Low-Dose Aspirin Use After Diagnosis of Colorectal Cancer Does Not Increase Survival: A Case–Control Analysis of a Population-Based Cohort

BACKGROUND & AIMS: Individuals who began taking low-dose aspirin before they were diagnosed with colorectal cancer were reported to have longer survival times than patients who did not take this drug. We investigated survival times of patients who begin taking low-dose aspirin after a diagnosis of colorectal cancer in a large population-based cohort study.

METHODS: We performed a nested case-control analysis using a cohort of 4794 patients diagnosed with colorectal cancer from 1998 through 2007, identified from the UK Clinical Practice Research Datalink and confirmed by cancer registries. There were 1559 colorectal cancer-specific deaths, recorded by the Office of National Statistics; these were each matched with up to 5 risk-set controls. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI), based on practitioner-recorded aspirin usage.

RESULTS: Overall, low-dose aspirin use after a diagnosis of colorectal cancer was not associated with colorectal cancer-specific mortality (adjusted OR = 1.06; 95% CI: 0.92-1.24) or all-cause mortality (adjusted OR = 1.06; 95% CI: 0.94-1.19). A dose-response association was not apparent; for example, low-dose aspirin use for more than 1 year after diagnosis was not associated with colorectal cancer-specific mortality (adjusted OR = 0.98; 95% CI: 0.82-1.19). There was also no association between low-dose aspirin usage and colon cancer-specific mortality (adjusted OR = 1.02; 95% CI: 0.83-1.25) or rectal cancer-specific mortality (adjusted OR = 1.10; 95% CI: 0.88-1.38).

CONCLUSIONS: In a large population-based cohort, low-dose aspirin usage after diagnosis of colorectal cancer did not increase survival time.

Radiological imaging in digital systems: the effect of exposure parameters in diagnostic quality and patient dose

Esta tese pretende contribuir para o estudo e análise dos factores relacionados com as técnicas de aquisição de imagens radiológicas digitais, a qualidade diagnóstica e a gestão da dose de radiação em sistema de radiologia digital. A metodologia encontra-se organizada em duas componentes. A componente observacional, baseada num desenho do estudo de natureza retrospectiva e transversal. Os dados recolhidos a partir de sistemas CR e DR permitiram a avaliação dos parâmetros técnicos de exposição utilizados em radiologia digital, a avaliação da dose absorvida e o índice de exposição no detector. No contexto desta classificação metodológica (retrospectiva e transversal), também foi possível desenvolver estudos da qualidade diagnóstica em sistemas digitais: estudos de observadores a partir de imagens arquivadas no sistema PACS. A componente experimental da tese baseou-se na realização de experiências em fantomas para avaliar a relação entre dose e qualidade de imagem. As experiências efectuadas permitiram caracterizar as propriedades físicas dos sistemas de radiologia digital, através da manipulação das variáveis relacionadas com os parâmetros de exposição e a avaliação da influência destas na dose e na qualidade da imagem. Utilizando um fantoma contrastedetalhe, fantomas antropomórficos e um fantoma de osso animal, foi possível objectivar medidas de quantificação da qualidade diagnóstica e medidas de detectabilidade de objectos. Da investigação efectuada, foi possível salientar algumas conclusões. As medidas quantitativas referentes à performance dos detectores são a base do processo de optimização, permitindo a medição e a determinação dos parâmetros físicos dos sistemas de radiologia digital. Os parâmetros de exposição utilizados na prática clínica mostram que a prática não está em conformidade com o referencial Europeu. Verifica-se a necessidade de avaliar, melhorar e implementar um padrão de referência para o processo de optimização, através de novos referenciais de boa prática ajustados aos sistemas digitais. Os parâmetros de exposição influenciam a dose no paciente, mas a percepção da qualidade de imagem digital não parece afectada com a variação da exposição. Os estudos que se realizaram envolvendo tanto imagens de fantomas como imagens de pacientes mostram que a sobreexposição é um risco potencial em radiologia digital. A avaliação da qualidade diagnóstica das imagens mostrou que com a variação da exposição não se observou degradação substancial da qualidade das imagens quando a redução de dose é efectuada. Propõe-se o estudo e a implementação de novos níveis de referência de diagnóstico ajustados aos sistemas de radiologia digital. Como contributo da tese, é proposto um modelo (STDI) para a optimização de sistemas de radiologia digital.

