Shalu Darshan

Expert Elicitation for the Judgment of Prion Disease Risk Uncertainties

There is a high level of uncertainty surrounding the potential for iatrogenic prion transmission through transplantation, medical instrument reuse, blood transfusion, and blood product use due to a lack of evidence-based research on this important risk issue. A group of specialists was enlisted to evaluate some of the knowledge gaps in this area using the “Classical Model,” a structured elicitation procedure for weighting and pooling expert judgment. The elicitation exercise was undertaken in March 2009 with 11 transmissible spongiform encephalopathy (TSE) experts who were first calibrated using a series of seed questions for which the answers are known; they were then asked to answer a number of target questions that are important for risk assessment purposes, but for which there remains high uncertainty at this time. The target questions focused on variant Creutzfeldt–Jakob disease (vCJD) prevalence, incubation times for vCJD, genetic susceptibility to prion disease, blood infectivity, prion reduction of blood and blood products, surgical instrument risks, and interspecies transmission of TSEs. The experts were also asked to perform pairwise risk rankings for 12 different potential routes of infection. Dura mater transplantation was seen as having the highest risk, while dental tissue grafts were viewed as presenting the lowest risk of iatrogenic transmission. The structured elicitation procedure provides a rational, auditable, and repeatable basis for obtaining useful information on prion disease risk issues, for which data are sparse.

Expert judgement and re-elicitation for prion disease risk uncertainties.

Much uncertainty surrounds transmission of transmissible spongiform encephalopathies (TSEs) through blood and blood derived products. A first expert elicitation with 14 experts was conducted in March 2008, and a second re-elicitation involving 11 experts was held a year later in March 2009. Both expert groups were calibrated using a series of seed questions for which values are known, and then were asked to provide their individual judgements on a set of seven target questions for which values are not known or have not been determined through conventional research. Questions dealing with uncertainty of TSE prevalence, genotype effects, susceptibility, and infectivity were answered by the experts. Elicitation can be used to obtain quantitative values for parameters affecting prion uncertainty gaps. We show that the method is amenable to re-elicitation over time allowing refinement of expert opinion as new knowledge becomes available for improved risk assessments where data gaps continue to exist.

Determinants of neurological disease: Synthesis of systematic reviews

&NA; Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome). Coffee and tea intake was associated with a decreased risk of onset of both dystonia and PD. Further understanding of the etiology of priority neurological conditions will be helpful in focusing future research initiatives and in the development of interventions to reduce the burden associated with neurological conditions in Canada and internationally. HighlightsWith population aging, the burden of neurological disease is increasing worldwide.Understanding the factors affecting the onset and progression of neurological disease through systematic review is essential for the development of strategies to reduce the burden of these diseases.Systematic review identified biological, demographic, environmental, genetic, lifestyle and pharmacological risk factors for specific neurological conditions.Several risk factors were associated with the onset of multiple conditions. Pesticides, for example, were associated with an increased risk of Alzheimers disease, amyotrophic lateral sclerosis, primary brain tumours, and Parkinsons disease.Helmet use was associated with a reduction in onset of neurotrauma, as well as all neurologic conditions for which head injury was a risk factor.The findings presented here should be viewed as provisional, pending a more in‐depth evaluation of the weight of evidence.Further research will also serve to fill current data gaps, particularly regarding risk factors for the progression of neurological disease.In the interim, the modifiable risk factors may be considered as potential candidates for the development of targeted interventions to reduce the burden of neurological disease in Canada and internationally.

Burden of neurological conditions in Canada

&NA; Neurological conditions are among the leading causes of disability in the Canadian population and are associated with a large public health burden. An increase in life expectancy and a declining birth rate has resulted in an aging Canadian population, and the proportion of age‐adjusted mortality due to non‐communicable diseases has been steadily increasing. These conditions are frequently associated with chronic disability and an increasing burden of care for patients, their families and caregivers. The National Population Health Study of Neurological Conditions (NPHSNC) aims to improve knowledge about neurological conditions and their impacts on individuals, their families, caregivers and health care system. The Systematic Review of Determinants of Neurological Conditions, a specific objective within the NPHSNC, is a compendium of systematic reviews on risk factors affecting onset and progression of the following 14 priority neurological conditions: Alzheimers disease (AD), amyotrophic lateral sclerosis (ALS), brain tumours (BT), cerebral palsy (CP), dystonia, epilepsy, Huntingtons disease (HD), hydrocephalus, multiple sclerosis (MS), muscular dystrophies (MD), neurotrauma, Parkinsons disease (PD), spina bifida (SB), and Tourettes syndrome (TS). The burden of neurological disease is expected to increase as the population ages, and this trend is presented in greater detail for Alzheimers and Parkinsons disease because the incidence of these two common neurological diseases increases significantly with age over 65 years. This article provides an overview of burden of neurological diseases in Canada to set the stage for the in‐depth systematic reviews of the 14 priority neurological conditions presented in subsequent articles in this issue. HighlightsNeurological conditions are among the leading causes of morbidity and mortality in Canada and internationally and affect people of all ages.The prevalence of neurological disease is expected to increase: the number of Canadians living with Alzheimers and Parkinsons disease is projected to double in 20 years.Adverse effects on physical and mental health can also result in negative socioeconomic impacts.Public health strategies to address the increasing burden of neurological disease need to be developed.

