E-learning-an interventional element of the PRiVENT project to improve weaning expertise.

BACKGROUND: PRiVENT (PRevention of invasive VENTilation) is an evaluation of a bundle of interventions aimed at the prevention of long-term invasive mechanical ventilation. One of these elements is an e-learning course for healthcare professionals to improve weaning expertise. The aim of our analysis is to examine the implementation of the course in cooperating intensive care units. METHODS: The course has been developed through a peer review process by pulmonary and critical care physicians in collaboration with respiratory therapists, supported by health services researchers and a professional e-learning agency. The e-learning platform "weLearn" was made available online to participating healthcare professionals. Feedback on the e-learning programme was obtained and discussed in quality circles (QCs). We measured the acceptance and use of the programme through access statistics. RESULTS: The e-learning course "Joint Prevention of Long-Term Ventilation" consists of 7 separate modules with practice-oriented training units as well as a cross-module area and corresponding interactive case studies. Users can receive 23 CME (continuing medical education) credits. The platform was released on July 1, 2021. By June 28, 2023, 214 users from 33 clinics had registered. Most users (77-98%) completed the modules, thus performing well in the test, where 90-100% passed. In the QCs, the users commended the structure and practical relevance of the programme, as well as the opportunity to earn CME credits. CONCLUSION: Especially for medical staff in intensive care units, where continuous training is often a challenge during shift work, e-learning is a useful supplement to existing medical training. TRIAL REGISTRATION: The PRiVENT study is registered at ClinicalTrials.gov (NCT05260853) on 02/03/2022.

Counterion effects on the mesomorphic and electrochemical properties of guanidinium salts.

Ionic liquid crystals (ILCs) combine the ion mobility of ionic liquids with the order and self-assembly of thermotropic mesophases. To understand the role of the anion in ILCs, wedge-shaped arylguanidinium salts with tetradecyloxy side chains were chosen as benchmark systems and their liquid crystalline self-assembly in the bulk phase as well as their electrochemical behavior in solution were studied depending on the anion. Differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X-ray diffraction (WAXS, SAXS) experiments revealed that for spherical anions, the phase width of the hexagonal columnar mesophase increased with the anion size, while for non-spherical anions, the trends were less clear cut. Depending on the anion, the ILCs showed different stability towards electrochemical oxidation and reduction with the most stable being the PF6 based compound. Cyclic voltammetry (CV) and density functional theory (DFT) calculations suggest a possible contribution of the guanidinium cation to the oxidation processes.

Dissolved Oxygen Relevantly Contributes to Systemic Oxygenation During Venovenous Extracorporeal Membrane Oxygenation Support.

When determining extracorporeal oxygen transfer (V ML O 2 ) during venovenous extracorporeal membrane oxygenation (VV ECMO) dissolved oxygen is often considered to play a subordinate role due to its poor solubility in blood plasma. This study was designed to assess the impact of dissolved oxygen on systemic oxygenation in patients with acute respiratory distress syndrome (ARDS) on VV ECMO support by differentiating between dissolved and hemoglobin-bound extracorporeal oxygen transfer. We calculated both extracorporeal oxygen transfer based on blood gas analysis using the measuring energy expenditure in extracorporeal lung support patients (MEEP) protocol and measured oxygen uptake by the native lung with indirect calorimetry. Over 20% of V ML O 2 and over 10% of overall oxygen uptake (VO 2 total ) were realized as dissolved oxygen. The transfer of dissolved oxygen mainly depended on ECMO blood flow (BF ML ). In patients with severely impaired lung function dissolved oxygen accounted for up to 28% of VO 2 total . A clinically relevant amount of oxygen is transferred as physically dissolved fraction, which therefore needs to be considered when determining membrane lung function, manage ECMO settings or guiding the weaning procedure.

Acremonium sp. diglycosidase-aid chemical diversification: valorization of industry by-products.

