[Retraction Note to: Comparison of sublingual and intravenous administration of lorazepam in psychiatric emergencies in emergency medical services]. / Retraction Note to: Vergleich von sublingualer und intravenöser Gabe von Lorazepam bei psychiatrischen Notfällen im Notarztdienst.

Retraction Note to: Anaesthesist 2018 https://doi.org/10.1007/s00101-018-0513-7 Die Schriftleitung von Der Anaesthesist zieht den Artikel [1] zurück. Die Autoren erhielten die Freigabe der Ethikkommission der Ärztekammer des Saarlandes in 2003. Das Design der Studie, die ab 2005 durchgeführt wurde, wurde jedoch von diesem Ethikvotum nicht vollumfänglich abgedeckt.

[Comparison of sublingual and intravenous administration of lorazepam in psychiatric emergencies in emergency medical services]. / Vergleich von sublingualer und intravenöser Gabe von Lorazepam bei psychiatrischen Notfällen im Notarztdienst.

BACKGROUND: Agitation is a frequent reason for emergency physician calls in psychiatric emergencies in the German preclinical emergency medical system. Benzodiazepines have proven to be effective in treating acute agitation. Although lorazepam has beneficial clinical and pharmacological properties it is hardly used by emergency physicians. The sublingual administration of lorazepam has many advantages compared to intravenous administration. MATERIAL AND METHODS: In an interventional trial lasting 18 months the efficacy, tolerance and onset of effects of sublingual and intravenous lorazepam in patients with agitation states in emergency duties were compared. The randomization to the intervention groups was subject to a time criterion. The sublingual administration of lorazepam over a period of 9 months was followed by an intravenous administration over the same period of time. The psychometric scales used were: PANSS-EC, CGI, CGI-Change, agitation-calmness evaluation scale, visual analog scale and sedation scale. Response to the intervention was defined by a 40% reduction on the PANSS-EC scale. RESULTS: A total of 37 individuals participated in the study (sublingual: n = 22, intravenous: n = 15). Lorazepam was effective in treating acute agitation. The effectiveness and tolerance of sublingual and intravenous lorazepam administration seems to be comparable. CONCLUSION: Sublingual administration of lorazepam is effective for treating acute agitation in emergency medical services.

[Pharmacotherapy of psychiatric acute and emergency situations: General principles]. / Pharmakotherapie von psychiatrischen Akut- und Notfallsituationen : Allgemeine Prinzipien.

The pharmacotherapy of psychiatric emergencies is essentially determined by the acuteness, the scene of the emergency, the diagnostic assessment and the special pharmacological profile of the drug used. As there are no specific drugs, syndromic treatment is carried out. For this, primarily antipsychotic drugs and benzodiazepines are available. This article gives an overview of the current state of treatment options for major psychiatric emergency syndromes, namely agitation, delirium, stupor and catatonia, anxiety and panic, as well as drug-induced emergencies.

[The situation of emergency psychiatry in Germany]. / Zur Situation der Notfall- und Akutpsychiatrie in Deutschland.

The impact of psychiatric emergencies for the care of patients in preclinical emergency medicine, in emergency departments and in psychiatric hospitals has been underestimated for a long time. There is still insufficient knowledge and a need for further research. There are, however, sufficient reasons to assume that annually approximately 500,000 patients with a psychiatric emergency receive treatment from a preclinical emergency physician and another 1.5 million in emergency departments in Germany. Further, approximately 500,000 patients are admitted to psychiatric hospitals as an emergency. The most frequent reasons are intoxication, agitation, aggressiveness and suicidal ideation, posing a threat of self-harm to the patient or to other persons and evoking other life-threatening conditions. Emergency psychiatry also plays a role in collective injuries, such as mass disasters, catastrophes and rampage situations. There is some evidence that the number of psychiatric emergencies is increasing. Reasons are, among others, changes in the services provided for inpatient and outpatient treatment, a reduction in stabilizing psychosocial factors and a general increase in the utilization of emergency healthcare services.

