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During analysis of a prospective multinational observation study of critically ill patients ≥80 years of age, the VIP2 study, we also studied the effects of differences in country consent for study inclusion. This is a post hoc analysis where the ICUs were analyzed according to requirement for study consent. Group A: ICUs in countries with no requirement for consent at admission but with deferred consent in survivors. Group B: ICUs where some form of active consent at admission was necessary either from the patient or surrogates. Patients’ characteristics, the severity of disease and outcome variables were compared. Totally 3098 patients were included from 21 countries. The median age was 84 years (IQR 81–87). England was not included because of changing criteria for consent during the study period. Group A (7 countries, 1200 patients), and group B (15 countries, 1898 patients) were comparable with age and gender distribution. Cognition was better preserved prior to admission in group B. Group A suffered from more organ dysfunction at admission compared to group B with Sequential Organ Failure Assessment score median 8 and 6 respectively. ICU survival was lower in group A, 66.2% compared to 78.4% in group B (p<0.001). We hence found profound effects on outcomes according to differences in obtaining consent for this study. It seems that the most severely ill elderly patients were less often recruited to the study in group B. Hence the outcome measured as survival was higher in this group. We therefore conclude that consent likely is an important confounding factor for outcome evaluation in international studies focusing on old patients.

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

[...]the majority of them survives, and in addition, several studies have demonstrated that elderly ICU survivors might accept their disabilities and accommodate to a degree of physical disability quite well, consider their quality of life to be good or satisfactory, and report good emotional and social well-being after hospital discharge [6]. According to this approach, for instance, parents of young children should be prioritized, then parents of teenagers, middle-aged people, then elderly. While there is no hard and fast rule for what is an unfulfilled life age for a person, most policies distributing lifesaving resources look to those under 18 as gaining priority while those in their 80s and beyond, who have had a chance to experience life and flourish as human being, receive lower priority.

Background and Objective Therapeutic drug monitoring of tacrolimus whole-blood concentrations is standard care in thoracic organ transplantation. Nevertheless, toxicity may appear with alleged therapeutic concentrations possibly related to variability in unbound concentrations. However, pharmacokinetic data on unbound concentrations are not available. The objective of this study was to quantify the pharmacokinetics of whole-blood, total, and unbound plasma tacrolimus in patients early after heart and lung transplantation. Methods Twelve-hour tacrolimus whole-blood, total, and unbound plasma concentrations of 30 thoracic organ recipients were analyzed with high-performance liquid chromatography–tandem mass spectrometry directly after transplantation. Pharmacokinetic modeling was performed using non-linear mixed-effects modeling. Results Plasma concentration was < 1% of the whole-blood concentration. Maximum binding capacity of erythrocytes was directly proportional to hematocrit and estimated at 2700 pg/mL (95% confidence interval 1750–3835) with a dissociation constant of 0.142 pg/mL (95% confidence interval 0.087–0.195). The inter-individual variability in the binding constants was considerable (27% maximum binding capacity, and 29% for the linear binding constant of plasma). Conclusions Tacrolimus association with erythrocytes was high and suggested a non-linear distribution at high concentrations. Monitoring hematocrit-corrected whole-blood tacrolimus concentrations might improve clinical outcomes in clinically unstable thoracic organ transplants. Clinical Trial Registration NTR 3912/EudraCT 2012-001909-24.

Purpose Survivors of critical illness often suffer from reduced health-related quality of life (HRQoL) due to long-term physical, cognitive, and mental health problems, also known as post-intensive care syndrome (PICS). Some intensive care unit (ICU) survivors even consider their state of health unacceptable. The aim of this study was to investigate the determinants of self-reported unacceptable outcome of ICU treatment. Methods Patients who were admitted to the ICU for at least 48 h and survived the first year after discharge completed validated questionnaires on overall HRQoL and the components of PICS and stated whether they considered their current state of health an acceptable outcome of ICU treatment. The effects of overall HRQoL and components of PICS on unacceptable outcome were studied using multiple logistic regression analysis. Results Of 1453 patients, 67 (5%) reported their health state an unacceptable outcome of ICU treatment. These patients had a lower score on overall HRQoL (EQ-5D-index value of 0.57 vs. 0.81; p  < 0.001), but we could not determine a cutoff value of the EQ-5D-index value that reliably identified unacceptable outcome. In the multivariate analysis, only the hospital anxiety and depression scale was significantly associated with an unacceptable outcome (OR 2.06, 99% CI 1.18–3.61). Conclusions Although there is a strong association between low overall HRQoL and self-reported unacceptable outcome of ICU treatment, patients with low overall HRQoL may still consider their outcome acceptable. The mental component of PICS, but not the physical and cognitive component, is strongly associated with self-reported unacceptable outcome.

