Axisa, B, Loftus, IM, Naylor, AR, Goodall, S, Jones, L, Bell, PRF & Thompson, MM 2002, 'Prospective, Randomized, Double-Blind Trial Investigating the Effect of Doxycycline on Matrix Metalloproteinase Expression Within Atherosclerotic Carotid Plaques', Stroke, vol. 33, no. 12, pp. 2858-2864.
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Background and Purpose—Elevated levels of matrix metalloproteinases (MMPs), particularly MMP-1 and MMP-9, have been implicated in plaque rupture. It has been suggested that inhibition of MMPs may stabilize vulnerable atherosclerotic plaques and improve clinical outcome. The aim of the study was to investigate the ability of doxycycline, a nonspecific MMP inhibitor, to reduce MMP concentration in carotid atheroma.Methods—The study design was a prospective, double-blind randomized trial. One hundred patients requiring carotid endarterectomy were randomized to receive 200 mg/d doxycycline or placebo for 2 to 8 weeks before surgery. During endarterectomy, carotid plaques were retrieved. The concentrations of MMPs and doxycycline were determined in the atherosclerotic tissue by enzyme-linked immunosorbent assay and high-performance liquid chromatography, respectively. Clinical events were recorded, as was the rate of preoperative embolization (transcranial Doppler).Results—Analysis of endarterectomized specimens demonstrated a mean doxycycline concentration of 6.0 μg/g wet weight in treated patients. Administration of doxycycline significantly reduced the concentration of MMP-1 in carotid plaques from a mean of 14.8 to 10.3 ng/100g wet weight (P=0.038). This difference was due to decreased MMP-1 transcript (P<0.001). There was no difference in any other MMP (MMP-2, -3, or -9) or tissue inhibitor of matrix metalloproteinases–1 or –2.Conclusions—Doxycycline penetrated atherosclerotic plaques with acceptable tissue levels. This resulted in a reduction in MMP-1 concentration because of decreased expression.
Bridges, JFP, Stewart, M, King, MT & van Gool, K 2002, 'Adapting portfolio theory for the evaluation of multiple investments in health with a multiplicative extension for treatment synergies', The European Journal of Health Economics, vol. 3, no. 1, pp. 47-53.
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Portfolio theory is central to the analysis of risk in many areas of economics but is seldom used appropriately in health economics. This contribution examines the use of portfolio theory in the context of cost-effectiveness analysis (CEA). A number of modifications are needed to apply portfolio analysis to the economic evaluation of health care interventions. First, the method of reporting the results of a CEA, and consequently some of the underlying assumptions, needs to be modified. Second, portfolio theory needs to be expressed in terms of effects on individuals aggregated to a population. Finally, one needs to allow for the possibility of synergy between the various health interventions. This paper derives a general formula for a portfolio of health care interventions that allows for synergies between interventions where the population effects are aggregated from individual effects. A number of special cases are also derived to highlight the nature of the formulation of the modified portfolio theory. We conclude that, while modified portfolio theory adds a theoretical foundation to health care evaluations, it may not be operational until estimates of the correlation between interventions are available, and the question of uncertainty is resolved in health care evaluation. Also, while a synergy may be present at the individual level, when aggregated over a large population it may not be significant given the standard assumption of constant returns to scale.
Crowther, M, Goodall, S, Jones, JL, Bell, PRF & Thompson, MM 2002, 'Localization of matrix metalloproteinase 2 within the aneurysmal and normal aortic wall', British Journal of Surgery, vol. 87, no. 10, pp. 1391-1400.
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Abstract Background Current research has shed new light on the role of matrix metalloproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the production of the MMP-2–MT1-MMP–tissue inhibitor of metalloproteinases (TIMP) 2 system within the wall of aortic aneurysms and in age-matched control arterial tissue. Methods Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression of MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hybridization and in situ zymography. Results All components of the MMP-2–TIMP-2–MT1-MMP enzyme system were detected in the arterial wall of both aneurysm and control samples, specifically in the medial tissue. The enzymes co-localized with medial smooth muscle cells. Gelatinolytic activity was localized to elastin fibres in normal and aneurysmal aorta. Conclusion The presence of MT1-MMP within the media of arterial tissue suggests a powerful pathway for the activation of MMP-2. The localization of the MMP-2–TIMP-2–MT1-MMP enzyme system to the medial laye...
De Abreu Lourenco, R & Wonder, M 2002, 'More than just currency conversion may be needed', British Medical Journal, vol. 17.
