Search

This thesis explores the historical uptake, impact, performance and outcomes of prenatal screening for fetal aneuploidy in Western Australia. New models were developed to evaluate the economic and clinical impact of new non-invasive cell free DNA (NIPT cfDNA) testing. NIPT can improve the detection of fetal Down syndrome and reduce invasive diagnostic testing and procedure related loss. These studies provide evidence to support the translation of NIPT into national public health policy.

© 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Objective: To provide data on how screen-positive and detection rates of first trimester prenatal screening for fetal Down syndrome vary with changes in the risk cut-off and maternal age to inform contingency criteria for publicly funded noninvasive prenatal testing. Materials and Methods: First trimester screening and diagnostic data were collected for all women attending for first trimester fetal aneuploidy screening in Western Australia between 2005 and 2009. Prenatal screening and diagnostic data were linked to pregnancy outcomes, including data from the Midwives' Notification System and the Western Australian Registry of Developmental Anomalies. The prevalence of Down syndrome and performance of screening by risk cut-off and/or for women >35 years were analysed. Results: The current screening risk cut-off of 1:300 has screen-positive and detection rates of 3.5% and 82%. The screen-positive rate increases by 0.7-0.8% for each 100 point change in risk, up to 19.2% at 1:2500 (96% detection rate). Including all women >35 years as screen positive would increase the screen-positive rate and detection rates to 30.2% and 97.2%. Conclusion: Variation in screening risk cut-off and the use of maternal age to assess eligibility for noninvasive testing could significantly impact the demand for, and cost of, the test. A contingent first trimester screening approach for risk assessment is superior to the use of a combination of screening and maternal age alone. These data will inform decisions regarding the criteria used to determine eligibility for publicly funded noninvasive prenatal testing.

Background: Mandatory fortification of wheat flour for bread-making was introduced in Australia in September 2009, toassist in the prevention of neural tube defects (NTD). NTD are twice as common in Aboriginal compared with non-Aboriginal infants, and folate levels are lower in the Aboriginal population.Aims: This study was undertaken to compare folate status and NTD in the Aboriginal population before and afterfortification.Methods: Postfortification, 95 Aboriginal men and nonpregnant women aged 16–44 years in metropolitan and regionalWestern Australia (WA) completed a rapid dietary assessment tool and had blood taken to measure red cell folate.Measures were compared with prefortification values obtained in an earlier study using the same methods. Data on NTDin Aboriginal infants were obtained from the WA Register of Developmental Anomalies.Results: No participant was folate de ficient. The mean red cell folate increased after fortification to 443 ng/mL for malesand 567 ng/mL for females. The mean difference between red cell folate after fortification compared with before was129 ng/mL for males (95% CI 81–177); t = 5.4; P < 0.0001) and 186 ng/mL for females (95% CI 139–233); t = 7.9;P < 0.0001). Most participants ate forti fied shop-bought bread at least weekly, resulting in an estimated additional folateintake per day of 178 (males) and 145 (females) dietary folate equivalents. NTD prevalence fell by 68% followingfortification (prevalence ratio 0.32 (CI 0.15–0.69)).Conclusions: The population health intervention of mandatory fortification of wheat flour for bread-making has had thedesired effect of increasing folate status and reducing NTD in the Australian Aboriginal population.

Background: The aim of newborn bloodspot screening (NBS) is to identify rare genetic and non - genetic conditions in children soon after birth in order to commence therapies that prevent the development of progressive, serious, and irreversible disabilities. Universal NBS program me s have been implemented in most countries, with minor adaptations to target conditions most relevant to the local healthcare environment. Aims: In this article, we describe the initiative s of international and Australian governments to develop policies to address the expansion of NBS in their healthcare systems. Methods: We have reviewed published public policies and literature to formulate recommendations based on clinical, social, legal, and ethical principles to inform a national governance and policy framework for Australia. Results: Australia n policy makers have been slow to develop a coordinated plan. While the experience from other governments can guide our national policy, there are specific areas that require further consideration by Australian health experts. Key reforms involve the separation of policy and operational activities, multidisciplinary decision - making and oversight by the Australian Health Ministers’ Advisory Council for policy direction. Conclusion: A formal national policy framework will guide the coordination of NBS service s that can adapt to the needs of Australian children and families.

Purpose - To describe cancer prevalence and hospital service utilization by prevalent cancer patients in Western Australia from 1992 to 2011. Methods - This study was a population-based cohort study using the Western Australia (WA) Cancer Registry (1982 to 2011) as the source of incident cancer cases. These data were linked to mortality (1982 to 2011) and hospital morbidity (1998 to 2011) records via the WA Data Linkage System to ascertain complete and limited-duration prevalence and cancer-related hospitalizations over time. Prevalence rates were calculated using estimated residential population data from the Australian Bureau of Statistics. Results - In 2011, one in every 27 people living in WA had been diagnosed with cancer at some time in their lifetime, and one in 68 had been diagnosed within the previous five years. Between 1992 and 2011, complete cancer prevalence in Western Australia increased by a magnitude of 2.5-fold. Forty-five and 44% of the increase in complete cancer prevalence in males and females between 1992 and 2011 can be attributed to prostate and breast cancer, respectively. The absolute number of cancer-related bed days increased 81 and 74% in males and females, respectively, diagnosed within one year, between 1998 and 2011. Conclusions - The prevalence of cancer and the burden it places on hospitals continues to rise, demanding ongoing efforts to prevent cancer through modifiable risk factors and better, more efficient use of health resources. Steps should to be taken to understand and address overdiagnosis and overtreatment

