Medical progress is reflected in the advance from broad clinical syndromes to mechanistically coherent diagnoses. By this metric, research in sepsis is far behind other areas of medicine—the word itself conflates multiple different disease mechanisms, whilst excluding noninfectious syndromes (e.g., trauma, pancreatitis) with similar pathogenesis. New technologies, both for deep phenotyping and data analysis, offer the capability to define biological states with extreme depth. Progress is limited by a fundamental problem: observed groupings of patients lacking shared causal mechanisms are very poor predictors of response to treatment. Here, we discuss concrete steps to identify groups of patients reflecting archetypes of disease with shared underlying mechanisms of pathogenesis. Recent evidence demonstrates the role of causal inference from host genetics and randomised clinical trials to inform stratification analyses. Genetic studies can directly illuminate drug targets, but in addition they create a reservoir of statistical power that can be divided many times among potential patient subgroups to test for mechanistic coherence, accelerating discovery of modifiable mechanisms for testing in trials. Novel approaches, such as subgroup identification in-flight in clinical trials, will improve efficiency. Within the next decade, we expect ongoing large-scale collaborative projects to discover and test therapeutically relevant sepsis archetypes.
Antiseptic bathing has garnered attention in an effort to reduce hospital-acquired infections. Previous studies have shown the efficacy of antiseptic bathing in high-risk environments, such as intensive care units (ICUs), using chlorhexidine. In this study we aimed to evaluate the effectiveness of octenidine as a potential alternative due to its established popularity and widespread use in Europe.
We compared the rates of ICU-acquired primary bacteremia and ICU-acquired multidrug-resistant organisms (MDROs) in a multicenter, cluster-randomized, double-blind, placebo-controlled, cross-over study using octenidine-impregnated and placebo washcloths. On 44 ICUs in 23 hospitals throughout Germany, we compared individual ICUs with themselves over two 12-month time periods. All data were obtained digitally via hospital information systems as individual ward-movement data and microbiological test results; both endpoints were algorithmically derived.
104,039 ICU episodes from 93,438 patients with 712,784 microbiological test results were analyzed, thereby detecting 1508 cases of ICU-acquired primary bacteremia and 1871 cases of ICU-acquired MDRO. Bathing with octenidine-impregnated washcloths prevented ICU-acquired primary bacteremia; a risk reduction of 17% was seen homogeneously across all participating ICUs (adjusted hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.75; 0.92], p = 0.0003). This reduction affected predominantly coagulase-negative staphylococci (53%) and enterococci (17%). However, no intervention effect was seen for ICU-acquired MDROs (adjusted HR 0.98, 95% CI [0.83; 1.15]). Heterogeneity among intra-ICU intervention effects on MDRO acquisition was substantial.
Antiseptic bathing with octenidine may be effective in preventing ICU-acquired primary bacteremia, particularly due to Gram-positive bacteria and common skin commensals.
Glycemic control poses a challenge in intensive care unit (ICU) patients and dysglycemia is associated with poor outcomes. Continuous glucose monitoring (CGM) has been successfully implemented in the type 1 diabetes out-patient setting and renewed interest has been directed into the transition of CGM into the ICU. This scoping review aimed to provide an overview of CGM accuracy in ICU patients to inform future research and CGM implementation.
We systematically searched PubMed and EMBASE between 5th of December 2023 and 21st of May 2024 and reported findings in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for scoping reviews (PRISMA-ScR). We assessed studies reporting the accuracy of CGM in the ICU and report study characteristics and accuracy outcomes.
We identified 2133 studies, of which 96 were included. Most studies were observational (91.7%), conducted in adult patients (74%), in mixed ICUs (47.9%), from 2014 and onward, and assessed subcutaneous CGM systems (80%) using arterial blood samples as reference test (40.6%). Half of the studies (56.3%) mention the use of a prespecified reference test protocol. The mean absolute relative difference (MARD) ranged from 6.6 to 30.5% for all subcutaneous CGM studies. For newer factory calibrated CGM, MARD ranged from 9.7 to 20.6%. MARD for intravenous CGM was 5–14.2% and 6.4–13% for intraarterial CGM.
In this scoping review of CGM accuracy in the ICU, we found great diversity in accuracy reporting. Accuracy varied depending on CGM and comparator, and may be better for intravascular CGM and potentially lower during hypoglycemia.
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