Introduction:Hydroxyethyl starch (HES) 130/0.38-0.45 is a synthetic colloid, which has been on the market since 1999. In recent years, concern about the use of HES has been raised because of serious adverse events, including acute kidney injury, bleeding and even increased mortality with its use. In the outlined systematic review, we aim to assess if the adverse effects of HES 130/0.38-0.45 in patients with sepsis could have been discovered earlier. Methods:We will conduct a systematic review with meta-analysis of randomised clinical trials in animals and patients and observational studies in patients comparing HES 130/0.38-0.45 vs any crystalloid in sepsis. The primary outcome will be all-cause mortality at longest follow-up. We will systematically search EMBASE, MEDLINE and the Cochrane Library for relevant literature. We will follow the recommendations by the Cochrane Handbook, the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Discussion: With the outlined systematic review, we aim to assess whether the adverse effects of HES 130/0.38-0.45 could have been discovered earlier by comparing summary effect estimates of harm from observational studies in patients and randomised trials in animals and patients. The results may have implications for future drug development and approval processes. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Johansen JR, Perner A, Brodtkorb JH, Møller MH. Use of hydroxyethyl starch in sepsis research:Protocol for a systematic review. Acta Anaesthesiol Scand.

The dihydroazulene/vinylheptafulvene (DHA/VHF) photocouple is a promising candidate for molecular solar heat batteries, storing and releasing energy in a closed cycle. Much work has been done on improving the energy storage capacity and the half-life of the high-energy isomer via substituent functionalization, but similarly important is keeping these improved properties in common polar solvents, along with being soluble in these, which is tied to the dipole properties. However, the number of possible derivatives makes an overview of this combinatorial space impossible both for experimental work and traditional computational chemistry. Due to the time-consuming nature of running many thousands of computations, we look to machine learning, which bears the advantage that once a model has been trained, it can be used to rapidly estimate approximate values for the given system. Applying a convolutional neural network, we show that it is possible to reach good agreement with traditional computations on a scale that allows us to rapidly screen tens of thousands of the DHA/VHF photocouple, eliminating bad candidates and allowing computational resources to be directed toward meaningful compounds.

Background After being used for more than a decade the use of hydroxyethyl starch (HES) 130/0.38–0.45 in clinical practice was discouraged because of serious adverse events including bleeding, acute kidney injury and death. But could these adverse effects have been discovered sooner? By comparing the summary effect estimates of the adverse effects of HES 130/0.38–0.45 in different study designs we aimed to disclose any signal of this. Methods We systematically searched MEDLINE, EMBASE and Cochrane Library and hand‐searched the reference lists of relevant studies to identify studies for inclusion. Eligible trials were randomised clinical trials (RCTs) and observational studies in patients with sepsis and randomised trials in animals with induced sepsis comparing HES 130/0.38–0.45 to any type of crystalloid. Relevant outcomes were all‐cause mortality at longest follow‐up, renal replacement therapy (RRT), acute kidney injury (AKI) and bleeding. We extracted data, conducted conventional meta‐analyses and assessed the risk of bias and the quality of evidence. Results We included 8 RCTs including 3,273 patients, 1 observational study including 379 patients and 5 randomised animal trials including 94 test animals. There was no suggestion of interaction in subgroup analyses comparing the different study designs for any outcomes (all‐cause mortality at longest follow‐up p = .33; RRT p = .70; AKI p = .63; bleeding p = .20). Conclusions We observed no interaction between the summary effect estimates of RCTs, observational studies in patients and randomised animal trials for any of the outcomes. Accordingly, we found no evidence indicating that the adverse effects of HES 130/0.38–0.45 could have been discovered sooner. Systematic review registration PROSPERO ID: CRD42018103422. Protocol Johansen JR, Perner A, Brodtkorb JH, Møller MH. Use of hydroxyethyl starch in sepsis research: Protocol for a systematic review. Acta Anaesthesiol Scand. 2019;63:814–818. https://doi.org/10.1111/aas.13345