[Psychotropic agents in emergency medicine]. / Psychopharmaka im Notarztdienst.

The aim of these two CME articles Psychotropic agents in emergency medicine and Psychopharmacotherapy in emergency medicine is to give an overview of drugs and their indications in the context of emergency psychiatry. Most relevant for prehospital care are benzodiazepines and antipsychotics, like lorazepam, diazepam, and haloperidol. But even newer antipsychotics could be suitable for emergency medicine. The efficacy of some of the newer antipsychotics, so-called atypical antipsychotics, has been studied in emergency psychiatric departments. The evidence whether these drugs provide the required efficacy, universality and safety profile in emergency medicine, in comparison to, for example, haloperidol, is presented in the following article.

[Psychopharmacotherapy in emergency medicine]. / Psychopharmakotherapie im Notarztdienst.

Part two of the CME article Psychotropic agents and psychopharmacotherapy in emergency medicine aims to give an understanding of the pharmacotherapy of psychiatric disorders in emergency medicine. In contrast to somatic emergencies, many emergency physicians are not familiar with the treatment of psychiatric emergencies, although there are guidelines and recommendations. In the following article, treatment recommendations for the 5 most common and relevant syndromes in emergency medicine (i.e., suicide, delirium, agitation, stupor, and syndromes due to psychopharmaceutical use) are described based on the German S2-Guideline Emergency Psychiatry that will be published soon.

[Suicidality: procedure in emergency cases]. / Suizidalität: Procedere im Notfall.

Emergency physicians (EP), paramedics and the staff of the emergency room play an increasingly important role in the medical and psychological emergency treatment of patients after suicide attempts, as well as in the crisis intervention of persons with acute suicidal tendencies. This article aims to give an overview of the prevalence rates, methods of suicide or attempted suicide and the problems faced by EPs when treating these patients. In addition, concepts are presented which allow an adequate risk assessment of suicidality and the options for primary crisis intervention. Paramedics and intensive care clinicians are increasingly confronted with this complex process with social, personal and medical aspects. In order to treat people in suicidal crises and/or after a suicide attempt and to provide a safe and optimal care for this often heterogeneous group of patients, clear guidelines are a prerequisite. The first assessment of the acute danger of suicide is of particular importance due to the resulting consequences and a clear approach is demonstrated for dealing with suicidal people. Furthermore, the legal principles are presented.

[Psychiatric care in emergency departments]. / Psychiatrische Versorgung in der Notaufnahme.

BACKGROUND: Psychiatric emergency situations (PES) are frequent in emergency departments (EDs). There are, however, only few investigations that focus on the prevalence of these patients or on diagnostic and therapeutic standards. These PESs in EDs should be treated according to standards comparable to medically disabled patients. Thus it is necessary to learn more about the diagnostic and therapeutic possibilities in EDs, about the procedures and the decision-making process whether these patients are transferred to further outpatient or inpatient treatment. MATERIALS AND METHODS: A survey was conducted in EDs throughout Germany and 1,073 were contacted and asked to participate. The questionnaire consisted of questions concerning the size of the ED and of the hospital (e.g. number of patients and physicians), the prevalence of psychiatric disorders, the diagnostic and therapeutic possibilities, standard procedures for dealing with PES and the method of care in six typical case reports. RESULTS: A total of 74 EDs participated (76% interdisciplinary EDs) with an average of 22,827 ± 12,303 patients per year in the ED. Psychiatry as a medical discipline was integrated into 10 EDs (14%) and psychiatric competence could be activated in 84% of EDs. Participating EDs reported prevalence rates of 15% mentally disordered patients and 9% of patients who required psychiatric diagnostic and therapeutic procedures. Of the patients 2% presented after suicide attempts and 3% were considered to be aggressive. Approximately 50% of all PESs were related to substance abuse disorders. An average of 2.5 ± 4.2 (range 0-25) members of the medical and nursing staff were injured during a 1-year period by violent patients. Legal actions against the will of patients were initiated in 81% of EDs. Standardized diagnostic screening instruments or self-rating questionnaires were used in only four EDs. As standard procedures for the diagnostic work-up of psychiatric patients (medical clearance) physical examination, measurement of heart rate and blood pressure and conducting of some laboratory tests (glucose, blood cell count, electrolytes and renal function) were named. Diazepam (91%), lorazepam (88%) and haloperidol (87%) were considered to be indispensable psychopharmacological agents in the ED. CONCLUSIONS: In the majority of participating EDs, diagnostic standards for PES were known but were not routinely applied. It has to be assumed that many psychiatric disorders, in particular suicide attempts and suicidal ideation are not discovered. In many EDs psychiatric knowledge was available but a psychiatric consultation was only rarely requested. Physicians in the ED report a high degree of legal uncertainty with psychiatric patients. The use of screening instruments is recommended.

