[AKTIN - The German Emergency Department Data Registry - real-time data from emergency medicine : Implementation and first results from 15 emergency departments with focus on Federal Joint Committee's guidelines on acuity assessment]. / Das AKTIN-Notaufnahmeregister ­ kontinuierlich aktuelle Daten aus der Akutmedizin : Ergebnisse des Registeraufbaus und erste Datenauswertungen aus 15 Notaufnahmen unter besonderer Berücksichtigung der Vorgaben des Gemeinsamen Bundesausschusses zur Ersteinschätzung.

BACKGROUND: Emergency care in Germany is in transition. Emergency departments (EDs) treat their patients based on symptoms and acuity. However, this perspective is not reflected in claims data. The aim of the AKTIN project was to establish an Emergency Department Data Registry as a data privacy-compliant infrastructure for the use of routine medical data. METHODS: Data from the respective documentation systems are continuously transmitted to local data warehouses using a standardized interface. They are available for several applications such as internal reports but also multicentre studies, in compliance with data privacy regulations. Based on a 12-months period we evaluate the population with focus on acuity assessment (triage) and vital parameters in combination with presenting complaints. RESULTS: For the period April 2018 to March 2019, 436,149 cases from 15 EDs were available. A triage level is documented in 86.0% of cases, and 70.5% were triaged within 10 min of arrival. Ten EDs collected a presenting complaint regularly (82.3%). The respective documentation of vital signs shows plausible patterns. CONCLUSIONS: The AKTIN registry provides an almost real-time insight into German EDs, regardless of the primary documentation system and health insurance claims data. The Federal Joint Committee's requirements are largely met. Standardized presenting complaints allow for symptom-based analyses as well as health surveillance.

Reliability, repeatability and comparison to normal of a set of new stereophotogrammetric parameters to detect trunk asymmetries.

Aesthetic impairment is a crucial issue in Adolescent Idiopathic Scoliosis (AIS), but to date no objective measurements are available. The aim of the study is to evaluate the repeatability of 17 parameters measured by surface topography in a group of AIS subjects and verify their diagnostic validity. The paper is divided into three cross-sectional observational studies. We evaluated 17 selected surface topography parameters that could be good predictors of scoliosis' impact on the patients' trunk. We analysed short-term (30 seconds, 38 subjects) and medium-term (90 minutes, 14 subjects) repeatability of surface topography measures and their diagnostic validity in AIS (74 subjects, 33 AIS patients and 41 healthy subjects). All examined parameters were highly correlated as far as short and medium-term repeatability is concerned. We found a statistically significant difference between the scoliosis group and the control group in 3 surface rotation parameters, 1 shoulder parameter and 3 waist parameters. In conclusion, surface topography showed a good repeatability. Moreover, some of its parameters are correlated with AIS, enabling us to find differences between pathological and healthy subjects. Thanks to these findings, it will be possible to develop a tool that can objectively evaluate aesthetics is AIS patients.

Impact of genetic and nongenetic factors on interindividual variability in 4ß-hydroxycholesterol concentration.

PURPOSE: Individual variability in the endogenous CYP3A metabolite 4ß-hydroxycholesterol (4ßOHC) is substantial, but to which extent this is determined by genetic and nongenetic factors remains unclear. The aim of the study was to evaluate the explanatory power of candidate genetic variants and key nongenetic factors on individual variability in 4ßOHC levels in a large naturalistic patient population. METHODS: We measured 4ßOHC concentration in serum samples from 655 patients and used multiple linear regression analysis to estimate the quantitative effects of CYP3A4*22, CYP3A5*3, and POR*28 variant alleles, comedication with CYP3A inducers, inhibitors and substrates, sex, and age on individual 4ßOHC levels. RESULTS: 4ßOHC concentration ranged >100-fold in the population, and the multiple linear regression model explained about one fourth of the variability (R 2 = 0.23). Only comedication with inducers or inhibitors, sex, and POR genotype were significantly associated with individual variability in 4ßOHC level. The estimated quantitative effects on 4ßOHC levels were greatest for inducer comedication (+>313%, P < 0.001), inhibitor comedication (-34%, P = 0.021), and female sex (+30%, P < 0.001), while only a modestly elevated 4ßOHC level was observed in carriers vs. noncarriers of POR*28 (+11%, P = 0.023). CONCLUSIONS: These findings suggest that the CYP3A4*22, CYP3A5*3, and POR*28 variant alleles are of limited importance for overall individual variability in 4ßOHC levels compared to nongenetic factors.