Modelação da qualidade do ar e da saúde humana: da mesoescala à dose

O actual, e crescente, padrão de consumo tem repercussões no ambiente que, inevitavelmente, se reflectem na saúde humana. A poluição atmosférica assume-se, na Europa, como um problema ambiental premente, por ter um elevado impacte na saúde dos cidadãos. Entre estes, há grupos particularmente vulneráveis, como os idosos, os doentes crónicos e as crianças. Vários estudos colocam em evidência a sensibilidade dos doentes asmáticos, em particular das crianças, à poluição atmosférica. No entanto, permanece por esclarecer o facto de a poluição atmosférica poder causar o aumento da prevalência desta doença, assim como a identificação dos principais poluentes atmosféricos responsáveis e os níveis de exposição seguros. O objectivo desta tese consiste no estudo da relação entre a poluição atmosférica e a saúde, contribuindo para o conhecimento nesta temática através do desenvolvimento de uma ferramenta e da sua aplicação a um caso de estudo concreto. Neste caso de estudo analisou-se a relação entre vários poluentes atmosféricos e o agravamento da sintomatologia em crianças asmáticas. Neste âmbito, foi desenvolvido o modelo doseAr, que possibilita o cálculo da exposição e da dose inalada, ao nível individual, de poluentes atmosféricos. Os resultados da aplicação do doseAr permitem a identificação dos microambientes onde a contribuição para a exposição e dose inalada de poluentes é mais relevante. Os microambientes interiores, em particular aqueles onde é desenvolvida actividade física exigente, são identificados como especialmente importantes. A relação entre a exposição e a dose inalada é claramente associada ao agravamento da asma nestas crianças, apesar dos níveis de poluição identificados serem baixos, face aos padrões de qualidade do ar existentes.

Estudo de otimização de imagem e dose em mamografia digital

O objetivo deste trabalho foi efetuar um estudo de otimização dos parâmetros de exposição do mamógrafo digital da marca GE, modelo Senographe DS instalado no Instituto Português de Oncologia de Coimbra (IPOC) baseado numa análise contraste detalhe e avaliar o impacto do resultado obtido na melhoria da capacidade de detecção clínica das estruturas da mama. O mamógrafo em estudo dispõe de um sistema de controle automático da exposição designado por sistema AOP (Automatic Optimization of Parameters) que foi otimizado pelo fabricante a partir da razão contraste ruído. O sistema AOP é usado na prática clínica na quase totalidade dos exames de mamografia realizados no IPOC. Tendo em conta o tipo de estrutura que se pretende visualizar na mamografia, nomeadamente estruturas de baixo contraste como as massas e estruturas de dimensão submilimétrica como as microcalcificações, a análise contraste detalhe poderia constituir uma abordagem mais adequada para o estudo de otimização dos parâmetros de exposição uma vez que permitiria uma avaliação conjunta do contraste, da resolução espacial e do ruído da imagem. Numa primeira fase do trabalho foi efetuada a caracterização da prática clínica realizada no mamógrafo em estudo em termos de espessura de mama comprimida “típica”, dos parâmetros técnicos de exposição e das opções de processamento das imagens aplicadas pelo sistema AOP (combinação alvo/filtro, tensão aplicada na ampola - kVp e produto corrente-tempo da ampola - mAs). Numa segunda fase foi realizado um estudo de otimização da qualidade da imagem versus dose na perspectiva dos parâmetros físicos. Para tal foi efetuada uma análise contrastedetalhe no objeto simulador de mama CDMAM e usada uma figura de mérito definida a partir do IQFinv (inverted image quality figure) e da dose glandular média. Os resultados apontaram para uma diferença entre o ponto ótimo resultante do estudo de otimização e o ponto associado aos parâmetros de exposição escolhidos pelo sistema AOP, designadamente no caso da mama pequena. Sendo a qualidade da imagem na perspectiva clínica um conceito mais complexo cujo resultado da apreciação de uma imagem de boa qualidade deve ter em conta as diferenças entre observadores, foi efetuado na última parte deste trabalho um estudo do impacto clínico da proposta de otimização da qualidade de imagem. A partir das imagens realizadas com o objeto simulador antropomórfico TOR MAM simulando uma mama pequena, seis médicos(as) radiologistas com mais de 5 anos de experiência em mamografia avaliaram as imagens “otimizadas” obtidas utilizando-se os parâmetros técnicos de exposição resultantes do estudo de otimização e a imagem resultante da escolha do sistema AOP. A análise estatística das avaliações feitas pelos médicos indica que a imagem “otimizada” da mama pequena apresenta uma melhor visualização das microcalcificações sem perda da qualidade da imagem na deteção de fibras e de massas em comparação com a imagem “standard”. Este trabalho permitiu introduzir uma nova definição da figura de mérito para o estudo de otimização da qualidade da imagem versus dose em mamografia. Permitiu também estabelecer uma metodologia consistente que pode facilmente ser aplicada a qualquer outro mamógrafo, contribuindo para a área da otimização em mamografia digital que é uma das áreas mais relevantes no que toca à proteção radiológica do paciente.

