Diagnostic and Prognostic Value of Serum Leptin in Critically Ill Patients with Acute versus Acute-on-Chronic Liver Failure.

Differentiation between acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) can be challenging in patients with de novo liver disease but is important to indicate the referral to a transplant center and urgency of organ allocation. Leptin, an adipocyte-derived cytokine that regulates energy storage and satiety, has multiple regulatory functions in the liver. We enrolled 160 critically ill patients with liver disease and 20 healthy individuals to measure serum leptin concentrations as a potential biomarker for diagnostic and prognostic purposes. Notably, patients with ALF had higher concentrations of serum leptin compared to patients with decompensated advanced chronic liver disease (dACLD) or ACLF (110 vs. 50 vs. 29 pg/mL, p < 0.001). Levels of serum leptin below 56 pg/mL excluded ALF in patients with acute hepatic disease, with a negative predictive value (NPV) of 98.8% in our cohort. Lastly, serum leptin did not show any dynamic changes within the first 48 h of ICU treatment, especially not in comparison with patients with ALF vs. ACLF or survivors vs. non-survivors. In conclusion, serum leptin may represent a helpful biomarker to exclude ALF in critically ill patients who present with acute liver dysfunction.

Pharmacist-Led Medication Management in Acute Geriatric Medicine and Its Associations with Rehospitalizations: A Cohort Study.

INTRODUCTION: Hospitalization and discharge in older patients are critical and clinical pharmacists have shown to ameliorate risks. Our objective was to assess their benefit as part of the geriatric team regarding rehospitalizations and related outcomes after discharge focusing on general practitioners' decision to continue or change discharge medication (GPD). METHODS: Prospective implementation study with 6-month follow-up in an acute geriatric clinic. Patients ≥70 years with comorbidities, impairments, and a current drug therapy were consecutively assigned to three groups: control group (CG), implementation group (IG), and wash-out group (WG). CG only received medication reconciliation (MR) at admission; IG and their hospital physicians received a pharmaceutical counseling and medication management; during WG, pharmaceutical counseling except for MR was discontinued. We used a negative-binomial model to calculate rehospitalizations and days spent at home as well as a recurrent events survival model to investigate recurrent rehospitalizations. RESULTS: One hundred thirty-two patients (mean age 82 years, 76 women [57.6%]) finished the project. In most of the models for rehospitalizations, a positive GPD led to fewer events. We also found an effect of pharmaceutical counseling on rehospitalizations and recurrent rehospitalizations in the CG versus WG but not in the CG versus IG models. 95.3% of medication recommendations by the pharmacist in the clinic setting were accepted. While the number of positive GPDs in CG was low (38%), pharmaceutical counseling directly to the GP in IG led to a higher number of positive GPDs (60%). DISCUSSION: Although rehospitalizations were not directly reduced by our intervention in the CG versus IG, the pharmacist's acceptance rate in the hospital was very high and a positive GPD led to fewer rehospitalization in most models.

Pharmaceutical Interventions for Inpatients with Liver Cirrhosis and Liver Transplantation: A Systematic Review of Experimental Studies.

Liver cirrhosis, which is considered one of the leading causes of death in the world, can lead to severe complications, and is often followed by a liver transplantation. These patients take an average of nine medications daily. If not managed adequately, it can be accompanied by serious drug-related problems. To reduce this risk, a clinical pharmacist may be included as part of the healthcare team to optimize medication therapy in this population. This study aimed to systematically identify the pharmaceutical interventions which reduced drug-related problems and improved medication therapy for adult hospitalized liver cirrhotic and liver transplant patients when compared to standard care. Three databases (PubMed, Embase, and CENTRAL) were systematically searched from the inception of each database to 25 October 2023, and interventional studies in the English language were included. The risk of bias was assessed according to RoB-I for the UBA study and RoB2 for the identified RCT. The detected interventions to reduce drug-related problems in liver cirrhotic and liver transplant patients were extracted and classified according to a "Hierarchy of Controls" model. Two studies from Germany and the USA met our inclusion criteria, respectively. In these studies, we identified two interventions that included education, expert consultation, and the monitoring of the immunosuppressive medications serum level. The main objective of the two included studies was improving patients' compliance through adherence. These pharmaceutical interventions identified were classified as administrative controls, which is one of the lowest levels in the "Hierarchy of Controls" with which to address a potential risk. Pharmaceutical interventions to optimize medication therapy were found to be rare in the examined population, and were limited to "administrative controls". These interventions were limited to transplant patients' education and the monitoring of the immunosuppressive medication serum levels. No interventional studies were found to have investigated pharmaceutical interventions in patients with liver cirrhosis. Especially regarding this patient group, future studies to reduce DRPs using pharmaceutical interventions are needed. This study received no external funding and its PROSPERO registration number is CRD42022309122.