Pregnancy outcomes after prenatal exposure to echinacea: the Norwegian Mother and Child Cohort Study.

INTRODUCTION: Previous studies have shown that echinacea is among the most widely used herbal medicines during pregnancy in Western countries. Despite its frequent use, we know little about the safety of this herbal medicine during pregnancy. The primary aim of this study was to study the consequences of the use of echinacea on malformations and common adverse pregnancy outcomes. Secondly, we aimed to characterize women using this herb in pregnancy. METHOD: This study is based on the Norwegian Mother and Child Cohort Study (MoBa) and included 68,522 women and their children. Information was retrieved from three self-administered questionnaires completed by the women in pregnancy weeks 17 and 30 and 6 months after birth. Information on pregnancy outcomes was retrieved from the Medical Birth Registry of Norway. Generalized estimating equations analyses were performed to assess the association between exposure to echinacea and pregnancy outcomes. Pearson's chi-square test was used to assess factors related to use of echinacea in pregnancy. RESULTS: Among 68,522 women, 363 (0.5 %) reported the use of echinacea during pregnancy. These women were characterized by high age and delivery before 2002 and were to a less extent smoking in pregnancy. The use of echinacea was not associated with an increased risk of malformations or adverse pregnancy outcomes. CONCLUSION: This study revealed no increased risk of malformations or adverse pregnancy outcomes after the use of echinacea in pregnancy. Studies on the safety of commonly used herbal medications are important to identify herbals that should be avoided in pregnancy.

Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy.

Histone deacetylase (HDAC) inhibitors (HDACis) are well-characterized anti-cancer agents with promising results in clinical trials. However, mechanistically little is known regarding their selectivity in killing malignant cells while sparing normal cells. Gene expression-based chemical genomics identified HDACis as being particularly potent against Down syndrome-associated myeloid leukemia (DS-AMKL) blasts. Investigating the antileukemic function of HDACis revealed their transcriptional and post-translational regulation of key autophagic proteins, including ATG7. This leads to suppression of autophagy, a lysosomal degradation process that can protect cells against damaged or unnecessary organelles and protein aggregates. DS-AMKL cells exhibit low baseline autophagy due to mammalian target of rapamycin (mTOR) activation. Consequently, HDAC inhibition repressed autophagy below a critical threshold, which resulted in accumulation of mitochondria, production of reactive oxygen species, DNA damage and apoptosis. Those HDACi-mediated effects could be reverted upon autophagy activation or aggravated upon further pharmacological or genetic inhibition. Our findings were further extended to other major acute myeloid leukemia subgroups with low basal level autophagy. The constitutive suppression of autophagy due to mTOR activation represents an inherent difference between cancer and normal cells. Thus, via autophagy suppression, HDACis deprive cells of an essential pro-survival mechanism, which translates into an attractive strategy to specifically target cancer cells.

Chemical composition of burnt smell caused by accidental fires: environmental contaminants.

The chemical composition of the odors typical of fires has recently been deciphered. Basically the constituents are mixtures of acetophenone, benzyl alcohol, hydroxylated derivatives of benzaldehyde, methoxylated and/or alkylated phenols and naphthalene. This finding makes it possible to develop objective, practical analytic measurement methods for the burnt smell as a contribution to improving fire damage assessment and remediation monitoring. With the aid of an artificially produced burnt smell and a panel of testers the odor detection threshold of a test mixture was determined olfactometrically to 2 µg m⁻³. Using a defined burnt-smell atmosphere in a test chamber, analytical methods with active sampling, the adsorbents XAD 7 and TENAX TA, and GC/MS measurement were then optimized and tested with a view to being able to carry out sensitive quantitative measurement of burnt smells. A further practical method with particular application to the qualitative characterization of this odor is based on the use of a new SPME (solid-phase microextraction) field sampler with DVB/CAR/PDMS (divinylbenzene/Carboxen™/polydimethylsiloxane) fibers.

