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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

A microsimulation study of the benefits and costs of screening for colorectal cancer

Stevenson, Christopher Eric, Chris.Stevenson@aihw.gov.au January 2001 (has links)
This thesis examines the benefits and costs of screening for colorectal cancer in the context of an organised population screening programme. It uses microsimulation modelling to derive an optimally cost-effective screening protocol for various combinations of the available screening tests. ¶ First a mathematical model for the natural history of colorectal cancer is derived, based on analyses of Australian population and hospital-based cancer registries combined with data from published studies. Then a model for population based screening is derived based mainly on data from published screening studies, including the four major published randomised controlled trials of faecal occult blood test (FOBT) screening. These two models are used to simulate the application of a screening programme to the Australian population. The simulations are applied to a period of 40 years following 1990 (the study’s base year), with both costs and benefits discounted back to the base year at an annual rate of 3%.¶ The models are applied to simulating a population screening programme based on FOBT with a colonoscopy follow up of positive tests. This simulation suggests that the optimal application of such a programme would be to offer annual screening to people aged 50 to 84 years. Such a programme would lead to a cumulative fall in years of life lost to colorectal cancer (YLL) of 28.5% at a cost per year of life saved (YLS) of $8,987. These costs and benefits are consistent with those arising from other currently funded health interventions. They are also consistent with the cost per YLS which Australian governments appear willing to pay for health interventions when justified on the basis of cost-effectiveness. The fall in colorectal cancer deaths from this screening programme should be first detectable by a national monitoring system after around three years of screening. However the full benefits from screening would not be realised before around 30 years of screening.¶ These simulations are based on the standard guaiac FOBT, but the results suggest that significant cost-effective gains could be made by using the newer immunochemical FOBT. Further cost-effect gains could be made by offering sigmoidoscopy every five years in addition to annual FOBT.¶ The models are then applied to simulating population screening programmes using colonoscopy and sigmoidoscopy as primary screening tools. Offering colonoscopy every ten years to all people aged from 45 to 85 leads to an overall fall in cumulative YLL of 37.6%, at a cost of $15,585 per YLS. Offering sigmoidoscopy every three years to all people aged 40 to 85 leads to an overall fall in cumulative YLL of 29.1%, at a cost of $4,862 per YLS. Both of these cost and benefit results are also consistent with the cost per YLS which Australian governments appear willing to pay. The fall in deaths with colonoscopy screening would also be detectable after three years of screening but the fall with sigmoidoscopy screening would not be detectable until after six years of screening. Sigmoidoscopy would need around 35 years of screening to reach its potential gains while colonoscopy screening would not reach its full potential during the 40 year screening period.¶ Finally the models are applied to targeting people at higher risk of cancer. The results show that offering colonoscopy every five years to people at higher risk because of a family history of colorectal cancer is a cost-effective addition to the annual FOBT screening programme.¶ An earlier version of chapter two of this thesis has been published as Stevenson CE 1995. Statistical models for cancer screening. Statistical Methods in Medical Research; 4: 19–23.¶ An expanded version of chapter two, along with parts of chapter one, has been published as Stevenson CE 1998. Models of screening. In: Encyclopedia of Biostatistics. Armitage P, Colton T, eds. John Wiley and Sons Ltd, pp 3999–4022.
2

Metabolite Profiling for New Advances in Biomarker Discovery, Cystic Fibrosis Screening and Drug Surveillance

