Christian Zöllner

Glutamatergic deficit and schizophrenia-like negative symptoms: new evidence from ketamine-induced mismatch negativity alterations in healthy male humans

Background Targeting the N-methyl-D-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine. Accordingly, it was the aim of the present study to investigate whether changes of MMN amplitudes during ketamine administration are associated with the emergence of schizophrenia-like negative symptoms in healthy volunteers. Methods We examined the impact of ketamine during an MMN paradigm with 64-channel electroencephalography (EEG) and assessed the psychopathological status using the Positive and Negative Syndrome Scale (PANSS) in healthy male volunteers using a single-blind, randomized, placebo-controlled crossover design. Low-resolution brain electromagnetic tomography was used for source localization. Results Twenty-four men were included in our analysis. Significant reductions of MMN amplitudes and an increase in all PANSS scores were identified under the ketamine condition. Smaller MMN amplitudes were specifically associated with more pronounced negative symptoms. Source analysis of MMN generators indicated a significantly reduced current source density (CSD) under the ketamine condition in the primary auditory cortex, the posterior cingulate and the middle frontal gyrus. Limitations The sample included only men within a tight age range of 20–32 years. Conclusion The MMN might represent a biomarker for negative symptoms in schizophrenia related to an insufficient NMDAR system and could be used to identify patients with schizophrenia with negative symptoms due to NMDAR dysfunction.

Simulationsbasiertes Training – Für den Notfall vorbereitet sein in Anästhesie und Notfallmedizin

ZusammenfassungÄrztliche Kompetenz ist ein Resultat aus dem Wissen, den Fertigkeiten, Fähigkeiten und persönlichen Einstellungen des Arztes. Diese Kompetenz wird theoretisch und praktisch im Studium sowie in der ärztlichen Weiterbildung erworben. Ärztliche Entscheidungen sind deshalb sowohl rational, erfahrungsbasiert als auch intuitiv. Die zu erwerbenden Kompetenzen können und sollen in der Medizin häufig nicht mehr nur am Patienten trainiert werden. Wie in den Simulationsszenarien im Bereich der Kernenergie oder der Luftfahrt ermöglicht es die Einführung moderner Simulationstrainings, seltene Komplikationen oder Notfallmaßnahmen außerhalb der unmittelbaren Patientenversorgung zu trainieren. In der Simulation erlangt der Arzt über die mehrmalige Wiederholung von Handlungsabläufen auch für seltene Prozeduren eine Routine, die sonst – wenn überhaupt – erst nach vielen Jahren der Berufserfahrung erreicht werden würde. Fehler können im simulationsbasierten Training erkannt und systematisch korrigiert werden. Auch die vielfältigen Interaktionen im Team, die sog. „soft skills“ lassen sich in einem solchen Training erfahren und einüben. Die im Rahmen eines Trainings durchgeführten Videoanalysen und damit ermöglichten Selbstreflexionen führen oftmals zur Korrektur der eigenen, und zur Verstärkung positiver Verhaltensweisen. Die Simulation geht somit weit über den Erwerb praktischer Fähigkeiten und Fertigkeiten hinaus und beinhaltet auch Programme (Crisis-Ressource-Management-Programme) zur Reduzierung des Schadenspotenzials aufgrund „menschlich-bedingter Zwischenfälle“. Die Ausbildung und ein regelmäßiges, realitätsnahes Simulations-Team-Training in diesen Programmen tragen zu einer messbaren Verbesserung der Sicherheitskultur, aber auch zur Mitarbeiterzufriedenheit bei.AbstractMedical expertise consists of knowledge, professional skills and individual attitudes. Training and education of this expertise starts in medical school and develops throughout the qualification process of anesthesists and emergency physicians. Medical decisions are not only rational but also intuitive. The combination of these characteristics cannot and should not be trained on patients. The implementation of modern simulation techniques offers the opportunity to train for emergency situations similar to training systems in the energy industry and aviation. Repetitive training of rare emergency situations brings routine to seldomly used procedures. In simulation training mistakes can be detected and systematically corrected. The team interactions and soft skills can also be focussed on. Video analysis gives the participant the opportunity for self-reflection and can lead to correction of individual behavior patterns. This dimension of education cannot be done in real patient care. This training goes far beyond the level of skills training. Through simulation training involves the whole team, the communication and the interaction between the team members in medically challenging situations. Crisis resource management leads to measurable improvements in patient safety and safety culture as well as personnel satisfaction.Medical expertise consists of knowledge, professional skills and individual attitudes. Training and education of this expertise starts in medical school and develops throughout the qualification process of anesthesists and emergency physicians. Medical decisions are not only rational but also intuitive. The combination of these characteristics cannot and should not be trained on patients. The implementation of modern simulation techniques offers the opportunity to train for emergency situations similar to training systems in the energy industry and aviation. Repetitive training of rare emergency situations brings routine to seldomly used procedures. In simulation training mistakes can be detected and systematically corrected. The team interactions and soft skills can also be focussed on. Video analysis gives the participant the opportunity for self-reflection and can lead to correction of individual behavior patterns. This dimension of education cannot be done in real patient care. This training goes far beyond the level of skills training. Through simulation training involves the whole team, the communication and the interaction between the team members in medically challenging situations. Crisis resource management leads to measurable improvements in patient safety and safety culture as well as personnel satisfaction.