[Necessity for treatment of psychiatric emergencies in the emergency medical service. Evaluation of the "indicator for psychiatric pharmacotherapy"]. / Behandlungsbedürftigkeit psychiatrischer Notfälle im Notarztdienst. Evaluierung des "Indikator für psychiatrische Pharmakotherapie"

BACKGROUND: Psychiatric emergency situations (PES) are common in the physician-based emergency medical system (EMS) in Germany. However, many emergency physicians (EP) feel insecure in assessing the necessity for treatment of these patients. The aim of this investigation was to evaluate whether a short, newly developed questionnaire (Indicator for Psychiatric Pharmacotherapy, IPP) is able to help EPs in deciding for or against pharmacological treatment. PATIENTS AND METHODS: The protocols of the EMS at the Saarland University Hospital were prospectively collected over a 1-year period and PESs were identified and analyzed in detail. The 7-item IPP, which focuses on the most relevant psychiatric symptoms, was to be completed for each PES. RESULTS: Among all calls for an EP (2,114) 250 (11.8%) were classified as a PES. The most frequent diagnoses were alcoholic intoxication, state of agitation and suicide attempts. Of the IPP questionnaires 193 could be evaluated and in 31.2% of all PESs a specific psychiatric medication was administered. These patients scored significantly higher in the IPP compared to those who did not receive medication (8.0 ± 3.9 compared to 5.6 ± 3.2, p < 0.001). The IPP items "anxiety", "agitation/aggression", "mood" and "physical symptoms/disorders" had the highest impact on the administration of psychotherapeutic drugs. DISCUSSION: The IPP can be a valuable tool to assess the necessity of pharmacological treatment for patients in PESs. The assessment of the symptom categories "anxiety", "agitation/aggression", "mood" and "physical symptoms/disorders" seems to be sufficient to estimate a need for treatment.

Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials.

The proteasome has emerged as an important clinically relevant target for the treatment of hematologic malignancies. Since the Food and Drug Administration approved the first-in-class proteasome inhibitor bortezomib (Velcade) for the treatment of relapsed/refractory multiple myeloma (MM) and mantle cell lymphoma, it has become clear that new inhibitors are needed that have a better therapeutic ratio, can overcome inherent and acquired bortezomib resistance and exhibit broader anti-cancer activities. Marizomib (NPI-0052; salinosporamide A) is a structurally and pharmacologically unique ß-lactone-γ-lactam proteasome inhibitor that may fulfill these unmet needs. The potent and sustained inhibition of all three proteolytic activities of the proteasome by marizomib has inspired extensive preclinical evaluation in a variety of hematologic and solid tumor models, where it is efficacious as a single agent and in combination with biologics, chemotherapeutics and targeted therapeutic agents. Specifically, marizomib has been evaluated in models for multiple myeloma, mantle cell lymphoma, Waldenstrom's macroglobulinemia, chronic and acute lymphocytic leukemia, as well as glioma, colorectal and pancreatic cancer models, and has exhibited synergistic activities in tumor models in combination with bortezomib, the immunomodulatory agent lenalidomide (Revlimid), and various histone deacetylase inhibitors. These and other studies provided the framework for ongoing clinical trials in patients with MM, lymphomas, leukemias and solid tumors, including those who have failed bortezomib treatment, as well as in patients with diagnoses where other proteasome inhibitors have not demonstrated significant efficacy. This review captures the remarkable translational studies and contributions from many collaborators that have advanced marizomib from seabed to bench to bedside.

