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Purpose Normative scores (norms) allow for comparisons between population(s) of interest and the general population, which is useful for burden of disease studies and cost-effectiveness analysis. The primary aim of this study was to estimate US visual analogue scale (EQ VAS) and utility-based norms for the EQ-5D-5L using the face-to-face sample. The secondary aim was to compare norms estimated in the face-to-face and online populations. Methods This study estimated population norms from two general population surveys: (a) face-to-face and (b) online. In these surveys, respondents provided their health state using the EQ-5D-5L health classifier and the EQ VAS. Descriptive statistics, including mean, standard deviation (SD), 95% confidence interval, and median for the 5L utility and EQ VAS were estimated for each sample and across relevant respondent characteristics to serve as the basis for US EQ-5D-5L norms Results Face-to-face sample respondents ( n  = 1134) were representative of the US adult general population. In this sample, mean (SD) utility decreased with increasing age until age 45 or greater (age 45–54: 0.816 (0.249) age 55–64: 0.815 (0.243) age 65–74: 0.824 (0.217) age 75 + : 0.811 (0.218)). With increasing age, more problems were reported on all dimensions except anxiety/depression; a smaller proportion of respondents age 65 and older reported problems with anxiety/depression (23.8%) as compared to the youngest respondents (42.1%). Online ( n  = 2018) mean utility and EQ VAS values were consistently lower than the face-to-face sample. Conclusions The availability of US EQ-5D-5L norms facilitates interpretation and understanding of general population and patient health.

Purpose Although the EQ-5D has a long history of use in a wide range of populations, the newer five-level version (EQ-5D-5L) has not yet had such extensive experience. This systematic review summarizes the available published scientific evidence on the psychometric properties of the EQ-5D-5L. Methods Pre-determined key words and exclusion criteria were used to systematically search publications from 2011 to 2019. Information on study characteristics and psychometric properties were extracted: specifically, EQ-5D-5L distribution (including ceiling and floor), missing values, reliability (test–retest), validity (convergent, known-groups, discriminate) and responsiveness (distribution, anchor-based). EQ-5D-5L index value means, ceiling and correlation coefficients (convergent validity) were pooled across the studies using random-effects models. Results Of the 889 identified publications, 99 were included for review, representing 32 countries. Musculoskeletal/orthopedic problems and cancer ( n  = 8 each) were most often studied. Most papers found missing values (17 of 17 papers) and floor effects (43 of 48 papers) to be unproblematic. While the index was found to be reliable (9 of 9 papers), individual dimensions exhibited instability over time. Index values and dimensions demonstrated moderate to strong correlations with global health measures, other multi-attribute utility instruments, physical/functional health, pain, activities of daily living, and clinical/biological measures. The instrument was not correlated with life satisfaction and cognition/communication measures. Responsiveness was addressed by 15 studies, finding moderate effect sizes when confined to studied subgroups with improvements in health. Conclusions The EQ-5D-5L exhibits excellent psychometric properties across a broad range of populations, conditions and settings. Rigorous exploration of its responsiveness is needed.

Background Since the introduction of the five-level version of the EQ-5D (5L), many studies have comparatively investigated the measurement properties of the original three-level version (3L) with the 5L version. Objective The aim of this study was to consolidate the available evidence on the performance of both instruments. Methods A systematic literature search of studies in the English and German languages was conducted (2007–January 2018) using the PubMed, EMBASE, and PsycINFO (EBSCO) databases, as well as the EuroQol Research Foundation website. Data were extracted and assessed on missing values, distributional properties, informativity indices (Shannon’s H′ and J′), inconsistencies, responsiveness, and test–retest reliability. Results Twenty-four studies were included in the review. Missing values and floor effects (percentage reporting the worst health state) were found to be negligible for both 3L and 5L (< 5%). From 18 studies, inconsistencies ranged from 0 to 10.6%, although they were generally well below 5%, with 9 studies reporting the most inconsistencies for Usual Activities (mean percentage 4.1%). Shannon’s indices were always higher for 5L than for 3L, and all but three studies reported lower ceiling effects (‘11111’) for 5L than for 3L. There is mixed and insufficient evidence on responsiveness and test–retest reliability, although results on index values showed better performance for 5L on test–retest reliability. Conclusion Overall, studies showed similar or better measurement properties of the 5L compared with the 3L, and evidence indicated moderately better distributional parameters and substantial improvement in informativity for the 5L compared with the 3L. Insufficient evidence on responsiveness and test–retest reliability implies further research is needed.

This study provides EQ-5D population norms for 20 countries (N = 163,838), which can be used to compare profiles for patients with specific conditions with data for the average person in the general population in a similar age and/or gender group. Descriptive EQ-5D data are provided for the total population, by gender and by seven age groups. Provided index values are based on European VAS for all countries, based on TTO for 11 countries and based on VAS for 10 countries. Important differences exist in EQ-5D reported health status across countries after standardizing for population structure. Self-reported health according to all five dimensions and EQ VAS generally decreased with increasing age and was lower for females. Mean self-rated EQ VAS scores varied from 70.4 to 83.3 in the total population by country. The prior living standards (GDP per capita) in the countries studied are correlated most with the EQ VAS scores (0.58), while unemployment appeared to be significantly correlated in people over the age of 45 only. A country's expenditure on health care correlated moderately with higher ratings on the EQ VAS (0.55). EQ-5D norms can be used as reference data to assess the burden of disease of patients with specific conditions. Such information, in turn, can inform policy-making and assist in setting priorities in health care.

The EQ-5D instrument is now used in many health systems as a health outcomes measure. Recently an EQ-5D valuation study was conducted for Trinidad and Tobago, but thus far there have been no population norms published for Trinidad and Tobago or for any Caribbean country. The objective of this study is to provide a set of population norms, and to investigate inequalities in health in Trinidad and Tobago. The EQ-5D-5L questionnaire was included in the 2012/2013 Adult Population Survey of the Global Entrepreneurship Monitor for Trinidad and Tobago. This survey covered a representative sample of 2,036 adults aged 18 and over. Demographic data and self-reported health using EQ-5D-5L were collected. The Trinidad and Tobago value set was used to obtain EQ-5D index values. The Kakwani index and logistic regression models were used to evaluate inequalities in health. Mean EQ-5D index values and EQ-VAS values were calculated by age group, ethnicity, gender, income, educational attainment, employment status and place of residence. The 10 most commonly observed EQ-5D-5L states accounted for 90% of the respondents. The mean VAS value for the sample was 83.6 and the mean EQ-5D-5L index value was 0.95. Pain/discomfort was found to be the EQ-5D dimension with the highest prevalence of reported problems with 22% of the population reporting pain at any level. Self-care was the dimension with the lowest prevalence of problems reported at any level (3%). Health declines with increasing age, and men reported fewer problems and higher levels of self-reported health than women. Age, gender and education level were found to be important drivers of health status as measured by the EQ-5D instrument. Being in a very low income group was also observed to affect EQ-VAS values among younger respondents. The population norms provided in this study can be used by clinicians, academics and policy makers in several ways. They can be used in comparing different demographic groups or patient groups, or as a basis for tracking the progress of patients through a treatment regimen. They can also provide a baseline for cost utility analysis of health interventions for Trinidad and Tobago.

Background The EQ-5D-5L and 15D are generic preference-accompanied health status measures with similar dimensions. In this study, we aim to compare the measurement properties of the EQ-5D-5L and 15D descriptive systems and index values in a general population sample. Methods In August 2021, an online cross-sectional survey was conducted in a representative adult general population sample (n = 1887). The EQ-5D-5L and 15D descriptive systems and index values were compared in terms of ceiling and floor, informativity (Shannon’s Evenness index), agreement, convergent and known-groups validity for 41 chronic physical and mental health conditions. Danish value sets were used to compute index values for both instruments. As a sensitivity analysis, index values were also estimated using the Hungarian EQ-5D-5L and Norwegian 15D value sets. Results Overall, 270 (8.6%) and 1030 (3.4*10 −6 %) unique profiles occurred on the EQ-5D-5L and 15D. The EQ-5D-5L dimensions (0.51–0.70) demonstrated better informativity than those of 15D (0.44–0.69). EQ-5D-5L and 15D dimensions capturing similar areas of health showed moderate or strong correlations (0.558–0.690). The vision, hearing, eating, speech, excretion and mental function 15D dimensions demonstrated very weak or weak correlations with all EQ-5D-5L dimensions, which may indicate potential room for EQ-5D-5L bolt-ons. The 15D index values showed lower ceiling than the EQ-5D-5L (21% vs. 36%). The mean index values were 0.86 for the Danish EQ-5D-5L, 0.87 for the Hungarian EQ-5D-5L, 0.91 for the Danish 15D and 0.81 for the Norwegian 15D. Strong correlations were found between the index values (Danish EQ-5D-5L vs. Danish 15D 0.671, Hungarian EQ-5D-5L vs. Norwegian 15D 0.638). Both instruments were able to discriminate between all chronic condition groups with moderate or large effect sizes (Danish EQ-5D-5L 0.688–3.810, Hungarian EQ-5D-5L 1.233–4.360, Danish 15D 0.623–3.018 and Norwegian 15D 1.064–3.816). Compared to the 15D, effect sizes were larger for the EQ-5D-5L in 88–93% of chronic condition groups. Conclusions This is the first study to compare the measurement properties of the EQ-5D-5L and 15D in a general population sample. Despite having 10 fewer dimensions, the EQ-5D-5L performed better than the 15D in many aspects. Our findings help to understand the differences between generic preference-accompanied measures and support resource allocation decisions.

Background A subset of critically ill COVID-19 patients develop a hyperinflammatory state. Anakinra, a recombinant interleukin-1 receptor antagonist, is known to be effective in several hyperinflammatory diseases. We investigated the effects of anakinra on inflammatory parameters and clinical outcomes in critically ill, mechanically ventilated COVID-19 patients with clinical features of hyperinflammation. Methods In this prospective cohort study, 21 critically ill COVID-19 patients treated with anakinra were compared to a group of standard care. Serial data of clinical inflammatory parameters and concentrations of multiple circulating cytokines were determined and aligned on start day of anakinra in the treatment group, and median start day of anakinra in the control group. Analysis was performed for day − 10 to + 10 relative to alignment day. Clinical outcomes were analyzed during 28 days. Additionally, three sensitivity analyses were performed: (1) using propensity score-matched groups, (2) selecting patients who did not receive corticosteroids, and (3) using a subset of the control group aimed to match the criteria (fever, elevated ferritin) for starting anakinra treatment. Results Baseline patient characteristics and clinical parameters on ICU admission were similar between groups. As a consequence of bias by indication, plasma levels of aspartate aminotransferase (ASAT) ( p  = 0.0002), ferritin ( p  = 0.009), and temperature ( p  = 0.001) were significantly higher in the anakinra group on alignment day. Following treatment, no relevant differences in kinetics of circulating cytokines were observed between both groups. Decreases of clinical parameters, including temperature ( p  = 0.03), white blood cell counts ( p  = 0.02), and plasma levels of ferritin ( p  = 0.003), procalcitonin ( p  = 0.001), creatinine ( p  = 0.01), and bilirubin ( p  = 0.007), were more pronounced in the anakinra group. No differences in duration of mechanical ventilation or ICU length of stay were observed between groups. Sensitivity analyses confirmed these results. Conclusions Anakinra is effective in reducing clinical signs of hyperinflammation in critically ill COVID-19 patients. A randomized controlled trial is warranted to draw conclusion about the effects of anakinra on clinical outcomes.

The COVID-19 pandemic forced many countries to implement confinement measures to limit the spread of the virus. Measuring the loss in terms of quality-adjusted life-years (QALYs) may provide a commensurable basis for comparing the impact of COVID-19. The aim of this research was to explore the impact of the first 21 days of COVID-19 lockdown on health-related quality of life (HRQoL) and associated QALY loss of the Spanish general population. A quota-based online survey was conducted in four waves with 500 general population respondents each: one conducted shortly before the lockdown (baseline) and 3 follow-ups conducted weekly. HRQoL data were collected using EQ-5D-5L. For comparison with pre-covid responses, data from the 2011-2012 National Health Survey was taken as reference. Data were analyzed using frequency analysis and logistic regression. QALY loss was estimated over the follow-up period and for the entire duration of the lockdown. Comparing the baseline results to the follow-up results shows little change with respect to the distributions of reported problems in any of the 5 dimensions during the follow-up period. However, results for anxiety/depression show a 32% increase in the proportion of reported problems. The Spanish population was estimated to accrue a total of 1,994,216 QALYs over the study period. Based on the reference data, the population should have accrued 2,054,737 QALYs, leading to a loss of 60,520 QALYs over 21 days. For the entire lockdown, the corresponding loss would be 285,310 QALYs. A population under a lockdown situation reported higher rates of anxiety/depression problems than in a regular situation. On a country-wide scope, this may lead to a substantial loss in terms of QALYs, especially over longer periods of time. This is the first study to directly assess the impact of the lockdown in terms of QALY loss on a country-wide level.

Inconsistency in the time trade-off (TTO) task in EQ-5D-5L occurs when a respondent gives a higher value to a logically worse health state, the occurrence of inconsistency compromises the quality of the data. It is not yet clear which factors are associated with individual level inconsistency. Relating inconsistency to the characteristics of the respondent, interviewer, and the interview process could be helpful in understanding the causes of inconsistency. The objective of this paper is to discover the factors associated with individual level inconsistencies. Twenty interviewers interviewed 1,296 respondents and each respondent valued 10 health states using the EQ-VT platform in 5 cities in China. At the respondent level, inconsistency was identified in terms of severity and quantity and related to the respondent's background characteristics, the time and iterations spent on the wheelchair example task, and the formal TTO tasks, using multilevel multinomial regression analyses. Interviewers' impact on inconsistencies was analyzed using single level multinomial regression analyses. In the full dataset, slight inconsistency was more related to the interview process (Time spent on TTO task: RRR = 1.246 with 95%CI: 1.076,1.441; time spent on Wheelchair example: RRR = 0.815 with 95%CI:0.699,0.952) while severe inconsistency was more related to respondent's gender (Gender: RRR = 2.347 with 95%CI:1.429,3.855). One Interviewer (Interviewer 7: RRR = 7.335 with 95%CI:1.908,28.195) and interviewer's experience (Sequence: RRR = 0.511 with 95%CI:0.385,0.678) in general showed strong influence over inconsistency in the TTO task. In conclusion, logical inconsistency in the valuation of EQ-5D-5L health states is associated not only with respondents' characteristics but also with interviewers' performance and the interview process. The role of interviewers and the importance of interviewer training may be more crucial than hitherto believed. This finding could be generalizable to other interviewer-administered health-state valuation study.

Intestinal epithelial cells and the intestinal microbiota are in a mutualistic relationship that is dependent on communication. This communication is multifaceted, but one aspect is communication through compounds produced by the microbiota such as the short-chain fatty acids (SCFAs) butyrate, propionate and acetate. Studying the effects of SCFAs and especially butyrate in intestinal epithelial cell lines like Caco-2 cells has been proven problematic. In contrast to the in vivo intestinal epithelium, Caco-2 cells do not use butyrate as an energy source, leading to a build-up of butyrate. Therefore, we used human induced pluripotent stem cell derived intestinal epithelial cells, grown as a cell layer, to study the effects of butyrate, propionate and acetate on whole genome gene expression in the cells. For this, cells were exposed to concentrations of 1 and 10 mM of the individual short-chain fatty acids for 24 h. Unique gene expression profiles were observed for each of the SCFAs in a concentration-dependent manner. Evaluation on both an individual gene level and pathway level showed that butyrate induced the biggest effects followed by propionate and then acetate. Several known effects of SCFAs on intestinal cells were confirmed, such as effects on metabolism and immune responses. The changes in metabolic pathways in the intestinal epithelial cell layers in this study demonstrate that there is a switch in energy homeostasis, this is likely associated with the use of SCFAs as an energy source by the induced pluripotent stem cell derived intestinal epithelial cells similar to in vivo intestinal tissues where butyrate is an important energy source.