Altered signaling in the descending pain modulatory system after short-term infusion of the μ-opioid agonist remifentanil

μ-Opioid receptor agonists are widely used within the contemporary treatment of pain, but abrupt opioid suspension, even after short-term infusion, can paradoxically increase the sensitivity to noxious stimuli, a phenomenon that has been, for example, reported after application of the fast-acting μ-opioid receptor agonist remifentanil. To investigate the mechanisms underlying the effects of discontinuation of remifentanil application on pain processing in the human CNS, we analyzed neuronal responses to thermal stimuli before and after a short-term infusion of remifentanil (30 min 0.1 μg/kg body weight/min) compared with control in the brain, brainstem, and spinal cord in drug-naive male volunteers using fMRI. Subsequent to remifentanil suspension, we observed reduced heat pain thresholds and increased neuronal responses in pain-encoding as well as in key regions of the descending pain-modulatory system, such as the periaqueductal gray matter, the nucleus cuneiformis, and the rostral ventromedial medulla. Moreover, the spinal pain-related multivoxel activity pattern showed an opioid-specific change after drug suspension. Importantly, remifentanil suspension increased the functional coupling between the nucleus cuneiformis and the rostral anterior cingulate cortex, and the coupling strength between the rostral anterior cingulate cortex and the nucleus cuneiformis correlated negatively with the individual pain threshold after opioid suspension. These findings demonstrate that, already subsequent to a short-term infusion of the μ-opioid receptor agonist remifentanil, signaling in the descending pain-modulatory system is fundamentally altered and that these changes are directly related to the behavioral sensitivity to pain. SIGNIFICANCE STATEMENT Opioids are widely used in modern medicine, but, in addition to their known side effects, it is increasingly recognized that opioids can also increase sensitivity to pain subsequent to their use. Using the fast-acting μ-opioid receptor agonist remifentanil and fMRI in healthy male volunteers, this study demonstrates how signaling changes occur along the entire descending pain-modulatory pathway after opioid discontinuation and how these alterations are closely linked to increased behavioral pain sensitivity. Particularly by revealing modified responses in pain-modulatory brainstem regions that have been previously demonstrated to be causally involved in acute opioid withdrawal effects in rodents, the data provide a plausible neuronal mechanism by which the increased sensitivity to pain after opioid suspension is mediated in humans.

