de Phillipson com duas pacientes, cuja análise indicou necessidade de psicoterapia psicanalítica, pois tinham fixações na posição esquizoparanóide e apresentavam dificuldade em lidar com perdas e baixa motivação para mudança e insigth. Conclusões: Com a aplicação do questionário e o registro das observações empíricas, este questionário de entrevista semidirigida preenche condições de melhor acessar e avaliar os conteúdos revelados pelos pacientes. As contradições entre as respostas e o discurso, no contato individual com o psicólogo, apontam a necessidade de investimento no preparo do paciente para a cirurgia e mais acentuadamente o acompanhamento psicológico no primeiro ano do pós-operatório. Há um pensamento mágico a ser trabalhado durante a aplicação do questionário sobre as crenças frente à cirurgia e o emagrecimento e assim convocar o paciente a ocupar o lugar do sujeito implicado em seu processo pré e pós-operatório. O TRO contribuiu na compreensão do diagnóstico psicodinâmico de pacientes com ganho de peso após cirurgia e reforçou a necessidade de maior investimento no pré-operatório.(AU)

Uso do protocolo no serviço de psicologia e avaliação psicodinâmica em candidatos à cirurgia bariátrica

A clínica da Obesidade Mórbida e a Cirurgia Bariátrica exige estudos e acompanhamentos do paciente. Os benefícios e riscos do emagrecimento por tratamento cirúrgico devem servir como ponto de alerta aos profissionais da saúde. O uso do questionário no serviço de psicologia é norteado pela escuta psicológica. Objetivos: 1) Descrever o perfil sócio-demográfico candidatos à cirurgia bariátrica. 2) Analisar a percepção dos pacientes sobre características de personalidade associadas à obesidade e transtornos alimentares. 3) Descrever os conteúdos psicodinâmicos da narrativa do sujeito e avaliar o sistema tensional inconsciente de dois pacientes por meio do Teste das Relações Objetais de Phillipson (TRO). Método: O delineamento metodológico com análise de dados pelo método epidemiológico e estudo de caso clínico, orientação psicanalítica. Na primeira etapa foram consultados 300 questionários do serviço de psicologia e na segunda dois pacientes com ganho de peso após 24 meses. São pacientes que procuraram tratamento em clínica especializada, em uma metrópole do sudeste brasileiro, sob consentimento pós-informado. Os questionários foram preenchidos por 227 mulheres e 73 homens; com média de idade igual a 36 anos; escolaridade ensino médio e superior, 53%; maioria casados; IMC entre grave e super mórbido (94,3%). Técnicas cirúrgicas indicadas Capella Bypass e Fobi-Capella (67%). Resultados: características psicológicas referidas pelos pacientes, a ansiedade apontou em 93,7% das respostas, seguidas por impulsividade, depressão, tolerância à frustração, baixa auto-estima, resolvedor de problemas dos outros (mais de 50%). No histórico familiar da obesidade está em mais de 70% depressão e uso do álcool em 30%; realização de psicoterapia (30%) e medicamentos para depressão e ansiedade (10%). Na segunda etapa, foi realizado o diagnóstico psicodinâmico, por meio do Teste das Relações Objetais de Phillipson com duas pacientes, cuja análise indicou necessidade de psicoterapia psicanalítica, pois tinham fixações na posição esquizoparanóide e apresentavam dificuldade em lidar com perdas e baixa motivação para mudança e insigth. Conclusões: Com a aplicação do questionário e o registro das observações empíricas, este questionário de entrevista semidirigida preenche condições de melhor acessar e avaliar os conteúdos revelados pelos pacientes. As contradições entre as respostas e o discurso, no contato individual com o psicólogo, apontam a necessidade de investimento no preparo do paciente para a cirurgia e mais acentuadamente o acompanhamento psicológico no primeiro ano do pós-operatório. Há um pensamento mágico a ser trabalhado durante a aplicação do questionário sobre as crenças frente à cirurgia e o emagrecimento e assim convocar o paciente a ocupar o lugar do sujeito implicado em seu processo pré e pós-operatório. O TRO contribuiu na compreensão do diagnóstico psicodinâmico de pacientes com ganho de peso após cirurgia e reforçou a necessidade de maior investimento no pré-operatório.(AU)

Competencias y contenidos comunes de salud pública del grado en farmacia de las universidades españolas

