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Background: Andexanet alfa is a modified recombinant inactive factor Xa (FXa) designed to reverse FXa inhibitors. ANNEXA-4 (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) was a multicenter, prospective, phase-3b/4, single-group cohort study that evaluated andexanet alfa in patients with acute major bleeding. The results of the final analyses are presented. Methods: Patients with acute major bleeding within 18 hours of FXa inhibitor administration were enrolled. Co-primary end points were anti-FXa activity change from baseline during andexanet alfa treatment and excellent or good hemostatic efficacy, defined by a scale used in previous reversal studies, at 12 hours. The efficacy population included patients with baseline anti-FXa activity levels above predefined thresholds (≥75 ng/mL for apixaban and rivaroxaban, ≥40 ng/mL for edoxaban, and ≥0.25 IU/mL for enoxaparin; reported in the same units used for calibrators) who were adjudicated as meeting major bleeding criteria (modified International Society on Thrombosis and Haemostasis definition). The safety population included all patients. Major bleeding criteria, hemostatic efficacy, thrombotic events (stratified by occurring before or after restart of either prophylactic [ie, a lower dose, for prevention rather than treatment] or full-dose oral anticoagulation), and deaths were assessed by an independent adjudication committee. Median endogenous thrombin potential at baseline and across the follow-up period was a secondary outcome. Results: There were 479 patients enrolled (mean age, 78 years; 54% male; 86% White); 81% were anticoagulated for atrial fibrillation, and the median time was 11.4 hours since last dose, with 245 (51%) on apixaban, 176 (37%) on rivaroxaban, 36 (8%) on edoxaban, and 22 (5%) on enoxaparin. Bleeding was predominantly intracranial (n=331 [69%]) or gastrointestinal (n=109 [23%]). In evaluable apixaban patients (n=172), median anti-FXa activity decreased from 146.9 ng/mL to 10.0 ng/mL (reduction, 93% [95% CI, 94–93]); in rivaroxaban patients (n=132), it decreased from 214.6 ng/mL to 10.8 ng/mL (94% [95% CI, 95–93]); in edoxaban patients (n=28), it decreased from 121.1 ng/mL to 24.4 ng/mL (71% [95% CI, 82–65); and in enoxaparin patients (n=17), it decreased from 0.48 IU/mL to 0.11 IU/mL (75% [95% CI, 79–67]). Excellent or good hemostasis occurred in 274 of 342 evaluable patients (80% [95% CI, 75–84]). In the safety population, thrombotic events occurred in 50 (10%) patients; in 16 patients, these occurred during treatment with prophylactic anticoagulation that began after the bleeding event. No thrombotic episodes occurred after oral anticoagulation restart. Specific to certain populations, reduction of anti-FXa activity from baseline to nadir significantly predicted hemostatic efficacy in patients with intracranial hemorrhage (area under the receiver operating characteristic curve, 0.62 [95% CI, 0.54–0.70]) and correlated with lower mortality in patients P =0.022; unadjusted P =0.003). Median endogenous thrombin potential was within the normal range by the end of andexanet alfa bolus through 24 hours for all FXa inhibitors. Conclusions: In patients with major bleeding associated with the use of FXa inhibitors, treatment with andexanet alfa reduced anti-FXa activity and was associated with good or excellent hemostatic efficacy in 80% of patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02329327.

Background: The coronavirus disease 2019 (COVID-19) global pandemic required a rapid and effective response. This included ethical and legally appropriate sharing of data. The European Commission (EC) called upon the Research Data Alliance (RDA) to recruit experts worldwide to quickly develop recommendations and guidelines for COVID-related data sharing. Purpose: The purpose of the present work was to explore how the RDA succeeded in engaging the participation of its community of scientists in a rapid response to the EC request. Methods: A survey questionnaire was developed and distributed among RDA COVID-19 work group members. A mixed-methods approach was used for analysis of the survey data. Results: The three constructs of radical collaboration (inclusiveness, distributed digital practices, productive and sustainable collaboration) were found to be well supported in both the quantitative and qualitative analyses of the survey data. Other social factors, such as motivation and group identity were also found to be important to the success of this extreme collaborative effort. Conclusions: Recommendations and suggestions for future work were formulated for consideration by the RDA to strengthen effective expert collaboration and interdisciplinary efforts.