Reply to Letter: Long-term learning effect is essential ☆

We appreciate Ecker et al. for their letter and their careful eading of our article “Peer education for BLS-training in schools? esults of a randomized-controlled, noninferiority trial.”1 The uthors note that long-term learning effects are essential for the valuation of effectiveness of peers as BLS-instructors at schools. ased on the proof-of-concept-design of our study the CPR-skills of he school children assessed immediately after the CPR-training is evertheless a necessary and feasible endpoint. But we agree with he authors that this study-endpoint is not sufficient to estimate the nfluence of different training-concepts on long-term learning. We ven would take it one step further: According to the intentionocused-paradigm bystander CPR-performance depends on skills, bility to act and intention to perform CPR.2 The intention to perorm CPR is directly influenced by attitudes about performing CPR nd perceived norms and self-efficacy about performing CPR. To stimate the value of peer-education all these variables influencng bystander-performance need to be discussed. For the aspect f skills our study demonstrates comparable pass-rates between he school children trained by peers and professionals immediately fter the training. As a side note: We did not test for difference etween the groups as stated by Ecker et al. but for non-inferiority f peer-led compared to professional-led training. However, we till do not know, if this is a short or long-lasting training effect, r if the skills may diminish faster or slower as compared to proessional trainers. Nevertheless, involving peer-instructors allows s to create a sustainable system where pupils trained by pupils et involved as peer-instructors later on. In this system acting as eer-instructor would refresh and deepen the CPR-skills acquired uring the first training based on the concept of spiral learning. or the aspect of intention to perform CPR we collected data about he impact of qualifying and acting as peer-instructors on selffficacy and will present this data soon. Regarding attitudes and orms about performing CPR, studies demonstrate, that teachng enhances intrinsic motivation for the subject.3 We observed n intensive discussion within the peer-instructors during the reparation phase about misconceptions and impeding factors o perform CPR in the population and experienced a lot of the eer-instructors as keen active promoters to overcome these misonceptions. This is in line with literature about peer-education in ther fields demonstrating sustainable change of values and norms ithin the peer-group and their social environment.4 Taking all

Simulationsbasiertes Training – Für den Notfall vorbereitet sein in Anästhesie und Notfallmedizin@@@Simulation-based training in anesthesia and emergency medicine: preparation for the unexpected: Auf dem Weg zu neuen Standards der Ausbildung in Deutschland@@@On the way to new standards of education in Germany