Glasziou, PP, Eckermann, SD, Mulray, SE, Simes, RJ, Martin, AJ, Kirby, AC, Hall, JP, Caleo, S, White, HD & Tonkin, AM 2002, 'Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?', MEDICAL JOURNAL OF AUSTRALIA, vol. 177, no. 8, pp. 428-434.
Goodall, S, Crowther, M, Bell, PR & Thompson, MM 2002, 'The association between venous structural alterations and biomechanical weakness in patients with abdominal aortic aneurysms', Journal of Vascular Surgery, vol. 35, no. 5, pp. 937-942.
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Objective: Abdominal aortic aneurysms (AAAs) are associated with generalized arterial dilation, torturosity, and altered matrix composition, which suggests a generalized systemic weakness throughout the entire vasculature. The aim of this study was to determine whether this phenomenon was present in the venous tissue of patients with AAA. Methods: A segment of inferior mesenteric vein was harvested from patients who underwent aneurysm repair (n = 11) or colectomy for diverticulosis (n = 11; control). Matrix composition of the vessel was determined with stereology, and dimensions were measured with a computerized image analysis system. Stress-strain measurements were calculated with elongation of inferior mesenteric vein tissue with a tensile-testing machine. Results: Histologic examination results showed fragmentation of elastin fibers within the medial layer of venous tissue obtained from patients with AAA. The medial elastin content in tissue from patients with aneurysms was 19.4%, compared with 26.8% in the control group (P = .018). Mechanical test results revealed a significant reduction in the tensile strength from 2.885 MPa in the control group to 1.405 MPa in the AAA group (P = .007). This reduction corresponded with a significant reduction of 59% in the stiffness of the vessel, with the mean Young's modulus of elasticity in the AAA group being 2.72 MPa, compared with 5.361 MPa in the control group (P = .0005). Conclusion: Reduction in tensile strength and stiffness in venous tissue from patients with AAA was associated with disruption and reduction of the elastin content of the vein wall. These changes are analogous to those observed in the arterial aneurysmal wall and confirm the systemic nature of this disorder.
Goodall, S, Porter, KE, Bell, PR & Thompson, MM 2002, 'Enhanced Invasive Properties Exhibited by Smooth Muscle Cells are Associated with Elevated Production of MMP-2 in Patients with Aortic Aneurysms', European Journal of Vascular and Endovascular Surgery, vol. 24, no. 1, pp. 72-80.
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Background: abdominal aortic aneurysms (AAA) are associated with excessive vascular matrix remodelling. Recent findings suggest a systemic overproduction of matrix metalloproteinases-2 (MMP-2) by vascular smooth muscle cells (SMC) may be pivotal aetiologically. SMC migration is facilitated by MMP mediated proteolysis of the basement membrane and extracellular matrix. Our aim was to see if enhanced MMP-2 production by these SMC exhibit increased invasion, in an in vitro model of migration. Method: SMC were derived from inferior mesenteric vein (IMV) harvested from patients undergoing aneurysm repair (n=6) or colectomy for diverticulosis (n=6, control). Using a modified Boyden chamber chemotaxis was measured towards platelet derived growth factor (PDGF) and foetal calf serum (FCS) and invasion through a Matrigel layer. MMP-2 production was quantified by ELISA and gelatin zymography.
Gool, KV, Lancsar, E, Viney, R, Hall, J & Haywood, P 2002, 'Diagnosis and prognosis of Australia&s health information for evidence-based policy', Journal of Health Services Research & Policy, vol. 7, no. 1_suppl, pp. 40-45.
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Without adequate information it is difficult to determine the success or failure of health policies. This paper assesses the adequacy of Australia&s health information for evidence-based policy. Three policy areas are analysed: the impact of changing the public and private health financing mix; waiting lists and waiting times; and pooling of funds. In each, the issue is analysed to identify the key policy questions, the available data and existing analyses are examined, and gaps in data availability and analysis are assessed. There is variability in the extent and usefulness of current health information. In terms of the impact of changing the financing mix, there is good information on the distribution of finance, but much less available on comparative use or efficiency of public and private hospitals. There is comprehensive information available on waiting lists and waiting times but little analysis of the implications of this for equity of access or the costs and benefits of reducing waiting times. There is insufficient information for the development of the capitation based formulae required for the introduction of the pooling of funds, nor enough information to assess the extent and impact of current cost-shifting which might be addressed by pooling funds. While the concept of evidence-based medicine has been embraced with regard to specific treatment decisions, there has not been a parallel investment in the use of evidence to drive policy decisions.