Objetivo: Consensuar competencias profesionales de salud pública del/de la egresado/a en farmacia y los contenidos básicos que debe incluir la materia de salud pública según el criterio de un grupo docente de salud pública del grado en farmacia procedente de distintas universidades públicas y privadas de España. Métodos: 1ª Reunión del Foro de Profesorado Universitario de Salud Pública del Grado en Farmacia, que tuvo lugar en la Facultad de Medicina de la Universidad Complutense de Madrid los días 19 y 20 de noviembre de 2013, en la que participaron 17 profesores/as. Los/las participantes disponían de sus propios programas docentes y de dos estudios previos sobre competencias profesionales en salud pública, para analizar las competencias y contenidos de salud pública del grado en farmacia. Se realizaron grupos de trabajo y se compartieron los resultados. Resultados: El mayor número de competencias fundamentales identificadas se corresponden con actividades de las funciones «Valorar las necesidades de salud de la población» y «Desarrollar políticas de salud». El programa final incluye contenidos básicos organizados en ocho bloques: Concepto de salud pública, Demografía sanitaria, Método epidemiológico, Medio ambiente y salud, Seguridad alimentaria, Epidemiología de los principales problemas de salud, Promoción y educación para la salud, y Planificación y gestión sanitaria. Conclusiones: La representación de prácticamente todas las facultades que imparten el grado en farmacia en España, y el consenso alcanzado en la descripción de competencias y contenidos, constituyen una base para unificar criterios que garanticen la mejora de la calidad docente y formativa.

Uso do protocolo no serviço de psicologia e avaliação psicodinâmica em candidatos à cirurgia bariátrica

A clínica da Obesidade Mórbida e a Cirurgia Bariátrica exige estudos e acompanhamentos do paciente. Os benefícios e riscos do emagrecimento por tratamento cirúrgico devem servir como ponto de alerta aos profissionais da saúde. O uso do questionário no serviço de psicologia é norteado pela escuta psicológica. Objetivos: 1) Descrever o perfil sócio-demográfico candidatos à cirurgia bariátrica. 2) Analisar a percepção dos pacientes sobre características de personalidade associadas à obesidade e transtornos alimentares. 3) Descrever os conteúdos psicodinâmicos da narrativa do sujeito e avaliar o sistema tensional inconsciente de dois pacientes por meio do Teste das Relações Objetais de Phillipson (TRO). Método: O delineamento metodológico com análise de dados pelo método epidemiológico e estudo de caso clínico, orientação psicanalítica. Na primeira etapa foram consultados 300 questionários do serviço de psicologia e na segunda dois pacientes com ganho de peso após 24 meses. São pacientes que procuraram tratamento em clínica especializada, em uma metrópole do sudeste brasileiro, sob consentimento pós-informado. Os questionários foram preenchidos por 227 mulheres e 73 homens; com média de idade igual a 36 anos; escolaridade ensino médio e superior, 53%; maioria casados; IMC entre grave e super mórbido (94,3%). Técnicas cirúrgicas indicadas Capella Bypass e Fobi-Capella (67%). Resultados: características psicológicas referidas pelos pacientes, a ansiedade apontou em 93,7% das respostas, seguidas por impulsividade, depressão, tolerância à frustração, baixa auto-estima, resolvedor de problemas dos outros (mais de 50%). No histórico familiar da obesidade está em mais de 70% depressão e uso do álcool em 30%; realização de psicoterapia (30%) e medicamentos para depressão e ansiedade (10%). Na segunda etapa, foi realizado o diagnóstico psicodinâmico, por meio do Teste das Relações Objetais de Phillipson com duas pacientes, cuja análise indicou necessidade de psicoterapia psicanalítica, pois tinham fixações na posição esquizoparanóide e apresentavam dificuldade em lidar com perdas e baixa motivação para mudança e insigth. Conclusões: Com a aplicação do questionário e o registro das observações empíricas, este questionário de entrevista semidirigida preenche condições de melhor acessar e avaliar os conteúdos revelados pelos pacientes. As contradições entre as respostas e o discurso, no contato individual com o psicólogo, apontam a necessidade de investimento no preparo do paciente para a cirurgia e mais acentuadamente o acompanhamento psicológico no primeiro ano do pós-operatório. Há um pensamento mágico a ser trabalhado durante a aplicação do questionário sobre as crenças frente à cirurgia e o emagrecimento e assim convocar o paciente a ocupar o lugar do sujeito implicado em seu processo pré e pós-operatório. O TRO contribuiu na compreensão do diagnóstico psicodinâmico de pacientes com ganho de peso após cirurgia e reforçou a necessidade de maior investimento no pré-operatório.(AU)

