Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.

Feasibility, safety and effectiveness of prednisolone and vitamin B1, B6, and B12 in patients with post-COVID-19-syndrome (PreVitaCOV) - protocol of a randomised, double-blind, placebo-controlled multicentre trial in primary care (phase IIIb).

BACKGROUND: After infection with SARS-CoV-2 a relevant proportion of patients complains about persisting symptoms, a condition termed Post-COVID-19-syndrome (PC19S). So far, possible treatments are under investigation. Among others, neurotropic vitamins and anti-inflammatory substances are potential options. Thus, the PreVitaCOV trial aims to assess feasibility, safety, and effectiveness of treating patients in primary care with prednisolone and/or vitamin B1, B6 and B12. METHODS: The phase IIIb, multi-centre randomised, double-blind, and placebo-controlled PreVitaCOV trial has a factorial design and is planned as a two-phase approach. The pilot phase assessed feasibility and safety and was transformed into a confirmatory phase to evaluate effectiveness since feasibility was proven. Adult patients with PC19S after a documented SARS-CoV-2 infection at least 12 weeks ago are randomly assigned to 4 parallel treatments: prednisolone 20 mg for five days followed by 5 mg for 23 days (trial drug 1), B vitamins (B1 (100 mg OD), B6 (50 mg OD), and B12 (500 µg OD)) for 28 days (trial drug 2), trial drugs 1 and 2, or placebo. The primary outcome of the pilot phase was defined as the retention rate of the first 100 patients. Values of ≥ 85% were considered as confirmation of feasibility, this criterion was even surpassed by a retention rate of 98%. After transformation, the confirmatory phase proceeds by enrolling 240 additional patients. The primary outcome for the study is the change of symptom severity from baseline to day 28 as assessed by a tailored Patient Reported Outcomes Measurement Information System (PROMIS) total score referring to five symptom domains known to be typical for PC19S (fatigue, dyspnoea, cognition, anxiety, depression). The confirmatory trial is considered positive if superiority of any treatment is demonstrated over placebo operationalised by an improvement of at least 3 points on the PROMIS total score (t-score). DISCUSSION: The PreVitaCOV trial may contribute to the understanding of therapeutic approaches in PC19S in a primary care context. TRIAL REGISTRATION: EudraCT: 2022-001041-20. DRKS: DRKS00029617. CLINICALTRIALS: gov: F001AM02222_1 (registered: 05 Dec 2022).

[Learning from Errors: Qualitative Analysis of Expert Reports on Malpractice in Family Medicine]. / Aus Fehlern lernen ­ qualitative Analyse von Gutachten zu hausärztlichen Behandlungsfehlern.

BACKGROUND: Expert committees of the German medical associations provide a free and out-of-court evaluation of putative cases of medical malpractice. They prepare reports that contain valuable information on process steps that precede the actual treatment error. The aim of the present study was to identify and systematically categorize individual process steps in the expert reports and thus to lay the foundations for the understanding of malpractice evaluation processes. METHODS: In this study, ten randomly selected and anonymized expert reports of the Expert Committee for Questions of Medical Liability of the District Medical Association of South Württemberg with identified GP treatment errors were evaluated, using the method of qualitative content analysis. In an iterative process, central elements of expert reports were classified into a deductively and inductively built category system. RESULTS: Six main categories with associated subcategories were identified: 1) structural aspects of the report, 2) doctor-patient communication, 3) medical course, 4) patient's experience, 5) action by the GP team, and 6) coordinative role in the health care system. The category system showed sufficient reliability with repeated use. CONCLUSION: This study offers an opportunity to learn from errors. The proposed system allows to structure the complexity of expert reports on GP malpractice and may thus serve as a tool in various contexts. In particular, it facilitates the preparation and comparative analysis of reports in a structured way. It could also be used in health care research as well as in education and training.

Using elemental staining and mapping techniques for simultaneous visualization of biological structures in the nucleus by multichannel electron microscopy.