Using expert judgments to improve chronic wasting disease risk management in Canada

ABSTARCT Chronic wasting disease (CWD) is a neurodegenerative, protein misfolding disease affecting cervids in North America in epidemic proportions. While the existence of CWD has been known for more than 40 years, risk management efforts to date have not been able to curtail the spread of this condition. An expert elicitation exercise was carried out in May 2011 to obtain the views of international experts on both the etiology of CWD and possible CWD risk management strategies. This study presents the results of the following three components of the elicitation exercise: (1) expert views of the most likely scenarios for the evolution of the CWD among cervid populations in Canada, (2) ranking analyses of the importance of direct and indirect transmission routes, and (3) rating analyses of CWD control measures in farmed and wild cervids. The implications of these findings for the development of CWD risk management strategies are described in a Canadian context.

Identifying recent trends in nanomedicine development

Medical nanotechnology is a recent emerging field with the intention to improve human health. The creation and rapid expansion of nanomedicine as a new research field in the last decade is the result of nanotechnologys convergence with biology, genetics, biochemistry, chemistry, physics, pharmacology and medicine. Within nanomedicine, two major categories have emerged: diagnostics (imaging) and therapeutics (drug delivery). Each of these branches has several nanoparticle types that are actively under research and development. While nanomedicine research and use of various nanoparticles in new applications have been categorised and reviewed for their potential utility in medicine, there has been little context of the emerging trends within nanomedicine or how the field is progressing. This article presents an overview of the trends for nanomedicine that are developing over time as measured by examining peer review research literature and patent databases.

Expert elicitation on the uncertainties associated with chronic wasting disease

ABSTRACT A high degree of uncertainty exists for chronic wasting disease (CWD) transmission factors in farmed and wild cervids. Evaluating the factors is important as it helps to inform future risk management strategies. Expert opinion is often used to assist decision making in a number of health, science, and technology domains where data may be sparse or missing. Using the “Classical Model” of elicitation, a group of experts was asked to estimate the most likely values for several risk factors affecting CWD transmission. The formalized expert elicitation helped structure the issues and hence provide a rational basis for estimating some transmission risk factors for which evidence is lacking. Considered judgments regarding environmental transmission, latency of CWD transmission, management, and species barrier were provided by the experts. Uncertainties for many items were determined to be large, highlighting areas requiring more research. The elicited values may be used as surrogate values until research evidence becomes available.

Lessons learned from bovine spongiform encephalopathy for the future management of the Canadian cattle industry

Globally, Canada is only a minor beef producing country, and yet ranks fourth among countries exporting beef products. That fact alone shows considerable market vulnerability. When coupled with dependence on corporate-owned slaughter capacity and heavy reliance on only one export market (the USA), that vulnerability is magnified. Economic losses from BSE in Canada following the occurrence of the first domestic case in May 2003 were disproportionately incurred by the farm producers. The debate around enhanced BSE testing to regain lost markets highlighted the lack of influence of farm producers on BSE risk management policy development, and the inability of Canadian groups such as the Canadian Beef Export Federation to reduce market vulnerability by accessing new markets. In future, government policies should promote and support market diversification. One possible approach to reduce market vulnerability would be to move towards a New Zealand style producer-owned model.

Prionet Canada: a network of centres of excellence for research into prions and prion diseases.

PrioNet Canadas strength in basic, applied, and social research is helping to solve the food, health safety, and socioeconomic problems associated with prion diseases. Prion diseases are transmissible, fatal neurodegenerative diseases of humans and animals. Examples of prion diseases include bovine spongiform encephalopathy (BSE, commonly known as “mad cow” disease), Creutzfeldt–Jakob disease in humans, and chronic wasting disease (CWD) in deer and elk. As of March 31, 2008, PrioNets interdisciplinary network included 62 scientific members, 5 international collaborators, and more than 150 students and young professionals working in partnership with 25 different government, nongovernment, and industry partners. PrioNets activities are developing strategies based on a sustained, rational approach that will mitigate, and ultimately control, prion diseases in Canada.

Challenges in managing the risks of chronic wasting disease

This article summarises efforts at disease surveillance and risk management of chronic wasting disease (CWD). CWD is a fatal neurodegenerative disease of cervids and is considered to be one of the most contagious of the transmissible spongiform encephalopathies (TSEs). Evidence has demonstrated a strong species barrier to CWD for both human and farm animals other than cervids. CWD is now endemic in many US states and two Canadian provinces. Past management strategies of selective culling, herd reduction, and hunter surveillance have shown limited effectiveness. The initial strategy of disease eradication has been abandoned in favour of disease control. CWD continues to spread geographically in North American and risk management is complicated by the presence of the disease in both wild (free-ranging) and captive (farmed) cervid populations. The article concludes that further evaluation by risk managers is required for optimal, cost-effective strategies for aggressive disease control.