Effects of environmental factors on the toxicity of pesticides to zebrafish embryos

During the last century mean global temperatures have been increasing. According to the predictions, the temperature change is expected to exceed 1.5ºC in this century and the warming is likely to continue. Freshwater ecosystems are among the most sensitive mainly due to changes in the hydrologic cycle and consequently changes in several physico-chemical parameters (e.g. pH, dissolved oxygen). Alterations in environmental parameters of freshwater systems are likely to affect distribution, morphology, physiology and richness of a wide range of species leading to important changes in ecosystem biodiversity and function. Moreover, they can also work as co-stressors in environments where organisms have already to cope with chemical contamination (such as pesticides), increasing the environmental risk due to potential interactions. Therefore, the objective of this work was to evaluate the effects of climate change related environmental parameters on the toxicity of pesticides to zebrafish embryos. The following environmental factors were studied: pH (3.0-12.0), dissolved oxygen level (0-8 mg/L) and UV radiation (0-500 mW/m2). The pesticides studied were the carbamate insecticide carbaryl and the benzimidazole fungicide carbendazim. Stressors were firstly tested separately in order to derive concentration- or intensity-response curves to further study the effects of binary combinations (environmental factors x pesticides) by applying mixture models. Characterization of zebrafish embryos response to environmental stress revealed that pH effects were fully established after 24 h of exposure and survival was only affected at pH values below 5 and above 10. Low oxygen levels also affected embryos development at concentrations below 4 mg/L (delay, heart rate decrease and edema), and at concentrations below 0.5 mg/L the survival was drastically reduced. Continuous exposure to UV radiation showed a strong time-dependent impact on embryos survival leading to 100% of mortality after 72 hours of exposure. The toxicity of pesticides carbaryl and carbendazim was characterized at several levels of biological organization including developmental, biochemical and behavioural allowing a mechanistic understanding of the effects and highlighting the usefulness of behavioural responses (locomotion) as a sensitive endpoint in ecotoxicology. Once the individual concentration response relationship of each stressor was established, a combined toxicity study was conducted to evaluate the effects of pH on the toxicity of carbaryl. We have shown that pH can modify the toxicity of the pesticide carbaryl. The conceptual model concentration addition allowed a precise prediction of the toxicity of the jointeffects of acid pH and carbaryl. Nevertheless, for alkaline condition both concepts failed in predicting the effects. Deviations to the model were however easy to explain as high pH values favour the hydrolysis of carbaryl with the consequent formation of the more toxic degradation product 1- naphtol. Although in the present study such explanatory process was easy to establish, for many other combinations the “interactive” nature is not so evident. In the context of the climate change few scenarios predict such increase in the pH of aquatic systems, however this was a first approach focused in the lethal effects only. In a second tier assessment effects at sublethal level would be sought and it is expectable that more subtle pH changes (more realistic in terms of climate changes scenarios) may have an effect at physiological and biochemical levels with possible long term consequences for the population fitness.

Personal Exposure to Grass Pollen: Relating Inhaled Dose to Background Concentration

Background Very few studies on human exposure to allergenic pollen have been conducted using direct methods, with background concentrations measured at city center monitoring stations typically taken as a proxy for exposure despite the inhomogeneous nature of atmospheric pollen concentrations. A 2003 World Health Organization report highlighted the need for an improved understanding of the relation between monitoring station data and actual exposure. Objective To investigate the relation between grass pollen dose and background concentrations measured at a monitoring station, to assess the fidelity of monitoring station data as a qualitative proxy for dose, and to evaluate the ratio of dose rate to background concentration. Methods Grass pollen dose data were collected in Aarhus, Denmark, in an area where grass pollen sources were prevalent, using Nasal Air Samplers. Sample collection lasted for approximately 25 to 30 minutes and was performed at 2-hour intervals from noon to midevening under moderate exercise by 2 individuals. Results A median ratio of dose rate to background concentration of 0.018 was recorded, with higher ratio values frequently occurring at 12 to 2 pm, the time of day when grass species likely to be present in the area are expected to flower. From 4 to 8 pm, dose rate and background concentration data were found to be strongly and significantly correlated (rs = 0.81). Averaged dose rate and background concentration data showed opposing temporal trends. Conclusion Where local emissions are not a factor, background concentration data constitute a good quantitative proxy for inhaled dose. The present ratio of dose rate to background concentration may aid the study of dose–response relations.