Hall, J, Kenny, P, King, M, Louviere, J, Viney, R & Yeoh, A 2002, 'Using stated preference discrete choice modelling to evaluate the introduction of varicella vaccination', HEALTH ECONOMICS, vol. 11, no. 5, pp. 457-465.
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Applications of stated preference discrete choice modelling (SPDCM) in health economics have been used to estimate consumer willingness to pay and to broaden the range of consequences considered in economic evaluation. This paper demonstrates how SPDCM can be used to predict participation rates, using the case of varicella (chickenpox) vaccination. Varicella vaccination may be cost effective compared to other public health programs, but this conclusion is sensitive to the proportion of the target population immunised. A choice experiment was conducted on a sample of Australian parents to predict uptake across a range of hypothetical programs. Immunisation rates would be increased by providing immunisation at no cost, by requiring it for school entry, by increasing immunisation rates in the community and decreasing the incidence of mild and severe side effects. There were two significant interactions; price modified the effect of both support from authorities and severe side effects. Country of birth was the only significant demographic characteristic. Depending on aspects of the immunisation program, the immunisation rates of children with Australian-born parents varied from 9% to 99% while for the children with parents born outside Australia they varied from 40% to 99%. This demonstrates how SPDCM can be used to understand the levels of attributes that will induce a change in the decision to immunise, the modification of the effect of one attribute by another, and subgroups in the population. Such insights can contribute to the optimal design and targeting of health programs. Copyright © 2002 John Wiley & Sons, Ltd.
Hall, JP, Wiseman, VL, King, MT, Ross, DL, Kovoor, P, Zecchin, RP, Moir, FM & Robert Denniss, A 2002, 'Economic evaluation of a randomised trial of early return to normal activities versus cardiac rehabilitation after acute myocardial infarction', Heart, Lung and Circulation, vol. 11, no. 1, pp. 10-18.
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Background: Although there have been a number of economic evaluations of cardiac rehabilitation after acute myocardial infarction (AMI), none has considered only low-risk patients or control groups with no rehabilitation at all. Methods: An economic evaluation was included in a randomised controlled trial of patients following uncomplicated AMI. Eligible patients were randomised to return to normal activities after 6 weeks of standard rehabilitation (REHAB, n = 70) or to early return to normal activities 2 weeks after AMI with no formal rehabilitation (ERNA, n = 72). Outcomes were assessed weekly for 6 weeks, then 3, 6 and 12 months post-AMI. Outcomes included four quality of life (QOL) measures (physical abilities, distress, usual/social activities, self-care) and four measures of return to normal activities (paid and unpaid return to any work and to pre-AMI level of work). Statistical analysis included repeated-measures regression (QOL outcomes) and survival analysis (work outcomes). Results: There were no statistically significant differences between the two groups in any of the outcomes measured or in the use of other health services. The net cost that could be saved by the health service by targeting rehabilitation to high-risk patients was approximately $300 (Australian, 1999) per low-risk patient. Conclusions: Early return to normal activities without formal rehabilitation is cost-effective for low-risk patients.
Louviere, J, Street, D, Carson, R, Ainslie, A, Deshazo, JR, Cameron, TA, Hensher, D, Kohn, R & Marley, T 2002, 'Dissecting the random component of utility', MARKETING LETTERS, vol. 13, no. 3, pp. 177-193.
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We illustrate and discuss several general issues associated with the random component of utility, or more generally 'unobserved variability'. We posit a general conceptual framework that suggests a variance components view as an appropriate structure for unobserved variability. This framework suggests that 'unobserved heterogeneity' is only one component of unobserved variability; hence, a more general view is required. We review a considerable amount of empirical research that suggests that random components are unlikely to be independent of systematic components, and random component variances are unlikely to be constant between or within individuals, time periods, locations, etc. We also review evidence that random components are functions of (elements of) systematic components. The latter suggests considerable caution in the use and interpretation of complex choice model specifications, in particular recently introduced forms of random parameter models that purport to estimate distributions of preference parameters. Several areas for future research are identified and discussed.
Pollicino, C, Viney, R & Haas, M 2002, 'Measuring health system resource use for economic evaluation: a comparison of data sources', Australian Health Review, vol. 25, no. 3, pp. 171-171.