The epidemiological modelling of major depressive disorder : application for the global burden of disease study 2010

Background Although the detrimental impact of major depressive disorder (MDD) at the individual level has been described, its global epidemiology remains unclear given limitations in the data. Here we present the modelled epidemiological profile of MDD dealing with heterogeneity in the data, enforcing internal consistency between epidemiological parameters and making estimates for world regions with no empirical data. These estimates were used to quantify the burden of MDD for the Global Burden of Disease Study 2010 (GBD 2010). Method Analyses drew on data from our existing literature review of the epidemiology of MDD. DisMod-MR, the latest version of the generic disease modelling system redesigned as a Bayesian meta-regression tool, derived prevalence by age, year and sex for 21 regions. Prior epidemiological knowledge, study- and country-level covariates adjusted sub-optimal raw data. Results There were over 298 million cases of MDD globally at any point in time in 2010, with the highest proportion of cases occurring between 25 and 34 years. Global point prevalence was very similar across time (4.4% (95% uncertainty: 4.2–4.7%) in 1990, 4.4% (4.1–4.7%) in 2005 and 2010), but higher in females (5.5% (5.0–6.0%) compared to males (3.2% (3.0–3.6%) in 2010. Regions in conflict had higher prevalence than those with no conflict. The annual incidence of an episode of MDD followed a similar age and regional pattern to prevalence but was about one and a half times higher, consistent with an average duration of 37.7 weeks. Conclusion We were able to integrate available data, including those from high quality surveys and sub-optimal studies, into a model adjusting for known methodological sources of heterogeneity. We were also able to estimate the epidemiology of MDD in regions with no available data. This informed GBD 2010 and the public health field, with a clearer understanding of the global distribution of MDD.

Global variation in the prevalence and incidence of major depressive disorder : a systematic review of the epidemiological literature

Background Summarizing the epidemiology of major depressive disorder (MDD) at a global level is complicated by significant heterogeneity in the data. The aim of this study is to present a global summary of the prevalence and incidence of MDD, accounting for sources of bias, and dealing with heterogeneity. Findings are informing MDD burden quantification in the Global Burden of Disease (GBD) 2010 Study. Method A systematic review of prevalence and incidence of MDD was undertaken. Electronic databases Medline, PsycINFO and EMBASE were searched. Community-representative studies adhering to suitable diagnostic nomenclature were included. A meta-regression was conducted to explore sources of heterogeneity in prevalence and guide the stratification of data in a meta-analysis. Results The literature search identified 116 prevalence and four incidence studies. Prevalence period, sex, year of study, depression subtype, survey instrument, age and region were significant determinants of prevalence, explaining 57.7% of the variability between studies. The global point prevalence of MDD, adjusting for methodological differences, was 4.7% (4.4–5.0%). The pooled annual incidence was 3.0% (2.4–3.8%), clearly at odds with the pooled prevalence estimates and the previously reported average duration of 30 weeks for an episode of MDD. Conclusions Our findings provide a comprehensive and up-to-date profile of the prevalence of MDD globally. Region and study methodology influenced the prevalence of MDD. This needs to be considered in the GBD 2010 study and in investigations into the ecological determinants of MDD. Good-quality estimates from low-/middle-income countries were sparse. More accurate data on incidence are also required.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Epidemiological data of seasonal variation in mood and behaviour