[Postoperative delirium in the critically ill]. / Postoperatives Delir beim Intensivpatienten.

Acute confusional states (delirium) occur in up to 80% of patients in the intensive care unit. Delirium is an important independent prognostic determinant of hospital outcome, including duration of mechanical ventilation, nursing home placement, functional decline and death. Additionally, it may herald systemic diseases such as sepsis and multi-organ failure. Recently, a number of new screening instruments have been validated for the monitoring of delirium in non-communicative patients receiving mechanical ventilation. Critical care patients should be routinely assessed for delirium and treated immediately using available preventive and therapeutic measures, both pharmacological and non-pharmacological, to improve the clinical course.

The dilemma of insight into illness in schizophrenia: self- and expert-rated insight and quality of life.

INTRODUCTION: A major subgroup of patients with acute schizophrenia lacks awareness of having a mental disorder. The aim of this study was to investigate the association of self- and expert-rated insight into illness with subjective quality of life (QOL). It was hypothesised that patients with greater self- and expert-rated insight into illness report lower QOL compared to patients with poor insight. METHOD: For the present study, patients with schizophrenia or schizoaffective disorders were investigated during in-patient treatment. Insight into illness was measured by the scale to assess unawareness of a mental disorder (SUMD), the insight scale and the PANSS. QOL was assessed with the modular system of quality of life (MSQoL). Results Fifty-nine patients entered the study. Self- and expert-rated illness insight were associated with poor QOL. Patients with good insight into illness reported significantly lower physical health (p < 0.05), vitality (p < 0.01), psychosocial (p < 0.01), affective (p < 0.01) and general QOL (p < 0.001) compared to patients with poor insight. Good insight was significantly associated with other parameters of clinical and social functioning and depressive symptoms. DISCUSSION: The results indicate that patients with acute schizophrenia and greater insight realise their restrictions more clearly, which contribute to poor QOL, but were stronger integrated in social networks. The inclusion of modules focussing on QOL related aspects of treatment from the beginning as well as a greater awareness of the physician for these questions and a strengthening of the therapeutic alliance might help improving insight without the risk of deteriorating mood and QOL.

Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and ceruloplasmin in patients with Alzheimer's disease.

Increasing evidence links Alzheimer's disease (AD) with misbalanced Cu homeostasis. Recently, we have shown that dietary Cu supplementation in a transgenic mouse model for AD increases bioavailable brain Cu levels, restores Cu, Zn-super oxide-1 activity, prevents premature death, and lowers A beta levels. In the present report we investigated AD patients with normal levels of A beta 42, Tau and Phospho-Tau in the cerebrospinal fluid (CSF) in comparison with AD patients exhibiting aberrant levels in these CSF biomarkers. The influence of these cerebrospinal fluid (CSF) diagnostic markers with primary dependent variables blood Cu, Zn and ceruloplasmin (CB) and secondary with CSF profiles of Cu, Zn and neurotransmitters was determined. Multivariate tests revealed a significant effect of factor diagnostic group (no AD diagnosis in CSF or AD diagnosis in CSF) for variables plasma Cu and CB (F=4.80; df=2, 23; p=0.018). Subsequent univariate tests revealed significantly reduced plasma Cu (-12.7%; F=7.05; df=1, 25; p=0.014) and CB (-14.1%; F=9.44; df=1, 24; p=0.005) levels in patients with aberrant CSF biomarker concentrations. Although only AD patients were included, the reduced plasma Cu and CB levels in patients with a CSF diagnosis of advanced AD supports previous observations that a mild Cu deficiency might contribute to AD progression.

[Not Available]. / Langfristige Alltagsbewältigung auf schmalem Grat.