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A key challenge for evaluators and health system planners is the identification, measurement and valuation of resource use for economic evaluation. Accurately capturing all significant resource use is particularly difficult in the Australian context where there is no comprehensive database from which researchers can draw. Evaluators and health system planners need to consider different approaches to data collection for estimating resource use for economic evaluation, and the relative merits of the different data sources available. This paper illustrates the issues that arise in using different data sources using a sub-sample of the data being collected for an economic evaluation. Specifically, it compares the use of Australia's largest administrative database on resource use, the Health Insurance Commission database, with the use of patient-supplied data. The extent of agreement and discrepancies between the two data sources is investigated. Findings from this study and recommendations as to how to deal with different data sources are presented.
Prvan, T & Street, DJ 2002, 'An annotated bibliography of application papers using certain classes of fractional factorial and related designs', Journal of Statistical Planning and Inference, vol. 106, no. 1-2, pp. 245-269.
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In this paper we provide an annotated bibliography of about 140 papers which have appeared in journals in a variety of areas in the last 5 years and in which a fractional factorial design has been used. For each reference, we have indicated the design or designs used and whether or not the responses are given in the paper. The level of detail given in these papers makes them suitable sources for examples in a course on the design and analysis of experiments. © 2002 Elsevier Science B.V. All rights reserved.
Treharne, GD, Boyle, JR, Goodall, S, Loftus, IM, Bell, PRF & Thompson, MM 2002, 'Marimastat inhibits elastin degradation and matrix metalloproteinase 2 activity in a model of aneurysm disease', British Journal of Surgery, vol. 86, no. 8, pp. 1053-1058.
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Abstract Background Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes have been linked to increased levels of endogenous metalloproteinases (MMPs) within the aorta, particularly MMP-2 and MMP-9. This provides a potential therapeutic target for pharmacological agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of marimastat (an MMP inhibitor) to reduce matrix degradation was assessed in a previously described model of aneurysm disease. Methods Porcine aortic segments (n = 12) were preincubated in exogenous pancreatic elastase for 24 h before culture in standard conditions for 13 days with marimastat 10−5, 10−6 and 10−7 mol/l. Control segments were cultured both without marimastat and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by substrate gel enzymography. The volume fractions of elastin and collagen were determined by stereological analysis of sections stained with Miller's elastin and van Gieson's stain. Results Stereological analysis demonstrated preservation of elastin in aorta treated with marimastat at 10–6 and 10–5 mol/l; this was significant at the latter concentration (P = 0·007). This was accompanied by a significant reduction in active MMP-2 activity in the samples treated with marimastat 10–5 mol/l (P < 0·01). Conclusion
van Gool, K, Haas, MR & Viney, R 2002, 'From flying doctor to virtual doctor: an economic perspective on Australia's telemedicine experience', JOURNAL OF TELEMEDICINE AND TELECARE, vol. 8, no. 5, pp. 249-254.
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Current funding mechanisms can impede the efficient use and integration of telemedicine services. Telemedicine has developed in Australia against a background of complex funding arrangements and interwoven health-care responsibilities. These impediments are not unique to telemedicine but are accentuated by its ability to cover different locations, clinical areas and purposes. There is also a link between economic evaluation and funding mechanisms for telemedicine. While economic evaluations provide important information for the efficient allocation of resources, the funding environment in which telemedicine is established is also crucial in ensuring that services are efficient. Given these complexities, should telemedicine be funded? We conclude that this will depend on: the objectives and priorities of the health system; the efficiency of telemedicine relative to that of other forms of health-care delivery; and the funding environment. In terms of resource allocation processes, the optimum scenario is likely to be where the decision to invest in telemedicine services is made taking local needs into account, but where considerations such as market structure and network compatibility are examined on a broader scale and balanced against the principles of efficiency and equity.
Viney, R, Lancsar, E & Louviere, J 2002, 'Discrete choice experiments to measure consumer preferences for health and healthcare', Expert Review of Pharmacoeconomics & Outcomes Research, vol. 2, no. 4, pp. 319-326.
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To investigate the impact of health policies on individual well-being, estimate the value to society of new interventions or policies, or predict demand for healthcare, we need information about individuals' preferences. Economists usually use market-based data to analyze preferences, but such data are limited in the healthcare context. Discrete choice experiments are a potentially valuable tool for elicitation and analysis of preferences and thus, for economic analysis of health and health programs. This paper reviews the use of discrete choice experiments to measure consumers' preferences for health and healthcare. The paper provides an overview of the approach and discusses issues that arise when using discrete choice experiments to assess individuals' preferences for health and healthcare.