The fungal diglycosidase α-rhamnosyl-ß-glucosidase I (αRßG I) from Acremonium sp. DSM 24697 catalyzes the glycosylation of various OH-acceptors using the citrus flavanone hesperidin. We successfully applied a one-pot biocatalysis process to synthesize 4-methylumbellipheryl rutinoside (4-MUR) and glyceryl rutinoside using a citrus peel residue as sugar donor. This residue, which contained 3.5 % [w/w] hesperidin, is the remaining of citrus processing after producing orange juice, essential oil, and peel-juice. The low-cost compound glycerol was utilized in the synthesis of glyceryl rutinoside. We implemented a simple method for the obtention of glyceryl rutinoside with 99 % yield, and its purification involving activated charcoal, which also facilitated the recovery of the by-product hesperetin through liquid-liquid extraction. This process presents a promising alternative for biorefinery operations, highlighting the valuable role of αRßG I in valorizing glycerol and agricultural by-products. KEYPOINTS: • αRßG I catalyzed the synthesis of rutinosides using a suspension of OPW as sugar donor. • The glycosylation of aliphatic polyalcohols by the αRßG I resulted in products bearing a single rutinose moiety. • αRßG I catalyzed the synthesis of glyceryl rutinoside with high glycosylation/hydrolysis selectivity (99 % yield).

Bacterial stigmasterol degradation involving radical flavin delta-24 desaturase and molybdenum-dependent C26 hydroxylase.

Sterols are ubiquitous membrane constituents that persist to a large extent in the environment due to their water insolubility and chemical inertness. Recently, an oxygenase-independent sterol degradation pathway was discovered in a cholesterol-grown denitrifying bacterium Sterolibacterium (S.) denitrificans. It achieves hydroxylation of the unactivated primary C26 of the isoprenoid side chain to an allylic alcohol via a phosphorylated intermediate in a four-step ATP-dependent enzyme cascade. However, this pathway is incompatible with the degradation of widely distributed steroids containing a double bond at C22 in the isoprenoid side chain such as the plant sterol stigmasterol. Here, we have enriched a prototypical delta-24 desaturase from S. denitrificans, which catalyzes the electron acceptor-dependent oxidation of the intermediate stigmast-1,4-diene-3-one to a conjugated (22,24)-diene. We suggest an α4ß4 architecture of the 440 kDa enzyme, with each subunit covalently binding an flavin mononucleotide cofactor to a histidyl residue. As isolated, both flavins are present as red semiquinone radicals, which can be reduced by stigmast-1,4-diene-3-one but cannot be oxidized even with strong oxidizing agents. We propose a mechanism involving an allylic radical intermediate in which two flavin semiquinones each abstract one hydrogen atom from the substrate. The conjugated delta-22,24 moiety formed allows for the subsequent hydroxylation of the terminal C26 with water by a heterologously produced molybdenum-dependent steroid C26 dehydrogenase 2. In conclusion, the pathway elucidated for delta-22 steroids achieves oxygen-independent hydroxylation of the isoprenoid side chain by bypassing the ATP-dependent formation of a phosphorylated intermediate.

Out-of-Hospital cardiac arrest & SmartphonE RespOndErS trial (HEROES Trial): Methodology and study protocol of a pre-post-design trial of the effect of implementing a smartphone alerting system on survival in out-of-hospital cardiac arrest.

Background: Since 2021, international guidelines for cardiopulmonary resuscitation recommend the implementation of so-called "life-saving systems". These systems include smartphone alerting systems (SAS), which enable dispatch centres to alert first responders via smartphone applications, who are in proximity of a suspected out-of-hospital cardiac arrest (OHCA). However, the effect of SAS on survival remains unknown. Aim: The aim is to assess the rate of survival to hospital discharge in adult patients with OHCA not witnessed by emergency medical services (EMS): before and after SAS implementation. Design: Multicentre, prospective, observational, intention-to-treat, pre-post design clinical trial. Population: Adults (aged ≥ 18 years), OHCA not witnessed by EMS, no traumatic cause for cardiac arrest, cardiopulmonary resuscitation initiated or continued by EMS. Setting: Dispatch-centre-based. Outcomes: Primary: survival to hospital discharge. Secondary: time to first compression, rate of basic life support measures before EMS arrival, rate of patients with shockable rhythm at EMS arrival, Cerebral Performance Category at hospital discharge, and duration of hospital stay. Sample size: Assuming an absolute difference in survival rates to hospital discharge of 4% in the two groups (11% before implementation of the SAS versus 15% after) and 80% power, and a type 1 error rate of 0.05, the required sample size is N = 1,109 patients per group (at least N = 2,218 evaluated patients in total). Conclusions: The HEROES trial will investigate the effects of a SAS on the survival rate after OHCA. Trial registration: German Clinical Trials Register (DRKS, ID: DRKS00032920).