Schizophrenic psychoses are among the most severe psychiatric illnesses and, in the majority of cases require several years of treatment, sometimes even for the rest of the patient's life. Of decisive importance for successful treatment is the involvement of all those concerned in a combined treatment strategy that includes pharmacological, psychotherapeutic and rehabilitative measures. The therapeutic aims are the reduction of symptoms, the prevention of relapses, and social and occupational reintegration.In pharmacotherapy, the latest antipsychotic agents have proven beneficial for relapse prophylaxis. Inadequate compliance, which is quite common, endangers the success of treatment. Psycho-educative measures that include family members can improve the acceptance of the illness and the readiness to undergo treatment and, together with psycho- and sociotherapeutic methods, can reduce symptoms and relapses.

[The role of copper in the pathophysiology of Alzheimer's disease]. / Zur Bedeutung von Kupfer für die Pathophysiologie der Alzheimer-Krankheit.

Alzheimer's dementia (AD) is a chronically progressive neurodegenerative disease. The key protein in the pathophysiology of AD is the amyloid precursor protein (APP) which releases the amyloid-beta peptide (Abeta) by proteolytic cleavage. APP is probably involved in the homeostasis of cellular copper (Cu) metabolism, because significantly changed Cu levels in the brain were found in AD patients as well as in mouse models. In vivo studies with transgenic mice showed that oral Cu supplements can restore lowered Cu levels in the brain to normal, can reduce Abeta production, and can reduce mortality of the animals. Currently, the influence of oral Cu supplementation (in addition to an established acetylcholinesterase inhibitor) on the progression of the disease is being studied in a prospective, double-blind, randomized and placebo-controlled longitudinal clinical trial in patients with mild AD.

[Panic as a mass phenomenon]. / Panik als Massenphänomen.

One of the greatest challenges in emergency medicine and in particular for emergency staff are disasters with huge amounts of victims. The development of a panic is a rare, but nonetheless an extreme escalation of an emergency situation. This paper describes the psychological and anthropological background of panic reactions and gives a summary of the current evidence in research. Accordingly, panic may be defined as the conclusive endpoint of an internal assessment that the probability to influence ones own survival in a life-threatening situation is close to zero. The possibilities and limitations of behavioral modifications according to strategies that are derived from cognitive and behavioral psychotherapy are discussed. It is crucial to detect situations at risk early and to correctly assess one's abilities for intervention. This ability can be learned with the help of assessment of behavior and self-programming. These methods may help emergency physicians to better assess the risk for the development of a panic following a disaster and thus may be useful in its prevention.

Hypericin-an inhibitor of proteasome function.

Hypericin is the presumed active moiety within Saint John's wort. Extracts of Saint John's wort are widely used as an effective treatment for depression. Available as "over-the-counter" drugs, they are frequently part of the self-medication of patients undergoing radiation therapy for malignant diseases. In addition to antidepressive properties, hypericin has been shown to be able to induce apoptosis and radiosensitize tumor cells, and to have antiinflammatory and phototoxic skin effects. However, the underlying mechanisms are not clear. In this study, we investigated possible inhibitory effects of hypericin on proteasome function and related pathways. Extracts from U373 human glioma cells were incubated with different concentrations of hypericin. Three proteasome activities were monitored using a fluorogenic peptide assay. Activity of the transcription factor NF-kappaB and protein levels of p65, p50, IkappaBalpha and caspase-3 were investigated by EMSA and Western blotting, respectively. Hypericin caused a dose-dependent and photoactivation-independent inhibition of proteasome function. Hypericin treatment (6.25-50 microM) inhibited NF-kappaB, caused accumulation of phosphorylated IkappaBalpha, decreased p50 protein levels and induced cleavage of p65 protein in U373 cells. These effects were observed in MCF-7 cells only at higher concentrations of hypericin (12.5-50 microM). Additionally, inhibition of NF-kappaB activity in U373 cells by hypericin was prevented by caspase inhibition. Although hypericin clearly inhibits proteasome function, its effect NF-kappaB DNA-binding activity was not exclusively proteasome-dependent. The underlying mechanism might also involve caspase activation, a consequence of proteasome inhibition.