De Abreu Lourenco, R 1970, 'Prognosis of patients with CML in chronic phase post interferon-alfa therapy treated with imatinib – a survival model', The American Society of Clinical Oncology. 38th Annual Meeting, Orlando, Florida.
Joseph, D, Chern, B, Pittman, K, Richardson, G, Schou, M, Kirkman, M, Lourenco, RD, Copeman, M & Lynch, K 1970, 'An assessment of patient preferences for intravenous zoledronic acid or pamidronate in, patients commencing bisphosphonate therapy for malignant disease in bone.', BLOOD, 44th Annual Meeting of the American-Society-of-Hematology, AMER SOC HEMATOLOGY, PHILADELPHIA, PENNSYLVANIA, pp. 388B-388B.
Joshua, DE, Chern, B, Dalley, D, Pittman, K, Smith, DK, Lowe, S, Copeman, M, Kevin, L & Lourenco, RD 1970, 'Resource use by zoledronic acid or pamidronate infusions in multiple myeloma and cancer.', BLOOD, 44th Annual Meeting of the American-Society-of-Hematology, AMER SOC HEMATOLOGY, PHILADELPHIA, PENNSYLVANIA, pp. 496B-496B.
Kenny, P, Hall, J, Viney, R, Yeoh, A & Haas, M CHERE 2002, Using qualitative methods to validate a stated preference survey for evaluating health services, CHERE Discussion Paper No 47, Sydney.
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This study used a qualitative approach to assess parents? opinions of a self-completed stated preference discrete choice modelling (SPDCM) questionnaire for assessing the uptake of a new childhood vaccination against chickenpox. The aim was to assess the way parents understood and used the technical information provided, the factors they deemed important to decisions about childhood immunisation and the extent to which these were consistent with the models produced by analysis of the questionnaire data. Following completion of the SPDCM questionnaire, 34 respondents participated in a semi-structured interview by telephone. Interview transcripts were analysed using content analysis. Comparisons were then made with the SPDCM questionnaire results. The technical information used to describe the program attributes appeared to be used appropriately by respondents, although their explanations indicated that their understanding did not always come from the questionnaire information. Only one respondent appeared to misunderstand the stated preference task, and a small number thought that the complexity and length should be reduced. The group results for the questionnaire data were supported by the qualitative study, with the notable features of the model being reflected in the views commonly expressed about the immunisation decision. Generally, the study provides support for the potential usefulness of the SPDCM methodology for predicting the uptake of a new vaccination.
Lind, B, Weatherburn, D, Chen, S, Shanahan, M, Lancsar, E & Haas, M NSW Bureau of Crime Statistics and Research 2002, New South Wales drug court evaluation: Cost-effectiveness, CHERE Project Report 17a, Sydney.
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In this report we examine an issue central to the creation of the NSW Drug Court: namely its cost-effectiveness, compared with conventional sanctions, in reducing drug-related crime. We were particularly fortunate in undertaking this evaluation, to receive the support and cooperation of the Drug Court and the Attorney General in evaluating the Drug Court using a randomised controlled trial. Randomised controlled trials, in which individuals are randomly allocated to ?treatment? and ?control? groups are recognised as being the ?gold standard? when it comes to outcome evaluation. They provide more assurance of control over extraneous factors which might otherwise bias an evaluation than any other form of research design. To our knowledge, this is the first occasion on which a criminal justice program in Australia has been evaluated using a randomised control design. The evaluation is a first in one other way as well. Very few evaluations of criminal justice or crime prevention programs (either in Australia or overseas) pay much heed to the cost of the program. This greatly hampers the capacity of Government to make rational decisions about the allocation of scarce resources across competing programs. Of course, decisions on programs which affect the liberty of citizens cannot, and should not, be made on the grounds of cost-effectiveness alone. Nevertheless it is to be hoped that our efforts will convince others of the feasibility and value of introducing cost-effectiveness analyses into criminal justice evaluation.
Viney, R, Pollicino, C, Lowin, A, Haywood, P & Fulham, M CHERE 2002, Review of Positron Emission Tomography at Royal Prince Alfred Hospital, CHERE Project Report No 18, Sydney.
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This report is a review of the clinical uses, impacts on clinical management, clinical outcome andresource use of Positron Emission Tomography (PET) at Royal Prince Alfred Hospital (RPAH).