[Self-organizing neural networks for automatic detection and classification of contrast (media) enhancement of lesions in dynamic MR-mammography]. / Selbstorganisierende neuronale Netze zur automatischen Detektion und Klassifikation von Kontrast(mittel)-verstärkten Läsionen in der dynamischen MR-Mammographie.

PURPOSE: Investigation and statistical evaluation of "Self-Organizing Maps," a special type of neural networks in the field of artificial intelligence, classifying contrast enhancing lesions in dynamic MR-mammography. MATERIAL AND METHODS: 176 investigations with proven histology after core biopsy or operation were randomly divided into two groups. Several Self-Organizing Maps were trained by investigations of the first group to detect and classify contrast enhancing lesions in dynamic MR-mammography. Each single pixel's signal/time curve of all patients within the second group was analyzed by the Self-Organizing Maps. The likelihood of malignancy was visualized by color overlays on the MR-images. At last assessment of contrast-enhancing lesions by each different network was rated visually and evaluated statistically. RESULTS: A well balanced neural network achieved a sensitivity of 90.5 % and a specificity of 72.2 % in predicting malignancy of 88 enhancing lesions. Detailed analysis of false-positive results revealed that every second fibroadenoma showed a "typical malignant" signal/time curve without any chance to differentiate between fibroadenomas and malignant tissue regarding contrast enhancement alone; but this special group of lesions was represented by a well-defined area of the Self-Organizing Map. DISCUSSION: Self-Organizing Maps are capable of classifying a dynamic signal/time curve as "typical benign" or "typical malignant." Therefore, they can be used as second opinion. In view of the now known localization of fibroadenomas enhancing like malignant tumors at the Self-Organizing Map, these lesions could be passed to further analysis by additional post-processing elements (e.g., based on T2-weighted series or morphology analysis) in the future.

Complete genome sequence of the marine planctomycete Pirellula sp. strain 1.

Pirellula sp. strain 1 ("Rhodopirellula baltica") is a marine representative of the globally distributed and environmentally important bacterial order Planctomycetales. Here we report the complete genome sequence of a member of this independent phylum. With 7.145 megabases, Pirellula sp. strain 1 has the largest circular bacterial genome sequenced so far. The presence of all genes required for heterolactic acid fermentation, key genes for the interconversion of C1 compounds, and 110 sulfatases were unexpected for this aerobic heterotrophic isolate. Although Pirellula sp. strain 1 has a proteinaceous cell wall, remnants of genes for peptidoglycan synthesis were found. Genes for lipid A biosynthesis and homologues to the flagellar L- and P-ring protein indicate a former Gram-negative type of cell wall. Phylogenetic analysis of all relevant markers clearly affiliates the Planctomycetales to the domain Bacteria as a distinct phylum, but a deepest branching is not supported by our analyses.

[A software tool for automatic image-based ventilation analysis using dynamic chest CT-scanning in healthy and in ARDS lungs]. / Software zur automatischen Quantifizierung von Belüftungszuständen bei akutem Lungenversagen in dynamischen CT-Aufnahmen der Lunge1.

PURPOSE: Density measurements in dynamic CT image series of the lungs allow one to quantify ventilated, hyperinflated, and atelectatic pulmonary compartments with high temporal resolution. Fast automatic segmentation of lung parenchyma and a subsequent evaluation of it's respective density values are a prerequisite for any clinical application of this technique. MATERIAL AND METHODS: For automatic lung segmentation in thoracic CT scans, an algorithm was developed which uses (a) different density masks, and (b) anatomic knowledge to differentiate heart, diaphragm and chest wall from ventilated and atelectatic lung parenchyma. With Animal Care Committee approval, the automated technique was tested in 8 anaesthetized ventilated pigs undergoing dynamic CT before and after induction of lavage-ARDS. Images were acquired in one supradiaphragmatic, cross-sectional slice (temporal resolution of 100 ms; slice thickness of 1 mm, high resolution reconstruction algorithm). In 120 CT images the total pixel number and the calculated MLD from the automatically segmentated lung were compared to the values obtained from an interactive lung segmentation. RESULTS: The software tool was able to read all image series (DICOM standard). Automatic and interactive segmentation were in high agreement (R(2) = 0.99 for the total number of pixels and the MLD). Originally, the most frequent error was misclassification of atelectasis as extrapulmonary solid tissue. CONCLUSION: An automatic software tool is presented for lung segmentation in healthy lungs and in ARDS. Aerated lung and atelectasis were identified with high accuracy. This post-processing tool allows for a quantitative, CT based assessment of ventilation and recruitment processes in the lung. Thus, it may help to optimize ventilation patterns in patients with ARDS.