Transmission electron microscopy (TEM) has been essential in defining the structural organization of the cell due to its ability to image cell structures at molecular resolution. However, the absence of colour has made it very difficult to compare the distributions and relationships of two or more types of biomolecules simultaneously if they lack clear morphological distinctions. Furthermore, single-channel information limits functional analysis, particularly in the nucleoplasm, where fibrillar material could be chromatin, ribonucleic acid or protein. Where specific stains exist to discriminate among these molecules, they cannot be combined because conventional TEM is a single-channel technology. A potential path around this barrier is through electron spectroscopic imaging (ESI). ESI can map the distributions of chemical elements within an ultrathin section. Here, we present methods to stain specific molecules with elements that ESI can visualize to enable multichannel electron microscopy.

Patients' Experiences With Therapeutic Approaches for Post-COVID Syndrome: Results of a Crowdsourced Research Survey.

Some patients develop multiple protracted sequelae after infection with SARS-CoV-2, collectively known as post-COVID syndrome or long COVID. To date, there is no evidence showing benefit of specific therapies for this condition, and patients likely resort to self-initiated therapies. We aimed to obtain information about therapies used by and needs of this population via inductive crowdsourcing research. Patients completed an online questionnaire about their symptoms and experiences with therapeutic approaches. Responses of 499 participants suggested few approaches (eg, mind-body medicine, respiratory therapy) had positive effects and showed a great need for patient-centered communication (eg, more recognition of this syndrome). Our findings can help design clinical studies and underscore the importance of the holistic approach to care provided by family medicine.

Comorbidity, life-style factors and healthcare utilization in incident chronic kidney disease: sex-specific analyses of claims data.

BACKGROUND: Chronic kidney disease (CKD) is common in aging men and women. In contrast to other European countries, Germany lacks CKD registries. The aim of this study was to determine the incidence of CKD stages 2-5 in men and women in Germany. Furthermore, differences between the sexes in terms of comorbidities, potentially inappropriate medications (PIM), and healthcare utilization were examined. METHODS: In this retrospective observational study, claims data from members of a statutory health insurance fund aged 18 years or older with incident CKD between 2011 and 2018 were analyzed. Incident CKD was defined as having two confirmed diagnoses of CKD stages 2-5 from outpatient care or one primary or secondary diagnosis from inpatient care. RESULTS: The age- and sex-standardized incidence of all CKD stages was 945/100 000 persons between 2011 and 2018. Incident CKD, especially stages 3 and 4, occurred more frequently in women, while the incidence of stages 2 and 5 was higher in men. While women visited their GP more frequently and were prescribed PIMs more often, men were more likely to visit a nephrologist and were more often hospitalized after the incident CKD diagnosis. CONCLUSION: More awareness needs to be raised towards the early detection of CKD and the use of PIMs, especially in women. Improved care coordination is needed to avoid an overprovision of patients with uncomplicated incident stages and ensure that patients with advanced CKD stages get timely access to specialist care.

[Point-of-care information in GP practices: Results of a survey among German GP specialists and GP trainees]. / Point-of-care-Recherche in der Hausarztpraxis ­ Ergebnisse einer Befragung von Fachärzt*innen und Ärzt*innen in Weiterbildung.

BACKGROUND: Specific questions often arise in the context of consultations regarding, for example, diagnostics and therapeutic management. This case-specific search for information is referred to as point-of-care information. In recent years, it has been influenced by an increase in digitalization and by the development of medical expert systems providing information for medical professionals. Data on the search behavior of German general practitioners (GPs) using digital media for obtaining point-of-care information have so far not been available. The aims of this study were to describe occasion-related point-of-care information as a function of the continuing education status and to identify requirements for online research platforms. METHODS: In a cross-sectional survey, 829 GP specialists (FÄ) and 475 physicians in training (ÄiW) were invited to answer a self-developed, partially standardized questionnaire. RESULTS: In total, 356 questionnaires were returned (response rate: 27%). Of these, 241 (68%) were answered by FÄ and 110 (31%) by ÄiW; five participants did not provide information on their specialist status. 66% of the FÄ and 89% of the ÄiW look up information every day. 46% of the FÄ and 73% of the ÄiW use their smartphone for this purpose. Both groups most often search for medical content (94%) and for information on medications (84%). Medical expert systems are more often used by ÄiW than by FÄ; 59% of the FÄ and 82% of the ÄiW are willing to pay a fee for these services. A quick overview and relevance of information were perceived as important criteria for good information sources. DISCUSSION: German GPs frequently search for occasion-related information. There are generation-related differences regarding, among other things, the use of and the receptiveness to fee-based expert systems. The clarity of presentation and the relevance of the information provided are important requirements of effective information platforms. CONCLUSION: The quick search for evidence-based information relevant to clinical practice presents a challenge, particularly in broad-range specialties such as general medicine. Web-based sources are becoming increasingly popular in this regard - a trend likely to intensify in future generations of physicians. This offers great potential for medical expert systems and app-based access to best-practice guidelines. These formats should be further developed in collaboration with scientific professional societies.