Comparison of Drug-Related Problems in COVID-19 and Non-COVID-19 Patients Provided by a German Telepharmacy Service for Rural Intensive Care Units.

Telepharmacy is used to bridge the persisting shortage of specialist ward-based pharmacists, particularly in intensive care units (ICU). During the coronavirus disease 2019 (COVID-19), pharmacotherapy was rapidly developed, which resulted in multiple changes of guidelines. This potentially led to a differing risk for drug-related problems (DRPs) in ICUs. In this study, DRPs were detected in telepharmacy consultations of a German state-wide telemedicine network for adult patients in rural ICUs. The analysis included ICUs of ten general care hospitals with a total of 514 patients and 1056 consultations. The aim of this retrospective, observational cohort study was to compare and analyze the DRPs resulting from ICU patients with or without COVID-19. Furthermore, known risk groups for severe COVID-19 progression (organ insufficiency [kidney, liver], obesity, sex, and/or older age) were investigated with their non-COVID-19 counterparts. As a result, in both groups patients with acute renal insufficiency and without renal replacement therapy showed a significantly higher risk of being affected by one or more DRPs compared to patients with normal renal function. In COVID-19 patients, the initial recommendation of therapeutic anticoagulation (ATC-code B01AB 'Heparin group') resulted in significantly more DRPs compared to non-COVID-19 patients. Therefore, COVID-19 patients with therapeutic anticoagulation and all ICU patients with renal insufficiency should be prioritized for telepharmacy consultations.

The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation. In previous studies, the administration of polyunsaturated fatty acids (PUFA) resulted in effects that might be beneficial in the treatment of AN, affecting the microbiome, body weight and executive functions. Therefore, the MiGBAN study aims to examine the effects of a nutritional supplementation with PUFA on the gut microbiome and body mass index (BMI) in patients with AN. METHODS: This is a longitudinal, double-blind, randomized, placebo-controlled trial. Within 2 years, 60 adolescent patients aged 12 to 19 years with AN will receive either PUFA or placebo for 6 months additional to treatment as usual. After 1 year, the long-term effect of PUFA on the gut microbiome and consecutively on BMI will be determined. Secondary outcomes include improvement of gastrointestinal symptoms, eating disorder psychopathology, and comorbidities. Additionally, the interaction of the gut microbiome with the brain (microbiome-gut-brain axis) will be studied by conducting MRI measurements to assess functional and morphological changes and neuropsychological assessments to describe cognitive functioning. Anti-inflammatory effects of PUFA in AN will be examined via serum inflammation and gut permeability markers. Our hypothesis is that PUFA administration will have positive effects on the gut microbiota and thus the treatment of AN by leading to a faster weight gain and a reduction of gastrointestinal problems and eating disorder psychopathology. DISCUSSION: Due to previously heterogeneous results, a systematic and longitudinal investigation of the microbiome-gut-brain axis in AN is essential. The current trial aims to further analyse this promising research field to identify new, effective therapeutic tools that could help improve the treatment and quality of life of patients. If this trial is successful and PUFA supplementation contributes to beneficial microbiome changes and a better treatment outcome, their administration would be a readily applicable additional component of multimodal AN treatment. TRIAL REGISTRATION: German Clinical Trials Register DRKS00017130 . Registered on 12 November 2019.

The WHO High 5s project: medication reconciliation in a German university hospital. A prospective observational cohort study.

