Mapping of the EQ-5D index from clinical outcome measures and demographic variables in patients with coronary heart disease.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: The EuroQoL 5D (EQ-5D) is a questionnaire that provides a measure of utility for cost-effectiveness analysis. The EQ-5D has been widely used in many patient groups, including those with coronary heart disease. Studies often require patients to complete many questionnaires and the EQ-5D may not be gathered. This study aimed to assess whether demographic and clinical outcome variables, including scores from a disease specific measure, the Seattle Angina Questionnaire (SAQ), could be used to predict, or map, the EQ-5D index value where it is not available. METHODS: Patient-level data from 5 studies of cardiac interventions were used. The data were split into two groups - approximately 60% of the data were used as an estimation dataset for building models, and 40% were used as a validation dataset. Forward ordinary least squares linear regression methods and measures of prediction error were used to build a model to map to the EQ-5D index. Age, sex, a proxy measure of disease stage, Canadian Cardiovascular Society (CCS) angina severity class, treadmill exercise time (ETT) and scales of the SAQ were examined. RESULTS: The exertional capacity (ECS), disease perception (DPS) and anginal frequency scales (AFS) of the SAQ were the strongest predictors of the EQ-5D index and gave the smallest root mean square errors. A final model was chosen with age, gender, disease stage and the ECS, DPS and AFS scales of the SAQ. ETT and CCS did not improve prediction in the presence of the SAQ scales. Bland-Altman agreement between predicted and observed EQ-5D index values was reasonable for values greater than 0.4, but below this level predicted values were higher than observed. The 95% limits of agreement were wide (-0.34, 0.33). CONCLUSIONS: Mapping of the EQ-5D index in cardiac patients from demographics and commonly measured cardiac outcome variables is possible; however, prediction for values of the EQ-5D index below 0.4 was not accurate. The newly designed 5-level version of the EQ-5D with its increased ability to discriminate health states may improve prediction of EQ-5D index values

A review of health utilities using the EQ-5D in studies of cardiovascular disease

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The EQ-5D has been extensively used to assess patient utility in trials of new treatments within the cardiovascular field. The aims of this study were to review evidence of the validity and reliability of the EQ-5D, and to summarise utility scores based on the use of the EQ-5D in clinical trials and in studies of patients with cardiovascular disease. Methods A structured literature search was conducted using keywords related to cardiovascular disease and EQ-5D. Original research studies of patients with cardiovascular disease that reported EQ-5D results and its measurement properties were included. Results Of 147 identified papers, 66 met the selection criteria, with 10 studies reporting evidence on validity or reliability and 60 reporting EQ-5D responses (VAS or self-classification). Mean EQ-5D index-based scores ranged from 0.24 (SD 0.39) to 0.90 (SD 0.16), while VAS scores ranged from 37 (SD 21) to 89 (no SD reported). Stratification of EQ-5D index scores by disease severity revealed that scores decreased from a mean of 0.78 (SD 0.18) to 0.51 (SD 0.21) for mild to severe disease in heart failure patients and from 0.80 (SD 0.05) to 0.45 (SD 0.22) for mild to severe disease in angina patients. Conclusions The published evidence generally supports the validity and reliability of the EQ-5D as an outcome measure within the cardiovascular area. This review provides utility estimates across a range of cardiovascular subgroups and treatments that may be useful for future modelling of utilities and QALYs in economic evaluations within the cardiovascular area.Published versio

Cryptic diversity within the major trypanosomiasis vector Glossina fuscipes revealed by molecular markers

Background: The tsetse fly Glossina fuscipes s.l. is responsible for the transmission of approximately 90% of cases of human African trypanosomiasis (HAT) or sleeping sickness. Three G. fuscipes subspecies have been described, primarily based upon subtle differences in the morphology of their genitalia. Here we describe a study conducted across the range of this important vector to determine whether molecular evidence generated from nuclear DNA (microsatellites and gene sequence information), mitochondrial DNA and symbiont DNA support the existence of these taxa as discrete taxonomic units. Principal Findings: The nuclear ribosomal Internal transcribed spacer 1 (ITS1) provided support for the three subspecies. However nuclear and mitochondrial sequence data did not support the monophyly of the morphological subspecies G. f.fuscipes or G. f. quanzensis. Instead, the most strongly supported monophyletic group was comprised of flies sampled fromEthiopia. Maternally inherited loci (mtDNA and symbiont) also suggested monophyly of a group from Lake Victoria basin and Tanzania, but this group was not supported by nuclear loci, suggesting different histories of these markers. Microsatellite data confirmed strong structuring across the range of G. fuscipes s.l., and was useful for deriving the interrelationship of closely related populations. Conclusion/Significance: We propose that the morphological classification alone is not used to classify populations of G. fuscipes for control purposes. The Ethiopian population, which is scheduled to be the target of a sterile insect release (SIT) programme, was notably discrete. From a programmatic perspective this may be both positive, given that it may reflect limited migration into the area or negative if the high levels of differentiation are also reflected in reproductive isolation between this population and the flies to be used in the release programme