[Neutralizing monoclonal antibodies in COVID-19: a case series in general practice]. / Neutralisierende monoklonale Antikörper bei COVID-19: eine Fallserie aus der Hausarztpraxis.

BACKGROUND: Neutralizing monoclonal antibodies (mAB) against SARS-CoV-2 reduce the severity of COVID-19 in patients with risk factors. Early administration at the onset of infection is critical for their efficacy. At this early stage of the disease, family physicians are often the first help for patients and thus central to the further course of the disease. To date, however, mAB have only rarely been used in general practice. The purpose of this case series is to demonstrate that the administration of mAB is safely feasible in the primary care setting. CASE REPORT: We report seven cases at risk for severe COVID-19. Two of them were not vaccinated, five had drug induced immunosuppression, and one patient was at high risk because of trisomy-21. All patients were successfully treated with the mAB Sotrovimab in a GP's practice in January/ February 2022. Two patients were treated making a house call. Based on the cases, clinical information and a hands-on handling of this therapy are described. CONCLUSIONS: Neutralizing mAB can be administered safely and with manageable effort in primary care setting and can help prevent a severe course and hospitalization in patients with COVID-19 and risk factors.

Persisting Symptoms After COVID-19.

BACKGROUND: After recovering from coronavirus disease 2019 (COVID-19), a considerable number of patients report long-term sequelae. The epidemiologic data vary widely in the studies published to date, depending on the study design and the patient cohorts analyzed. Using a population-based approach, we report symptoms and clinical characteristics following COVID-19 (long COVID), focusing on symptoms ≥ 12 weeks (post-COVID-19). METHODS: In three German administrative districts, all adult patients with a diagnosis of COVID-19 confirmed by polymerase chain reaction (PCR) between March and September 2020 (n = 4632) were invited to complete a questionnaire. Predictors for post-COVID-19 were identified by multiple ordinal regression analysis. Study registration: DRKS00023069. RESULTS: A total of 1459 patients were included in the study, 175 (12%) of whom had been hospitalized for treatment of the acute phase of COVID-19. The prevalence of post-COVID-19 was 72.6% (n = 127) and 46.2% (n = 588) for hospitalized and non-hospitalized patients, respectively. The most frequently occurring long-term symptoms were fatigue (41.5% of all symptoms ≥ 12 weeks, n = 297), physical exhaustion (40.8%, n = 292), difficulty in concentrating (30.6%, n = 219), and loss of the senses of taste (25.9%, n = 185) and smell (25.5%, n = 182). Quality of life was significantly impaired in patients with post-COVID-19. The strongest risk factors for post-COVID-19 were female sex, overall severity of comorbidities, and severity of acute COVID-19. CONCLUSION: Patients who are not hospitalized also frequently experience continued symptoms following COVID-19. The heterogeneity of symptoms calls for a multi - disciplinary stepped-care approach, for which identification of patients at risk is crucial. A limitation of the study is the lack of a control group.

[The Logic Model - a rationale for an encompassing evaluation framework of the German Competence Centers for Postgraduate Medical Education in general practice]. / Das Logische Modell als Grundlage für ein strukturiertes Konzept der Evaluation und Qualitätssicherung der Kompetenzzentren Weiterbildung Allgemeinmedizin.

