Browsing by Issue Date, starting with "2022-04-19"
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- Measurement error in self-reported risk factors for cardiovascular disease: results from the first Portuguese National Health Examination SurveyPublication . Kislaya, Irina; Nunes, Baltazar; Tolonen, HannaABSTRACT - Accurate data on cardiovascular disease risk factors are essential for the design and evaluation of public health policies. Currently, self-reported data on hypertension and hypercholesterolemia constitute a primary data source for population health monitoring at European and national level. This thesis aimed to evaluate accuracy of self-reported data on hypertension and hypercholesterolemia, to quantify, and to correct measurement error bias using data from the first Portuguese Health Examination Survey (INSEF). Measurements of blood pressure and total cholesterol concentrations were used as gold-standards to estimate measurement error bias, sensitivity and specificity of selfreports, investigate error impact on outcome-exposure associations and illustrate application of multiple imputation for bias correction. Despite all the efforts to limit the error through design and fieldwork procedures, self-reported data underestimated prevalence of hypertension and hypercholesterolemia in Portuguese population. Being unequally distributed among socioeconomic subgroups, measurement errors resulted in underestimation of socioeconomic inequalities in younger and overestimation in older age groups. The study results highlight the importance of measurement error bias analysis when using self-reported data. Results from multiple imputation show the approach feasibility for measurement error bias adjustment in prevalence estimates and outcome-exposure associations when individual-level validation data is available. Health statistics on cardiovascular disease risk factors derived from self-reports should be used with caution. Integration of objective measurements in large-scale health surveys will improve the accuracy of epidemiological information on hypertension and hypercholesterolemia. RESUMO - Informação epidemiológica de qualidade sobre os fatores de risco para doenças cardiovasculares é essencial para formulação e avaliação das políticas de saúde. Atualmente, os dados autoreportados sobre hipertensão e hipercolesterolemia constituem uma fonte primária de informação para monitorização da saúde da população a nível europeu e nacional. O objetivo desta tese é avaliar a qualidade dos dados autoreportados sobre hipertensão e hipercolesterolemia, quantificar e corrigir o viés de medição assocados à informação autoreportada utilizando os dados do primeiro Inquérito Nacional de Saúde com Exame Físico (INSEF). Considerando medições diretas da tensão arterial e do colesterol total como padrão, estimou-se a sensibilidade e a especificidade dos dados autoreportados, avaliou-se o impacto do erro da medição nas estimativas da prevalências e medidas de associação. Adicionalmente, o trabalho desenvolvido ilustrou a aplicação de imputação múltipla para correção de viés de medição. Os dados autoreportados subestimaram a prevalência de hipertensão e hipercolesterolemia na população portuguesa comparativamente às medições diretas. O grau diferencial de viés por estatuto socioeconómico leva a subestimação das desigualdades socioeconómicas nos mais jovens e superestimação nos grupos com a idade mais avançada. Os resultados do estudo realçam a importância da análise de viés associados à medição na utilização dos dados autoreportados. Os resultados da imputação múltipla indicam a viabilidade desta estratégia no ajuste das estimativas da prevalência e medidas de associação quando estão disponíveis a nível individual os dados das medições diretas. As estatísticas de saúde derivadas dos dados autoreportados devem ser usadas com cautela. A integração das medições objetivas nos inquéritos de saúde de base populacional permitirá obter informação epidemiológica de melhor qualidade para monitorização da hipertensão e hipercolesterolemia.
- Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses ExamplePublication . Santos, Juliana Inês; Gonçalves, Mariana; Matos, Liliana; Moreira, Luciana; Carvalho, Sofia; Prata, Maria João; Coutinho, Maria Francisca; Alves, SandraOver recent decades, the many functions of RNA have become more evident. This molecule has been recognized not only as a carrier of genetic information, but also as a specific and essential regulator of gene expression. Different RNA species have been identified and novel and exciting roles have been unveiled. Quite remarkably, this explosion of novel RNA classes has increased the possibility for new therapeutic strategies that tap into RNA biology. Most of these drugs use nucleic acid analogues and take advantage of complementary base pairing to either mimic or antagonize the function of RNAs. Among the most successful RNA-based drugs are those that act at the pre-mRNA level to modulate or correct aberrant splicing patterns, which are caused by specific pathogenic variants. This approach is particularly tempting for monogenic disorders with associated splicing defects, especially when they are highly frequent among affected patients worldwide or within a specific population. With more than 600 mutations that cause disease affecting the pre-mRNA splicing process, we consider lysosomal storage diseases (LSDs) to be perfect candidates for this type of approach. Here, we introduce the overall rationale and general mechanisms of splicing modulation approaches and highlight the currently marketed formulations, which have been developed for non-lysosomal genetic disorders. We also extensively reviewed the existing preclinical studies on the potential of this sort of therapeutic strategy to recover aberrant splicing and increase enzyme activity in our diseases of interest: the LSDs. Special attention was paid to a particular subgroup of LSDs: the mucopolysaccharidoses (MPSs). By doing this, we hoped to unveil the unique therapeutic potential of the use of this sort of approach for LSDs as a whole.