In diesem einleitenden Beitrag werden unterschiedliche Definitionen, theoretische Ansatze und Richtlinien von Corporate Social Responsibility (CSR) und Interkulturellem Management vorgestellt sowie Schnittpunkte der beiden zentralen Konzepte aufgezeigt und diskutiert. Die Aufarbeitung der wissenschaftlichen Diskussion ermoglicht dabei nicht nur ein grundlegendes Verstandnis der Thematik, sondern dient insbesondere der inhaltlichen Einordnung der nachfolgenden Artikel, welche – basierend auf ihrer jeweiligen Herangehensweise und ihrem speziellen Themenfokus – im Anschluss dargestellt werden. Im Fazit und Ausblick werden schlieslich einige Feststellungen der interdisziplinaren Betrachtung von CSR und Interkulturellem Management kurz skizziert.

Hintergrund Aufgrund der fast unverandert ungunstigen Prognose von Patienten nach kardiopulmonaler Wiederbelebung stellt sich dem Intensivmediziner haufig die Frage nach Begrenzung einer aktiven Therapie bei prolongiertem Koma auch unter medizinisch-ethischen Aspekten. Die Vorgeschichte des Patienten sowie die Umstande der Reanimation liefern hierzu nur unzuverlassige Entscheidungshilfen.

This article examines the question whether rejection experiences negatively relate to the social trust of Children Born of War (CBOW) and if this connection is mediated by sense of self-worth. CBOW is a group of people born out of relations during war- and post-war times, involving one parent being a foreign soldier, a para-military officer, rebel or other person directly participating in the hostilities, while the other parent is a member of the native population. Also children born to child soldiers and children fathered by members of a peacekeeping troop are included within this group. These children, due to their biological background, often grow up in a surrounding in which they are perceived as child of the enemy. The general hypothesis is that, due to their exposure to rejection experiences by their caregivers as well as by the society, CBOW are less likely to develop trust. It is further assumed that this relationship is mediated by the sense of self-worth. A structural equation model was applied to test the relation using a sample of Norwegian children born of war. Results indicate that CBOW who experience rejection share a lower sense of self-worth, which is further connected to lower trust, whereas no direct association between rejection experiences and trust was found.

Witnessed collapse, bystander resuscitation and the use of automated external defibillators for defibrillatable arrhythmias, are recognized as strong predictors for a good prognosis after cardiac arrest. In addition, patient care after return of spontaneous circulation (ROSC), i.e. postresuscitation care, has been identified as an important factor for survival. It is necessary to differentiate between measures for treating the underlying cause of the cardiac arrest and measures for limiting reperfusion injury after global hypoxia and ischemia. The importance of urgent coronary angiography in cases of ST-elevation myocardial infarction (STEMI) and for patients with suspected cardiac origin without STEMI, especially with hemodynamic instability is emphasized in the current European Resuscitation Council (ERC) guidelines. In order to minimize reperfusion injury targeted temperature management (32-36 °C) is advised, rewarming must be controlled and fever and hyperthermia avoided. The mean arterial pressure should be adjusted to allow sufficient urine production (1 ml/kg/h) and blood glucose should be ≤10 mmol/l (≤180 mg/dl). Analgosedation is necessary in most patients, especially with the use of targeted temperature management. Convulsive seizures must be consistently treated. Cardiac arrest centers provide a treatment strategy for postresuscitation care involving emergency percutaneous coronary angiography, targeted temperature management and comprehensive neurological evaluation for estimating the prognosis. Whether establishing these centers will actually lead to improved survival still needs to be proven.

Der fortgeschriebene Minimale Notfalldatensatz MIND3 ist ein Kerndatensatz, der eine definierte und von der DIVI autorisierte Menge an Merkmalen und Merkmalsbeschreibungen enthalt, die zur Dokumentation der prahospitalen Notfallrettung durch Rettungs- und Notarztdienst erforderlich sind. Der modulare Aufbau ermoglicht eine situations- und einsatzgerechte Dokumentation auf einem Basismodul-DIVI-Notfalleinsatzprotokoll und entsprechenden Zusatzmodulen. Mit einer IT-gestutzten Datenerfassung werden die Grundlagen fur ein medizinisches Qualitatsmanagement gelegt.