Acute hypoxia reduces plasma myostatin independent of hypoxic dose

Background: Muscle atrophy is seen ~ 25 % of patients with cardiopulmonary disorders, such as chronic obstructive pulmonary disorder and chronic heart failure. Multiple hypotheses exist for this loss, including inactivity, inflammation, malnutrition and hypoxia. Healthy individuals exposed to chronic hypobaric hypoxia also show wasting, suggesting hypoxia alone is sufficient to induce atrophy. Myostatin regulates muscle mass and may underlie hypoxic-induced atrophy. Our previous work suggests a decrease in plasma myostatin and increase in muscle myostatin following 10 hours of exposure to 12 % O2. Aims: To establish the effect of hypoxic dose on plasma myostatin concentration. Concentration of plasma myostatin following two doses of normobaric hypoxia (10.7 % and 12.3 % O2) in a randomised, single-blinded crossover design (n = 8 lowlanders, n = 1 Sherpa), with plasma collected pre (0 hours), post (2 hours) and 2 hours following (4 hours) exposure. Results: An effect of time was noted, plasma myostatin decreased at 4 hours but not 2 hours relative to 0 hours (p = 0.01; 0 hours = 3.26 [0.408] ng.mL-1, 2 hours = 3.33, [0.426] ng.mL-1, 4 hours = 2.92, [0.342] ng.mL-1). No difference in plasma myostatin response was seen between hypoxic conditions (10.7 % vs. 12.3 % O2). Myostatin reduction in the Sherpa case study was similar to the lowlander cohort. Conclusions: Decreased myostatin peptide expression suggests hypoxia in isolation is sufficient to challenge muscle homeostasis, independent of confounding factors seen in chronic cardiopulmonary disorders, in a manner consistent with our previous work. Decreased myostatin peptide may represent flux towards peripheral muscle, or a reduction to protect muscle mass. Chronic adaption to hypoxia does not appear to protect against this response, however larger cohorts are needed to confirm this. Future work will examine tissue changes in parallel with systemic effects.

Radiation dose rates and exposure associated to Technologically Enhanced Naturally Occurring Radioactive Materials (TENORM) at locations of a Portuguese coal-fired power plant

Coal contains trace quantities of natural radionuclides such as Th-232, U-235, U-238, as well as their radioactive decay products and 40K. These radionuclides can be released as fly ash in atmospheric emissions from coal-fired power plants, dispersed into the environment and deposited on the surrounding top soils. Therefore, the natural radiation background level is enhanced and consequently increase the total dose for the nearby population. A radiation monitoring programme was used to assess the external dose contribution to the natural radiation background, potentially resulting from the dispersion of coal ash in past atmospheric emissions. Radiation measurements were carried out by gamma spectrometry in the vicinity of a Portuguese coal-fired power plant. The radiation monitoring was achieved both on and off site, being the boundary delimited by a 20 km circle centered in the stacks of the coal plant. The measured radionuclides concentrations for the uranium and thorium series ranged from 7.7 to 41.3 Bq/kg for Ra-226 and from 4.7 to 71.6 Bq/kg for Th-232, while K-40 concentrations ranged from 62.3 to 795.1 Bq/kg. The highest values were registered near the power plant and at distances between 6 and 20 km from the stacks, mainly in the prevailing wind direction. The absorbed dose rates were calculated for each sampling location: 13.97-84.00 ηGy/h, while measurements from previous studies carried out in 1993 registered values in the range of 16.6-77.6 ηGy/h. The highest values were registered at locations in the prevailing wind direction (NW-SE). This study has been primarily done to assess the radiation dose rates and exposure to the nearby population in the surroundings of a coal-fired power plant. The results suggest an enhancement or at least an influence in the background radiation due to the coal plant past activities.