The aim of this study was to test the hypothesis that blood glucose amplitude variability (BGAV) is associated with mortality in critically ill patients. A prospectively collected multicenter data set including all glucose measurements during intensive care unit (ICU) treatment and outcome was analyzed. We used logistic regression to assess the association between hospital mortality and standard deviation (SD), mean amplitude of glycemic excursions (MAGE), mean absolute glucose change per hour (MAG), and glycemic lability index (GLI). The analysis was adjusted for ICU, Acute Physiology And Chronic Health Evaluation IV–expected mortality, the presence of severe hypoglycemia, mean glucose, mean glucose measurement interval, and interaction between the latter 2. There were 855 032 glucose measurements included of 20 375 patients admitted to 37 Dutch ICUs in 2008 and 2009. Median Acute Physiology And Chronic Health Evaluation IV–predicted mortality was 14%, and median glucose was 7.3 mmol/L. In all patients combined, adjusted hospital mortality was associated with SD and MAGE, but not with MAG and GLI. In surgical patients, adjusted hospital mortality was associated with SD, MAGE, and MAG, but not GLI. In medical patients, adjusted mortality was associated with SD but not with other BGAV measures. Not all BGAV measures were associated with mortality. Blood glucose amplitude variability as quantified by SD was consistently independently associated with hospital mortality.

Background and Objective High variability in tacrolimus pharmacokinetics directly after lung transplantation (LuTx) may increase the risk for acute kidney injury (AKI) and transplant rejection. The primary objective was to compare pharmacokinetic variability in patients receiving tacrolimus orally versus intravenously early after LuTx. Methods Pharmacokinetic and clinical data from 522 LuTx patients transplanted between 2010 and 2020 in two university hospitals were collected to compare orally administered tacrolimus to intravenous tacrolimus early post-transplantation. Tacrolimus blood concentration variability, measured as intrapatient variability (IPV%) and  percentage of time within the therapeutic range (TTR%), was analyzed within the first 14 days after LuTx. Secondary outcomes were AKI, acute rejection, length of stay in the intensive care unit (ICU), and mortality in the ICU and during hospital admission. Results We included 224 patients in the oral and 298 in the intravenous group. The mean adjusted IPV% was 10.8% (95% confidence interval [CI] 6.9–14.6; p < 0.001) higher in the oral group (27.2%) than the intravenous group (16.4%). The mean TTR% was 7.3% (95% CI − 11.3 to − 3.4; p < 0.001) lower in the oral group (39.6%) than in the intravenous group (46.9%). The incidence of AKI was 46.0% for oral and 42.6% for intravenous administration (adjusted odds ratio [OR] 1.2; 95% CI 0.8–1.8; p = 0.451). The frequencies of clinically diagnosed acute rejection in the oral and intravenous groups were nonsignificant (24.6% vs 17.8%; OR 1.5 [95% CI 1.0–2.3; p = 0.059]). ICU and hospital mortality rate and ICU length of stay were similar. Conclusions Administering tacrolimus orally directly after LuTx leads to a higher variability in blood concentrations compared to intravenous administration. There was no difference in the occurrence of AKI or transplant rejection.

Supporting this, previous studies found lower levels of B2GPI after lipopolysaccharide (the main component of the outer membrane of bacteria) infusion in humans and male mice [3, 4]. [...]we hypothesized that B2GPI levels can differentiate between sepsis and non-infectious critically ill patients. In 48 h following ICU admission, blood was sampled twice to measure the maximum level of B2GPI using a semi-automated sandwich ELISA on a Freedom EVO platform (Tecan) with goat anti-human beta-2-glycoprotein-1 and HRP-coupled goat-human beta-2-glycoprotein-1 antibodies (both Cedarlane). SEE PDF] We showed that B2GPI could differentiate between patients with and without sepsis. [...]patients with lower B2GPI levels in the first 48 h developed more nosocomial infections.