BACKGROUND: Ensuring medication accuracy during transitions in care is one of the five highly prevalent patient safety problems focused on within the World Health Organization High 5s Project. Medication reconciliation is a standardized patient care process that can be used to address this problem. The aim of the current study is to implement medication reconciliation in a German university hospital. METHODS: The study was conducted at the Emergency Department of the University Hospital Aachen, Germany. All discrepancies between the Best Possible Medication History and the Admission Medication Order were documented and classified as documentation errors or medication errors. The type of error was also recorded. A negative binomial regression model was used to test several factors influencing the number of discrepancies. RESULTS: The medications of 105 patients were reconciled. The mean number of discrepancies per patient was 4.6± 3.6, with a total of 298 medication errors and 189 documentation errors. The most common type of medication error was the omission of a drug (n=208; 69.8 %). In the negative binomial regression analysis, the care status (p=0.0015) as well as the number of preadmission drugs (p=0.0007) were significantly associated with medication errors. DISCUSSION: A high number of discrepancies was detected and analysed. Patients admitted from nursing homes were less likely to have discrepancies in their medication reconciliation, perhaps because a structured documentation system for medications is already in place at nursing homes including error prone products (special dosage forms or food supplements). CONCLUSIONS: In this study, medication reconciliation was implemented at a German full-care university hospital. The actual number of discrepancies observed strongly indicates the need for medication reconciliation at hospital admission.

Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice.

Background: Asparaginases are common chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia as a single or combinational therapy. Accompanying hepatotoxicity makes its use in elderly patients with pre-conditions, as obesity or other hepatopathies, difficult. Various hepatoprotective compounds like, L-carnitine, are discussed to ameliorate the induced hepatotoxicity. Methods: Here we aimed to establish a mouse model to study the effect of asparaginases (L-asparaginase and Oncaspar) and L-carnitine on Western-diet-induced hepatosteatosis in mice. Dose-escalation studies were performed to analyze asparaginases induced hepatotoxicity in C57BL/6 mice with normal or fatty livers. Subsequently, the effect of L-carnitine to improve the induced toxicity was tested. Results: Our results showed mild-to-moderate hepatotoxic effects while the Western-diet induced a higher degree of vacuolization and hepatocyte damage in liver tissue. Testing of L-carnitine in the established models did not show any protective effect on the toxicity or impairment of the efficacy of asparaginases. Conclusion: The here established models were able to demonstrate the asparaginase-induced hepatotoxic effects which were enhanced by the Western-diet. However, to test potential ameliorating drugs, the models might need some improvements.

A Combined Administration of Testosterone and Arginine Vasopressin Affects Aggressive Behavior in Males.

Aggressive behavior is modulated by many factors, including personality and cognition, as well as endocrine and neural changes. To study the potential effects on the reaction to provocation, which was realized by an ostensible opponent subtracting money from the participant, we administered testosterone (T) and arginine vasopressin (AVP) or a respective placebo (PL). Forty males underwent a functional magnetic resonance imaging session while performing a provocation paradigm. We investigated differential hormone effects and the potential influence of Machiavellian traits on punishment choices (monetary subtractions by the participant) in the paradigm. Participants in the T/AVP group subtracted more money when they were not provoked but showed increased activation in the inferior frontal gyrus and inferior parietal lobule during feedback compared to PL. Higher Machiavellian traits significantly increased punishing behavior independent of provocation only in this group. The pilot study shows that T/AVP affects neural and behavioral responses during a provocation paradigm while personality characteristics, such as Machiavellian trait patterns, specifically interact with hormonal influences (T/AVP) and their effects on behavior.

Interventions to Reduce Medication Dispensing, Administration, and Monitoring Errors in Pediatric Professional Healthcare Settings: A Systematic Review.

Introduction: Pediatric patients cared for in professional healthcare settings are at high risk of medication errors. Interventions to improve patient safety often focus on prescribing; however, the subsequent stages in the medication use process (dispensing, drug administration, and monitoring) are also error-prone. This systematic review aims to identify and analyze interventions to reduce dispensing, drug administration, and monitoring errors in professional pediatric healthcare settings. Methods: Four databases were searched for experimental studies with separate control and intervention groups, published in English between 2011 and 2019. Interventions were classified for the first time in pediatric medication safety according to the "hierarchy of controls" model, which predicts that interventions at higher levels are more likely to bring about change. Higher-level interventions aim to reduce risks through elimination, substitution, or engineering controls. Examples of these include the introduction of smart pumps instead of standard pumps (a substitution control) and the introduction of mandatory barcode scanning for drug administration (an engineering control). Administrative controls such as guidelines, warning signs, and educational approaches are lower on the hierarchy and therefore predicted by this model to be less likely to be successful. Results: Twenty studies met the inclusion criteria, including 1 study of dispensing errors, 7 studies of drug administration errors, and 12 studies targeting multiple steps of the medication use process. A total of 44 interventions were identified. Eleven of these were considered higher-level controls (four substitution and seven engineering controls). The majority of interventions (n = 33) were considered "administrative controls" indicating a potential reliance on these measures. Studies that implemented higher-level controls were observed to be more likely to reduce errors, confirming that the hierarchy of controls model may be useful in this setting. Heterogeneous study methods, definitions, and outcome measures meant that a meta-analysis was not appropriate. Conclusions: When designing interventions to reduce pediatric dispensing, drug administration, and monitoring errors, the hierarchy of controls model should be considered, with a focus placed on the introduction of higher-level controls, which may be more likely to reduce errors than the administrative controls often seen in practice. Trial Registration Prospero Identifier: CRD42016047127.

