Iron status and the risk of sepsis and severe COVID-19: a two-sample Mendelian randomization study

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Insomnia symptoms and risk of bloodstream infections : prospective data from the prospective population-based Nord-Trøndelag Health Study (HUNT), Norway

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Trends in mortality after a sepsis hospitalization : a nationwide prospective registry study from 2008 to 2021

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Long-term temporal trends in incidence rate and case fatality of sepsis and COVID-19-related sepsis in Norwegian hospitals, 2008-2021: a nationwide registry study

Objectives: To estimate temporal trends in incidence rate (IR) and case fatality during a 14-year period from 2008 to 2021, and to assess possible shifts in these trends during the COVID-19 pandemic. Setting: All Norwegian hospitals 2008–2021. Participants: 317 705 patients ≥18 year with a sepsis International Classification of Diseases 10th revision code retrieved from The Norwegian Patient Registry. Primary and secondary measures: Annual age-standardised IRs with 95% CIs. Poisson regression was used to estimate changes in IRs across time, and logistic regression was used to estimate ORs for in-hospital death. Results: Among 12 619 803 adult hospitalisations, a total of 317 705 (2.5%) hospitalisations in 222 832 (70.0%) unique patients met the sepsis criteria. The overall age-standardised IR of a first sepsis admission was 246/100 000 (95% CI 245 to 247), whereas the age-standardised IR of all sepsis admissions was 352/100 000 (95% CI 351 to 354). In the period 2009–2019, the annual IR for a first sepsis episode was stable (IR ratio (IRR) per year, 0.999; 95% CI 0.994 to 1.004), whereas for recurrent sepsis the IR increased (annual IRR, 1.048; 95% CI 1.037 to 1.059). During the COVID-19 pandemic, the IRR for a first sepsis was 0.877 (95% CI 0.829 to 0.927) in 2020 and 0.929 (95% CI 0.870 to 0.992) in 2021, and for all sepsis it was 0.870 (95% CI 0.810 to 0.935) in 2020 and 0.908 (95% CI 0.840 to 0.980) in 2021, compared with the previous 11-year period. Case fatality among first sepsis admissions declined in the period 2009–2019 (annual OR 0.954 (95% CI 0.950 to 0.958)), whereas case fatality increased during the COVID-19 pandemic in 2020 (OR 1.061 (95% CI 1.001 to 1.124) and in 2021 (OR 1.164 (95% CI 1.098 to 1.233)). Conclusion: The overall IR of sepsis increased from 2009 to 2019, due to an increasing IR of recurrent sepsis, and indicates that sepsis awareness with updated guidelines and education must continue.publishedVersio

The detrimental effects of intestinal injury mediated by inflammation are limited in cardiac arrest patients: A prospective cohort study

Background: Ischaemic intestines could be a driver of critical illness through an inflammatory response. We have previously published reports on a biomarker for intestinal injury, plasma Intestinal Fatty Acid Binding Protein (IFABP), and inflammatory biomarkers after out-of-hospital cardiac arrest (OHCA). In this post-hoc study we explored the potential indirect effects of intestinal injury mediated through the inflammatory response on organ dysfunction and mortality. Methods: We measured IFABP and twenty-one inflammatory biomarkers in 50 patients at admission to intensive care unit after OHCA. First, we stratified patients on median IFABP and compared biomarkers between “low” and “high” IFABP. Second, by causal mediation analysis, we assessed effects of IFABP through the two most important inflammatory biomarkers, interleukin (IL)-6 and terminal complement complex (TCC), on day two circulatory variables, Sequential Organ Failure Assessment (SOFA)-score, and 30-day mortality. Results: Cytokines and complement activation were higher in the high IFABP group. In mediation analysis, patients on the 75th percentile of IFABP, compared to the 25th percentile, had 53% (95% CI, 33–74; p < 0.001) higher risk of dying, where 13 (95% CI, 3–23; p = 0.01) percentage points were mediated through an indirect effect of IL-6. Similarly, the indirect effect of IFABP through IL-6 on SOFA-score was significant, but smaller than potential other effects. Effects through IL-6 on circulatory variables, and all effects through TCC, were not statistically significant and/or small. Conclusion: Effects of intestinal injury mediated through inflammation on organ dysfunction and mortality were limited. Small, but significant, effects through IL-6 were noted.Trial registration: ClinicalTrials.gov: NCT02648061

Associations of obesity and lifestyle with the risk and mortality of bloodstream infection in a general population: a 15-year follow-up of 64 027 individuals in the HUNT Study

Background: Bloodstream infections (BSI) cause considerable morbidity and mortality, and primary prevention should be a priority. Lifestyle factors are of particular interest since they represent a modifiable target. Methods: We conducted a prospective cohort study among participants in the population-based Norwegian HUNT2 Survey, where 64 027 participants were followed from 1995–97 through 2011 by linkage to prospectively recorded information on BSI at local and regional hospitals. The exposures were: baseline body mass index (BMI) measurements; and self-reported smoking habits, leisure time physical activity and alcohol intake. The outcomes were hazard ratios (HR) of BSI and BSI mortality. Results: During 810 453 person-years and median follow-up of 14.8 years, 1844 (2.9%) participants experienced at least one BSI and 396 (0.62%) died from BSI. Compared with normal weight participants (BMI 18.5–24.9 kg/m2), the age- and sex-adjusted risk of a first-time BSI was 31% [95% confidence interval (CI) 14–51%] higher at BMI 30.0–34.9 kg/m2, 87% (95% CI 50–135%) higher at BMI 35.0–39.9 kg/m2 and 210% (95% CI 117–341%) higher at BMI ≥ 40.0 kg/m2. The risk of BSI mortality was similarly increased. Compared with never-smokers, current smokers had 51% (95% CI 34–70%) and 75% (95% CI 34–129%) higher risks of BSI and BSI mortality, respectively. Physically inactive participants had 71% (95% CI 42–107%) and 108% (95% CI 37–216%) higher risks of BSI and BSI mortality, respectively, compared with the most physically active

Association of Genetically Predicted Insomnia with Risk of Sepsis: A Mendelian Randomization Study

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Iron status and the risk of sepsis and severe COVID-19: a two-sample Mendelian randomization study

Observational studies have indicated an association between iron status and risk of sepsis and COVID-19. We estimated the effect of genetically-predicted iron biomarkers on risk of sepsis and risk of being hospitalized with COVID-19, performing a two-sample Mendelian randomization study. For risk of sepsis, one standard deviation increase in genetically-predicted serum iron was associated with odds ratio (OR) of 1.14 (95% confidence interval [CI] 1.01–1.29, P = 0.031). The findings were supported in the analyses for transferrin saturation and total iron binding capacity, while the estimate for ferritin was inconclusive. We found a tendency of higher risk of hospitalization with COVID-19 for serum iron; OR 1.29 (CI 0.97–1.72, P = 0.08), whereas sex-stratified analyses showed OR 1.63 (CI 0.94–2.86, P = 0.09) for women and OR 1.21 (CI 0.92–1.62, P = 0.17) for men. Sensitivity analyses supported the main findings and did not suggest bias due to pleiotropy. Our findings suggest a causal effect of genetically-predicted higher iron status and risk of hospitalization due to sepsis and indications of an increased risk of being hospitalized with COVID-19. These findings warrant further studies to assess iron status in relation to severe infections, including the potential of improved management

Insomnia symptoms and risk of bloodstream infections: prospective data from the prospective population-based Nord-Trøndelag Health Study (HUNT), Norway

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