Enzymatic defluorination of a terminally monofluorinated pentyl moiety: oxidative or hydrolytic mechanism?

Fluorination of organic compounds plays an important role in the chemical and pharmaceutical industry and is often applied in order to improve physicochemical parameters or modify pharmacological properties. While oxidative and reductive defluorination have been shown to be responsible for the metabolic degradation of organofluorine compounds, the involvement of hydrolytic mechanisms catalyzed by human enzymes has not been reported so far. Here, we investigated the enzymatic defluorination of terminally monofluorinated aliphates with [1-(5-fluoropentyl)-1H-indol-3-yl]-1-naphthalenyl-methanone (AM-2201) as a model substance. We performed in vitro biotransformation using pooled human liver microsomes (pHLM) and human recombinant cytochrome P450 (CYP) assays. In order to elucidate the underlying mechanisms, modified incubation conditions were applied including the use of deuterium labeled AM-2201 (d2 -AM-2201). Identification of the main metabolites and analysis of their isotopic composition was performed by liquid-chromatography coupled to time-of-flight-mass-spectrometry (LC-QToF-MS). Quantification of the metabolites was achieved with a validated method based on liquid-chromatography-tandem-mass-spectrometry (LC-MS/MS). CYP 1A2 mediated defluorination of d2 -AM-2201 revealed an isotopic pattern of the defluorinated 5-hydroxypentyl metabolite (5-HPM) indicating a redox mechanism with an aldehyde as a plausible intermediate. In contrast, formation of 5-HPM by pHLM was observed independently of the presence of atmospheric oxygen or co-factors regenerating the redox system. pHLM incubation of d2 -AM-2201 confirmed the hypothesis of a non-oxidative mechanism involved in the defluorination of the 5-fluoropentyl moiety. So far, enzymatically catalyzed, hydrolytic defluorination was only described in bacteria and other prokaryotes. The presented data prove the involvement of a hydrolytic mechanism catalyzed by human microsomal enzymes other than CYP. Significance Statement Elucidating the mechanisms involved in the enzymatic detoxification of organofluorine compounds is crucial for enhancing our understanding and facilitating the design and development of drugs with improved pharmacokinetic profiles. The carbon-fluorine bond possesses a high binding energy, which suggests that non-activated fluoroalkanes would not undergo hydrolytic cleavage. However, our study provides evidence for the involvement of a non-oxidative mechanism catalyzed by human liver enzymes. It is important to consider CYP-independent, hydrolytic defluorination, when investigating the pharmacokinetic properties of fluorinated xenobiotics.

Role of multidrug-resistant bacteria in weaning from invasive mechanical ventilation.