BACKGROUND: The Competence Centers for Postgraduate Medical Education (KW) established throughout Germany represent complex programs to increase the efficiency and quality of postgraduate medical education in general practice. So-called Logic Models serve as the framework for evaluations and quality management processes of complex programs in many areas. The aim of this article is to develop such a model, using the example of the Competence Center in Baden-Württemberg (KWBW) in order to structure its complex program logic and use it as a framework for future evaluations and quality management processes. METHODS: The adaptation of the Logic Model to the KWBW took place in an informal, nominal group process with employees and participants of the program. RESULTS: We identified 76 core elements of the KWBW. These core elements were classified in one of the five pillars of the Logic Model (input, activity, output, outcome and impact) and categorized according to fields of action and target groups. DISCUSSION: The Logic Model, which was developed using the KWBW as an example, identifies and structures important core elements of a complex postgraduate medical training program for the first time. It seems to be well suited for visualizing the internal logic of this complex program and the interaction of the various elements within the KWBW. It can thus be used as the basis for a comprehensive and systematic evaluation concept and for quality assurance. CONCLUSION: The model is also a prerequisite for comparative research questions of other university programs for postgraduate medical education and thus offers an opportunity for cooperative development efforts. This article therefore contributes to promoting quality in continuing medical training.

Instant Visual Odometry Initialization for Mobile AR.

Mobile AR applications benefit from fast initialization to display world-locked effects instantly. However, standard visual odometry or SLAM algorithms require motion parallax to initialize (see Figure 1) and, therefore, suffer from delayed initialization. In this paper, we present a 6-DoF monocular visual odometry that initializes instantly and without motion parallax. Our main contribution is a pose estimator that decouples estimating the 5-DoF relative rotation and translation direction from the 1-DoF translation magnitude. While scale is not observable in a monocular vision-only setting, it is still paramount to estimate a consistent scale over the whole trajectory (even if not physically accurate) to avoid AR effects moving erroneously along depth. In our approach, we leverage the fact that depth errors are not perceivable to the user during rotation-only motion. However, as the user starts translating the device, depth becomes perceivable and so does the capability to estimate consistent scale. Our proposed algorithm naturally transitions between these two modes. Our second contribution is a novel residual in the relative pose problem to further improve the results. The residual combines the Jacobians of the functional and the functional itself and is minimized using a Levenberg-Marquardt optimizer on the 5-DoF manifold. We perform extensive validations of our contributions with both a publicly available dataset and synthetic data. We show that the proposed pose estimator outperforms the classical approaches for 6-DoF pose estimation used in the literature in low-parallax configurations. Likewise, we show our relative pose estimator outperforms state-of-the-art approaches in an odometry pipeline configuration where we can leverage initial guesses. We release a dataset for the relative pose problem using real data to facilitate the comparison with future solutions for the relative pose problem. Our solution is either used as a full odometry or as a pre-SLAM component of any supported SLAM system (ARKit, ARCore) in world-locked AR effects on platforms such as Instagram and Facebook.

Developing a seminar curriculum for the Competence Center for General Practice in Baden-Wuerttemberg - a progress report.

Aim: The seminar program of the KWBW Verbundweiterbildungplus® is offered by the Competence Center for Postgraduate Medical Education in Baden-Württemberg (KWBW) for physicians specializing in general practice (GP trainees). Attendance is a voluntary one comprised of 48 curricular units of 45 minutes each per GP trainee. This seminar program is meant to be attended in parallel to the postgraduate medical education in clinic or practice. The intention behind this project was to develop objectives, topics and a feasible structure for a seminar curriculum while taking time and financial constraints into account. Method: The Kern cycle was applied in an open, modified nominal group consensus technique in the form of an iterative process. Participating were 17 experts from the departments of general practice at the universities in Freiburg, Heidelberg, Tuebingen and Ulm, plus a pediatrician. Results: The main objective was defined as empowering GP trainees to independently provide high-quality primary care, including in rural areas. A basic curriculum was defined based on relevant frameworks, such as the 2018 Model Regulation for Postgraduate Medical Training (Musterweiterbildungsordnung/MWBO) and the Competency-based Curriculum General Practice (KCA). Overall, the seminar curriculum has 62 basic modules with 2 curricular units each (e.g. Basic Principles of General Practice, Chest Pain, Billing) and another 58 two-unit modules on variable topics (e.g. digitalization, travel medicine) adding up to 240 (124+116) curricular units. A blueprint with a rotation schedule for all of the teaching sites in Baden-Württemberg allows regular attendance by n=400 GP trainees over a period of five years, with individual variability in terms of program length. Conclusion: The model entails a five-year, flexible program to accompany the postgraduate medical education in general practice which can also be implemented in multicenter programs and those with high enrollments. The model's focus is on acquisition of core competencies for general practice. Despite the current shift to eLearning seminars due to SARS-CoV, the program's implementation is being continued, constantly evaluated, and used to further develop the KWBW Verbundweiterbildungplus® program.

