Early Economic Evaluation of Diagnostic Technologies: Experiences of the NIHR Diagnostic Evidence Co-operatives

Diagnostic tests are expensive and time-consuming to develop. Early economic evaluation using decision modeling can reduce commercial risk by providing early evidence on cost-effectiveness. The National Institute for Health Research Diagnostic Evidence Co-operatives (DECs) was established to catalyze evidence generation for diagnostic tests by collaborating with commercial developers; DEC researchers have consequently made extensive use of early modeling. The aim of this article is to summarize the experiences of the DECs using early modeling for diagnostics. We draw on 8 case studies to illustrate the methods, highlight methodological strengths and weaknesses particular to diagnostics, and provide advice. The case studies covered diagnosis, screening, and treatment stratification. Treatment effectiveness was a crucial determinant of cost-effectiveness in all cases, but robust evidence to inform this parameter was sparse. This risked limiting the usability of the results, although characterization of this uncertainty in turn highlighted the value of further evidence generation. Researchers evaluating early models must be aware of the importance of treatment effect evidence when reviewing the cost-effectiveness of diagnostics. Researchers planning to develop an early model of a test should also 1) consult widely with clinicians to ensure the model reflects real-world patient care; 2) develop comprehensive models that can be updated as the technology develops, rather than taking a “quick and dirty” approach that may risk producing misleading results; and 3) use flexible methods of reviewing evidence and evaluating model results, to fit the needs of multiple decision makers. Decision models can provide vital information for developers at an early stage, although limited evidence mean researchers should proceed with caution

Clostridium difficile in Ready-to-Eat Salads, Scotland

Of 40 ready-to-eat salads, 3 (7.5%) were positive for Clostridium difficile by PCR. Two isolates were PCR ribotype 017 (toxin A–, B+), and 1 was PCR ribotype 001. Isolates were susceptible to vancomycin and metronidazole but variably resistant to other antimicrobial drugs. Ready-to-eat salads may be potential sources for virulent C. difficile

Staging Uveal Melanoma with Whole-Body Positron-Emission Tomography/Computed Tomography and Abdominal Ultrasound: Low Incidence of Metastatic Disease, High Incidence of Second Primary Cancers

PURPOSE: The purpose of this study was to report the results of staging primary uveal melanoma with whole-body (18) fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) and abdominal ultrasound. MATERIALS AND METHODS: From January 2012, patients with uveal melanoma over 4 mm in thickness were staged with FDG PET/CT and abdominal ultrasound. RESULTS: Over 2 years, 108 patients with medium-to-large melanoma underwent dual imaging. According to the tumor, node, and metastasis classification, there were 75% T3, 11% T2, and 14% T1 uveal melanomas. Only, three of 108 patients (2.8%) were found to have metastatic uveal melanoma. All three had liver metastases confirmed following biopsy; one of three had additional extrahepatic widespread metastases. In these three patients, liver findings using both imaging techniques were consistent in one patient. In the second case, abdominal ultrasound missed the diagnosis of metastatic disease; however, FDG PET/CT revealed intense metabolic activity of the liver. In the third case, PET/CT missed the liver metastases; however, this was identified on abdominal ultrasound. PET/CT identified incidental second primary malignancies in 10 patients (9%). Second malignancies were found in the lung, breast, colon, thyroid, and adrenal gland. Abdominal ultrasound detected benign hepatic abnormalities in 20 patients (18%). CONCLUSIONS: Whole-body PET/CT and abdominal ultrasound complement each other in the staging of uveal melanoma. Benign hepatic abnormalities found using ultrasound is common. Of importance, a second asymptomatic primary malignancy associated with uveal melanoma was detected almost one in 10 patients

An International Partnership of 12 Anatomy Departments - Improving Global Health through Internationalization of Medical Education

Background: At a time of global interconnectedness, the internationalization of medical education has become important. Anatomy as an academic discipline, with its close connections to the basic sciences and to medical education, can easily be connected with global health and internationalization of medical education. Here the authors present an international program based on a partnership between twelve anatomy departments in ten countries, on four continents. Details of a proposed plan for the future direction of the program are also discussed. Objective: The aim is to improve global healthcare by preparing future global healthcare leaders via early international networking, international collaboration and exchange, intercultural experience, and connecting two seemingly distant academic disciplines - anatomy and global health - via internationalization of medical education. Methods: Based in the anatomy course, the program involved early international collaboration between preclinical medical and dental students. The program provided a stepwise progression for learning about healthcare and intercultural topics beyond pure anatomy education - starting with virtual small groups of international students, who subsequently presented their work to a larger international audience during group videoconferences. The above progressed to in-person visits for research internships in the basic sciences within industrialized countries. Findings: Students appreciated the international and intercultural interaction, learned about areas outside the scope of anatomy (e.g., differences in healthcare education and delivery systems, Public and Global Health challenges, health ethics, and cultural enrichment), and valued the exchange travel for basic sciences research internships and cultural experience. Conclusions: This unique collaboration of international anatomy departments can represent a new role for the medical anatomy course beyond pure anatomy teaching - involving areas of global health and internationalization of medical education - and could mark a new era of international collaboration among anatomists.Peer reviewe

