Psychometric properties of the EQ-5D-5L for aboriginal Australians: a multi-method study

Introduction: In Australia, health-related quality of life (HRQoL) instruments have been adopted in national population surveys to inform policy decisions that affect the health of Aboriginal and Torres Strait Islanders. However, Western-developed HRQoL instruments should not be assumed to capture Indigenous conceptualization of health and well-being. In our study, following recommendations for cultural adaptation, an Indigenous Reference Group indicated the EQ-5D-5L as a potentially valid instrument to measure aspects of HRQoL and endorsed further psychometric evaluation. Thus, this study aimed to investigate the construct validity and reliability of the EQ-5D-5L in an Aboriginal Australian population. Methods: The EQ-5D-5L was applied in a sample of 1012 Aboriginal adults. Dimensionality was evaluated using Exploratory Graph Analysis. The Partial Credit Model was employed to evaluate item performance and adequacy of response categories. Area under the receiver operating characteristic curve (AUROC) was used to investigate discriminant validity regarding chronic pain, general health and experiences of discrimination. Results: The EQ-5D-5L comprised two dimensions, Physiological and Psychological, and reliability was adequate. Performance at an item level was excellent and the EQ-5D-5L individual items displayed good discriminant validity. Conclusions: The EQ-5D-5L is a suitable instrument to measure five specific aspects (Mobility, Self-Care, Usual activities, Pain/Discomfort, Anxiety/Depression) of Aboriginal and Torres Strait Islander HRQoL. A future research agenda comprises the investigation of other domains of Aboriginal and Torres Strait Islander HRQoL and potential expansions to the instrument.Pedro Henrique Ribeiro Santiago, Dandara Haag, Davi Manzini Macedo, Gail Garvey, Megan Smith, Karen Canfell ... et al

Hamiltonian lattice QCD at finite density: equation of state in the strong coupling limit

The equation of state of Hamiltonian lattice QCD at finite density is examined in the strong coupling limit by constructing a solution to the equation of motion corresponding to an effective Hamiltonian describing the ground state of the many body system. This solution exactly diagonalizes the Hamiltonian to second order in field operators for all densities and is used to evaluate the vacuum energy density from which we obtain the equation of state. We find that up to and beyond the chiral symmetry restoration density the pressure of the quark Fermi sea can be negative indicating its mechanical instability. Our result is in qualitative agreement with continuum models and should be verifiable by future lattice simulations of strongly coupled QCD at finite density.Comment: 27 pages, 6 figures. Uses ReVTeX4 and BiBTeX. Revised versio

TIGIT blockade repolarizes AML-associated TIGIT(+) M2 macrophages to an M1 phenotype and increases CD47-mediated phagocytosis

BACKGROUND: Leukemia-associated macrophages (LAMs) represent an important cell population within the tumor microenvironment, but little is known about the phenotype, function, and plasticity of these cells. The present study provides an extensive characterization of macrophages in patients with acute myeloid leukemia (AML). METHODS: The phenotype and expression of coregulatory markers were assessed on bone marrow (BM)-derived LAM populations, using multiparametric flow cytometry. BM and blood aspirates were obtained from patients with newly diagnosed acute myeloid leukemia (pAML, n=59), patients in long-term remission (lrAML, n=8), patients with relapsed acute myeloid leukemia (rAML, n=7) and monocyte-derived macrophages of the blood from healthy donors (HD, n=17). LAM subpopulations were correlated with clinical parameters. Using a blocking anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody or mouse IgG2a isotype control, we investigated polarization, secretion of cytokines, and phagocytosis on LAMs and healthy monocyte-derived macrophages in vitro. RESULTS: In pAML and rAML, M1 LAMs were reduced and the predominant macrophage population consisted of immunosuppressive M2 LAMs defined by expression of CD163, CD204, CD206, and CD86. M2 LAMs in active AML highly expressed inhibitory receptors such as TIGIT, T-cell immunoglobulin and mucin-domain containing-3 protein (TIM-3), and lymphocyte-activation gene 3 (LAG-3). High expression of CD163 was associated with a poor overall survival (OS). In addition, increased frequencies of TIGIT(+) M2 LAMs were associated with an intermediate or adverse risk according to the European Leukemia Network criteria and the FLT3 ITD mutation. In vitro blockade of TIGIT shifted the polarization of primary LAMs or peripheral blood-derived M2 macrophages toward the M1 phenotype and increased secretion of M1-associated cytokines and chemokines. Moreover, the blockade of TIGIT augmented the anti-CD47-mediated phagocytosis of AML cell lines and primary AML cells. CONCLUSION: Our findings suggest that immunosuppressive TIGIT(+) M2 LAMs can be redirected into an efficient effector population that may be of direct clinical relevance in the near future