DiBattista, Alicia January 2018 (has links)
The role of biological markers (biomarkers) in public health, pediatric medicine and clinical toxicology cannot be understated. Clinically validated biomarkers used in newborn screening (NBS) serve to detect individuals at risk for a disease in the population, pre-symptomatically diagnose affected neonates early in life and/or accurately predict disease progression and treatment responses to therapy. However, there is urgent need for the discovery of more specific biomarkers that can improve screening accuracy in a high throughput, cost-effective yet ethical manner. The major objectives of this thesis were to develop innovative nontargeted metabolite profiling methodologies based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) for early detection of treatable genetic diseases, as well as comprehensive surveillance of drugs of abuse (DoA) in high risk subjects. Chapter II introduces a multiplexed MSI-CE-MS strategy for confirmatory testing of known biomarkers for various inborn errors of metabolism from a dried blood spot (DBS) that was rigorously validated using proficiency test specimens from Centres for Disease Control and Prevention (CDC) and authentic neonatal samples from Newborn Screening Ontario (NSO) with quality assurance. Additionally, MSI-CE-MS together with temporal signal pattern recognition revealed for the first time a novel class of pathognomonic marker elevated in galactosemia, namely N-galactated amino acids. Chapter III describes an untargeted metabolomic study to discover biomarkers of cystic fibrosis (CF) to reduce the high false positive rate and widespread carrier identification by current two-tiered NBS algorithms that rely on genetic testing. A panel of metabolites from retrospective DBS specimens, including several amino acids, ophthalmic acid and an unknown peptide, allowed for differentiation of asymptomatic CF neonates from screen-positive yet unaffected carriers and transient hypertrypsinogenemic cases. Chapter IV develops and validates a high throughput MSI-CE-MS assay for rapid screening for DoA and their metabolites in human urine with improved specificity and broad spectrum coverage as compared to classic targeted immunoassays. This method can also applied to ensure compliance, drug efficacy and patient safety while detecting for potential substitution or adulteration when using high resolution MS/MS. In summary, this thesis contributes an innovative methodology and data workflow for biomarker discovery for improved neonatal screening of rare genetic diseases in the population, which was also applied for more effective drug surveillance strategies in public health given the alarming worldwide opioid crisis. / Thesis / Doctor of Philosophy (PhD)
3

L’évaluation des impacts d’un dépistage de porteurs de maladies génétiques : la perspective des personnes visées par le dépistage

Bussod, Ilona 08 1900 (has links)
Au Québec, les personnes ayant une ascendance géographique des régions du Saguenay-Lac- Saint-Jean, de Charlevoix et de la Haute-Côte-Nord ont une prévalence plus élevée que le reste de la population québécoise d’être porteurs de certaines maladies héréditaires récessives. Depuis 2018, une offre de tests de porteurs en ligne est proposée par le Ministère de la Santé et des Services Sociaux du Québec pour quatre maladies autosomiques récessives : l’acidose lactique congénitale, la tyrosinémie héréditaire de type 1, la neuropathie sensitivomotrice avec ou sans agénésie du corps calleux et l’ataxie récessive spastique de Charlevoix-Saguenay. Ce même dépistage peut être offert en contexte clinique, chez des adultes éligibles lors de consultations en lien avec un désir de grossesse ou une grossesse en cours. Les objectifs de ce projet de recherche sont (1) de décrire l’expérience des patients ayant eu accès au dépistage de porteurs en contexte clinique et (2) d’identifier, analyser et comparer les enjeux éthiques soulevés par un dépistage de porteurs dans le cadre d’un programme structuré versus un dépistage de porteurs en contexte clinique. Pour ce faire, une série de questionnaires destinée aux patients auxquels le dépistage a été offert lors d’un rendez-vous en clinique a été mise en place et une analyse éthique à l’aide d’un cadre éthique de santé publique a été réalisée. À la lumière de ce projet, l’autonomie décisionnelle du patient est mise de l’avant. Des pistes de réflexion ainsi que des recommandations ont été développées afin de répondre au mieux aux besoins des personnes qui considèrent avoir recours à des tests de porteurs. / In Quebec, people with geographical ancestry from the Saguenay-Lac-Saint-Jean, Charlevoix and Haute-Côte-Nord regions have a higher prevalence than the rest of the Quebec population of being carriers of specific recessive hereditary diseases. Since 2018, online carrier testing has been offered by the Ministère de la Santé et des Services Sociaux du Québec for four autosomal recessive diseases: congenital lactic acidosis, hereditary tyrosinemia type 1, sensitivomotor neuropathy with or without agenesis of the corpus callosum and Charlevoix-Saguenay recessive spastic ataxia. This same screening can be offered in a clinical setting, to eligible adults during consultations related to a pregnancy desire or a pregnancy in progress. The objectives of this research project are (1) to describe the experience of patients who have had access to carrier screening in a clinical setting and (2) to identify, analyze and compare the ethical issues raised by carrier screening in a structured program versus carrier screening in a clinical setting. To this end, a series of questionnaires was administered to patients who were offered screening during a clinic appointment, and an ethical analysis was carried out using a public health ethics framework. In the light of this project, the patient's decision-making autonomy is emphasized. A number of ideas and recommendations have been developed to best meet the needs of people considering carrier testing.

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