The Association Between the Peroxisome Proliferator-Activated Receptor-γ2 (PPARG2) Pro12Ala Gene Variant and Type 2 Diabetes Mellitus: A HuGE Review and Meta-Analysis

The peroxisome proliferator-activated receptor-γ gene (PPARG) has been implicated in the etiology of type 2 diabetes mellitus and has been investigated in numerous epidemiologic studies. In this Human Genome Epidemiology review, the authors assessed this relation in an updated meta-analysis of 60 association studies. Electronic literature searches were conducted on September 14, 2009. Population-based cohort, case-control, cross-sectional, or genome-wide association studies reporting associations between the PPARG Pro12Ala gene variant (rs1801282) and type 2 diabetes were included. An updated literature-based meta-analysis involving 32,849 type 2 diabetes cases and 47,456 controls in relation to the PPARG Pro12Ala variant was conducted. The combined overall odds ratio, calculated by per-allele genetic model random-effects meta-analysis for type 2 diabetes and the Pro12Ala polymorphism, was 0.86 (95% confidence interval: 0.81, 0.90). The analysis indicated a moderate level of heterogeneity attributable to genuine variation in gene effect size (I2 = 37%). This may reflect the variation observed between ethnic populations and/or differences in body mass index. Work on PPARG Pro12Ala should now focus on the observed heterogeneity in the magnitude of the association between populations. Further investigations into gene-gene and gene-environment interactions may prove enlightening

肩腱板損傷の超音波解析

This Discussion Meeting Issue of the Philosophical Transactions A had its genesis in a Discussion Meeting of the Royal Society which took place on 10–11 October 2011. The Discussion Meeting, entitled ‘Warm climates of the past: a lesson for the future?’, brought together 16 eminent international speakers from the field of palaeoclimate, and was attended by over 280 scientists and members of the public. Many of the speakers have contributed to the papers compiled in this Discussion Meeting Issue. The papers summarize the talks at the meeting, and present further or related work. This Discussion Meeting Issue asks to what extent information gleaned from the study of past climates can aid our understanding of future climate change. Climate change is currently an issue at the forefront of environmental science, and also has important sociological and political implications. Most future predictions are carried out by complex numerical models; however, these models cannot be rigorously tested for scenarios outside of the modern, without making use of past climate data. Furthermore, past climate data can inform our understanding of how the Earth system operates, and can provide important contextual information related to environmental change. All past time periods can be useful in this context; here, we focus on past climates that were warmer than the modern climate, as these are likely to be the most similar to the future. This introductory paper is not meant as a comprehensive overview of all work in this field. Instead, it gives an introduction to the important issues therein, using the papers in this Discussion Meeting Issue, and other works from all the Discussion Meeting speakers, as exemplars of the various ways in which past climates can inform projections of future climate. Furthermore, we present new work that uses a palaeo constraint to quantitatively inform projections of future equilibrium ice sheet change

Instrumentation for fluorescence lifetime measurement using photon counting

We describe the evolution of HORIBA Jobin Yvon IBH Ltd, and its time-correlated single-photon counting (TCSPC) products, from university research beginnings through to its present place as a market leader in fluorescence lifetime spectroscopy. The company philosophy is to ensure leading-edge research capabilities continue to be incorporated into instruments in order to meet the needs of the diverse range of customer applications, which span a multitude of scientific and engineering disciplines. We illustrate some of the range of activities of a scientific instrument company in meeting this goal and highlight by way of an exemplar the performance of the versatile DeltaFlex instrument in measuring fluorescence lifetimes. This includes resolving fluorescence lifetimes down to 5 ps, as frequently observed in energy transfer, nanoparticle metrology with sub-nanometre resolution and measuring a fluorescence lifetime in as little as 60 μs for the study of transient species and kinetics

Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors

Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. METHODS: The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. RESULTS: There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10- 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10- 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10- 6 and P = 3 × 10- 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10- 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes. CONCLUSION: In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts