Head-to-head comparison between the EQ-5D-5L and the EQ-5D-3L in general population health surveys

Background

The EQ-5D has been frequently used in national health surveys. This study is a head-to-head comparison to assess how expanding the number of levels from three (EQ-5D-3L) to five in the new EQ-5D-5L version has improved its distribution, discriminatory power, and validity in the general population.

Methods

A representative sample (N?=?7554) from the Catalan Health Interview Survey 2011–2012, aged ≥18, answered both EQ-5D versions, and we evaluated the response redistribution and inconsistencies between them. To assess validity of this redistribution, we calculated the mean of the Visual Analogue Scale (VAS), which measures perceived health. The discriminatory power was examined with Shannon Indices, calculated for each dimension separately. Spanish preference value sets were applied to obtain utility indices, examining their distribution with statistics of central tendency and dispersion. We estimated the proportion of individuals reporting the best health state in EQ-5D-5L and EQ-5D-3L within groups of specific chronic conditions and their VAS mean.

Results

A very small reduction in the percentage of individuals with the best health state was observed, from 61.8% in EQ-5D-3L to 60.8% in EQ-5D-5L. In contrast, a large proportion of individuals reporting extreme problems in the 3 L version moved to severe problems (level 4) in the 5 L version, particularly for pain/discomfort (75.5%) and anxiety/depression (66.4%). The average proportion of inconsistencies was 0.9%. The pattern of the perceived health VAS mean confirmed the hypothesis established a priori, supporting the validity of the observed redistribution. Shannon index showed that absolute informativity was higher in the 5 L version for all dimensions. The means (SD) of the Spanish EQ-5D-3L and EQ-5D-5L indices were 0.87 (0.25) and 0.89 (0.22). The proportion of individuals with the best health state within each specific chronic condition was very similar, regardless of the EQ-5D version (≤?30% in half of the 28 chronic conditions).

Conclusion

Although the proportion of individuals with the best possible health state is still very high, our findings support that the increase of levels provided by the EQ-5D-5L contributed to the validity and discriminatory power of this new version to measure health in general population, as in the national health surveys.

     

Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock

OBJECTIVE: To assess whether combination antibiotic therapy improves outcome of severe community-acquired pneumonia in the subset of patients with shock. DESIGN: Secondary analysis of a prospective observational, cohort study. SETTING: Thirty-three intensive care units (ICUs) in Spain. PATIENTS: Patients were 529 adults with community-acquired pneumonia requiring ICU admission. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Two hundred and seventy (51%) patients required vasoactive drugs and were categorized as having shock. The effects of combination antibiotic therapy and monotherapy on survival were compared using univariate analysis and a Cox regression model. The adjusted 28-day in-ICU mortality was similar (p = .99) for combination antibiotic therapy and monotherapy in the absence of shock. However, in patients with shock, combination antibiotic therapy was associated with significantly higher adjusted 28-day in-ICU survival (hazard ratio, 1.69; 95% confidence interval, 1.09-2.60; p = .01) in a Cox hazard regression model. Even when monotherapy was appropriate, it achieved a lower 28-day in-ICU survival than an adequate antibiotic combination (hazard ratio, 1.64; 95% confidence interval, 1.01-2.64). CONCLUSIONS: Combination antibiotic therapy does not seem to increase ICU survival in all patients with severe community-acquired pneumonia. However, in the subset of patients with shock, combination antibiotic therapy improves survival rates.     

Trained immunity in organ transplantation

Consistent induction of donor‐specific unresponsiveness in the absence of continuous immunosuppressive therapy and toxic effects remains a difficult task in clinical organ transplantation. Transplant immunologists have developed numerous experimental treatments that target antigen‐presentation (signal 1), costimulation (signal 2), and cytokine production (signal 3) to establish transplantation tolerance. While promising results have been obtained using therapeutic approaches that predominantly target the adaptive immune response, the long‐term graft survival rates remain suboptimal. This suggests the existence of unrecognized allograft rejection mechanisms that contribute to organ failure. We postulate that trained immunity stimulatory pathways are critical to the immune response that mediates graft loss. Trained immunity is a recently discovered functional program of the innate immune system, which is characterized by nonpermanent epigenetic and metabolic reprogramming of macrophages. Since trained macrophages upregulate costimulatory molecules (signal 2) and produce pro‐inflammatory cytokines (signal 3), they contribute to potent graft reactive immune responses and organ transplant rejection. In this review, we summarize the detrimental effects of trained immunity in the context of organ transplantation and describe pathways that induce macrophage training associated with graft rejection.     

