Do hospitals have a higher mortality rate on weekend admissions? An observational study to analyse weekend effect on urgent admissions to hospitals in Catalonia

Background 'Weekend effect' is a term used to describe the increased mortality associated with weekend emergency admissions to hospital, in contrast with admission on weekdays. The objective of the present study is to determine whether the weekend effect is present in hospitals in Catalonia. Methods We analysed all urgent admissions in Catalonia in 2018, for a group of pathologies. Two groups were defined (those admitted on a weekday and those admitted on a weekend). We obtained mortality at 3, 7, 15 and 30 days, and applied a proportions test to both groups. Additionally, we used Cox's regression for mortality at 30 days, using the admission on a weekend as the exposition, adjusting by socioeconomic and clinical variables. We used the hospital discharge database and the Central Registry of the Insured Population. Results 72 427 admissions for the selected pathologies during 2018 were found. No statistically significant differences in mortality at 30 days (p=0.524) or at 15 days (p=0.119) according to the day of admission were observed. However, significant differences were found in mortality at 7 days (p=0.025) and at 3 days (p=0.002). The hazard rate associated with the weekend was 1.13 (95% CI: 1.04 to 1.23). By contrast, the adjusted HR of the weekend interaction with time was 0.99 (95% CI: 0.99 to 1.00). Conclusions There is a weekend effect, but it is not constant in time. This could suggest the existence of dysfunctions in the quality of care during the weekend

Advance directives and real-world end-of-life clinical practice : a case-control study

Background Advance directives (ADs) have been legally regulated to promote autonomy over health decisions among patients who later lose decision-making capacity. Aims and objectives To analyse the differences in clinical practice at end of life among people who had completed an AD versus those who had not. Methods Retrospective case-control study (1:2), matched by age, sex, year, cause of death and region of residence. The data sources used were the ADs registry, central registry of insured persons, hospital discharge, pharmacy and billing databases, and the mortality registry. Conditional logistic regression models (crude and adjusted by socioeconomic level) were performed. The outcome variable was the frequency of medical procedures performed during the last year of life. Results 1723 people with ADs who died in Catalonia during 2014-2015 were matched with 3446 dead controls (without ADs). Thoracentesis was the procedure with the greatest reduction among women with an AD (adjusted OR (OR adj) 0.54, 95% CI: 0.32 to 0.89) in conjunction with artificial nutrition (OR adj 0.54, 95% CI: 0.31 to 0.95). Intubation was the procedure with the greatest reduction (OR adj 0.56, 95% CI: 0.33 to 0.94) among men. Slight differences could be seen in the case of cancer deaths. There were no relevant differences when adjusting by socioeconomic level. Conclusions ADs are an effective tool to adjust the realisation of some procedures at end of life. These results can help better plan for the treatment of patients with ADs, as well as increase the awareness among clinical personnel, families and the general population

A gene co-association network regulating gut microbial communities in a Duroc pig population

Background: Analyses of gut microbiome composition in livestock species have shown its potential to contribute to the regulation of complex phenotypes. However, little is known about the host genetic control over the gut microbial communities. In pigs, previous studies are based on classical "single-gene-single-trait" approaches and have evaluated the role of host genome controlling gut prokaryote and eukaryote communities separately. Results: In order to determine the ability of the host genome to control the diversity and composition of microbial communities in healthy pigs, we undertook genome-wide association studies (GWAS) for 39 microbial phenotypes that included 2 diversity indexes, and the relative abundance of 31 bacterial and six commensal protist genera in 390 pigs genotyped for 70 K SNPs. The GWAS results were processed through a 3-step analytical pipeline comprised of (1) association weight matrix; (2) regulatory impact factor; and (3) partial correlation and information theory. The inferred gene regulatory network comprised 3561 genes (within a 5 kb distance from a relevant SNP-P < 0.05) and 738,913 connections (SNP-to-SNP co-associations). Our findings highlight the complexity and polygenic nature of the pig gut microbial ecosystem. Prominent within the network were 5 regulators, PRDM15, STAT1, ssc-mir-371, SOX9 and RUNX2 which gathered 942, 607, 588, 284 and 273 connections, respectively. PRDM15 modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency and regulates the production of Th1- and Th2-type immune response. The signal transducer STAT1 has long been associated with immune processes and was recently identified as a potential regulator of vaccine response to porcine reproductive and respiratory syndrome. The list of regulators was enriched for immune-related pathways, and the list of predicted targets includes candidate genes previously reported as associated with microbiota profile in pigs, mice and human, such as SLIT3, SLC39A8, NOS1, IL1R2, DAB1, TOX3, SPP1, THSD7B, ELF2, PIANP, A2ML1, and IFNAR1. Moreover, we show the existence of host-genetic variants jointly associated with the relative abundance of butyrate producer bacteria and host performance

