The Abdominal Pain Unit (APU). Study protocol of a standardized and structured care pathway for patients with atraumatic abdominal pain in the emergency department: A stepped wedged cluster randomized controlled trial.

This study aims to improve emergency department (ED) care for patients suffering from atraumatic abdominal pain. An application-supported pathway for the ED will be implemented, which supports quick, evidence-based, and standardized diagnosis and treatment steps for patients with atraumatic abdominal pain at the ED. A mixed-methods multicentre cluster randomized controlled stepped wedge trial design will be applied. A total of 10 hospitals with EDs (expected n = 2.000 atraumatic abdominal pain patients) will consecutively (every 4 months) be randomized to apply the intervention. Inclusion criteria for patients are a minimum age of 18 years, suffering from atraumatic abdominal pain and being insured with a German statutory health insurance. Primary outcomes: acute pain score at time of discharge from ED, duration of treatment at the ED, patient-reported satisfaction. Secondary endpoints include patient safety and quality of care parameters, process evaluation parameters, and costs and cost-effectiveness parameters. Quantitative data will be gathered from patient-surveys, clinical records, and routine data from hospital information systems as well as from a participating German statutory health insurance. Descriptive and analytic statistical analysis will be performed to provide summaries and associations for primary patient-reported outcomes, process measures, quality measures, and costs. Qualitative data collection consists of participatory patient observations and semi-structured expert interviews, which will be inductively analysed. Findings will be disseminated in publications in peer-reviewed journals, on conferences, as well as via a project website. To ensure data protection, appropriate technical and organisational measures will be taken. Trial registration: DRKS00021052.

[The way to routine data from 16 emergency departments for cross-sectoral health services research : Experiences, challenges and solution approaches from the extraction of pseudonymous data for the INDEED project]. / Der Weg zu Routinedaten aus 16 Notaufnahmen für die sektorenübergreifende Versorgungsforschung : Erfahrungen, Herausforderungen und Lösungsansätze aus der Extraktion pseudonymer Daten für das Projekt INDEED.

BACKGROUND: In Germany there is currently no health reporting on cross-sectoral care patterns in the context of an emergency department care treatment. The INDEED project (Utilization and trans-sectoral patterns of care for patients admitted to emergency departments in Germany) collects routine data from 16 emergency departments, which are later merged with outpatient billing data from 2014 to 2017 on an individual level. AIM: The methodological challenges in planning of the internal merging of routine clinical and administrative data from emergency departments in Germany up to the final data extraction are presented together with possible solution approaches. METHODS: Data were selected in an iterative process according to the research questions, medical relevance, and assumed data availability. After a preparatory phase to clarify formalities (including data protection, ethics), review test data and correct if necessary, the encrypted and pseudonymous data extraction was performed. RESULTS: Data from the 16 cooperating emergency departments came mostly from the emergency department and hospital information systems. There was considerable heterogeneity in the data. Not all variables were available in every emergency department because, for example, they were not standardized and digitally available or the extraction effort was judged to be too high. CONCLUSION: Relevant data from emergency departments are stored in different structures and in several IT systems. Thus, the creation of a harmonized data set requires considerable resources on the part of the hospital as well as the data processing unit. This needs to be generously calculated for future projects.

INDEED-Utilization and Cross-Sectoral Patterns of Care for Patients Admitted to Emergency Departments in Germany: Rationale and Study Design.

Introduction: The crowding of emergency departments (ED) has been a growing problem for years, putting the care of critically ill patients increasingly at risk. The INDEED project's overall aim is to get a better understanding of ED utilization and to evaluate corresponding primary health care use patterns before and after an ED visit while driving forward processes and methods of cross-sectoral data merging. We aim to identify adequate utilization of EDs and potentially avoidable patient contacts as well as subgroups and clusters of patients with similar care profiles. Methods: INDEED is a joint endeavor bringing together research institutions and hospitals with EDs in Germany. It is headed by the Charité-Universitätsmedizin Berlin, collaborating with Otto von Guericke University Magdeburg, Technische Universität Berlin, the Central Research Institute of Ambulatory/Outpatient Health Care in Germany (Zi), and the AOK Research Institute as part of the Federal Association of AOK, as well as experts in the technological, legal, and regulatory aspects of medical research (TMF). The Institute for Information Technology (OFFIS) was involved as the trusted third party of the project. INDEED is a retrospective study of approximately 400,000 adult patients with statutory health insurance who visited the ED of one of 16 participating hospitals in 2016. The routine hospital data contain information about treatment in the ED and, if applicable, about the subsequent hospital stay. After merging the patients' hospital data from 2016 with their outpatient billing data from 2 years before to 1 year after the ED visit (years 2014-2017), a harmonized dataset will be generated for data analyses. Due to the complex data protection challenges involved, first results will be available in 2021. Discussion: INDEED will provide knowledge on extracting and harmonizing large scale data from varying routine ED and hospital information systems in Germany. Merging these data with the corresponding outpatient care data of patients offers the opportunity to characterize the patient's treatment in outpatient care before and after ED use. With this knowledge, appropriate interventions may be developed to ensure adequate patient care and to avoid adverse events such as ED crowding.