BACKGROUND: Although multidrug-resistant bacteria (MDR) are common in patients undergoing prolonged weaning, there is little data on their impact on weaning and patient outcomes. METHODS: This is a retrospective analysis of consecutive patients who underwent prolonged weaning and were at a university weaning centre from January 2018 to December 2020. The influence of MDR colonisation and infection on weaning success (category 3a and 3b), successful prolonged weaning from invasive mechanical ventilation (IMV) with or without the need for non-invasive ventilation (NIV) compared with category 3c (weaning failure 3cI or death 3cII) was investigated. The pathogen groups considered were: multidrug-resistant gram-negative bacteria (MDRGN), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). RESULTS: A total of 206 patients were studied, of whom 91 (44.2%) showed evidence of MDR bacteria (32% VRE, 1.5% MRSA and 16% MDRGN), with 25 patients also meeting the criteria for MDR infection. 70.9% of the 206 patients were successfully weaned from IMV, 8.7% died. In 72.2% of cases, nosocomial pneumonia and other infections were the main cause of death. Patients with evidence of MDR (infection and colonisation) had a higher incidence of weaning failure than those without evidence of MDR (48% vs. 34.8% vs. 21.7%). In multivariate analyses, MDR infection (OR 4.9, p = 0.004) was an independent risk factor for weaning failure, along with male sex (OR 2.3, p = 0.025), Charlson Comorbidity Index (OR 1.2, p = 0.027), pH (OR 2.7, p < 0.001) and duration of IMV before admission (OR 1.01, p < 0.001). In addition, MDR infection was the only independent risk factor for death (category 3cII), (OR 6.66, p = 0.007). CONCLUSION: Patients with MDR infection are significantly more likely to die during the weaning process. There is an urgent need to develop non-antibiotic approaches for the prevention and treatment of MDR infections as well as clinical research on antibiotic stewardship in prolonged weaning as well as in ICUs.

Improving Medical Photography in a Level 1 Trauma Center by Implementing a Specialized Smartphone-Based App in Comparison to the Usage of Digital Cameras: Prospective Panel Study.

BACKGROUND: Medical photography plays a pivotal role in modern health care, serving multiple purposes ranging from patient care to medical documentation and education. Specifically, it aids in wound management, surgical planning, and medical training. While digital cameras have traditionally been used, smartphones equipped with specialized apps present an intriguing alternative. Smartphones offer several advantages, including increased usability and efficiency and the capability to uphold medicolegal standards more effectively and consistently. OBJECTIVE: This study aims to assess whether implementing a specialized smartphone app could lead to more frequent and efficient use of medical photography. METHODS: We carried out this study as a comprehensive single-center panel investigation at a level 1 trauma center, encompassing various settings including the emergency department, operating theaters, and surgical wards, over a 6-month period from June to November 2020. Using weekly questionnaires, health care providers were asked about their experiences and preferences with using both digital cameras and smartphones equipped with a specialized medical photography app. Parameters such as the frequency of use, time taken for image upload, and general usability were assessed. RESULTS: A total of 65 questionnaires were assessed for digital camera use and 68 for smartphone use. Usage increased significantly by 5.4 (SD 1.9) times per week (95% CI 1.7-9.2; P=.005) when the smartphone was used. The time it took to upload pictures to the clinical picture and archiving system was significantly shorter for the app (mean 1.8, SD 1.2 min) than for the camera (mean 14.9, SD 24.0 h; P<.001). Smartphone usage also outperformed the digital camera in terms of technical failure (4.4% vs 9.7%; P=.04) and for the technical process of archiving (P<.001) pictures to the picture archiving and communication system (PACS) and display images (P<.001) from it. No difference was found in regard to the photographer's intent (P=.31) or reasoning (P=.94) behind the pictures. Additionally, the study highlighted that potential concerns regarding data security and patient confidentiality were also better addressed through the smartphone app, given its encryption capabilities and password protection. CONCLUSIONS: Specialized smartphone apps provide a secure, rapid, and user-friendly platform for medical photography, showing significant advantages over traditional digital cameras. This study supports the notion that these apps not only have the potential to improve patient care, particularly in the realm of wound management, but also offer substantial medicolegal and economic benefits. Future research should focus on additional aspects such as patient comfort and preference, image resolution, and the quality of photographs, as well as seek to corroborate these findings through a larger sample size.

Refined diet consumption increases neuroinflammatory signalling through bile acid dysmetabolism.