Aim: To investigate using a Western Australian (WA) genealogical database for the identification of single gene and chromosome disorders among families. Method: Hospital admissions for single gene and chromosome disorders recorded during 2000–2006 were identified from the WA Hospital Morbidity Data System. The proportion of these conditions occurring in family groups was then identified using genealogical links created through the WA Family Connections Genealogical Project. Results: There were 216 family clusters among 11,303 people who were recorded as having a genetic or chromosomal disorder on their hospital admission record. The most common single gene conditions found to occur in multiple family members included blood clotting disorders such as Factor VIII deficiency and Von Willebrand’s disease, followed by cystic fibrosis, myotonic dystrophies, neurofibromatosis, tuberous sclerosis, and osteogenesis imperfecta. Discussion: Single gene disorders most commonly occurring in multiple family members have been identified using the WA Family Connections Genealogical Project. These disorders reflect the most common single gene disorders requiring hospital admission, but which are not fatal before reproductive age and do not result in a loss of fertility. They are also restricted to disorders with earlier onset, as the WA Family Connections Genealogical Project currently covers 2–3 of the most recent generations. This study demonstrates the utility of record linkage genealogies to identify kindred with genetic disorders, offering a rich resource of information for focused genetic epidemiological research.

Background: Public deliberation is recommended for obtaining citizeninput to policy development when policies involve contested ethicaldimensions, diverse perspectives on how to trade-off competing publicinterests and low public awareness of these perspectives. Several normshave been proposed for the design of deliberative methods. Evidence isscarce regarding whether such norms are achievable in practice.Purpose: This paper refers to principles of deliberative democracytheory to describe a deliberative public forum on biobanking.Practical challenges and contextual facilitators of achieving deliberativeideals are discussed, along with factors that influenced use ofthe forum output in policy development.Method: The forumranfor4 daysovertwoweekends inPerth,WesternAustralia. Key methodological features were socio-demographic stratificationto randomly recruit a mini-public of citizens for discursiverepresentation,provisionof informationinclusiveofdiverseperspectivesand framed for difference, provision of a fair way for reasoning andcollectivedecisionmakingandadoptionofprocessestoachievepublicity,accountability and independence from undue institutional influence.Results: Most design principles were achieved in practice, with thefundamental exception of representativeness. Factors influencingthese outcomes, and the use of deliberated outputs to develop policy,included institutional characteristics, the design involvement ofdeliberative experts and quality of the outputs when compared toother consultation methods.Conclusions: Public deliberations can achieve design ideals andinfluence (ethics-based) public health policy. The representation ofhard to reach citizens and their views needs further consideration,particularly as this relates to the procedural legitimacy of ethicalanalyses and the just inclusion of deliberative citizen advice withinthe broader policy-making process.

Background: Deliberative public engagement is recommendedfor policy development in contested ethical areas.Scholars provide little guidance on how deliberative outputscan be translated to policy. This paper describes the processeswe undertook to design a deliberative public forum forcitizens to develop recommendations on biobanking thatwere adopted as health policy. Method: The 4-day forum,held in 2008 in Perth, Western Australia, was designed in collaborationwith academic experts. Deliberant recommendationswere recorded in a formal report presented to policymakers.Deliberations were audio-taped and transcribed.Translation involved transcript analyses, comparison of recommendationsto other stakeholder views and post-forumconsultations. Results: Sixteen citizens made recommendationson ethical, legal and social issues related to biobanking.Most recommendations were translated into biobankingguidelines, with which Western Australia government healthagencies must comply. The value of deliberative public participationin policy-making was most evident when tradeoffsin competing interests, hopes and concerns were required. Translation issues included the impact of a smallnumber of participants with limited socio-demographic diversityon procedural and policy legitimacy. Conclusions:Assessing the sufficiency of diversity in citizen representationwas central to the deliberation-to-translation process.Institutional context facilitated the uptake of deliberationand translation processes. The use of these processes influencedpolicy substance and credibility among stakeholdersand contributed to the state government directive that policycompliance be mandatory. We urge others to publish deliberation-to-translation processes so that best-practicesmay be identified.

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that causes marked elevation in plasma cholesteroland premature coronary heart disease. There are at least 45,000 people with FH in Australia and New Zealand, but the vast majority remainsundetected and those diagnosed with the condition are inadequately treated.To bridge this major gap in coronary prevention the FH Australasia Network (Australian Atherosclerosis Society) has developed a consensusmodel of care (MoC) for FH. The MoC is based on clinical experience, expert opinion, published evidence and consultations with a widespectrum of stakeholders, and has been developed for use primarily by specialist centres intending starting a clinical service for FH. This MoCaims to provide a standardised, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes.The MoC for FH is presented as a series of recommendations and algorithms focusing on the standards required for the detection, diagnosis,assessment and management of FH in adults and children. The process involved in cascade screening and risk notification, the backbonefor detecting new cases of FH, is detailed. Guidance on treatment is based on risk stratifying patients, management of non-cholesterol riskfactors, safe and effective use of statins, and a rational approach to follow-up of patients. Clinical and laboratory recommendations are givenfor genetic testing. An integrative system for providing best clinical care is described.This MoC for FH is not prescriptive and needs to be complemented by good clinical judgment and adjusted for local needs and resources.After initial implementation, the MoC will require critical evaluation, development and appropriate modification.