Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

Thesis (Ph. D.)--Case Western Reserve University, 2006. / [School of Medicine] Department of Epidemiology and Biostatistics. Includes bibliographical references. Available online via OhioLINK's ETD Center.

Earlier retrospective noise exposure assessments for use in epidemiological research were not adequately characterized because they did not properly account for use of hearing protection devices (HPD) which would result in potential misclassification. Exposure misclassification has been shown to attenuate exposure-outcomes relations. In the case of already subtle relationships such as noise and cardiovascular diseases, this would potentially annihilate any association. We investigated two approaches using Workers’ Compensation Board (WorkSafe BC) audiometric surveillance data to (i) re-assess the noise exposure in a cohort of lumber mill workers in British Columbia using data on the use of HPD and the determinants of their use available through WorkSafe BC, and (ii) test the validity of the new exposure measures by testing their predictions of noise-induced hearing loss, a well-established association. Work history, noise exposure measurements, and audiometric surveillance data were merged together, forming job-exposure-audiometric information for each of 13,147 lumber mill workers. Correction factors specific to each type and class of HPD were determined based on research and standards. HPD-relevant correction factors were created using 1) deterministic methods and self-reported HPD use after filling gaps in the exposure history, or 2) a model of the determinants of use of HPD, then adjusting noise estimates according to the methods’ predictions and attenuation factors. For both methods, the HPD-adjusted and unadjusted noise exposure estimates were cumulated across all jobs each worker held in a cohort-participating lumber mill. Finally, these noise metrics were compared by examining how well each predicted hearing loss. Analyses controlled for gender, age, race as well as medical and non-occupational risk factors. Both methods led to a strengthening of the noise-hearing loss relationships compared to methods using HPD-unadjusted noise estimates. The method based on the modeling of HPD use had the best performance with a four-fold increase in the slope compared to the unadjusted noise-hearing loss slope. Accounting for HPD use in noise exposure assessment is necessary since we have shown that misclassification attenuated the exposure-response relationships. Exposure-response analyses subsequent to exposure reassessment provide predictive validity and gives confidence in the exposure adjustment methods. / Medicine, Faculty of / Population and Public Health (SPPH), School of / Graduate

This thesis examined associations between ecological indicators of residential radon and fine particulate matter air pollution (PM2.5) and lung cancer mortality using data from the American Cancer Society Cancer Prevention Study-II (CPS-II) prospective cohort. Nearly 1.2 million CPS-II participants were recruited in 1982. Mean county-level residential radon concentrations were linked to study participants according to ZIP code information at enrollment (mean (SD) = 53.5 (38.0) Bq/m3). Cox proportional hazards regression models were used to obtain adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for lung cancer mortality associated with radon. After necessary exclusions, a total of 811,961 participants in 2,754 counties were retained for analysis. A significant positive linear trend was observed between categories of radon concentrations and lung cancer mortality (p = 0.02). A 15% (95% CI 1 - 31%) increase in the risk of lung cancer mortality was observed per each 100 Bq/m3 radon. Radon was also positively associated with chronic obstructive pulmonary disease mortality (HR per each 100 Bq/m3 = 1.13, 95% CI 1.05 - 1.21). No clear associations were observed between radon and non-respiratory mortality. In lifelong never smokers (n = 188,699), each 10 µg/m3 increase in mean metropolitan statistical area PM2.5 concentrations was associated with a 15-27% increase in the risk of lung cancer death which strengthened among individuals with a history of asthma or any prevalent chronic lung disease at enrollment (p for interaction < 0.05). There was no association between PM2.5 and mortality from non-malignant respiratory disease. In conclusion, this thesis observed significant positive associations between ecological indicators of residential radon and PM2.5 concentrations and lung cancer mortality. These findings further support efforts to reduce radon concentrations in homes to the lowest possible level and strengthens the evidence that ambient concentrations of PM2.5 measured in recent decades are associated with small but measurable increases in lung cancer mortality. Further research is needed to better understand possible complex inter-relationships between environmental risk factors, chronic lung disease, and lung cancer.