Over recent decades, dietary patterns have changed significantly due to the increasing availability of convenient, ultra-processed refined foods. Refined foods are commonly depleted of key bioactive compounds, which have been associated with several deleterious health conditions. As the gut microbiome can influence the brain through a bidirectional communication system known as the 'microbiota-gut-brain axis', the consumption of refined foods has the potential to affect cognitive health. In this study, multi-omics approaches were employed to assess the effect of a refined diet on the microbiota-gut-brain axis, with a particular focus on bile acid metabolism. Mice maintained on a refined low-fat diet (rLFD), consisting of high sucrose, processed carbohydrates and low fibre content, for eight weeks displayed significant gut microbial dysbiosis, as indicated by diminished alpha diversity metrics (p < 0.05) and altered beta diversity (p < 0.05) when compared to mice receiving a chow diet. Changes in gut microbiota composition paralleled modulation of the metabolome, including a significant reduction in short-chain fatty acids (acetate, propionate and n-butyrate; p < 0.001) and alterations in bile acid concentrations. Interestingly, the rLFD led to dysregulated bile acid concentrations across both the colon (p < 0.05) and the brain (p < 0.05) which coincided with altered neuroinflammatory gene expression. In particular, the concentration of TCA, TDCA and T-α-MCA was inversely correlated with the expression of NF-κB1, a key transcription factor in neuroinflammation. Overall, our results suggest a novel link between a refined low-fat diet and detrimental neuronal processes, likely in part through modulation of the microbiota-gut-brain axis and bile acid dysmetabolism.

Risk factors for long-term invasive mechanical ventilation: a longitudinal study using German health claims data.

BACKGROUND: Long-term invasive mechanical ventilation (IMV) is a major burden for those affected and causes high costs for the health care system. Early risk assessment is a prerequisite for the best possible support of high-risk patients during the weaning process. We aimed to identify risk factors for long-term IMV within 96 h (h) after the onset of IMV. METHODS: The analysis was based on data from one of Germany's largest statutory health insurance funds; patients who received IMV ≥ 96 h and were admitted in January 2015 at the earliest and discharged in December 2017 at the latest were analysed. OPS and ICD codes of IMV patients were considered, including the 365 days before intubation and 30 days after discharge. Long-term IMV was defined as evidence of invasive home mechanical ventilation (HMV), IMV ≥ 500 h, or readmission with (re)prolonged ventilation. RESULTS: In the analysis of 7758 hospitalisations, criteria for long-term IMV were met in 38.3% of cases, of which 13.9% had evidence of HMV, 73.1% received IMV ≥ 500 h and/or 40.3% were re-hospitalised with IMV. Several independent risk factors were identified (p < 0.005 each), including pre-diagnoses such as pneumothorax (OR 2.10), acute pancreatitis (OR 2.64), eating disorders (OR 1.99) or rheumatic mitral valve disease (OR 1.89). Among ICU admissions, previous dependence on an aspirator or respirator (OR 5.13), and previous tracheostomy (OR 2.17) were particularly important, while neurosurgery (OR 2.61), early tracheostomy (OR 3.97) and treatment for severe respiratory failure such as positioning treatment (OR 2.31) and extracorporeal lung support (OR 1.80) were relevant procedures in the first 96 h after intubation. CONCLUSION: This comprehensive analysis of health claims has identified several risk factors for the risk of long-term ventilation. In addition to the known clinical risks, the information obtained may help to identify patients at risk at an early stage. Trial registration The PRiVENT study was retrospectively registered at ClinicalTrials.gov (NCT05260853). Registered at March 2, 2022.

BN-Phenanthrene- and BN-Pyrene-Based Fluorescent Uridine Analogues.

Two unprecedented fluorescent nucleosides that feature BN-doped polycyclic aromatic hydrocarbons are presented. One of them, having a BN-modified phenanthrene moiety incorporated, shows blue fluorescence but suffers from poor stability under aqueous conditions. The other nucleoside comprises an internally BN-doped pyrene as the chromophore. It shows green fluorescence in various solvents and is stable under aqueous and alkaline conditions.

An Enzymatic Cofactor Regeneration System for the in-Vitro Reduction of Isolated C=C Bonds by Geranylgeranyl Reductases.