One-Stage Revision Arthroplasty Using Cementless Stem for Infected Hip Arthroplasties

The objective of this retrospective study was to evaluate our results with one-stage revision using cementless femoral stem for infected hip arthroplasties. Twenty-four patients were included in the study. The acetabular component was cemented in 9 cases. In 2 patients a structured bone allograft was necessary to fill an acetabular defect. After a mean follow-up of 44.6 months, 23 patients showed no signs of infection (95.8%), the mean functional response according to the Merle d’Aubigné scale was 13.8 and the mean Harris Hip Score was 65.4. One-stage revision hip arthroplasty using cementless femoral stem was associated with a high success rate.     

Highly reactive 2-deoxy-2-iodo-d-allo and d-gulo pyranosyl sulfoxide donors ensure β-stereoselective glycosylations with steroidal aglycones

The preparation of well-defined d-xylo and d-ribo glycosides represents a synthetic challenge due to the limited configurational availability of starting materials and the laborious synthesis of homogeneous 2-deoxy-β-glycosidic linkages, in particular that of the sugar-steroid motif, which represents the “stereoselective determining step” of the overall synthesis. Herein we describe the use of 2-deoxy-2-iodo-glycopyranosyl sulfoxides accessible from widely available d-xylose and d-ribose monosaccharides as privileged glycosyl donors that permit activation at very low temperature. This ensures a precise kinetic control for a complete 1,2-trans stereoselective glycosylation of particularly challenging steroidal aglycones.

Highly stereoselective synthesis of challenging steroidal 2-deoxy-β-glycosides with d-xylo and d-ribo configurations enabled by low temperature activation of 2-deoxy-2-iodoglycopyranosyl sulfoxides.     

DnaK dependence of mutant ethanol oxidoreductases evolved for aerobic function and protective role of the chaperone against protein oxidative damage in Escherichia coli

The adhE gene of Escherichia coli encodes a multifunctional ethanol oxidoreductase (AdhE) that catalyzes successive reductions of acetyl-CoA to acetaldehyde and then to ethanol reversibly at the expense of NADH. Mutant JE52, serially selected for acquired and improved ability to grow aerobically on ethanol, synthesized an AdhE(A267T/E568K) with two amino acid substitutions that sequentially conferred improved catalytic properties and stability. Here we show that the aerobic growth ability on ethanol depends also on protection of the mutant AdhE against metal-catalyzed oxidation by the chaperone DnaK (a member of the Hsp70 family). No DnaK protection of the enzyme is evident during anaerobic growth on glucose. Synthesis of DnaK also protected E. coli from H2O2 killing under conditions when functional AdhE is not required. Our results therefore suggest that, in addition to the known role of protecting cells against heat stress, DnaK also protects numerous kinds of proteins from oxidative damage.     

Genetic specificity of a plant–insect food web: Implications for linking genetic variation to network complexity