Opportunities and challenges of e-learning in vocational training in General Practice - a project report about implementing digital formats in the KWBW-Verbundweiterbildungplus.

Background: The task of the Competence Centers for vocational training (KW) is to increase the attractiveness and quality of vocational (=post-graduate) training in general practice. For this purpose, they offer, among other things, a structured seminar program for post-graduate trainees in general practice (GP-trainees). During the Covid-19 pandemic the seminar program of the KWBW-Verbundweiterbildungplus® in Baden-Württemberg was converted to digital formats. The goal of the paper is to evaluate the acceptance by the GP-trainees and lecturers, to describe experiences with the conversion to e-learning and to derive recommendations with regard to the future orientation of seminar programs in post-graduate as well as continuing medical education. The implementation was based on a modified Kern-cycle and aimed at offering eight teaching units of 45 minutes each to a large number of GP-trainees. It tried to maintain the high quality of content and education as well as the interactive character of the previous seminars. For this purpose, the events were designed as synchronous webinars (six units) with asynchronous preparation and post-processing (two units) according to the flipped classroom method. The evaluation by the participating GP-trainees and lecturers was performed online using a multi-center developed and pre-piloted questionnaire. Results and discussion: N=101 GP-trainees participated in the evaluation of five individual seminar days in the second quarter of 2020 (response rate 97%). 58% (N=59) of the trainees were satisfied or very satisfied with the implementation. 82% (n=83) rated pre-tasks as helpful. 99% (n=100) would participate in an online seminar again. For 52% (n=53) of the trainees, the attitude towards e-learning had changed positively. The main advantages mentioned were no travel, save in time and costs as well as increased flexibility. The main disadvantages mentioned were less personal interaction and technical obstacles. The high acceptance of the new digital format showed the fundamental potential of e-learning in continuing medical education. The experiences can be a source of inspiration for other departments and KW. However, it also shows that important goals of KW, such as the personal interaction of the peer group, could not be achieved. In the future, it is important to develop a suitable mix of presence and digital formats with the aim to improve the attractiveness as well as sustainability of continuing medical education.

[A Sweet Drink with Consequences]. / Ein süsser Drink mit Folgen.

A Sweet Drink with Consequences Abstract. Intoxications with ethylene glycol are rare, however, small quantities from the substance can be life-threatening. Regarding the treatment it is important to recognize the intoxication quickly and to immediately start the appropriate treatment. Intoxications with ethylene glycol or with methanol should always be considered as differential diagnosis in patients with severe metabolic acidosis. It is also very important to calculate the osmolal gap.

Novel Tumor Pretargeting System Based on Complementary l-Configured Oligonucleotides.