Cofactor regeneration systems are of major importance for the applicability of oxidoreductases in biocatalysis. Previously, geranylgeranyl reductases have been investigated for the enzymatic reduction of isolated C=C bonds. However, an enzymatic cofactor-regeneration system for in vitro use is lacking. In this work, we report a ferredoxin from the archaea Archaeoglobus fulgidus that regenerates the flavin of the corresponding geranylgeranyl reductase. The proteins were heterologously produced, and the regeneration was coupled to a ferredoxin reductase from Escherichia coli and a glucose dehydrogenase from Bacillus subtilis, thereby enabling the reduction of isolated C=C bonds by purified enzymes. The system was applied in crude, cell-free extracts and gave conversions comparable to those of a previous method using sodium dithionite for cofactor regeneration. Hence, an enzymatic approach to the reduction of isolated C=C bonds can be coupled with common systems for the regeneration of nicotinamide cofactors, thereby opening new perspectives for the application of geranylgeranyl reductases in biocatalysis.

Redox Out of the Box: Catalytic Versatility Across NAD(P)H-Dependent Oxidoreductases.

The asymmetric reduction of double bonds using NAD(P)H-dependent oxidoreductases has proven to be an efficient tool for the synthesis of important chiral molecules in research and on industrial scale. These enzymes are commercially available in screening kits for the reduction of C=O (ketones), C=C (activated alkenes), or C=N bonds (imines). Recent reports, however, indicate that the ability to accommodate multiple reductase activities on distinct C=X bonds occurs in different enzyme classes, either natively or after mutagenesis. This challenges the common perception of highly selective oxidoreductases for one type of electrophilic substrate. Consideration of this underexplored potential in enzyme screenings and protein engineering campaigns may contribute to the identification of complementary biocatalytic processes for the synthesis of chiral compounds. This review will contribute to a global understanding of the promiscuous behavior of NAD(P)H-dependent oxidoreductases on C=X bond reduction and inspire future discoveries with respect to unconventional biocatalytic routes in asymmetric synthesis.

Screening for Palliative Care Need in Oncology: Validation of Patient-Reported Outcome Measures.

CONTEXT: Leading oncology societies recommend monitoring symptoms and support needs through patient-reported outcome measures (PROMs), but their use for assessing specialist palliative care (SPC) need has not yet been explored. Research on SPC integration has focused on staff-assessed screening tools, which are time-consuming. OBJECTIVES: This study aimed to assess the diagnostic validity of the Integrated Palliative Outcome Scale (IPOS) and NCCN Distress Thermometer (NCCN DT) in identifying need for SPC in patients with incurable cancer. METHODS: In a cross-sectional study, patients with incurable cancer (prognosis <2 years) completed PROMs. In an independent process, the palliative care consultation service (PCCS) assessed the need for SPC in each patient through multiprofessional case review, and this was used as the reference standard. ROC analyses were employed to determine diagnostic validity. RESULTS: Of the 208 participants, 71 (34.1 %) were classified as having SPC need by the PCCS. Aiming for a minimum sensitivity of 80%, a cut-off of ≥2 items with high/very high burden in the IPOS resulted in a 90.2% sensitivity (specificity = 50; AUC = 0.791; CI 95%= 0.724-0.858). A cut-off of ≥5 resulted in a sensitivity of 80 % for NCCN DT (specificity = 49.5 %; AUC = 0.687; CI 95% = 0.596-0.777). CONCLUSION: PROMs are useful for identifying SPC need in cancer patients. Their implementation might facilitate timely integration of SPC. Future research should focus on an integrated assessment approach with PROMs that combines the requirements of the different specialties to save patient and staff resources.

Automatic measurement of departing times in smartphone alerting systems: A pilot study.

Aim: Smartphone alerting systems (SAS) alert volunteers in close vicinity of suspected out-of-hospital cardiac arrest. Some systems use sophisticated algorithms to select those who will probably arrive first. Precise estimation of departing times and travel times may help to further improve algorithms. We developed a global positioning system (GPS) based method for automatic measurements of departing times. The aim of this pilot study was to evaluate feasibility and precision of the method. Methods: Region of Lifesavers alerting app (iOS/ Android, version 3.0, FirstAED ApS, Denmark) was used in this study. 27 experiments were performed with 9 students, who were instructed to stay in their flats during the study days. A geofence was set for each alarm in the alerting system with a radius of 10 m (8 cases), 15 m (10 cases), and 20 m (9 cases) around the GPS position at which the alarm was accepted in the app. The system logged responders as being departed when the smartphone position was registered outside the geofence. The students were instructed to manually start a stopwatch at the time of the alert and to stop the stopwatch once they had entered the street in front of their flat. Results: The median difference between automatically and manually retrieved times were -16 seconds [interquartile range IQR 50 seconds] (geofence 10 m), 30 seconds [IQR 25 seconds] (15 m), and 20 seconds [IQR 13 seconds] (20 m), respectively. The 20 m geofence was associated with the smallest interquartile range. Conclusion: Departing times of volunteer responders in SAS can be retrieved automatically using GPS and a geofence.