DTDs go XML schema--a tools perspective.

Document Type Definitions (DTDs) are widely used to describe the structure of XML documents. The Clinical Document Architecture (CDA) and the Guideline Element Model (GEM) are examples from the healthcare domain. XML schemas provide another way to describe types of XML documents. In this paper we aim to advocate XML schemas from the perspective of an ANSI standard, the XML based CDA from HL7 (ANSI/HL7 CDA R1.0-2000). It turned out that existing tools do not fully exploit the knowledge contained in DTDs and XML schemas. The result of this study is a set of tools (DTD to XML Schema translator, DTD and XML schema browser, XML editor), which can be downloaded from the official W3C site and which work with any DTD and XML schema.

Automatic detection and quantification of ground-glass opacities on high-resolution CT using multiple neural networks: comparison with a density mask.

OBJECTIVE: We compared multiple neural networks with a density mask for the automatic detection and quantification of ground-glass opacities on high-resolution CT under clinical conditions. SUBJECTS AND METHODS: Eighty-four patients (54 men and 30 women; age range, 18-82 years; mean age, 49 years) with a total of 99 consecutive high-resolution CT scans were enrolled in the study. The neural network was designed to detect ground-glass opacities with high sensitivity and to omit air-tissue interfaces to increase specificity. The results of the neural network were compared with those of a density mask (thresholds, -750/-300 H), with a radiologist serving as the gold standard. RESULTS: The neural network classified 6% of the total lung area as ground-glass opacities. The density mask failed to detect 1.3%, and this percentage represented the increase in sensitivity that was achieved by the neural network. The density mask identified another 17.3% of the total lung area to be ground-glass opacities that were not detected by the neural network. This area represented the increase in specificity achieved by the neural network. Related to the extent of the ground-glass opacities as classified by the radiologist, the neural network (density mask) reached a sensitivity of 99% (89%), specificity of 83% (55%), positive predictive value of 78% (18%), negative predictive value of 99% (98%), and accuracy of 89% (58%). CONCLUSION: Automatic segmentation and quantification of ground-glass opacities on high-resolution CT by a neural network are sufficiently accurate to be implemented for the preinterpretation of images in a clinical environment; it is superior to a double-threshold density mask.

[Automated detection of spleen volume by spiral CT scans using neural networks and "fuzzy logic"]. / Automatische Berechnung des Milzvolumens aus Spiral-CT-Daten mit Hilfe neuronaler Netze und "Fuzzy Logik".

PURPOSE: To assess spleen segmentation and volumentry in spiral CT scans with and without pathological changes of splenic tissue. METHODS: The image analysis software HYBRIKON is based on region growing, self-organized neural nets, and fuzzy-anatomic rules. The neural nets were trained with spiral CT data from 10 patients, not used in the following evaluation on spiral CT scans from 19 patients. An experienced radiologist verified the results. The true positive and false positive areas were compared in terms to the areas marked by the radiologist. The results were compared with a standard thresholding method. RESULTS: The neural nets achieved a higher accuracy than the thresholding method. Correlation coefficient of the fuzzy-neural nets: 0.99 (thresholding: 0.63). Mean true positive rate: 90% (thresholding: 75%), mean false positive rate: 5% (thresholding > 100%). Pitfalls were caused by accessory spleens, extreme changes in the morphology (tumors, metastases, cysts), and parasplenic masses. CONCLUSIONS: Self-organizing neural nets combined with fuzzy rules are ready for use in the automatic detection and volumetry of the spleen in spiral CT scans.

A new generation of remote data entry: using WAP-phones in clinical trials.

