Economic value of narrow-band imaging versus white light endoscopy for the diagnosis and surveillance of Barrett's esophagus: Cost-consequence model.

Barrett's esophagus (BE) is an abnormality arising from gastroesophageal reflux disease that can progressively evolve into a sequence of dysplasia and adenocarcinoma. Progression of Barrett's esophagus into dysplasia is monitored with endoscopic surveillance. The current surveillance standard requests random biopsies plus targeted biopsies of suspicious lesions under white-light endoscopy, known as the Seattle protocol. Recently, published evidence has shown that narrow-band imaging (NBI) can guide targeted biopsies to identify dysplasia and reduce the need for random biopsies. We aimed to assess the health economic implications of adopting NBI-guided targeted biopsy vs. the Seattle protocol from a National Health Service England perspective. A decision tree model was developed to undertake a cost-consequence analysis. The model estimated total costs (i.e. staff and overheads; histopathology; adverse events; capital equipment) and clinical implications of monitoring a cohort of patients with known/suspected BE, on an annual basis. In the simulation, BE patients (N = 161,657 at Year 1; estimated annual increase: +20%) entered the model every year and underwent esophageal endoscopy. After 7 years, the adoption of NBI with targeted biopsies resulted in cost reduction of £458.0 mln vs. HD-WLE with random biopsies (overall costs: £1,966.2 mln and £2,424.2 mln, respectively). The incremental investment on capital equipment to upgrade hospitals with NBI (+£68.3 mln) was offset by savings due to the reduction of histological examinations (-£505.2 mln). Reduction of biopsies also determined savings for avoided adverse events (-£21.1 mln). In the base-case analysis, the two techniques had the same accuracy (number of correctly identified cases: 1.934 mln), but NBI was safer than HD-WLE. Budget impact analysis and cost-effectiveness analyses confirmed the findings of the cost-consequence analysis. In conclusion, NBI-guided targeted biopsies was a cost-saving strategy for NHS England, compared to current practice for detection of dysplasia in patients with BE, whilst maintaining at least comparable health outcomes for patients.

Economic value of narrow band imaging versus white light endoscopy for the characterization of diminutive polyps in the colon: systematic literature review and cost-consequence model.

AIMS: To demonstrate the economic implication of adopting narrow-band imaging (NBI) for the characterization of diminutive polyps in the colon from an English payer perspective. MATERIALS AND METHODS: A decision-tree model was undertaken to perform a cost-consequence and budget impact analysis from the NHS England perspective in the UK, over a 7-year time horizon. Clinical inputs came from the published literature (both randomized controlled trials and meta-analyses) identified through a systematic literature review, and cost inputs came from national list prices and unpublished internal market data. Deterministic sensitivity analysis (DSA) was conducted on the budget impact results to assess their robustness. RESULTS: Optical diagnosis with NBI offered cost savings vs white light endoscopy (WLE) over 7 years due to reductions in histological exams, resections, and associated adverse events, while having minimal impact on health outcomes. Budget impact analysis demonstrated annual cost savings of £141 192 057 over 7 years, with histological exams being the biggest cost driver. DSA showed these results to be robust, but most sensitive to the cost of tariff with and without biopsy, and the cost of histological exam. Break-even analysis to explore how changing the unit cost and number of biopsies per patient would change the budget impact found NBI consistently offered net savings, even if the cost of biopsy was £0. LIMITATIONS: Although every effort was made to ensure robustness of results, as with any model, there were some limitations including a lack of published data for certain clinical inputs and potential variation between model inputs and real-life cost and market share values. CONCLUSIONS: Optical diagnosis with NBI was found to be equally effective compared with the standard of care (WLE), while potentially enabling cost savings from the NHS England perspective.

Functional compensation of primary and secondary metabolites by duplicate genes in Arabidopsis thaliana.

It is well known that knocking out a gene in an organism often causes no phenotypic effect. One possible explanation is the existence of duplicate genes; that is, the effect of knocking out a gene is compensated by a duplicate copy. Another explanation is the existence of alternative pathways. In terms of metabolic products, the relative roles of the two mechanisms have been extensively studied in yeast but not in any multi-cellular organisms. Here, to address the functional compensation of metabolic products by duplicate genes, we quantified 35 metabolic products from 1,976 genes in knockout mutants of Arabidopsis thaliana by a high-throughput Liquid chromatography-Mass spectrometer (LC-MS) analysis. We found that knocking out either a singleton gene or a duplicate gene with distant paralogs in the genome tends to induce stronger metabolic effects than knocking out a duplicate gene with a close paralog in the genome, indicating that only duplicate genes with close paralogs play a significant role in functional compensation for metabolic products in A. thaliana. To extend the analysis, we examined metabolic products with either high or low connectivity in a metabolic network. We found that the compensatory role of duplicate genes is less important when the metabolite has a high connectivity, indicating that functional compensation by alternative pathways is common in the case of high connectivity. In conclusion, recently duplicated genes play an important role in the compensation of metabolic products only when the number of alternative pathways is small.

Toward genome-wide metabolotyping and elucidation of metabolic system: metabolic profiling of large-scale bioresources.

An improvement in plant production is increasingly important for a sustainable human society. For this purpose, understanding the mechanism of plant production, that is, the plant metabolic system, is an immediate necessity. After the sequencing of the Arabidopsis genome, it has become possible to obtain a bird's eye view of its metabolism by means of omics such as transcriptomics and proteomics. Availability of thousands of transcriptome data points in the public domain has resulted in great advances in the methodology of functional genomics. Metabolome data can be a "gold mine" of biological findings. However, as the total throughput of metabolomics is far lower than that of transcriptomics due to technical difficulties, there is currently no publicly available large-scale metabolome dataset that is comparable in size to the transcriptome dataset. Recently, we established a novel methodology, termed widely targeted metabolomics, which can generate thousands of metabolome data points in a high-throughput manner. We previously conducted a targeted metabolite analysis of large-scale Arabidopsis bioresources, namely transposon-tagged mutants and accessions, to make a smaller dataset of metabolite accumulation. In this paper, we release approximately 3,000 metabolic profiles obtained by targeted analysis for 36 metabolites and discuss the possible regulation of amino acid accumulation.