Cost-Effectiveness of Personalized Screening for Colorectal Cancer Based on Polygenic Risk and Family History.

Background: There is growing evidence for personalizing colorectal cancer screening based on risk factors. We compared the cost-effectiveness of personalized colorectal cancer screening based on polygenic risk and family history to uniform screening.

Methods: Using the MISCAN-Colon model, we simulated a cohort of 100 million 40-year-olds, offering them uniform or personalized screening.

Initial evaluation of thyroid dysfunction - Are simultaneous TSH and fT4 tests necessary?

Objective: Guidelines for thyroid function evaluation recommend testing TSH first, then assessing fT4 only if TSH is out of the reference range (two-step), but many clinicians initially request both TSH and fT4 (one-step). Given limitations of previous studies, we aimed to compare the two-step with the one-step approach in an unselected community-dwelling study population, and develop a prediction score based on clinical parameters that could identify at-risk patients for thyroid dysfunction.

Design: Cross-sectional analysis of the population-based Busselton Health Study.

The log TSH-free T4 relationship in a community-based cohort is nonlinear and is influenced by age, smoking and thyroid peroxidase antibody status.

Background: The TSH-T4 relationship was thought to be inverse log-linear, but recent cross-sectional studies of selected populations report a complex, nonlinear relationship. The TSH-T4 relationship has not been evaluated in an unselected, community-based cohort, and there are limited data regarding clinical factors which affect it.

Objective: To analyse the TSH-free T4 relationship in a community-based cohort.

Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals.

Age-related changes in thyroid function: a longitudinal study of a community-based cohort.

Context: In cross-sectional studies, serum TSH concentrations increase with age. This has not been examined longitudinally, and it is uncertain whether the TSH increase reflects healthy aging or occult thyroid failure.

Methods: We measured serum TSH, free T(4), thyroid peroxidase, and thyroglobulin antibodies in 1100 participants in the 1981 and 1994 Busselton Health Surveys and derived a reference group of 908 individuals without thyroid disease or thyroid antibodies.

Significant association between thyroid hormones and erythrocyte indices in euthyroid subjects.

Objective: Hypothyroidism and hyperthyroidism are each associated with anaemia, but relationships between thyroid function and erythrocyte indices in euthyroid subjects have not been examined. The aim of this study was to examine these relationships in a community-based cohort.

Design, Subjects And Measurements: Linear regression models with free T4, free T3 and TSH as predictors of erythrocyte indices and serum iron parameters were fitted to data from a cohort of 1179 participants in the 1994 Busselton health study and a subset of 1011 euthyroid participants.

Investigations of thyroid hormones and antibodies based on a community health survey: the Busselton thyroid study.

Objective: Overt or subclinical thyroid dysfunction is common within the community, yet the significance of subtle anomalies in thyroid function tests remains contentious. The aims of this study were to: (a) establish reference intervals for serum-free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid antibodies (antithyroperoxidase, TPOAb and antithyroglobulin, TgAb) in the Busselton community of south-western Western Australia; and (b) determine the prevalence of thyroid hormone anomalies in this community.

Subjects And Design: In 1981, 2115 adults residing in Busselton participated in a cross-sectional health survey that involved blood collection and a questionnaire on lifestyle and general health history.

Human gene patents: the possible impacts on genetic services healthcare.

The patent system has been seen as a critical factor driving innovation in clinical medicine, particularly in medical devices and diagnostic assays. The licence terms and business model proposed by Myriad Genetics Inc. for testing the hereditary breast cancer susceptibility genes BRCA1 and BRCA2 could stifle innovation (particularly if other companies adopt similar business models), and are likely to limit the ability to provide high quality public genetic testing services in Australia.

Distribution and metabolism of topically applied progesterone in a rat model.

This study investigated the transdermal uptake and subsequent tissue distribution of [(3)H]progesterone applied in a commercially available progesterone cream in a rat model. Concentrations of lipid- and water-soluble metabolites of [(3)H]progesterone were also measured in plasma, urine and selected tissues (uterus, liver, kidney, salivary gland) 3 h after its topical application. Female rats were ovariectomized and adrenalectomized to remove all endogenous progesterone, and 4 weeks later were anaesthetized and 150 mg Pro-Feme cream (containing progesterone 3.