Predicting Genitourinary Injuries in Polytraumatized Patients-Development of the GUIPP Scoring System.

BACKGROUND: The genitourinary system is not as commonly affected as many other organ systems in severely injured patients. Although a delayed and missed diagnosis of genitourinary injuries (GUIs) can severely compromise long-term outcomes, these injuries are frequently overlooked. Therefore, we present a scoring system designed to assist emergency physicians in diagnosing GUIs in severely injured patients. METHODS: The data were obtained from the TraumaRegister DGU® from the years 2015-2021. All severely injured patients (ISS ≥ 16) ≥16 years of age and treated in Germany, Austria, or Switzerland were included in this study. We excluded patients who were transferred out early (48 h), and all patients with isolated traumatic brain injury. After the univariate analysis of the relevant predictive factors, we developed a scoring system using a binary logistic regression model. RESULTS: A total of 70,467 patients were included in this study, of which 4760 (6.8%) sustained a GUI. Male patients (OR: 1.31, 95% CI [1.22, 1.41]) injured in motorcycle accidents (OR: 1.70, 95% CI [1.55, 1.87]), who were under 60 years of age (OR: 1.59, 95% CI [1.49, 1.71]) and had sustained injuries in multiple body regions (OR: 6.63, 95% CI [5.88, 7.47]), and suffered severe pelvic girdle injuries (OR: 2.58, 95% CI [2.29, 2.91]) had the highest odds of sustaining a GUI. With these predictive factors combined, a novel scoring system, the GUIPP score, was developed. It showed good validity, with an AUC of 0.722 (95% CI [0.71; 0.73]). CONCLUSION: Predicting GUI in severely injured patients remains a challenge for treating physicians, but is extremely important to prevent poor outcomes for affected patients. The GUIPP score can be utilized to initiate appropriate diagnostic steps early on in order to reduce the delayed and missed diagnosis of GUI, with scores ≥ 9 points making GUIs very likely.

Interrater agreement of multi-professional case review as reference standard for specialist palliative care need: a mixed-methods study.

BACKGROUND: A wide variety of screening tools for the need for specialist palliative care (SPC) have been proposed for the use in oncology. However, as there is no established reference standard for SPC need to compare their results with, their sensitivity and specificity have not yet been determined. The aim of the study was to explore whether SPC need assessment by means of multi-professional case review has sufficient interrater agreement to be employed as a reference standard. METHODS: Comprehensive case descriptions were prepared for 20 inpatients with advanced oncologic disease at the University Hospital Freiburg (Germany). All cases were presented to the palliative care teams of three different hospitals in independent, multi-professional case review sessions. The teams assessed whether patients had support needs in nine categories and subsequently concluded SPC need (yes / no). Interrater agreement regarding SPC need was determined by calculating Fleiss' Kappa. RESULTS: In 17 out of 20 cases the three teams agreed regarding their appraisal of SPC need (substantial interrater agreement: Fleiss' Kappa κ = 0.80 (95% CI: 0.55-1.0; p < 0.001)). The number of support needs was significantly lower for patients who all teams agreed had no SPC need than for those with agreed SPC need. CONCLUSIONS: The proposed expert case review process shows sufficient reliability to be used as a reference standard. Key elements of the case review process (e.g. clear definition of SPC need, standardized review of the patients' support needs) and possible modifications to simplify the process are discussed. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00021686, registered 17.12.2020.