Epidemiologic studies have adapted to the genomics era by forming large international consortia to overcome issues of large data volume and small sample size. Whereas both cohort and well-conducted case-control studies can inform disease risk from genetic susceptibility, cohort studies offer the additional advantages of assessing lifestyle and environmental exposure-disease time sequences often over a life course. Consortium involvement poses several logistical and ethical issues to investigators, some of which are unique to cohort studies, including the challenge to harmonize prospectively collected lifestyle and environmental exposures validly across individual studies. An open forum to discuss the opportunities and challenges of large-scale cohorts and their consortia was held in June 2009 in Banff, Canada, and is summarized in this report.

theresa.j.ochoa@uth.tmc.edu / Article / BACKGROUND: Enteropathogenic Escherichia coli (EPEC) strains are pediatric pathogens commonly isolated from both healthy and sick children with diarrhea in areas of endemicity. The aim of this study was to compare the bacterial load of EPEC isolated from stool samples from children with and without diarrhea to determine whether bacterial load might be a useful tool for further study of this phenomenon. METHODS: EPEC was detected by polymerase chain reaction (PCR) of colonies isolated on MacConkey plates from 53 diarrheal and 90 healthy children aged <2 years. DNA was isolated from stool samples by cetyltrimethylammonium bromide extraction. To standardize quantification by quantitative real-time PCR (qRT-PCR), the correlation between fluorescence threshold cycle and copy number of the intimin gene of EPEC E2348/69 was determined. RESULTS: The detection limit of qRT-PCR was 5 bacteria/mg stool. The geometric mean load in diarrhea was 299 bacteria/mg (95% confidence interval [CI], 77-1164 bacteria/mg), compared with 29 bacteria/mg (95% CI, 10-87 bacteria/mg) in control subjects (P = .016). Bacterial load was significantly higher in children with diarrhea than in control subjects among children <12 months of age (178 vs 5 bacteria/mg; P = .006) and among children with EPEC as the sole pathogen (463 vs 24 bacteria/mg; P = .006). CONCLUSIONS: EPEC load measured by qRT-PCR is higher in diarrheal than in healthy children. qRT-PCR may be useful to study the relationship between disease and colonization in settings of endemicity.

Felicidade é um constructo multidimensional que pode ser definido como ograu em que uma pessoa avalia a qualidade geral de sua vida como favorável; ela tem sido associada com vários desfechos e medidas de saúde. A transição da infância para a adolescência envolve uma série de mudanças físicas e especialmente psicológicas, e oimpacto das doenças bucais pode ser percebido como um obstáculo para o desenvolvimento social dos indivíduos.Osobjetivos do presente trabalho foram estudar a influência das condições de saúde bucal, condição socioeconômica e uso de serviços no grau de felicidade durante o período de transição da infância para a adolescência;identificar os fatores associados à mudança do grau de felicidade e avaliar o incremento dos problemas de saúde bucal na amostra após 2 anos de acompanhamento. A coleta de dados ocorreu em 2 momentos, nos anos de 2012 e 2014. Foram feitos exames clínicos para avaliar as condições de saúde bucal (cárie dentária, má oclusão, traumatismo dentário e condição gengival), entrevistas para avaliar o grau de felicidade (medido com a Escala Subjetiva de Felicidade-SHS) e o impacto das condições de saúde bucal na qualidade de vida (medido com o Child Perceptions QuestionnaireCPQ11-14), além de questionários enviados aos responsáveis para avaliar a condição socioeconômica da família, variáveis demográficas e de uso de serviços dacriança. Para a análise dos fatores relacionados ao grau de felicidadefoi utilizado um modelo linear multinível para medidas repetidas ao longo do tempo, comentrada de variáveis hierarquizada de acordo com um modelo conceitual; para análise dos fatores associados à mudança no grau de felicidadefoi utilizada regressão logística multinomial.Das 1134 crianças examinadas no baseline, 770 foram reavaliadas após 2 anos(taxa de resposta de 67,9 por cento), e foi observado um aumento na prevalência de problemas bucais (experiência