The aim of this study was to measure seasonal variation in mood and behaviour. The dual vulnerability and latitude effect hypothesis, the risk of increased appetite, weight and other seasonal symptoms to develop metabolic syndrome, and perception of low illumination in quality of life and mental well-being were assessed. These variations are prevalent in persons who live in high latitudes and need balancing of metabolic processes to adapt to environmental changes due to seasons. A randomized sample of 8028 adults aged 30 and over (55% women) participated in an epidemiological health examination study, The Health 2000, applying the probability proportional to population size method for a range of socio-demographic characteristics. They were present in a face-to-face interview at home and health status examination. The questionnaires included the modified versions of the Seasonal Pattern Assessment Questionnaire (SPAQ) and Beck Depression Inventory (BDI), the Health Related Quality of Life (HRQoL) instrument 15D, and the General Health Questionnaire (GHQ). The structured and computerized Munich Composite International Diagnostic Interview (M-CIDI) as part of the interview was used to assess diagnoses of mental disorders, and, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria were assessed using all the available information to detect metabolic syndrome. A key finding was that 85% of this nationwide representative sample had seasonal variation in mood and behaviour. Approximately 9% of the study population presented combined seasonal and depressive symptoms with a significant association between their scores, and 2.6% had symptoms that corresponded to Seasonal Affective Disorder (SAD) in severity. Seasonal variations in weight and appetite are two important components that increase the risk of metabolic syndrome. Other factors such as waist circumference and major depressive disorder contributed to the metabolic syndrome as well. Persons reported of having seasonal symptoms were associated with a poorer quality of life and compromised mental well-being, especially if indoors illumination at home and/or at work was experienced as being low. Seasonal and circadian misalignments are suggested to associate with metabolic disorders, and could be remarked if individuals perceive low illumination levels at home and/or at work that affect the health-related quality of life and mental well-being. Keywords: depression, health-related quality of life, illumination, latitude, mental well-being, metabolic syndrome, seasonal variation, winter.

Molecular and epidemiological aspects of Streptococcus pyogenes disease in Finland: Severe infections and bacterial, non-necrotizing cellulitis

Streptococcus pyogenes (group A streptococcus) is an important human pathogen, causing a wide array of infections ranging in severity. The majority of S. pyogenes infections are mild upper respiratory tract or skin infections. Severe, invasive infections, such as bacteraemia, are relatively rare, but constitute a major global burden with a high mortality. Certain streptococcal types are associated with a more severe disease and higher mortality. Bacterial, non-necrotizing cellulitis and erysipelas are localised infections of the skin, and although they are usually not life-threatening, they have a tendency to recur and therefore cause substantial morbidity. Despite several efforts aimed at developing an effective and safe vaccine against S. pyogenes infections, no vaccine is yet available. In this study, the epidemiology of invasive S. pyogenes infections in Finland was described over a decade of national, population-based surveillance. Recent trends in incidence, outcome and bacterial types were investigated. The beta-haemolytic streptococci causing cellulitis and erysipelas infections in Finland were studied in a case-control study. Bacterial isolates were characterised using both conventional and molecular typing methods, such as the emm typing, which is the most widely used typing method for beta-haemolytic streptococci. The incidence of invasive S. pyogenes disease has had an increasing trend during the past ten years in Finland, especially from 2006 onwards. Age- and sex-specific differences in the incidence rate were identified, with men having a higher incidence than women, especially among persons aged 45-64 years. In contrast, more infections occurred in women aged 25-34 years than men. Seasonal patterns with occasional peaks during the midsummer and midwinter were observed. Differences in the predisposing factors and underlying conditions of patients may contribute to these distinctions. Case fatality associated with invasive S. pyogenes infections peaked in 2005 (12%) but remained at a reasonably low level (8% overall during 2004-2007) compared to that of other developed countries (mostly exceeding 10%). Changes in the prevalent emm types were associated with the observed increases in incidence and case fatality. In the case-control study, acute bacterial non-necrotizing cellulitis was caused predominantly by Streptococcus dysgalactiae subsp. equisimilis, instead of S. pyogenes. The recurrent nature of cellulitis became evident. This study adds to our understanding of S. pyogenes infections in Finland and provides a basis for comparison to other countries and future trends. emm type surveillance and outcome analyses remain important for detecting such changes in type distribution that might lead to increases in incidence and case fatality. Bacterial characterisation serves as a basis for disease pathogenesis studies and vaccine development.

Atrial remodeling in atrial fibrillation : Epidemiological, clinical and magnetocardiographic aspects