This paper presents an introduction to a new approach in the field of clinical trial information technology. During the last years, more and more modern tools have found their ways to the different tasks during the design, the realization and data processing in the clinical trial. Choosing tools depends on a variety of conditions and aspects that have to be considered. Besides issues in the field of trial software, the focus of research also turns over to special hardware used in the trial. The Wireless Markup Language (WML) offers the possibility of using handheld devices like mobile phones (handy) or Personal Digital Assistants (PDA) for remote data entry. These widespread, easy to use hardware devices could use wireless access to the standard internet for use in their applications. This combination seems to become a success because of the existing infrastructure, the ongoing efforts in improving and enlarging the internet platform and not at last because the approach is so similar to the well accepted World Wide Web (WWW). As today this technology has not yet matured, different criteria have to be mentioned when choosing hard- and software for this application. We will show some aspects related especially to modern handheld devices and the belonging software.

Calming admins and managers--experiences from four years using thin client technology in a hospital environment.

End user desktop computers in a hospital are often full-blown and rich featured PCs. But the distribution of this kind of "computing power" causes big efforts in administration and maintenance and--considering the total cost of owning a PC--is associated with high expenditures of financial and human resources. At the university hospital of Cologne thin client technology is used as an end user desktop device wherever possible. Experiences from four years using this technology are described in this paper.

Symptom reporting in cancer patients II: relations to social desirability, negative affect, and self-reported health behaviors.

BACKGROUND: Patients' appraisal of somatic symptoms is correlated with their negative affect. The authors have investigated whether social desirability is associated with patients' symptom and health behavior reporting. METHODS: One hundred fourteen surgical cancer patients who participated in either an outpatient or an inpatient follow-up care program filled out the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the New Social Desirability Scale, and a health behavior checklist. RESULTS: Patients' reports of somatic symptoms were correlated inversely with social desirability (r = -0.50) and positively with negative affect (r = 0.72). When objective health and demographic variables (e.g., prognosis, adjuvant therapy prior to follow-up, and gender) were entered first in hierarchical multiple regression analyses, social desirability and negative affect accounted for an additional 16% and 36% of the symptom variance, respectively. Similar results were found when global quality of life was the dependent variable. Self-reported health behaviors were explained only through the set of health and demographic variables (14%), and social desirability and negative affect did not account for additional variance. On the average, patients reported that they had a median of 4.7 (out of a list of 21) self-initiated health behaviors, and 11% of the patients admitted to having used unproven therapies. CONCLUSIONS: Symptom reports do not give a pure picture of patients' health status, but they are strongly correlated with social desirability and negative affect. Detection of such psychologic variables is essential to understanding the dynamics of quality of life. In applied settings, quality-of-life measures should be used together with conventional criteria. As practical experience and scientific understanding grow, the relative positioning of these patient-oriented versus clinic-oriented endpoints will become clear.

[The Cologne Guidelines Conference: computer-assisted clinical practice guidelines in clinical diagnosis]. / Die Kölner Leitlinien-Konferenz: Computergestützte Leitlinien zur klinischen Diagnostik.

Eighteen clinical practice guidelines on interdisciplinary diagnostic issues were developed at the University Hospital of Cologne, Germany. The guideline committee is organized and directed by the quality control program, which also includes the local Cochrane initiative and a wide range of organizational topics. During guideline development, questions of differential diagnosis were addressed to the same extent as the organizational and financial realization. Broad consideration was given to medicolegal implications, but need for interspecialty cooperation was judged to be more critical and even more relevant in this regard. Guidelines were primarily developed as algorithms and translated to text versions secondarily. Critical steps in the decision tree were supported by rated literature and recommendations weighte by criteria as used in evidence-based medicine. For implementation, guidelines were presented to colleagues in a series of short lectures, as print versions containing all literature used in the developing process, and in hypertext format, which is accessible via intranet. Three levels of presentation were chosen in the html-version: algorithm, decision, and information. The former is due to orientation in the guideline, the second displays the binary question, and the latter makes the scientific background available, together with literature and links for more information. Efforts to check effectiveness are currently been made, questions of efficiency will be addressed in future.

Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy.