de cárie, prevalência de má oclusão, prevalência de sangramento e placa dental). O modelo multinível final foi composto por variáveis socioeconômicas da família, pelo uso de serviços e pelas condições clínicas de saúde bucal e autopercepção.Adolescentes de famílias com menor renda(p=0,030), que viviam em residências com maior aglomeração(p<0,001), cujas mães tinham um menor nível de escolaridade(p=0,014), que utilizavam o serviço odontológico por motivos de dor ou em busca de tratamentos(p=0,039), que possuíam um número maior de dentes com cavidades de cárie não tratada(p=0,010)e que relatavam maior impacto das condições de saúde bucal na qualidade de vida (p<0,001)apresentaram um pior grau de felicidade. O modelo multinomial final indicou uma associação entre experiência de cárie e autopercepção e a mudança no grau de felicidade: adolescentes com um maior número de dentes cariados, perdidos ou obturados (OR=1,16-1,19, p=0,018-0,037) e com escores mais altos no CPQ11-14 (OR=1,04-1,07, p=0,000-0,014) tinham uma maior chance de pertencer às categorias mais desfavoráveis de trajetória de felicidade. Esses resultados evidenciam a importância de políticas públicas inclusivas e promoção de saúde bucal para o desenvolvimento psicossocial de adolescentes / Happiness is a multidimensional construct and can be defined as the degree to which a person evaluates the quality of his life as a whole as favorably; It has been associated with several health outcomes and measures. The transition from childhood to adolescence involves a number of physical and especially psychological changes, and the impact of oral diseases can be perceived as an obstacle to the social development of individuals. The objectives of this paper were to investigate the influence of oral health conditions, socioeconomic status and use of dental services on subjective happiness during the transition from childhood to adolescence; to identify the factors associated with the change in the perception of happiness and to evaluate the incidence of oral health problems in the sample after 2 years of follow-up. Data collection was performed at two periods, in 2012 and 2014. Clinical examinations were performed to evaluate oral health conditions (dental caries, malocclusion, dental trauma and gingival condition), interviews were conducted to evaluate the subjective happiness (using the Subjective Happiness Scale -SHS ) and the impact of oral health conditions on quality of life (using the Child Perception Questionnaire -CPQ11-14), questionnaires were sent to the parents to assess socioeconomic family characteristics, demographic variables and the use of dental services. To analyse the factors associated with the subjective happiness, data were fitted into a linear multilevel model for repeated measures and hierarchical selection of variables; to analyze the factors associated with changes in happiness, data were fitted into a multinomial logistic model. From 1134 children examined in the baseline, 770 were reevaluated after 2 years (response rate of 67.9 per cent), and it was observed an increase in the prevalence of oral health conditions (experience of dental caries, prevalence of malocclusion, gingival bleeding and dental plaque). In the multilevel model, following adjustment, there was an association between the mean score of SHS and socioeconomic variables, the use of dental services, clinical conditions and self-perception. Adolescents from lower income families (p = 0.030), who lived in households with worse overcrowding (p<0.001), whose mothers had lower levels of education (p = 0.014), who used dental services due to pain or to seek dental treatment (p= 0.039), which had a higher number of cavitated caries lesions (p = 0.010) and who reported higher impact of oral health conditions on quality of life (p <0.001) presented to a worse degree of happiness. The multinomial final model indicated an association between dental caries experience and self-perception and the changes in happiness over time: adolescents with a greater number of teeth decayed, missng orfilled (OR = 1.16-1.19, p = 0.018-0.037), and with higher CPQ11-14 scores (OR = 1.04-1.07, p = 0.000-0.014) had a higher chance of being in the most unfavorable categories of happiness trajectory. These results highlight the importance of inclusive publicpolicies and oral health promotion for the psychosocial development of adolescents