Ultrafine Particles in Ambient Air of an Urban Area: Dose Implications for Elderly

Due to their detrimental effects on human health, the scientific interest in ultrafine particles (UFP) has been increasing, but available information is far from comprehensive. Compared to the remaining population, the elderly are potentially highly susceptible to the effects of outdoor air pollution. Thus, this study aimed to (1) determine the levels of outdoor pollutants in an urban area with emphasis on UFP concentrations and (2) estimate the respective dose rates of exposure for elderly populations. UFP were continuously measured over 3 weeks at 3 sites in north Portugal: 2 urban (U1 and U2) and 1 rural used as reference (R1). Meteorological parameters and outdoor pollutants including particulate matter (PM10), ozone (O3), nitric oxide (NO), and nitrogen dioxide (NO2) were also measured. The dose rates of inhalation exposure to UFP were estimated for three different elderly age categories: 64–70, 71–80, and >81 years. Over the sampling period levels of PM10, O3 and NO2 were in compliance with European legislation. Mean UFP were 1.7 × 104 and 1.2 × 104 particles/cm3 at U1 and U2, respectively, whereas at rural site levels were 20–70% lower (mean of 1 ×104 particles/cm3). Vehicular traffic and local emissions were the predominant identified sources of UFP at urban sites. In addition, results of correlation analysis showed that UFP were meteorologically dependent. Exposure dose rates were 1.2- to 1.4-fold higher at urban than reference sites with the highest levels noted for adults at 71–80 yr, attributed mainly to higher inhalation rates.

Modelling the Contribution of 40K, 232Th and 226Ra to Radiation Dose and Risk from Airborne Discharges of Coal-Fired Power Plants

Coal contains trace elements and naturally occurring radionuclides such as 40K, 232Th, 238U. When coal is burned, minerals, including most of the radionuclides, do not burn and concentrate in the ash several times in comparison with their content in coal. Usually, a small fraction of the fly ash produced (2-5%) is released into the atmosphere. The activities released depend on many factors (concentration in coal, ash content and inorganic matter of the coal, combustion temperature, ratio between bottom and fly ash, filtering system). Therefore, marked differences should be expected between the by-products produced and the amount of activity discharged (per unit of energy produced) from different coal-fired power plants. In fact, the effects of these releases on the environment due to ground deposition have been received some attention but the results from these studies are not unanimous and cannot be understood as a generic conclusion for all coal-fired power plants. In this study, the dispersion modelling of natural radionuclides was carried out to assess the impact of continuous atmospheric releases from a selected coal plant. The natural radioactivity of the coal and the fly ash were measured and the dispersion was modelled by a Gaussian plume estimating the activity concentration at different heights up to a distance of 20 km in several wind directions. External and internal doses (inhalation and ingestion) and the resulting risk were calculated for the population living within 20 km from the coal plant. In average, the effective dose is lower than the ICRP’s limit and the risk is lower than the U.S. EPA’s limit. Therefore, in this situation, the considered exposure does not pose any risk. However, when considering the dispersion in the prevailing wind direction, these values are significant due to an increase of 232Th and 226Ra concentrations in 75% and 44%, respectively.

Radioactivity levels of 238U and 232Th decay series and related dose rates in the surroundings of a coal power plant using high resolution g-spectrometry

Gamma radiations measurements were carried out in the vicinity of a coal-fired power plant located in the southwest coastline of Portugal. Two different gamma detectors were used to assess the environmental radiation within a circular area of 20 km centred in the coal plant: a scintillometer (SPP2 NF, Saphymo) and a high purity germanium detector (HPGe, Canberra). Fifty urban and suburban measurements locations were established within the defined area and two measurements campaigns were carried out. The results of the total gamma radiation ranged from 20.83 to 98.33 counts per second (c.p.s.) for both measurement campaigns and outdoor doses rates ranged from 77.65 to 366.51 Gy/h. Natural emitting nuclides from the U-238 and Th-232 decay series were identified as well as the natural emitting nuclide K-40. The radionuclide concentration from the uranium and thorium series determined by gamma spectrometry ranged from 0.93 to 73.68 Bq/kg, while for K-40 the concentration ranged from 84.14 to 904.38 Bq/kg. The obtained results were used primarily to define the variability in measured environmental radiation and to determine the coal plant’s influence in the measured radiation levels. The highest values were measured at two locations near the power plant and at locations between the distance of 6 and 20 km away from the stacks, mainly in the prevailing wind direction. The results showed an increase or at least an influence from the coal-fired plant operations, both qualitatively and quantitatively.