Endogenous advanced glycation endproducts (AGEs) include chemically crosslinking species (glycotoxins) that contribute to the vascular and renal complications of diabetes mellitus (DM). Renal excretion of the catabolic products of endogenous AGEs is impaired in patients with diabetic or nondiabetic kidney disease (KD). The aim of this study was to examine the oral absorption and renal clearance kinetics of food AGEs in DM with KD and whether circulating diet-derived AGEs contain active glycotoxins. Thirty-eight diabetics (DM) with or without KD and five healthy subjects (NL) received a single meal of egg white (56 g protein), cooked with (AGE-diet) or without fructose (100 g) (CL-diet). Serum and urine samples, collected for 48 hr, were monitored for AGE immunoreactivity by ELISA and for AGE-specific crosslinking reactivity, based on complex formation with 125I-labeled fibronectin. The AGE-diet, but not the CL-diet, produced distinct elevations in serum AGE levels in direct proportion to amount ingested (r = 0.8, P < 0.05): the area under the curve for serum ( approximately 10% of ingested AGE) correlated directly with severity of KD; renal excretion of dietary AGE, although normally incomplete (only approximately 30% of amount absorbed), in DM it correlated inversely with degree of albuminuria, and directly with creatinine clearance (r = 0.8, P < 0.05), reduced to <5% in DM with renal failure. Post-AGE-meal serum exhibited increased AGE-crosslinking activity (two times above baseline serum AGE, three times above negative control), which was inhibited by aminoguanidine. In conclusion, (i) the renal excretion of orally absorbed AGEs is markedly suppressed in diabetic nephropathy patients, (ii) daily influx of dietary AGEs includes glycotoxins that may constitute an added chronic risk for renal-vascular injury in DM, and (iii) dietary restriction of AGE food intake may greatly reduce the burden of AGEs in diabetic patients and possibly improve prognosis.

Automatic detection of ground glass opacities on lung HRCT using multiple neural networks.

The purpose of this study was to implement neural networks and expert rules for the automatic detection of ground glass opacities (GG) on high-resolution computed tomography (HRCT). Different approaches using self-organizing neural nets as well as classifications of lung HRCT with and without the use of explicit textural parameters have been applied in preliminary studies. In the present study a hybrid network of three single nets and an expert rule was applied for the detection of GG on 120 HRCT scans from 20 patients suffering from different lung diseases. Single nets alone were not capable to reliably detect or exclude GG since the false-positive rate was greater than 100 % with regard to the area truly involved, more than 50 pixels throughout, and the true-positive rate was greater than 95 %. The hybrid network correctly classified 91 of 120 scans. Mild GG was false positive in 15 cases with less than 50 pixels, which was judged not clinically relevant. The pitfalls were: partial volume effects of bronchovascular bundles and the chest wall. Motion artefacts and diaphragm were responsible for 11 misclassifications. Hybrid networks represent a promising tool for an automatic pathology-detecting system. They are ready to use as a diagnostic assistant for detection, quantification and follow-up of ground glass opacities, and further applications are underway.

The role of communication servers in the architecture of healthcare information systems.

Communication between departmental subsystems within a hospital information system (HIS) is more and more supported by dedicated communication servers (CS). One of the main advantages is a centralized and standardized flow of information. Beside this "classic" approach a communication server may be embedded on at least two other hierarchical levels in the architecture of healthcare information systems: in an organizational unit within a hospital (subsystem) but also in large scale healthcare information systems covering aspects of communication between the involved external healthcare providers.

Use of nanogold- and fluorescent-labeled antibody Fv fragments in immunocytochemistry.

Recombinant antibody fragments are emerging as a versatile tool in both basic research and medical therapy. We describe the procedures for direct labeling of engineered antibody fragments (Fv) with fluorescein or nanogold and their use in fluorescence and immunoelectron microscopy, respectively. The Fv fragments were produced in Escherichia coli, purified by one-step Strep tag affinity chromatography, chemically labeled with the marker, and employed in microscopy to localize epitopes on the membrane protein bacteriorhodopsin in purple membranes of Halobacterium halobium and the cytochrome c oxidase of Paracoccus denitrificans. In both cases, methods involving directly labeled antibody fragments show results identical to those in which antibodies or Fv fragments are detected by a secondarily labeled conjugate. The multifunctional design of the recombinant Fv fragments, however, offers more all-around applications in immunocytochemistry. The directly labeled Fv fragments, half the size of an Fab fragment, are at the molecular level the smallest antibody fragments yet described for visualization of biomolecules in microscopy.