Discrete Choice Modeling for the Quantification of Health States: The Case of the EQ-5D

ObjectivesProbabilistic models have been developed to establish the relative merit of subjective phenomena by means of specific judgmental tasks involving discrete choices (DCs). The attractiveness of these DC models is that they are embedded in a strong theoretical measurement framework and are based on relatively simple judgmental tasks. The aim of our study was to determine whether the values derived from a DC experiment are comparable to those obtained using other valuation techniques, in particular the time trade-off (TTO).MethodsTwo hundred nine students completed several tasks in which we collected DC, rank, visual analog scale, and TTO responses. DC data were also collected in a general population sample (N = 444). The DC experiment was designed using a Bayesian approach, and involved 60 choices between two health states and a comparison of all health states to being dead. The DC data were analyzed using a conditional logit and a rank-ordered logit model, relying, respectively, on TTO values and the value for being dead to anchor the DC-derived values to the 0 to 1 quality-adjusted life-year (QALY) scale.ResultsAlthough modeled DC data broadly replicated the pattern found in TTO responses, the DC consistently produced higher values. The two methods for anchoring DC-derived values on the QALY scale produced similar results.ConclusionsOn the basis of the high level of comparability between DC-derived values and TTO values, future valuation studies based on a combination of these two techniques may be considered. The results further suggest that DC can potentially be used as a substitute for TTO.     

Visual analogue scales: scale recalibration by patients with dementia and their proxies

Background

Visual analogue scales (VAS) are often used to measure health-related quality of life (HRQoL). However, when such scales contain ambiguous anchors like “best imaginable health state,” they produce answers that are difficult to interpret, as such anchors are interpreted differently by respondents of different age. This phenomenon that people’s interpretation of subjective response scales changes in response to changing circumstances is known as scale recalibration. The current study attempts to investigate whether scale recalibration in a patient sample with cognitive limitations and proxies differs from the general population.

Methods

The participants in the current study were 151 pairs of community-dwelling patients with dementia and their proxies. They were administered three VASs with different upper anchors; (A) “best imaginable health state,” (B) “best imaginable health state for someone your age,” and (C) “best imaginable health state for a 25-year-old.” From literature, we inferred a conceptual model for the general population that predicts the ordinal relationship of the VASs to be B ≥ A ≥ C. This rank order is tested by repeated measure ANOVA’s in the aforementioned populations.

Results

VAS scores of patients with dementia were in line with the conceptual model. Proxy VAS scores for assessing patient HRQoL were not in line with the model: A > B > C. In addition, proxy VAS scores for assessing their own health were not in line with the model: A > B > C.

Conclusion

Patients with dementia use the VAS in a similar way to the general population. Proxies assessing either patients or themselves differ from the general population.     

Ageing Is Associated with a Prolonged Fever Response in Human Endotoxemia

The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-α), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-α and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.     

Hypotension during endotoxemia in aged humans.

BACKGROUND: and objective The aim of this study was to determine possible age-associated differences in human blood pressure regulation during an immunological challenge in healthy subjects. METHODS: Eight healthy young volunteers (median age 24 yr) and nine healthy elderly volunteers (median age 66 yr) received an intravenous bolus injection of Escherichia coli endotoxin (2 ng kg(-1)). Blood pressure, heart rate and core temperature were monitored during the first 7 h. Plasma catecholamine concentrations were measured at hourly intervals. RESULTS: The elderly showed a significantly more pronounced decrease in mean arterial pressure 4-7 h after endotoxin administration compared with the young controls (ANOVA; age x time; P < 0.0005). This mainly reflected a decrease in the systolic blood pressure in the elderly. The heart rate of both groups increased without difference between groups. Increased plasma epinephrine concentrations were found 2-3 h after endotoxin administration in both groups. Five hours after the endotoxin challenge, the epinephrine concentration had returned to control values in the elderly group only, in spite of decreased blood pressure. CONCLUSION: In conclusion, healthy elderly subjects fail to maintain a constant mean arterial pressure in response to the immunological challenge of endotoxemia.     

FDG-PET and detection of distant metastases and simultaneous tumors in head and neck squamous cell carcinoma: a comparison with chest radiography and chest CT

Detection of distant metastases and second primary tumors in patients with head and neck squamous cell carcinoma (HNSCC) is of importance because of the impact on treatment and prognosis. The aim of this study was to assess the value of whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) in detecting distant metastases and second primary tumors below clavicular level in HNSCC compared to chest CT and chest radiography (CXR). Patient records of 149 consecutive patients with a primary HNSCC in whom a whole-body FDG-PET for initial staging was performed were reviewed. FDG-PET showed a sensitivity and specificity for detecting distant disease of 92% and 93%, respectively. Chest CT (n=82) showed a sensitivity and a specificity of 74% and 61% respectively. CXR (n=106) showed a sensitivity and a specificity of 41% and 91%, respectively. FDG-PET was shown to be able to detect distant metastases and second primary tumors in HNSCC with a high sensitivity and specificity. The higher sensitivity of PET compared to chest CT is mainly due to the detection of extrapulmonary malignancy. Sensitivity of PET and CT were similar in detecting intrapulmonary malignancy, but PET specificity was significantly higher. FDG-PET helps to determine the nature of pulmonary lesions and might be considered as a first diagnostic modality for detecting distant disease in advanced HNSCC.     

Down-regulation of the inhibitor of growth 1 (ING1) tumor suppressor sensitizes p53-deficient glioblastoma cells to cisplatin-induced cell death

Impaired tumor suppressor functions, such as deficient p53, are characteristic for glioblastoma multiforme (GBM) and can cause resistance to DNA-damaging agents like cisplatin. We have recently shown that the INhibitor of Growth 1 (ING1) tumor suppressor is down-regulated in malignant gliomas and that the decrease of ING1 expression correlates with histological grade of malignancy, suggesting a role for ING1 in the pathogenesis and progression of malignant gliomas. Based on this background, the purpose of our current study was to examine the potential impact of ING1 protein levels on DNA-damage response in GBM. Using LN229 GBM cells, which express ING1 proteins and harbor mutant TP53, we are the first to show that DNA damage by cisplatin or ionizing radiation differentially induced the two major ING1 splicing isoforms. The p47 ^ING1a isoform, that promotes deacetylation of histones, thus formation of heterochromatic regions of DNA, which are less susceptible to DNA damage, was preferentially induced by >50-fold. This might represent a response to protect DNA from damage. Also, ING1 knockdown by siRNA accelerated transit of cells through G₁ phase, consistent with ING1 serving a tumor suppressor function, and caused cells to enter apoptosis more rapidly in response to cisplatin. Our results indicate that malignant gliomas may down-regulate ING1 to allow more efficient tumor growth and progression. Also, ING1 down-regulation may sensitize GBM cells with deficient p53 to treatment with cisplatin. U. G. Tallen and M. Truss contributed equally to this work.