Atrial fibrillation is the most common arrhythmia requiring treatment. This Thesis investigated atrial fibrillation (AF) with a specific emphasis on atrial remodeling which was analysed from epidemiological, clinical and magnetocardiographic (MCG) perspectives. In the first study we evaluated in real-life clinical practice a population-based cohort of AF patients referred for their first elective cardioversion (CV). 183 consecutive patients were included of whom in 153 (84%) sinus rhythm (SR) was restored. Only 39 (25%) of those maintained SR for one year. Shorter duration of AF and the use of sotalol were the only characteristics associated with better restoration and maintenance of SR. During the one-year follow-up 40% of the patients ended up in permanent AF. Female gender and older age were associated with the acceptance of permanent AF. The LIFE-trial was a prospective, randomised, double-blinded study that evaluated losartan and atenolol in patients with hypertension and left ventricular hypertrophy (LVH). Of the 8,851 patients with SR at baseline and without a history of AF 371 patients developed new-onset AF during the study. Patients with new-onset AF had an increased risk of cardiac events, stroke, and increased rate of hospitalisation for heart failure. Younger age, female gender, lower systolic blood pressure, lesser LVH in ECG and randomisation to losartan therapy were independently associated with lower frequency of new-onset AF. The impact of AF on morbidity and mortality was evaluated in a post-hoc analysis of the OPTIMAAL trial that compared losartan with captopril in patients with acute myocardial infarction (AMI) and evidence of LV dysfunction. Of the 5,477 randomised patients 655 had AF at baseline, and 345 patients developed new AF during the follow-up period, median 3.0 years. Older patients and patients with signs of more serious heart disease had and developed AF more often. Patients with AF at baseline had an increased risk of mortality (hazard ratio (HR) of 1.32) and stroke (HR 1.77). New-onset AF was associated with increased mortality (HR 1.82) and stroke (HR of 2.29). In the fourth study we assessed the reproducibility of our MCG method. This method was used in the fifth study where 26 patients with persistent AF had immediately after the CV longer P-wave duration and higher energy of the last portion of atrial signal (RMS40) in MCG, increased P-wave dispersion in SAECG and decreased pump function of the atria as well as enlarged atrial diameter in echocardiography compared to age- and disease-matched controls. After one month in SR, P-wave duration in MCG still remained longer and left atrial (LA) diameter greater compared to the controls, while the other measurements had returned to the same level as in the control group. In conclusion is not a rare condition in either general population or patients with hypertension or AMI, and it is associated with increased risk of morbidity and mortality. Therefore, atrial remodeling that increases the likelihood of AF and also seems to be relatively stable has to be identified and prevented. MCG was found to be an encouraging new method to study electrical atrial remodeling and reverse remodeling. RAAS-suppressing medications appear to be the most promising method to prevent atrial remodeling and AF.

Identification and Epidemiological Typing of Campylobacter strains isolated from Patients in Finland

C. jejuni constitutes the majority of Campylobacter strains isolated from patients in Finland, and C. coli strains are also reported. To improve the species identification, a combination of phenotype- and genotype-based methods was applied. Standardising the cell suspension turbidity in the hippurate hydrolysis test enabled the reliable identification of hippurate-positive Campylobacter strains as C. jejuni. The detection of species-specific genes by PCR showed that about 30% of the hippurate-negative strains were C. jejuni. Three typing methods, serotyping, PCR-RFLP analysis of LOS biosynthesis genes and pulsed-field gel electrophoresis (PFGE) were evaluated as epidemiological typing tools for C. jejuni. The high number of non-typeable strains lowered the discriminatory ability of serotyping. PCR-RFLP typing offered high discrimination for both serotypeable and non-typeable strains, but the correlation between serotypes and RFLP-types was not high enough to enable its use for molecular serotyping of non-typeable strains. PFGE was a highly discriminative typing method. Although the use of two restriction enzymes generally increases the discriminatory ability, KpnI alone offered almost as high discrimination as the use of SmaI and KpnI. The characteristic seasonal distribution of Campylobacter infections with a peak in summer and low incidence in winter was mainly due to domestically acquired infections. Of the C. jejuni strains, 41% were of domestic origin compared to only 17% of the C. coli strains. Serotypes Pen 12, Pen 6,7 and Pen 27 were significantly associated with domestic C. jejuni infections, Pen 1,44, Pen 3 and Pen 37 with travel-related infections. Pen 2 and Pen 4-complex were common both in domestic and travel-related infections. Serotype Pen 2 was less common among patients 60 years or older than in younger patients, more prevalent in Western Finland than in other parts of the country and more prevalent than other serotypes in winter. The source of Pen 2 infections may be related to cattle, since Pen 2 is the most common serotype in isolates from Finnish cattle. PFGE subtypes among isolates from patients and chickens during the summer 2003 and from cattle during the whole year were compared. The analysis of indistinguishable SmaI/KpnI subtypes suggested that up to 31% of the human infections may have been mediated by chickens and 19% by cattle. Human strains isolated during two one-year sampling periods were studied by PFGE. Of the domestic strains, 69% belonged to SmaI subtypes found during both sampling periods. Four SmaI subtypes accounted for 45% of the domestic strains, further typing of these subtypes by KpnI revealed six temporally persistent SmaI/KpnI subtypes. They were only occasionally identified in travel-related strains, and therefore, can be considered to be national subtypes. Each subtype was associated with a serotype: Pen 2, Pen 12, Pen 27, Pen 4-complex, Pen 41, and Pen 57. Five of these subtypes were identified in cattle (S5/K27, S7/K1, S7/K2, S7/K5 and S64/K19), and two in chickens (S7/K1 and S64/K19) with a temporal association with human infections in 2003. Cattle are more likely potential sources of these persistent subtypes, since long-term excretion of Campylobacter strains by cattle has been reported.