Theory predicts that intraspecific genetic variation can increase the complexity of an ecological network. To date, however, we are lacking empirical knowledge of the extent to which genetic variation determines the assembly of ecological networks, as well as how the gain or loss of genetic variation will affect network structure. To address this knowledge gap, we used a common garden experiment to quantify the extent to which heritable trait variation in a host plant determines the assembly of its associated insect food web (network of trophic interactions). We then used a resampling procedure to simulate the additive effects of genetic variation on overall food-web complexity. We found that trait variation among host-plant genotypes was associated with resistance to insect herbivores, which indirectly affected interactions between herbivores and their insect parasitoids. Direct and indirect genetic effects resulted in distinct compositions of trophic interactions associated with each host-plant genotype. Moreover, our simulations suggest that food-web complexity would increase by 20% over the range of genetic variation in the experimental population of host plants. Taken together, our results indicate that intraspecific genetic variation can play a key role in structuring ecological networks, which may in turn affect network persistence.Network theory has provided both a conceptual and a quantitative approach for mapping interactions between species and making predictions about how the gain or loss of species will affect the structure and dynamics of ecological networks (1–3). Representing a network at the species level, however, makes the implicit assumption that each species consists of a homogenous population of individuals, all of which interact equally with individuals of different species. However, most populations are heterogeneous mixtures of individuals that vary in their phenotypes, and there is growing evidence that this intraspecific variation is an important factor governing the assembly of ecological communities (4–6). Consequently, there is a clear need to account for the role of intraspecific variation in structuring ecological networks (7).Genetic variation is a key driver of intraspecific variation and many studies have now demonstrated direct and indirect genetic effects on species interactions (8–10) and the composition of communities across multiple trophic levels (11–14). This prior work forms a clear expectation that intraspecific genetic variation is capable of scaling up to affect the structure of an ecological network. In particular, we expect that network structure will be affected by genetic variation through at least two different mechanisms. For a food web (network of trophic interactions), genetic variation in the quality of a basal resource may alter the (i) abundances or (ii) phenotypes of consumer species or both (15). These direct genetic effects on consumers may then have cascading effects on the strength of trophic interactions between consumers and their predators (15), resulting in distinct compositions of trophic interactions associated with different genotypes of the basal resource (Fig. 1). If such genetic specificity in the composition of trophic interactions occurs, then theory predicts that increasing genetic variation will result in more interactions per species (6, 16) and therefore greater food-web complexity (Fig. 2). Moreover, greater complexity may in turn affect food-web dynamics, as more complex food webs are predicted to be more robust to species extinctions (3, 17). However, whether genetic variation is capable of scaling up to affect food-web complexity is currently unclear.Open in a separate windowFig. 1.Genetic specificity of trophic interactions in a plant–insect food web. The species comprising the food web in this study include a host plant (coastal willow, S. hookeriana), four herbivorous galling insects, and six insect parasitoids (species details in Materials and Methods). The plant–insect food web consists of 16 trophic interactions (4 willow–gall and 12 gall–parasitoid) aggregated from all plant individuals sampled in this common garden experiment, whereas each genotype subweb represents the trophic interactions aggregated from all plant individuals of the corresponding genotype. We depicted three genotype subwebs (of 26) to illustrate the differences in trophic interactions associated with each willow genotype. The width of each gray segment is proportional to the number of individuals associated with each trophic interaction. Note that we scaled the width of trophic interactions to be comparable among genotype subwebs, but not between subwebs and the aggregated food web, to emphasize the differences among subwebs.Open in a separate windowFig. 2.Conceptual model of how increasing genetic variation (number of shades of green circles) results in greater food-web complexity (number of interactions per species). If different genotypes of a basal resource are associated with distinct compositions of trophic interactions (i.e., genetic specificity of trophic interactions), then increasing genetic variation in the resource will result in a more complex food web because of the increase in the number of interactions per species at all three trophic levels. Colors correspond to different trophic levels (green, basal resource; blue, primary consumer; orange, secondary consumer), whereas different shapes within each trophic level correspond to different species.In this study, we quantify the genetic specificity of trophic interactions and use these data to simulate the additive effects of genetic variation on food-web complexity. To do this, we used a common garden experiment of a host plant (26 genotypes of coastal willow, Salix hookeriana) and its associated food web of insect galls and parasitoids (Fig. 1). We focused on this plant–insect food web for three reasons. First, we have demonstrated in previous work that S. hookeriana (hereafter, willow) displays heritable variation in traits associated with leaf quality (36 traits, mean H² = 0.72) and plant architecture (4 traits, mean H² = 0.27), some of which are also associated with resistance to its community of galling herbivores (18). Second, the unique biology of galling insects makes them ideal for building quantitative food webs. In particular, galls provide a refuge for larva from attack by most generalist predators (19); therefore, galls and their natural enemies often form a distinct subset of the larger food web associated with host plants. In our system, all of the natural enemies are insect parasitoids that complete their development within the gall after parasitizing larva, making it easy to identify and quantify all of the trophic interactions within this food web. Third, the biology of galls is also ideal for identifying the mechanisms mediating trophic interactions. In particular, gall size is a key trait that affects the ability of parasitoids to successfully oviposit through the gall wall and into the larva within the gall (i.e., larger galls provide a refuge from parasitism) (20). Moreover, gall size is determined, in part, by the genotype of the plant (20), so we have a clear mechanism by which genetic variation can affect the strength of trophic interactions. Taken together, our study seeks to examine how intraspecific genetic variation influences the structure of ecological networks. In doing so, our study takes a crucial step toward a more predictive understanding of how the gain or loss of genetic variation will affect the dynamics of ecological networks.