Gengivite é a doença periodontal mais prevalente em todas as populações. No entanto, existe uma grande variedade entre as estimativas de prevalência (50-100%) entre diferentes estudos epidemiológicos. O objetivo do presente estudo foi avaliar as mudanças na gengivite após 4 anos e determinar os possíveis fatores de proteção em adultos brasileiros de Porto Alegre. Na avaliação inicial, uma amostra representativa de 1.023 adultos com 35 anos ou mais foi obtida por meio de uma estratégia de amostragem probabilística de múltiplos estágios. Após 4 anos, 402 indivíduos com pelo menos 1 dente foram reexaminados. Foi aplicado um questionário estruturado e foi realizado o índice de sangramento gengival (ISG) em quatro sítios de todos os dentes. Os indivíduos foram dicotomizados como aqueles que apresentaram reduções em ISG acima de 15% e aqueles que apresentaram reduções inferiores a 15% ou aumento do ISG. Os modelos de regressão de Poisson foram ajustados para estimar os riscos relativos (RR) e intervalos de confiança de 95% (IC 95%). A extensão geral dos sítios com ISG reduziu significativamente de 25.9% para 20.1%. Esta redução foi maior e significativa nas superfícies livres (34.1% para 24.0%), enquanto nas superfícies proximais a redução não foi significativa (17.9% para 16.1%). O percentual de indivíduos com redução de ISG ≥ 15% em todos os sítios e apenas em superfícies livres foi de 31.0% e 38.8%, respectivamente. Para todas as superfícies, a frequência de escovação auto-referida ≥ 2 vezes/dia aumentou a probabilidade de redução de ISG em 72% em comparação com ≤ 1 vez/dia (RR = 1.72; IC 95%: 1.01-3.16). Para superfícies livre, a frequência de escovação e o tabagismo permaneceram associados, e os indivíduos com peso normal apresentaram uma probabilidade 26% maior de redução de ISG do que indivíduos obesos com excesso de peso (RR = 1.26; IC 95%: 1.01-1.62). Em conclusão, foi observada uma redução na extensão da gengivite ao longo do tempo nesta população brasileira. A frequência de escovação e o peso normal foram fatores protetores para gengivite. Fumar reduziu gengivite ao longo do tempo, mas provavelmente devido ao seu efeito de vasoconstrição na margem gengival. / Gingivitis is the most prevalent periodontal disease in all populations. However, there is a great variety between estimates of prevalence of gingivitis (50-100%) among different epidemiological studies. The aim of the present study was to assess changes in gingivitis over 4 years and to determine possible protective factors in Brazilian adults. At baseline, a representative sample of 1,023 adults 35 years and older was obtained using a multistage probability sampling strategy. After 4 years, 402 individuals with at least 1 tooth were re-examined. A structured questionnaire was applied and gingival bleeding index (GB) was performed at four sites of all teeth. Individuals were dichotomized into those showing reductions in GB higher than 15% and those showing reductions under 15% or increase in GB. Poisson regression models were fitted to estimate relative risks (RR) and 95% confidence intervals (95%CI). The overall extent of sites with GB reduced significantly from 25.9% to 20.1%. This reduction was higher and significative in free surfaces (34.1% to 24.0%), whereas in proximal surfaces the reduction was not significant (17.9% to 16.1%). The percentage of individuals with GB reduction ≥15% in all sites and only free sites was 31.0% and 38.8%, respectively. For all surfaces, self-reported brushing frequency ≥2 times/day increased the probability of reducing GB by 72% compared to ≤1/day (RR=1.72; 95%CI 1.01-3.16). For each 10 packyears smoked, the probability of reduction in GB was 3% higher (RR=1.03; 95%CI 1.01-1.04). For free surfaces, brushing frequency and smoking remained associated, and normal weight individuals had 26% higher probability of reducing GB than overweight-obese individuals (RR=1.26; 95%CI 1.01-1.62). In conclusion, it was observed a reduction in the extension of gingivitis over time in this Brazilian population. Brushing frequency and normal weight were found to be protective factors for gingivitis. Smoking reduced gingivitis over time, but probably due to its vasoconstriction effect on the gingival margin.