Unnatural mirror image l-configured oligonucleotides (L-ONs) are a convenient substance class for the application as complementary in vivo recognition system between a tumor specific antibody and a smaller radiolabeled effector molecule in pretargeting approaches. The high hybridization velocity and defined melting conditions are excellent preconditions of the L-ON based methodology. Their high metabolic stability and negligible unspecific binding to endogenous targets are superior characteristics in comparison to their d-configured analogs. In this study, a radiopharmacological evaluation of a new l-ONs based pretargeting system using the epidermal growth factor receptor (EGFR) specific antibody cetuximab (C225) as target-seeking component is presented. An optimized PEGylated 17mer-L-DNA was conjugated with p-SCN-Bn-NOTA (NOTA') to permit radiolabeling with the radionuclide 64Cu. C225 was modified with the complementary 17mer-L-DNA (c-L-DNA) strand as well as with NOTA' for radiolabeling and use for positron emission tomography (PET). Two C225 conjugates were coupled with 1.5 and 5.0 c-L-DNA molecules, respectively. In vitro characterization was done with respect to hybridization studies, competition and saturation binding assays in EGFR expressing squamous cell carcinoma cell lines A431 and FaDu. The modified C225 derivatives exhibited high binding affinities in the low nanomolar range to the EGFR. PET and biodistribution experiments on FaDu tumor bearing mice with directly 64Cu-labeled NOTA'3-C225-(c-L-DNA)1.5 conjugate revealed that a pretargeting interval of 24 h might be a good compromise between tumor accumulation, internalization, blood background, and liver uptake of the antibody. Despite internalization of the antibody in vivo pretargeting experiments showed an adequate hybridization of 64Cu-radiolabeled NOTA'-L-DNA to the tumor located antibody and a good tumor-to-muscle ratio of about 11 resulting in a clearly visible image of the tumor after 24 h up to 72 h. Furthermore, low accumulation of radioactivity in organs responsible for metabolism and excretion was determined. The presented results indicate a high potential of complementary L-ONs for the pretargeting approach which can also be applied to therapeutic radionuclides such as 177Lu, 90Y, 186Re, or 188Re.

Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury.

BACKGROUND: New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma. METHODS: This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery. RESULTS: Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers. CONCLUSIONS: In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance to biomarkers. The discriminative performance of both plasma and urine biomarkers was reduced by preexisting chronic kidney disease.

Towards a Computable Data Corpus of Temporal Correlations between Drug Administration and Lab Value Changes.

BACKGROUND: The analysis of electronic health records for an automated detection of adverse drug reactions is an approach to solve the problems that arise from traditional methods like spontaneous reporting or manual chart review. Algorithms addressing this task should be modeled on the criteria for a standardized case causality assessment defined by the World Health Organization. One of these criteria is the temporal relationship between drug intake and the occurrence of a reaction or a laboratory test abnormality. Appropriate data that would allow for developing or validating related algorithms is not publicly available, though. METHODS: In order to provide such data, retrospective routine data of drug administrations and temporally corresponding laboratory observations from a university clinic were extracted, transformed and evaluated by experts in terms of a reasonable time relationship between drug administration and lab value alteration. RESULT: The result is a data corpus of 400 episodes of normalized laboratory parameter values in temporal context with drug administrations. Each episode has been manually classified whether it contains data that might indicate a temporal correlation between the drug administration and the change of the lab value course, whether such a change is not observable or whether a decision between those two options is not possible due to the data. In addition, each episode has been assigned a concordance value which indicates how difficult it is to assess. This is the first open data corpus of a computable ground truth of temporal correlations between drug administration and lab value alterations. DISCUSSION: The main purpose of this data corpus is the provision of data for further research and the provision of a ground truth which allows for comparing the outcome of other assessments of this data with the outcome of assessments made by human experts. It can serve as a contribution towards systematic, computerized ADR detection in retrospective data. With this lab value curve data as a basis, algorithms for detecting temporal relationships can be developed, and with the classification made by human experts, these algorithms can immediately be validated. Due to the normalization of the lab value data, it allows for a generic approach rather than for specific or solitary drug/lab value combinations.

Brain-computer interfacing in amyotrophic lateral sclerosis: Implications of a resting-state EEG analysis.

Despite decades of research on EEG-based brain-computer interfaces (BCIs) in patients with amyotrophic lateral sclerosis (ALS), there is still little known about how the disease affects the electromagnetic field of the brain. This may be one reason for the present failure of EEG-based BCI paradigms for completely locked-in ALS patients. In order to help understand this failure, we have recorded resting state data from six ALS patients and thirty-two healthy controls to investigate for group differences. While similar studies have been attempted in the past, none have used high-density EEG or tried to distinguish between physiological and non-physiological sources of the EEG. We find an ALS-specific global increase in gamma power (30-90 Hz) that is not specific to the motor cortex, suggesting that the mechanism behind ALS affects non-motor cortical regions even in the absence of comorbid cognitive deficits.

