Background:In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19.Objective:Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19.Methods:This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand.Results:As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024.Conclusions:This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment.Trial Registration:ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359International Registered Report Identifier (IRRID):DERR1-10.2196/48183
MULTIFILE
Background & aims: Low muscle mass and -quality on ICU admission, as assessed by muscle area and -density on CT-scanning at lumbar level 3 (L3), are associated with increased mortality. However, CT-scan analysis is not feasible for standard care. Bioelectrical impedance analysis (BIA) assesses body composition by incorporating the raw measurements resistance, reactance, and phase angle in equations. Our purpose was to compare BIA- and CT-derived muscle mass, to determine whether BIA identified the patients with low skeletal muscle area on CT-scan, and to determine the relation between raw BIA and raw CT measurements. Methods: This prospective observational study included adult intensive care patients with an abdominal CT-scan. CT-scans were analysed at L3 level for skeletal muscle area (cm2) and skeletal muscle density (Hounsfield Units). Muscle area was converted to muscle mass (kg) using the Shen equation (MMCT). BIA was performed within 72 h of the CT-scan. BIA-derived muscle mass was calculated by three equations: Talluri (MMTalluri), Janssen (MMJanssen), and Kyle (MMKyle). To compare BIA- and CT-derived muscle mass correlations, bias, and limits of agreement were calculated. To test whether BIA identifies low skeletal muscle area on CT-scan, ROC-curves were constructed. Furthermore, raw BIA and CT measurements, were correlated and raw CT-measurements were compared between groups with normal and low phase angle. Results: 110 patients were included. Mean age 59 ± 17 years, mean APACHE II score 17 (11–25); 68% male. MMTalluri and MMJanssen were significantly higher (36.0 ± 9.9 kg and 31.5 ± 7.8 kg, respectively) and MMKyle significantly lower (25.2 ± 5.6 kg) than MMCT (29.2 ± 6.7 kg). For all BIA-derived muscle mass equations, a proportional bias was apparent with increasing disagreement at higher muscle mass. MMTalluri correlated strongest with CT-derived muscle mass (r = 0.834, p < 0.001) and had good discriminative capacity to identify patients with low skeletal muscle area on CT-scan (AUC: 0.919 for males; 0.912 for females). Of the raw measurements, phase angle and skeletal muscle density correlated best (r = 0.701, p < 0.001). CT-derived skeletal muscle area and -density were significantly lower in patients with low compared to normal phase angle. Conclusions: Although correlated, absolute values of BIA- and CT-derived muscle mass disagree, especially in the high muscle mass range. However, BIA and CT identified the same critically ill population with low skeletal muscle area on CT-scan. Furthermore, low phase angle corresponded to low skeletal muscle area and -density. Trial registration: ClinicalTrials.gov (NCT02555670).
Eggshell particles as bio-ceramic in sustainable bioplastic engineering – ESP-BIOPACK Plastics make our lives easier in many ways. However, if they are not properly disposed of, they end up in the environment. Recently, biodegradable biopolymers, such as polylactic acid (PLA) and polyhydroxy alkanoates (PHAs), have moved towards alternatives for applications such as sustainable packaging. The major limitations of these biopolymers are the high cost, which is due to the high cost of the starting materials and the small volumes, and the poor thermal and mechanical properties such as limited processability and low impact resistance. Attempts to modify PHAs have been researched in many ways, such as blending various biodegradable polymers or mixing inorganic mineral fillers. Eggshell (10 million tons per year by 2030) is a natural bio-ceramic mineral with a unique chemical composition of calcium carbonate (>95% calcite). So far it has been regarded as a zero-value waste product, but it could be a great opportunity as raw material to reduce the cost of biopolymers and to improve properties, including the decomposition process at the end-of-life. In this project, we aim to develop eggshell particles that serve as bio-fillers in biopolymers to lower the cost of the product, to improve mechanical properties and to facilitate the validation of end-of-life routes, therefore, economically enhance the wide applications of such. The developed bioplastic packaging materials will be applied in SME partner EGGXPERT’s cosmetics line but also in other packaging applications, such as e.g. biodegradable coffee capsules. To be able to realize the proposed idea, the partnership between Chemelot Innovation and Learning Labs (CHILL), EGGXPERT B.V. and the Research Centre Material Sciences of Zuyd University of Applied Sciences is needed to research the physical, mechanical and end-of-life influences of eggshell particles (ESP) in biopolymers such as PLA and PHA and optimize their performance.
In vrijwel elk bedrijf waarin assemblage plaatsvindt wordt gebruik gemaakt van instructies in de ondersteuning van assemblageprocessen. Nauwkeurige, actuele, begrijpelijke en effectieve werkinstructies zijn cruciaal voor het efficiënt en foutloos uitvoeren van de assemblageprocessen en zijn daarom essentieel in de maak-industrie. Assemblagetaken zijn steeds vaker uniek van aard (kleinere oplages, grotere productdiversiteit), waardoor het aantal verschillende, specifieke instructies toeneemt. Tevens zijn de assemblagemedewerkers steeds diverser: sommige van deze werknemers zijn goed geschoold (MBO) en ervaren, maar soms hebben ze weinig opleiding genoten, en ze hebben soms zelfs een arbeidshandicap die vraagt om specifieke ondersteuning voor de reguliere arbeidsmarkt (sociale ondernemingen). Er is een dringende en toenemende vraag naar ‘flexibele werkinstructies’: maatwerk op productgebied, en maatwerk op persoonsgebied. De assemblage-instructies worden nu vaak eenmalig opgesteld voor een nieuw product (of een variant daarvan), door mensen (werkbegeleider, productontwerper, procesmanager) die niet speciaal expertise hebben op het vlak van instructieve communicatie. Zij zijn gebaat bij een gebruiksvriendelijk, efficiënt en flexibel systeem voor het opstellen en beheren van heldere werkinstructies. Hiervoor moet een systematische aanpak ontwikkeld worden die bedrijfsspecifiek, context afhankelijk ingevuld kan worden. Dit vereist onderzoek op drie samenhangende aspecten: contexten van werkinstructies, passende werkinstructies, en proces van opstellen van passende werkinstructies. In dit project onderzoeken we aan de hand van een aantal casussen de bedrijfscontext voor werkinstructies, ontwerpen we een generieke aanpak, toolbox, voor het opstellen (indien mogelijk automatisch generen) en beheren van werkinstructies. Als dat op orde is, kan de vervolgstap gezet worden waarin digitale werkinstructies met moderne technologieën in het werkproces of in de werkplaats geïntegreerd kunnen worden. Mixed reality oplossingen zoals bijvoorbeeld de hololens, bieden hier waardevolle mogelijkheden. Centraal in dit project staat om samen met het mkb een toolbox te maken voor het flexibel genereren van werkinstructies.