Relationship between the EQ-5D index and measures of clinical outcomes in selected studies of cardiovascular interventions.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: The EuroQoL 5D (EQ-5D) has been widely used in studies of cardiac disease, but its measurement properties in this group are not well established. The study aimed to quantify the relationship between measures commonly used in studies of cardiac disease and the EQ-5D index across different levels of disease severity. METHODS: Patient-level data from 7 studies of cardiac interventions were used, which included randomised trials and observational studies. Relationships between the EQ-5D index and commonly used cardiac measures, Canadian Cardiovascular Society (CCS) angina severity class, treadmill exercise time (ETT) and scales of the Seattle Angina Questionnaire (SAQ) were examined. Mixed effects linear regression was used to assess these relationships, with the EQ-5D index as the response. RESULTS: Study sample sizes ranged from 68 to 2419. Mean baseline EQ-5D index ranged from 0.77 in patients at diagnosis (95% CI 0.75, 0.78) to 0.43 in patients with advanced disease (95% CI 0.39, 0.48) and differed significantly across studies (p < 0.001). There was evidence of a ceiling effect in patients at diagnosis. The minimum clinically important difference of a one minute increase in ETT was associated with a 0.019 (95% CI 0.014, 0.025) increase in EQ-5D index. One class increase in CCS was associated with a 0.11 (95% CI 0.09, 0.13) decrease in EQ-5D index. A 10 unit increase in SAQ scales was associated with increases between 0.04 and 0.07 in EQ-5D index (95% CIs 0.03, 0.05 and 0.05, 0.08). Tests of heterogeneity indicated the EQ-5D-covariate relationships were consistent across levels of disease severity for ETT and the treatment satisfaction scale of the SAQ, but heterogeneous for age, gender, CCS angina class and other scales of the SAQ. CONCLUSION: The EQ-5D index varies with coronary disease severity. The relationship between the EQ-5D index and an outcome measure used in cardiac intervention studies, ETT, was consistent across disease severity levels, but the relationship between demographic variables, CCS angina class and most of the SAQ scales and the EQ-5D index was heterogeneous for patients with different levels of coronary disease. Differences in the EQ-5D index associated with clinically important differences in cardiac measures can be quantified and vary between three important examples - angina class, ETT and SAQ

Measurement of gut permeability using fluorescent tracer agent technology

Abstract The healthy gut restricts macromolecular and bacterial movement across tight junctions, while increased intestinal permeability accompanies many intestinal disorders. Dual sugar absorption tests, which measure intestinal permeability in humans, present challenges. Therefore, we asked if enterally administered fluorescent tracers could ascertain mucosal integrity, because transcutaneous measurement of differentially absorbed molecules could enable specimen-free evaluation of permeability. We induced small bowel injury in rats using high- (15 mg/kg), intermediate- (10 mg/kg), and low- (5 mg/kg) dose indomethacin. Then, we compared urinary ratios of enterally administered fluorescent tracers MB-402 and MB-301 to urinary ratios of sugar tracers lactulose and rhamnose. We also tested the ability of transcutaneous sensors to measure the ratios of absorbed fluorophores. Urinary fluorophore and sugar ratios reflect gut injury in an indomethacin dose dependent manner. The fluorophores generated smooth curvilinear ratio trajectories with wide dynamic ranges. The more chaotic sugar ratios had narrower dynamic ranges. Fluorophore ratios measured through the skin distinguished indomethacin-challenged from same day control rats. Enterally administered fluorophores can identify intestinal injury in a rat model. Fluorophore ratios are measureable through the skin, obviating drawbacks of dual sugar absorption tests. Pending validation, this technology should be considered for human use

Efficient replication of pneumonia virus of mice (PVM) in a mouse macrophage cell line

Pneumonia virus of mice (PVM; family Paramyxoviridae, subfamily Pneumovirinae) is a natural respiratory pathogen of rodent species and an important new model for the study of severe viral bronchiolitis and pneumonia. However, despite high virus titers typically detected in infected mouse lung tissue in vivo, cell lines used routinely for virus propagation in vitro are not highly susceptible to PVM infection. We have evaluated several rodent and primate cell lines for susceptibility to PVM infection, and detected highest virus titers from infection of the mouse monocyte-macrophage RAW 264.7 cell line. Additionally, virus replication in RAW 264.7 cells induces the synthesis and secretion of proinflammatory cytokines relevant to respiratory virus disease, including tumor necrosis factor-α (TNF-α), interferon-β (IFN-β), macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β) and the functional homolog of human IL-8, mouse macrophage inflammatory peptide-2 (MIP-2). Identification and characterization of a rodent cell line that supports the replication of PVM and induces the synthesis of disease-related proinflammatory mediators will facilitate studies of molecular mechanisms of viral pathogenesis that will complement and expand on findings from mouse model systems