The COMPRAM Methodology and Complex Societal Problems-an Analysis of the Case of Children Born of War During and after wars children are born where the father is a member of an occupation or peacekeeping force and the mother a local citizen. Securing the human rights of children born of war is often highly complex and involves researchers and practitioners from different disciplines. The Compram methodology on handling complex societal problems will be applied to analyse whether the methodology is suitable on this group of war-affected children. The Compram methodology is a multi disciplined, multi level, multi actor methodology based on the theory of societal complexity. The methodology gives guidelines to handle real life complex societal problems.

The aim of this paper is to analyse the existence of political milieus in the eastern and western German electorate by using the concepts of lifestyle and social milieu. After introducing these ideas a theoretical approach will be taken which integrates them by pointing out their similarities and differences. Finally, empirical analyses of lifestyle groups and social milieus in the eastern and western German population will be carried out with the aim of ascertaining the existence of political social milieus in reunified Germany. The results indicate that the German electorate to some extent is still characterised by political milieus.

No abstract available.

Political Trust and Disenchantment with Politics contributes fresh empirical findings to research on the relationship between trust and participation. The results indicate that the citizens of European societies and beyond are far from an universal retreat from the political sphere.

In this article, I discuss some of the thoughts and experiences I have had over the past decade both through my work at the ZA-EUROLAB1 and as a former Erasmus free mover student. The first idea I introduce concerns the necessary prerequisite for the enhancement of mobility in Europe: the harmonisation of qualifications. With the imminent entrance of the East European states into the EU this seems an increasingly pressing issue. Second, I address the need for interdisciplinary research in the social sciences. Third, I discuss the importance of interational vertical and horizontal networks. Finally, I highlight the role that institutions such as the ZA-EUROLAB have in addressing some of these issues. However, before turning to these topics, I would like briefly to discuss why research mobility in the early stages of one's career is so important for later mobility.

Sudden cardiac death is still the leading cause of mortality in Europe and the USA. The incidence increases with age and the underlying cause is in most cases coronary artery disease. The typical sequence is ventricular tachycardia which deteriorates to ventricular fibrillation and is terminated by asystole. If cardiac arrest is witnessed and recognized as such, sufficient basic life support is crucial for survival with chestcompression playing an outstanding role. Access to AED’s in public places is an important addition to basic life support.

The introduction of intravenous thrombolytic therapy started the new era of reperfusion therapy in ST elevation myocardial infarction. The addition of aspirin almost halved mortality in patients with ST elevation infarction. Primary coronary intervention (PCI) often in combination with stent implantation instead of thrombolytic therapy increases infracted-artery patency and reduces mortality, number of re-infarction and stroke even further. However, studies comparing the benefits of both therapeutic regimens often included patients with long symptom duration (up to 12 hours and more). In addition, there are differences in long term treatment after myocardial infarction in both groups since the addition of thienopyridines to standard treatment after stent implantation. The routine combination of thrombolytic therapy and immediate PCI (facilitated PCI) did not prove beneficial whereas a pharamacoinvasive strategy including thrombolytic therapy and PCI at a later time point could be beneficial. Subgroup analysis in the studies comparing PCI and thrombolytic therapy suggested a beneficial effect for patients receiving thrombolytic therapy early after symptom onset (≥ 2 h). Therefore, a strategic concept of thrombolytic therapy early after symptom onset in patients presenting with ST elevation myocardial infarction combined with either rescue intervention when indicated or planned PCI is currently tested in the so STREAM-study (STrategic Reperfusion Early After Myocardial Infarction). Hopefully this study will clarify the role of thrombolytic therapy in ST Elevation myocardial infarction compared to PCI alone.