Leveraging host-genetics and gut microbiota to determine immunocompetence in pigs

The gut microbiota influences host performance playing a relevant role in homeostasis and function of the immune system. The aim of the present work was to identify microbial signatures linked to immunity traits and to characterize the contribution of host-genome and gut microbiota to the immunocompetence in healthy pigs. To achieve this goal, we undertook a combination of network, mixed model and microbial-wide association studies (MWAS) for 21 immunity traits and the relative abundance of gut bacterial communities in 389 pigs genotyped for 70K SNPs. The heritability (h 2 ; proportion of phenotypic variance explained by the host genetics) and microbiability (m 2 ; proportion of variance explained by the microbial composition) showed similar values for most of the analyzed immunity traits, except for both IgM and IgG in plasma that was dominated by the host genetics, and the haptoglobin in serum which was the trait with larger m 2 (0.275) compared to h 2 (0.138). Results from the MWAS suggested a polymicrobial nature of the immunocompetence in pigs and revealed associations between pigs gut microbiota composition and 15 of the analyzed traits. The lymphocytes phagocytic capacity (quantified as mean fluorescence) and the total number of monocytes in blood were the traits associated with the largest number of taxa (6 taxa). Among the associations identified by MWAS, 30% were confirmed by an information theory network approach. The strongest confirmed associations were between Fibrobacter and phagocytic capacity of lymphocytes (r = 0.37), followed by correlations between Streptococcus and the percentage of phagocytic lymphocytes (r = -0.34) and between Megasphaera and serum concentration of haptoglobin (r = 0.26). In the interaction network, Streptococcus and percentage of phagocytic lymphocytes were the keystone bacterial and immune-trait, respectively. Overall, our findings reveal an important connection between gut microbiota composition and immunity traits in pigs, and highlight the need to consider both sources of information, host genome and microbial levels, to accurately characterize immunocompetence in pigs. The online version contains supplementary material available at 10.1186/s42523-021-00138-9

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Frequency of health-care service use and severity of illness in undocumented migrants in Catalonia, Spain : a population-based, cross-sectional study

Background: In Spain, legislation was passed in 2012 excluding undocumented migrants from the public health-care system. Catalonia was one of the Spanish regions that did not implement this legislation, and continued to guarantee access to health care to the whole population. We aimed to analyse health-care use and health status among undocumented migrants in Catalonia, and compare health-care use and health status with legal residents classified according to their socioeconomic position (SEP). Methods: We did a population-based, cross-sectional study, with administrative individual data. The study included the resident population in Catalonia, Spain, in 2017, aged younger than 65 years and with a maximum annual income of less than €18 000 per year, and classified into three socioeconomic (SEP) groups-low SEP, very low SEP, and undocumented migrants. Indicators regarding health-care service use (primary care, emergency care, mental health care, acute care), drug prescriptions, and selected chronic and infectious diseases were analysed. Findings: Between Jan 1 and Dec 31, 2017, 4 071 988 residents of Catalonia were included in this study; undocumented migrants represented 2·8% (n=113 450) of this population. Of all undocumented migrants, 25 942 (61·0%) female participants aged 15-64 years and 19 819 (46·0%) male participants aged 15-64 years attended primary health-care centres: these rates were lower than in individuals with a very low SEP (84·8% in female participants and 72·1% in male participants). Hospital admission rates among male participants aged 15-64 years in the very low SEP group were more than three times as high as in undocumented migrants (111·6 vs 35·7). The highest tuberculosis rate was found in undocumented male migrants (incidence rate 4·35 [95% CI 3·55-5·16]). Interpretation: Undocumented migrants made less use of health-care services than those in the low and very low SEP groups, but for some infectious diseases, incidence was higher in undocumented migrants. These results constitute an additional argument to support the maintenance of universal health coverage for all citizens. Funding: None