Unenhanced CT imaging is highly sensitive to exclude pheochromocytoma: A multicenter study

Background: A substantial proportion of all pheochromocytomas is currently detected during the evaluation of an adrenal incidentaloma. Recently, it has been suggested that biochemical testing to rule out pheochromocytoma is unnecessary in case of an adrenal incidentaloma with an unenhanced attenuation value ≤10Hounsfield Units (HU) at computed tomography (CT). Objectives: We aimed to determine the sensitivity of the 10HU threshold value to exclude a pheochromocytoma. Methods: Retrospective multicenter study with systematic reassessment of preoperative unenhanced CT scans performed in patients in whom a histopathologically proven pheochromocytoma had been diagnosed. Unenhanced attenuation values were determined independently by two experienced radiologists. Sensitivity of the 10HU threshold was calculated, and interobserver consistency was assessed using the intraclass correlation coefficient (ICC). Results: 214 patients were identified harboring a total number of 222 pheochromocytomas. Maximum tumor diameter was 51 (39–74)mm. The mean attenuation value within the region of interest was 36±10HU. Only one pheochromocytoma demonstrated an attenuation value ≤10HU, resulting in a sensitivity of 99.6% (95% CI: 97.5–99.9). ICC was 0.81 (95% CI: 0.75–0.86) with a standard error of measurement of 7.3HU between observers. Conclusion: The likelihood of a pheochromocytoma with an unenhanced attenuation value ≤10HU on CT is very low. The interobserver consistency in attenuation measurement is excellent. Our study supports the recommendation that in patients with an adrenal incidentaloma biochemical testing for ruling out pheochromocytoma is only indicated in adrenal tumors with an unenhanced attenuation value >10HU

Psychometric properties of the EQ-5D-3L in South Australia: a multi-method non-preference-based validation study

Published online: 06 Feb 2022.OBJECTIVE: Although HRQoL tools such as the EQ-5D-3L are significant in determining health status, these measures have not been validated in general populations in Australia. This study aims to psychometrically validate the EQ-5D-3L in a large population sample in Australia for the first time. METHODS: The EQ-5D-3L was included in the Dental Care and Oral Health study (DCOHS), conducted in a South Australian population sample. The participants were 23-91 years old, and 44.1% were male. The EQ-5D-3L was responded to on a three-point rating scale ("none"/"no", "some" and "extremely"/"unable"/"confined"). We employed the area under the receiver operating characteristic curve (AUROC) to evaluate whether the EQ-5D-3L total score could identify participants with diagnosed diseases and mental health disorders. Psychometric validation of the EQ-5D-3L investigated dimensionality with Exploratory Graph Analysis, model fit, floor/ceiling effects and criterion validity. RESULTS: The EQ-5D-3L comprised two dimensions, Activities and Symptoms. According to Root Mean Squared Error of Approximation (RMSEA) (.950), the 2-dimensional structure showed excellent model fit with good reliability for the Activities subscale (Ωc = 0.80 - 95% CI [0.77, 0.83]), and poor reliability for the Symptom subscale (Ωc =0.56 - 95% CI [0.53, 0.58]). The EQ-5D-3L showed adequate reliability (Ωc= 0.70 - 95% CI [0.67, 0.72]). The EQ-5D-3L showed good discrimination for diagnosed diseases (ranging from 64.3% to 86.3%). Floor/ceiling effects were observed across all items. The EQ-5D-3L total score discriminated between respondents who were experiencing health conditions (e.g. cancer, cardiovascular disease, stroke) from healthy individuals. DISCUSSION: Despite the ceiling effects, the EQ-5D-3L displayed good psychometric properties as an HRQoL measure and discriminated between health states in the general South Australian population. Further research should investigate the psychometric properties of the EQ-5D-5L in South Australia and whether an increased number of response categories can mitigate the observed ceiling effects.Mehrsa Zakershahrak, Pedro Henrique Ribeiro Santiago, Sneha Sethi, Dandara Haag, Lisa Jamieson and David Brenna