The prognosis of patients who have been resuscitated after cardiac arrest is still unfavourable and long-term results have only slightly improved. As a consequence, intensivists are frequently confronted with the question of limiting active therapeutic efforts for patients in prolonged coma. The history of the patient and circumstances of the resuscitation are of limited value with regard to reliable decisions.Clinical and electrophysiological neurologic techniques as well as biomarkers and diagnostic imaging are, therefore, the basis for prognostication and potential consecutive therapeutic decisions. Sedation, relaxation and particularly therapeutic hypothermia have great influence on the test results. These influences have to be excluded before results can be validated. With regard to therapeutic hypothermia a reliable neurologic evaluation as a basis for limiting treatment is only possible after rewarming. Moreover results of multiple tests should be in agreement before a decision to limit treatment can be made. Finally it must be kept in mind that the absence of unfavourable test results is not proof of a good prognosis.The decision to limit treatment can not be made on the basis of a single adverse prognostic sign, but requires a comprehensive clinical diagnostic assessment.

To assess the prognostic relevance of cardiac troponin T (cTnT) values and their serial changes as measured with a high-sensitivity assay in acute ischaemic stroke.In total, 1016 consecutive acute ischaemic stroke patients were registered prospectively within a two-year period. High-sensitivity cTnT was quantitated on admission and the following day. Patients were stratified into three groups: below the 99 th percentile of a healthy reference population (14 ng/l; n = 409), moderately elevated cTnT (below the median of remaining patients, 14-30 ng/l; n=299) and high cTnT (30 ng/l; n = 308). Outcome measures were unfavourable outcome (modified Rankin Scale ≥ 2 at hospital discharge, n=604) and in-hospital mortality (n = 36). Peak cTnT levels were significantly associated with unfavourable outcome (adjusted odds ratios versus reference for moderately elevated cTnT 1.7, 95% confidence interval [CI] 1.1-2.7 and for high cTnT 3.1, 95% CI 1.8-5.6). The optimal cut-off for determining unfavourable outcome proved to be 16 ng/l. Adding this cut-off to clinical variables led to a significant improvement of c-statistics (0.851 versus 0.838, p=0.02). Dynamic changes (δ ≥ 50%) of cTnT were detected in 137 patients (13%). Multiple Cox regression analysis showed an independent association of dynamic changes in cTnT with in-hospital mortality (hazard ratio 2.3, 95% CI 1.1-4.7). The model-fitting (p0.001) and c-statistics (0.889 versus 0.863, p = 0.08) improved most after dynamic change in cTnT had been added to a regression model which included clinical variables alone.Our study adds novel findings relevant for interpretation of highly sensitive cTnT assays in acute ischaemic stroke: a) Myocardial injury is detectable in more than half of patients; b) even moderately elevated cTnT is associated with unfavourable outcome (optimal cut-off 16 ng/l); and c) dynamic changes in cTnT indicate an increased risk of in-hospital death.

The introduction of intravenous thrombolytic therapy started the new era of reperfusion therapy in ST elevation myocardial infarction. The addition of aspirin almost halved mortality in patients with ST elevation infarction. Primary coronary intervention (PCI) often in combination with stent implantation instead of thrombolytic therapy increases infracted-artery patency and reduces mortality, number of re-infarction and stroke even further. However, studies comparing the benefits of both therapeutic regimens often included patients with long symptom duration (up to 12 hours and more). In addition, there are differences in long term treatment after myocardial infarction in both groups since the addition of thienopyridines to standard treatment after stent implantation. The routine combination of thrombolytic therapy and immediate PCI (facilitated PCI) did not prove beneficial whereas a pharamacoinvasive strategy including thrombolytic therapy and PCI at a later time point could be beneficial. Subgroup analysis in the studies comparing PCI and thrombolytic therapy suggested a beneficial effect for patients receiving thrombolytic therapy early after symptom onset (≥ 2 h). Therefore, a strategic concept of thrombolytic therapy early after symptom onset in patients presenting with ST elevation myocardial infarction combined with either rescue intervention when indicated or planned PCI is currently tested in the so STREAM-study (STrategic Reperfusion Early After Myocardial Infarction). Hopefully this study will clarify the role of thrombolytic therapy in ST Elevation myocardial infarction compared to PCI alone.