Introdução: A influência da depressão pós-acidente vascular cerebral (AVC) como preditor de mortalidade é pouca investigada. Assim, nosso objetivo foi avaliar a influência da depressão na sobrevida em longo prazo nos participantes do Estudo de Mortalidade e Morbidade do Acidente Vascular Cerebral (Estudo EMMA), uma coorte em andamento no Hospital Universitário da Universidade de São Paulo, Brasil. Métodos: Foi avaliada prospectivamente uma subamostra de 191 indivíduos com 35 anos ou mais, acometidos por acidente vascular cerebral do tipo isquêmico e hemorrágico, participantes do Estudo EMMA. As características do AVC na admissão hospitalar, além dos dados sociodemográficos e fatores de risco cardiovasculares foram avaliados de acordo com o primeiro episódio de depressão após o evento agudo. O rastreamento de depressão foi realizado com cada participante através de entrevista telefônica com o questionário \"Patient Health Questionnaire-9\" [transtorno depressivo maior (escore &#8805; 10 pontos) e depressão menor (escore &#8805; cinco pontos)] 30 dias após o evento agudo e periodicamente durante um ano de seguimento. As análises de mortalidade foram realizadas através das curvas de sobrevivência de Kaplan-Meier e pelas razões de risco (\"hazard ratio\") proporcionais que foram calculadas por modelos de regressão logística de Cox ajustados para potenciais fatores de confusão. Resultados: Nesta subamostra de 191 participantes do estudo EMMA, 164 (85,9%) indivíduos foram diagnosticados com acidente vascular cerebral isquêmico e 27 (14,1%) com acidente vascular cerebral hemorrágico. A frequência geral de transtorno depressivo maior foi de 25,1% (48/191) e a frequência de depressão menor foi de 57,1% (109/191) durante um ano de seguimento, independentemente do subtipo de AVC. Foi observada uma taxa de sobrevida menor entre os indivíduos que desenvolveram transtorno depressivo maior pós-AVC em comparação com aqueles que não desenvolveram esta condição após um ano de seguimento (85,4% vs. 96,5%, log-rank p = 0,006). Após análise de regressão de Cox múltipla, observamos um risco maior de mortalidade por todas as causas dentre aqueles que desenvolveram transtorno depressivo maior em comparação aos participantes sem transtorno depressivo maior (razão de risco = 5,97; IC 95% =1,43-24,91, p = 0,01). Os participantes que desenvolveram depressão menor não apresentaram diferenças estatisticamente significativas nas taxas de sobrevida pós-AVC comparativamente aos que não apresentaram estes sintomas (93,2% vs. 94%, log-rank p = 0,94); assim como não apresentaram um aumento no risco de morte em até um ano de seguimento (razão de risco = 0,76; IC 95% = 0,18 3,19, p = 0,71). Conclusão: Nossos resultados sugerem que a ocorrência do primeiro episódio de transtorno depressivo maior foi um preditor potencial de mau prognóstico caracterizado por um risco aumentado de morte um ano após o AVC / Introduction: The influence of post-stroke depression as a predictor of mortality is poorly investigated. Thus, our aim was to evaluate the influence of depression on long-term survival in participants from the Study of Stroke Mortality and Morbidity (EMMA Study), an ongoing stroke cohort performed in the Hospital Universitário da Universidade de São Paulo, Brazil. Methods: We prospectively evaluated a subset of 191 EMMA participants with 35 years or more, affected by ischemic and hemorrhagic stroke. The stroke characteristics at hospital admission, as well as, sociodemographic and cardiovascular risk factors were evaluated according to the first episode of depression after acute event. Screening of depression was conducted by telephone interview with each participant using \"Patient Health Questionnaire-9\" [major depressive disorder (score &#8805; 10 points) and minor depression (score &#8805; five points)] 30 days after acute event and periodically during one year of follow-up. Mortality analyzes were performed using Kaplan-Meier survival curves and the hazard proportional ratios were calculated by Cox logistic regression models adjusted for potential confounders. Results: In this subsample of 191 EMMA participants, 164 (85.9%) patients were diagnosed with ischemic stroke and 27 (14.1%) with hemorrhagic stroke. The overall frequency of major depressive disorder was 25.1% (48/191) and lower depression rate was 57.1% (109/191) during one year of follow-up, regardless of stroke subtype. It was observed a lower survival rate among individuals who developed major depressive disorder after stroke compared to those who did not develop this condition after one year of follow-up (85.4% vs. 96.5% was observed, log-rank p = 0.006). After multiple Cox regression analysis, we observed an increased all-cause mortality among those who developed major depressive disorder when compared to participants without major depressive disorder (risk ratio = 5.97, 95% CI = 1.43 to 24.91, p = 0.01). Participants who developed minor depression showed no statistically significant differences in post-stroke survival rates compared to those without these symptoms (93.2% vs. 94%, log-rank p = 0.94); as well as, they did not show an increased risk of death within one year of follow-up (risk ratio = 0.76, 95% CI = 0.18 to 3.19, p = 0.71). Conclusion: Our results suggest that the occurrence of the first episode of major depressive disorder was a potential predictor of poor prognosis characterized by an increased risk of death one year after the stroke