Identification of an amino acid determinant of pH regiospecificity in a seed lipoxygenase from Momordica charantia.

Lipoxygenases (LOX) form a heterogeneous family of lipid peroxidizing enzymes, which catalyze specific dioxygenation of polyunsaturated fatty acids. According to their positional specificity of linoleic acid oxygenation plant LOX have been classified into linoleate 9- and linoleate 13-LOX and recent reports identified a critical valine at the active site of 9-LOX. In contrast, more bulky phenylalanine or histidine residues were found at this position in 13-LOX. We have recently cloned a LOX-isoform from Momordica charantia and multiple amino acid alignments indicated the existence of a glutamine (Gln599) at the position were 13-LOX usually carry histidine or phenylalanine residues. Analyzing the pH-dependence of the positional specificity of linoleic acid oxygenation we observed that at pH-values higher than 7.5 this enzyme constitutes a linoleate 13-LOX whereas at lower pH, 9-H(P)ODE was the major reaction product. Site-directed mutagenesis of glutamine 599 to histidine (Gln599His) converted the enzyme to a pure 13-LOX. These data confirm previous observation suggesting that reaction specificity of certain LOX-isoforms is not an absolute enzyme property but may be impacted by reaction conditions such as pH of the reaction mixture. We extended this concept by identifying glutamine 599 as sequence determinant for such pH-dependence of the reaction specificity. Although the biological relevance for this alteration switch remains to be investigated it is of particular interest that it occurs at near physiological conditions in the pH-range between 7 and 8.

The multigene family encoding germin-like proteins of barley. Regulation and function in Basal host resistance.

Germin-like proteins (GLPs) have been shown to be encoded by multigene families in several plant species and a role of some subfamily members in defense against pathogen attack has been proposed based on gene regulation studies and transgenic approaches. We studied the function of six GLP subfamilies of barley (Hordeum vulgare) by selecting single mRNAs for gene expression studies as well as overexpression and gene-silencing experiments in barley and Arabidopsis (Arabidopsis thaliana). Expression of all six subfamilies was high in very young seedlings, including roots. The expression pattern gradually changed from developmental to conditional with increasing plant age, whereby pathogen attack and exogenous hydrogen peroxide application were found to be the strongest signals for induction of several GLP subfamilies. Transcripts of four of five GLP subfamilies that are expressed in shoots were predominantly accumulating in the leaf epidermis. Transient overexpression of HvGER4 or HvGER5 as well as transient silencing by RNA interference of HvGER3 or HvGER5 protected barley epidermal cells from attack by the appropriate powdery mildew fungus Blumeria graminis f. sp. hordei. Silencing of HvGER4 induced hypersusceptibility. Transient and stable expression of subfamily members revealed HvGER5 as a new extracellular superoxide dismutase, and protection by overexpression could be demonstrated to be dependent on superoxide dismutase activity of the encoded protein. Data suggest a complex interplay of HvGER proteins in fine regulation of basal resistance against B. graminis.

The germinlike protein GLP4 exhibits superoxide dismutase activity and is an important component of quantitative resistance in wheat and barley.

Germinlike proteins (GLP) are encoded in plants by a gene family with proposed functions in plant development and defense. Genes of GLP subfamily 4 of barley (HvGLP4, formerly referred to as HvOxOLP) and the wheat orthologue TaGLP4 (formerly referred to as TaGLP2a) were previously found to be expressed in pathogen-attacked epidermal tissue of barley and wheat leaves, and the corresponding proteins are proposed to accumulate in the apoplast. Here, the role of HvGLP4 and TaGLP4 in the defense of barley and wheat against Blumeria graminis (DC.) E. O. Speer, the cereal powdery mildew fungus, was examined in an epidermal transient expression system and in transgenic Arabidopsis thaliana plants overexpressing His-tagged HvGLP4. Leaf extracts of transgenic Arabidopsis overexpressing HvGLP4 contained a novel His-tagged protein with superoxide dismutase activity and HvGLP4 epitopes. Transient overexpression of TaGLP4 and HvGLP4 enhanced resistance against B. graminis in wheat and barley, whereas transient silencing by RNA interference reduced basal resistance in both cereals. The effect of GLP4 overexpression or silencing was strongly influenced by the genotype of the plant. The data suggest that members of GLP subfamily 4 are components of quantitative resistance in both barley and wheat, acting together with other, as yet unknown, plant components.