Does single-source create an added value? Evaluating the impact of introducing x4T into the clinical routine on workflow modifications, data quality and cost-benefit.

OBJECTIVES: The first objective of this study is to evaluate the impact of integrating a single-source system into the routine patient care documentation workflow with respect to process modifications, data quality and execution times in patient care as well as research documentation. The second one is to evaluate whether it is cost-efficient using a single-source system in terms of achieved savings in documentation expenditures. METHODS: We analyzed the documentation workflow of routine patient care and research documentation in the medical field of pruritus to identify redundant and error-prone process steps. Based on this, we established a novel documentation workflow including the x4T (exchange for Trials) system to connect hospital information systems with electronic data capture systems for the exchange of study data. To evaluate the workflow modifications, we performed a before/after analysis as well as a time-motion study. Data quality was assessed by measuring completeness, correctness and concordance of previously and newly collected data. A cost-benefit analysis was conducted to estimate the savings using x4T per collected data element and the additional costs for introducing x4T. RESULTS: The documentation workflow of patient care as well as clinical research was modified due to the introduction of the x4T system. After x4T implementation and workflow modifications, half of the redundant and error-prone process steps were eliminated. The generic x4T system allows direct transfer of routinely collected health care data into the x4T research database and avoids manual transcription steps. Since x4T has been introduced in March 2012, the number of included patients has increased by about 1000 per year. The average entire documentation time per patient visit has been significantly decreased by 70.1% (from 1116±185 to 334±83 s). After the introduction of the x4T system and associated workflow changes, the completeness of mandatory data elements raised from 82.2% to 100%. In case of the pruritus research study, the additional costs for introducing the x4T system are €434.01 and the savings are 0.48ct per collected data element. So, with the assumption of a 5-year runtime and 82 collected data elements per patient, the amount of documented patients has to be higher than 1102 to create a benefit. CONCLUSION: Introduction of the x4T system into the clinical and research documentation workflow can optimize the data collection workflow in both areas. Redundant and cumbersome process steps can be eliminated in the research documentation, with the result of reduced documentation times as well as increased data quality. The usage of the x4T system is especially worthwhile in a study with a large amount of collected data or a high number of included patients.

Low-flow CO2 removal integrated into a renal-replacement circuit can reduce acidosis and decrease vasopressor requirements.

INTRODUCTION: Lung-protective ventilation in patients with ARDS and multiorgan failure, including renal failure, is often paralleled with a combined respiratory and metabolic acidosis. We assessed the effectiveness of a hollow-fiber gas exchanger integrated into a conventional renal-replacement circuit on CO2 removal, acidosis, and hemodynamics. METHODS: In ten ventilated critically ill patients with ARDS and AKI undergoing renal- and respiratory-replacement therapy, effects of low-flow CO2 removal on respiratory acidosis compensation were tested by using a hollow-fiber gas exchanger added to the renal-replacement circuit. This was an observational study on safety, CO2-removal capacity, effects on pH, ventilator settings, and hemodynamics. RESULTS: CO2 elimination in the low-flow circuit was safe and was well tolerated by all patients. After 4 hours of treatment, a mean reduction of 17.3 mm Hg (-28.1%) pCO2 was observed, in line with an increase in pH. In hemodynamically instable patients, low-flow CO2 elimination was paralleled by hemodynamic improvement, with an average reduction of vasopressors of 65% in five of six catecholamine-dependent patients during the first 24 hours. CONCLUSIONS: Because no further catheters are needed, besides those for renal replacement, the implementation of a hollow-fiber gas exchanger in a renal circuit could be an attractive therapeutic tool with only a little additional trauma for patients with mild to moderate ARDS undergoing invasive ventilation with concomitant respiratory acidosis, as long as no severe oxygenation defects indicate ECMO therapy.