Designing nutrition-based interventional trials for the future: addressing the known knowns

Abstract The consistent decline in critical illness mortality has a significant effect on trial design, whereby either an improbable effect sizes or large number of patients are required. The signal-to-noise ratio is of particular interest for the critically ill. When considering the potential signal, interventions need to match outcomes in regard to biological plausibility. Provision of nutrition is a complex decision with many underappreciated aspects of noise. However, a fundamental interaction is often not accounted for time. Working as a community to evolve trial design will be our challenge for nutrition interventions in the critically ill for the future

Changes in hemostasis parameters in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia complicated by endocarditis or thromboembolic events : a prospective gender-age adjusted cohort study

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB) - a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender-age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p <0.05), elevated antithrombin III at day 90 (p <0.01), prolonged activated partial thromboplastin time at days 4 and 10 (p <0.05), and enhanced thrombin-antithrombin complex at day 4 (p <0.01). Thromboembolic events (N = 8), compared to controls (N = 34), significantly increased thrombin-antithrombin complex at day 4 (p <0.05). In receiver operating characteristic analysis, the changes in these hemostasis parameters at day 4 predicted endocarditis and thromboembolic events (p <0.05). No differences in hemoglobin, thrombocyte, prothrombin fragment, thrombin time, factor VIII, D-dimer or fibrinogen levels were observed between cases and controls. The results suggest that nonfatal MS-SAB patients present marginal hemostasis parameter changes that, however, may have predictability for endocarditis or thromboembolic events. Larger studies are needed to further assess the connection of hemostasis to complications in SAB.Peer reviewe

Early goal-directed nutrition versus standard of care in adult intensive care patients: the single-centre, randomised, outcome assessor-blinded EAT-ICU trial

Purpose: We assessed the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult intensive care unit (ICU) patients. Methods: We randomised acutely admitted, mechanically ventilated ICU patients expected to stay longer than 3 days in the ICU. In the EGDN group we estimated nutritional requirements by indirect calorimetry and 24-h urinary urea aiming at covering 100% of requirements from the first full trial day using enteral and parenteral nutrition. In the standard of care group we aimed at providing 25 kcal/kg/day by enteral nutrition. If this was not met by day 7, patients were supplemented with parenteral nutrition. The primary outcome was physical component summary (PCS) score of SF-36 at 6 months. We performed multiple imputation for data of the non-responders. Results: We randomised 203 patients and included 199 in the intention-to-treat analyses; baseline variables were reasonably balanced between the two groups. The EGDN group had less negative energy (p &lt; 0.001) and protein (p &lt; 0.001) balances in the ICU as compared to the standard of care group. The PCS score at 6 months did not differ between the two groups (mean difference 0.0, 95% CI -5.9 to 5.8, p = 0.99); neither did mortality, rates of organ failures, serious adverse reactions or infections in the ICU, length of ICU or hospital stay, or days alive without life support at 90 days. Conclusions: EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as compared to standard nutrition care in acutely admitted, mechanically ventilated, adult ICU patients.Rigshospitalet; Fresenius Kabi; European Society for Clinical Nutrition and Metabolism (ESPEN); COSMED; Medinor/MedGraphics; CSL Behring; Ferring PharmaceuticalsSCI(E)ARTICLE111637-16474