Introdução: A capilaroscopia periungueal (CPU) tem sido relacionada ao dano a órgãos-alvo na esclerose sistêmica (ES). No entanto, estudos relativos à gravidade das alterações da CPU com a mortalidade evidenciam resultados discrepantes. Este estudo tem como objetivo verificar associação da gravidade da microangiopatia periférica na CPU com o risco de morte na ES. Pacientes e métodos: Cento e setenta pacientes com ES foram prospectivamente avaliados e acompanhados em média de 9,3 anos. Além da avaliação clínica, os pacientes foram submetidos à sorologia, testes de função pulmonar, ecocardiograma e tomografia computadorizada pulmonar de alta resolução (TCAR). A perda capilar na CPU foi avaliada pelo escore avascular (EA), que varia de 0 a 3. O número médio de ectasias, megacapillaries e hemorragias por dedo também foi registrado. O modelo de Cox proporcional Uni e Multivariado foi utilizado para analisar a associação do escore avascular com o risco de morte através da associação Hazard ratio (HR). Resultados: Por análise de Cox univariada, o escore avascular associado à mortalidade foi estatisticamente significativo (HR = IC 1.54, 95%: 1.13-2.09, p = 0.006), mas outras variáveis capilaroscópicas (número de ectasias, megacapillaries e hemorragias por dedo) não foram (p> 0,40 para todos os testes). Após o ajuste para escore de pele, idade, sexo, origem étnica, e sinais de isquemia digital, a associação entre o escore avascular perdeu significância estatística (HR = 1.23, IC: 0.84-1.81, p = 0.276). Também não houve associação significativa do escore avascular quando ajustado para uma combinação de resultados de exames complementares. Conclusões: A gravidade da desvascularização na CPU está relacionada a um maior risco de mortalidade na ES; No entanto, a associação não é estatisticamente significativa após ajuste para outras variáveis clínicas e laboratoriais. Apesar do fato de não mostrar uma associação independente do EA com a mortalidade, consideramos que é útil na avaliação de pacientes com diagnóstico de esclerose sistêmica, uma vez que pode dar uma visão geral e confiável da gravidade da doença. / Introduction: The nailfold capillaroscopy (NCF) has been related to end-organ damage in Systemic sclerosis (SSc). However, studies relating the severity of NCF alterations with mortality have rendered mixed results. This study aims to verify the association of the severity of peripheral microangiopathy in the NFC with the risk of death in SSc. Patients and methods: One hundred and seventy SSc patients were prospectively evaluated and followed a mean of 9.3 years. Besides clinical evaluation, patients underwent serology, pulmonary function tests, Doppler echocardiography, and pulmonary high resolution computed tomography (HRCT). Capillary loss on NCF was evaluated using the avascular score (AS), ranging from 0 to 3. The mean number of ectasias, megacapillaries and hemorrhages per finger was also recorded; univariate and multivariate Cox proportional models were used to analyze the association of the AS with the risk of death using hazard ratios (HR). Results: By univariate Cox analysis, the AS was statistically significantly associated with mortality (HR = 1.54, 95% CI: 1.13 to 2.09, p = 0.006), but other capillaroscopic variables (number of ectasias, megacapillaries and hemorrhages per finger) were not (p> 0.40 for all tests). After adjustment for skin score, age, gender, ethnic background, and signs of digital ischemia, the association between the AS weakened and lost statistical significance (HR = 1.23, CI: 0.84 to 1.81, p=0.276). There was also no significant association of the avascular score when adjusted for a combination of results of complementary tests. Conclusions: The severity of devascularization on NCF is related to a higher risk of mortality in SSc; however, the association disappeared after adjustment for other clinical and laboratory variables. Despite the fact that we were not able to show an independent association of the AS with mortality, we consider it useful in the evaluation in patients diagnosed with systemic sclerosis, since it can give a general view and reliable view of the severity of the disease.