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- Hemingway, H, et al.
(author)
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The effectiveness and cost-effectiveness of biomarkers for the prioritisation of patients awaiting coronary revascularisation: a systematic review and decision model.
- 2010
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In: Health Technology Assessment. - : National Coordinating Centre for Health Technology Assessment. - 1366-5278 .- 2046-4924. ; 14:9, s. 1-178
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the effectiveness and cost-effectiveness of a range of strategies based on conventional clinical information and novel circulating biomarkers for prioritising patients with stable angina awaiting coronary artery bypass grafting (CABG).DATA SOURCES: MEDLINE and EMBASE were searched from 1966 until 30 November 2008.REVIEW METHODS: We carried out systematic reviews and meta-analyses of literature-based estimates of the prognostic effects of circulating biomarkers in stable coronary disease. We assessed five routinely measured biomarkers and the eight emerging (i.e. not currently routinely measured) biomarkers recommended by the European Society of Cardiology Angina guidelines. The cost-effectiveness of prioritising patients on the waiting list for CABG using circulating biomarkers was compared against a range of alternative formal approaches to prioritisation as well as no formal prioritisation. A decision-analytic model was developed to synthesise data on a range of effectiveness, resource use and value parameters necessary to determine cost-effectiveness. A total of seven strategies was evaluated in the final model.RESULTS: We included 390 reports of biomarker effects in our review. The quality of individual study reports was variable, with evidence of small study (publication) bias and incomplete adjustment for simple clinical information such as age, sex, smoking, diabetes and obesity. The risk of cardiovascular events while on the waiting list for CABG was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients with a mean of 59 days at risk). Risk factors associated with an increased risk, and included in the basic risk equation, were age, diabetes, heart failure, previous myocardial infarction and involvement of the left main coronary artery or three-vessel disease. The optimal strategy in terms of cost-effectiveness considerations was a prioritisation strategy employing biomarker information. Evaluating shorter maximum waiting times did not alter the conclusion that a prioritisation strategy with a risk score using estimated glomerular filtration rate (eGFR) was cost-effective. These results were robust to most alternative scenarios investigating other sources of uncertainty. However, the cost-effectiveness of the strategy using a risk score with both eGFR and C-reactive protein (CRP) was potentially sensitive to the cost of the CRP test itself (assumed to be 6 pounds in the base-case scenario).CONCLUSIONS: Formally employing more information in the prioritisation of patients awaiting CABG appears to be a cost-effective approach and may result in improved health outcomes. The most robust results relate to a strategy employing a risk score using conventional clinical information together with a single biomarker (eGFR). The additional prognostic information conferred by collecting the more costly novel circulating biomarker CRP, singly or in combination with other biomarkers, in terms of waiting list prioritisation is unlikely to be cost-effective.
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- Janzon, Anders, 1978, et al.
(author)
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Exploring the microbial resistome in river sediments exposed to extraordinary high levels of antibiotics
- 2010
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In: 35th FEBS Congress: Molecules of Life.
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Conference paper (other academic/artistic)abstract
- The rapid development and propagation of antibiotic resistance in pathogenic and opportunistic bacteria is a major threat to public health worldwide. The phenomenon has been widely studied in the clinical setting, but comparatively little is known about the prevalence and diversity of antibiotic resistance in communities of environmental bacteria, often referred to as the environmental resistome. As the external environment may function as a reservoir of resistance genes to human pathogens, we are interested in how environmental bacteria are affected by antibiotic pollution. We have previously isolated microbial DNA from river sediments taken up- and downstream from a water treatment plant that processes waste water from several pharmaceutical plants producing antibiotics. In a previous study, we used deep sequencing to identify unprecedented frequencies of known resistance genes to several classes of antibiotics in these samples. In this study, we aim to functionally characterize the resistome in a more open and exploratory way by screening genomic DNA libraries transformed into sensitive hosts. To generate the libraries, several experimental strategies were explored, including mechanical shearing and enzymatic digestion of the isolated DNA followed by blunt- or sticky end cloning into different plasmids, subsequently transformed into sensitive E. coli. Pros and cons of the different strategies will be discussed along with preliminary results of the screening against selected antibiotics.
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