ZusammenfassungÄrztliche Kompetenz ist ein Resultat aus dem Wissen, den Fertigkeiten, Fähigkeiten und persönlichen Einstellungen des Arztes. Diese Kompetenz wird theoretisch und praktisch im Studium sowie in der ärztlichen Weiterbildung erworben. Ärztliche Entscheidungen sind deshalb sowohl rational, erfahrungsbasiert als auch intuitiv. Die zu erwerbenden Kompetenzen können und sollen in der Medizin häufig nicht mehr nur am Patienten trainiert werden. Wie in den Simulationsszenarien im Bereich der Kernenergie oder der Luftfahrt ermöglicht es die Einführung moderner Simulationstrainings, seltene Komplikationen oder Notfallmaßnahmen außerhalb der unmittelbaren Patientenversorgung zu trainieren. In der Simulation erlangt der Arzt über die mehrmalige Wiederholung von Handlungsabläufen auch für seltene Prozeduren eine Routine, die sonst – wenn überhaupt – erst nach vielen Jahren der Berufserfahrung erreicht werden würde. Fehler können im simulationsbasierten Training erkannt und systematisch korrigiert werden. Auch die vielfältigen Interaktionen im Team, die sog. „soft skills“ lassen sich in einem solchen Training erfahren und einüben. Die im Rahmen eines Trainings durchgeführten Videoanalysen und damit ermöglichten Selbstreflexionen führen oftmals zur Korrektur der eigenen, und zur Verstärkung positiver Verhaltensweisen. Die Simulation geht somit weit über den Erwerb praktischer Fähigkeiten und Fertigkeiten hinaus und beinhaltet auch Programme (Crisis-Ressource-Management-Programme) zur Reduzierung des Schadenspotenzials aufgrund „menschlich-bedingter Zwischenfälle“. Die Ausbildung und ein regelmäßiges, realitätsnahes Simulations-Team-Training in diesen Programmen tragen zu einer messbaren Verbesserung der Sicherheitskultur, aber auch zur Mitarbeiterzufriedenheit bei.AbstractMedical expertise consists of knowledge, professional skills and individual attitudes. Training and education of this expertise starts in medical school and develops throughout the qualification process of anesthesists and emergency physicians. Medical decisions are not only rational but also intuitive. The combination of these characteristics cannot and should not be trained on patients. The implementation of modern simulation techniques offers the opportunity to train for emergency situations similar to training systems in the energy industry and aviation. Repetitive training of rare emergency situations brings routine to seldomly used procedures. In simulation training mistakes can be detected and systematically corrected. The team interactions and soft skills can also be focussed on. Video analysis gives the participant the opportunity for self-reflection and can lead to correction of individual behavior patterns. This dimension of education cannot be done in real patient care. This training goes far beyond the level of skills training. Through simulation training involves the whole team, the communication and the interaction between the team members in medically challenging situations. Crisis resource management leads to measurable improvements in patient safety and safety culture as well as personnel satisfaction.Medical expertise consists of knowledge, professional skills and individual attitudes. Training and education of this expertise starts in medical school and develops throughout the qualification process of anesthesists and emergency physicians. Medical decisions are not only rational but also intuitive. The combination of these characteristics cannot and should not be trained on patients. The implementation of modern simulation techniques offers the opportunity to train for emergency situations similar to training systems in the energy industry and aviation. Repetitive training of rare emergency situations brings routine to seldomly used procedures. In simulation training mistakes can be detected and systematically corrected. The team interactions and soft skills can also be focussed on. Video analysis gives the participant the opportunity for self-reflection and can lead to correction of individual behavior patterns. This dimension of education cannot be done in real patient care. This training goes far beyond the level of skills training. Through simulation training involves the whole team, the communication and the interaction between the team members in medically challenging situations. Crisis resource management leads to measurable improvements in patient safety and safety culture as well as personnel satisfaction.

Simulationsbasiertes Training – Für den Notfall vorbereitet sein in Anästhesie und NotfallmedizinSimulation-based training in anesthesia and emergency medicine: preparation for the unexpected