Molecular methods for the epidemiological analysis of methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae

Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae are major health problems worldwide, both found in symptomless carriage but also causing even life-threatening infections. The aim of this thesis was to characterise MRSA and S. pneumoniae in detail by using several molecular typing methods for various epidemiological purposes: clonality analysis, epidemiological surveillance, outbreak investigation, and virulence factor analysis. The characteristics of MRSA isolates from the strain collection of the Finnish National Infectious Disease Register (NIDR) and pneumococcal isolates collected from military recruits and children with acute otitis media (AOM) were analysed using various typing techniques. Antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), spa typing, staphylococcal cassette chromosome mec (SCCmec) typing, and the detection of Panton-Valentine leukocidin (PVL) genes were performed for MRSA isolates. Pneumococcal isolates were analysed using antimicrobial susceptibility testing, serotyping, MLST, and by detecting pilus islet 1 (PI-1) and 2 (PI-2) genes. Several international community- and hospital-associated MRSA clones were recognised in Finland. The genetic diversity among MRSA FIN-4 isolates and among FIN-16 isolates was low. Overall, MRSA blood isolates from 1997 to 2006 were genetically diverse. spa typing was found to be a highly discriminatory, rapid and accurate typing method and it also qualifies as the primary typing method in countries with a long history of PFGE-based MRSA strain nomenclature. However, additional typing by another method, e.g. PFGE, is needed in certain situations to be able to provide adequate discrimination for epidemiological surveillance and outbreak investigation. An outbreak of pneumonia was associated with one pneumococcal strain among military recruits, previously healthy young men living in a crowded setting. The pneumococcal carriage rate after the outbreak was found to be exceptionally high. PI-1 genes were detected at a rather low prevalence among pneumococcal isolates from children with AOM. However, the study demonstrated that PI-1 has existed among pneumococcal isolates prior to pneumococcal conjugate vaccine and the increased antimicrobial resistance era. Moreover, PI-1 was found to associate with the serotype rather than the genotype. This study adds to our understanding of the molecular epidemiology of MRSA strains in Finland and the importance of an appropriate genotyping method to be able to perform high-level laboratory-based surveillance of MRSA. Epidemiological and molecular analyses of S. pneumoniae add to our knowledge of the characteristics of pneumococcal strains in Finland.

A method of assessing air toxics concentrations in urban areas using mobile platform measurements.

The objective of this paper is to demonstrate an approach to characterize the spatial variability in ambient air concentrations using mobile platform measurements. This approach may be useful for air toxics assessments in Environmental Justice applications, epidemiological studies, and environmental health risk assessments. In this study, we developed and applied a method to characterize air toxics concentrations in urban areas using results of the recently conducted field study in Wilmington, DE. Mobile measurements were collected over a 4- x 4-km area of downtown Wilmington for three components: formaldehyde (representative of volatile organic compounds and also photochemically reactive pollutants), aerosol size distribution (representing fine particulate matter), and water-soluble hexavalent chromium (representative of toxic metals). These measurements were,used to construct spatial and temporal distributions of air toxics in the area that show a very strong temporal variability, both diurnally and seasonally. An analysis of spatial variability indicates that all pollutants varied significantly by location, which suggests potential impact of local sources. From the comparison with measurements at the central monitoring site, we conclude that formaldehyde and fine particulates show a positive correlation with temperature, which could also be the reason that photochemically generated formaldehyde and fine particulates over the study area correlate well with the fine particulate matter measured at the central site.