ZusammenfassungÄrztliche Kompetenz ist ein Resultat aus dem Wissen, den Fertigkeiten, Fähigkeiten und persönlichen Einstellungen des Arztes. Diese Kompetenz wird theoretisch und praktisch im Studium sowie in der ärztlichen Weiterbildung erworben. Ärztliche Entscheidungen sind deshalb sowohl rational, erfahrungsbasiert als auch intuitiv. Die zu erwerbenden Kompetenzen können und sollen in der Medizin häufig nicht mehr nur am Patienten trainiert werden. Wie in den Simulationsszenarien im Bereich der Kernenergie oder der Luftfahrt ermöglicht es die Einführung moderner Simulationstrainings, seltene Komplikationen oder Notfallmaßnahmen außerhalb der unmittelbaren Patientenversorgung zu trainieren. In der Simulation erlangt der Arzt über die mehrmalige Wiederholung von Handlungsabläufen auch für seltene Prozeduren eine Routine, die sonst – wenn überhaupt – erst nach vielen Jahren der Berufserfahrung erreicht werden würde. Fehler können im simulationsbasierten Training erkannt und systematisch korrigiert werden. Auch die vielfältigen Interaktionen im Team, die sog. „soft skills“ lassen sich in einem solchen Training erfahren und einüben. Die im Rahmen eines Trainings durchgeführten Videoanalysen und damit ermöglichten Selbstreflexionen führen oftmals zur Korrektur der eigenen, und zur Verstärkung positiver Verhaltensweisen. Die Simulation geht somit weit über den Erwerb praktischer Fähigkeiten und Fertigkeiten hinaus und beinhaltet auch Programme (Crisis-Ressource-Management-Programme) zur Reduzierung des Schadenspotenzials aufgrund „menschlich-bedingter Zwischenfälle“. Die Ausbildung und ein regelmäßiges, realitätsnahes Simulations-Team-Training in diesen Programmen tragen zu einer messbaren Verbesserung der Sicherheitskultur, aber auch zur Mitarbeiterzufriedenheit bei.AbstractMedical expertise consists of knowledge, professional skills and individual attitudes. Training and education of this expertise starts in medical school and develops throughout the qualification process of anesthesists and emergency physicians. Medical decisions are not only rational but also intuitive. The combination of these characteristics cannot and should not be trained on patients. The implementation of modern simulation techniques offers the opportunity to train for emergency situations similar to training systems in the energy industry and aviation. Repetitive training of rare emergency situations brings routine to seldomly used procedures. In simulation training mistakes can be detected and systematically corrected. The team interactions and soft skills can also be focussed on. Video analysis gives the participant the opportunity for self-reflection and can lead to correction of individual behavior patterns. This dimension of education cannot be done in real patient care. This training goes far beyond the level of skills training. Through simulation training involves the whole team, the communication and the interaction between the team members in medically challenging situations. Crisis resource management leads to measurable improvements in patient safety and safety culture as well as personnel satisfaction.Medical expertise consists of knowledge, professional skills and individual attitudes. Training and education of this expertise starts in medical school and develops throughout the qualification process of anesthesists and emergency physicians. Medical decisions are not only rational but also intuitive. The combination of these characteristics cannot and should not be trained on patients. The implementation of modern simulation techniques offers the opportunity to train for emergency situations similar to training systems in the energy industry and aviation. Repetitive training of rare emergency situations brings routine to seldomly used procedures. In simulation training mistakes can be detected and systematically corrected. The team interactions and soft skills can also be focussed on. Video analysis gives the participant the opportunity for self-reflection and can lead to correction of individual behavior patterns. This dimension of education cannot be done in real patient care. This training goes far beyond the level of skills training. Through simulation training involves the whole team, the communication and the interaction between the team members in medically challenging situations. Crisis resource management leads to measurable improvements in patient safety and safety culture as well as personnel satisfaction.

Postoperatives Management der Gerinnung

Hintergrund: Das Gerinnungsmanagement in der postoperativen Phase stellt eine komplexe Herausforderung dar. Einerseits führt eine bereits präoperativ vorbestehende oder intraoperativ erworbene Beeinträchtigung der Blutgerinnung zu einem erhöhten Risiko für Nachblutungen. Andererseits sind Patienten in der postoperativen Phase einem erhöhten Risiko für thromboembolische Komplikationen ausgesetzt. Zudem drängen vermehrt neue orale Antikoagulanzien und Thrombozytenaggregationshemmer auf den Markt, für deren perioperativen Einsatz noch wenig Erfahrung besteht. Methode: Literaturübersicht. Ergebnisse: Das postoperative Gerinnungsmanagement sollte individualisiert nach einer Diagnostik mit klassischen Gerinnungstests und Point-of-Care(POC)-Diagnoseverfahren erfolgen. Verglichen mit dem intraoperativen Gerinnungsmanagement bestehen Unterschiede. Schlussfolgerungen: Das Ziel des postoperativen Gerinnungsmanagements ist eine Gerinnungsaktivität, die eine suffiziente Wundheilung zulässt, ohne thromboembolische Ereignisse zu begünstigen. Im Falle einer postoperativen Blutung sollte zur Diagnostik neben den klassischen Gerinnungstests auf viskoelastische POC-Verfahren zurückgegriffen werden. Neben der bedarfsadaptierten Substitution von Gerinnungsfaktoren ist die Aufrechterhaltung der Rahmenbedingungen der Gerinnung von entscheidender Bedeutung (Normothermie, physiologischer pH-Wert, Normokalziämie). Die Fortführung einer bestehenden Antikoagulation mit neuen oralen Antikoagulanzien ist eine Einzelfallentscheidung. Für ihren perioperativen Einsatz gib es noch keine Leitlinien.