Interventions to Reduce Pediatric Prescribing Errors in Professional Healthcare Settings: A Systematic Review of the Last Decade.

INTRODUCTION: Pediatric medication therapy is prone to errors due to the need for pharmacokinetic and pharmacodynamic individualization and the diverse settings in which pediatric patients are treated. Prescribing errors have been reported as the most common medication error. OBJECTIVES: The aim of this review was to systematically identify interventions to reduce prescribing errors and corresponding patient harm in pediatric healthcare settings and to evaluate their impact. METHODS: Four databases were systematically screened (time range November 2011 to December 2019), and experimental studies were included. Interventions to reduce prescribing errors were extracted and classified according to a 'hierarchy of controls' model. RESULTS: Forty-five studies were included, and 70 individual interventions were identified. A bundle of interventions was more likely to reduce prescribing errors than a single intervention. Interventions classified as 'substitution or engineering controls' were more likely to reduce errors in comparison with 'administrative controls', as is expected from the hierarchy of controls model. Fourteen interventions were classified as substitution or engineering controls, including computerized physician order entry (CPOE) and clinical decision support (CDS) systems. Administrative controls, including education, expert consultations, and guidelines, were more commonly identified than higher level controls, although they may be less likely to reduce errors. Of the administrative controls, expert consultations were most likely to reduce errors. CONCLUSIONS: Interventions to reduce pediatric prescribing errors are more likely to be successful when implemented as part of a bundle of interventions. Interventions including CPOE and CDS that substitute risks or provide engineering controls should be prioritized and implemented with appropriate administrative controls including expert consultation.

[Metformin Therapy During Surgical Interventions and Iodinated Contrast Agent Use]. / Metformin-Therapie bei operativen Eingriffen und Gabe jodhaltiger Kontrastmittel.

Metformin as first-line treatment in type 2 diabetes mellitus (T2 D) shows benefits in terms of reducing cardiovascular events, but the risk of a lactic acidosis as a serious adverse event especially in patients with decreased renal function is still relevant. Since the perioperative management of Metformin or its use in diagnostic procedures with contrast agents is inconsistent in literature and different in practice, the results of various guidelines are reviewed below showing the current state of evidence. Despite many guidelines, the evidence on both issues is low, as they are mainly based on consensus recommendations. The guidelines are still based on weak data and many international recommendations have clearly different statements. A fundamental problem with drugs is that expert information does specify eGFR limits for dose reduction, but not the method to be used. Depending on the formula, this can then lead to different treatment decisions. At present, it is not possible to give reliable recommendations for practice with the aim of minimising the interruption of therapy. For this reason, only a strictly conservative approach with 48-hour breaks before and after both measures can be recommended at present. For the situations mentioned in this overview, the question of the right approach has not yet been conclusively and definitely answered, therefore further studies should be carried out.

Comparison of two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock: A two-center pilot study.

BACKGROUND: Due to high pharmacokinetic variability, standard doses of meropenem are frequently inadequate in septic patients. Therapeutic drug monitoring of meropenem is not widely available; therefore, improved empiric dosing recommendations are needed. OBJECTIVES: This study aimed to compare the attainment of pharmacologic targets for two common empirical dosing regimens for meropenem in patients with septic shock. METHODS: Two empiric dosing schemes for meropenem were compared using extended infusions (120 minutes) in 32 patients with septic shock in the intensive care units at two different hospitals. One regimen was 3 × 2 g meropenem/24 h for two days, followed by 3 × 1 g meropenem/24 h; the other regimen was 4 × 1 g meropenem/24 h. Serum meropenem concentrations were measured for the first 72 h of therapy, and pharmacokinetic modelling was performed to define the percentage of time the free drug concentration was above various target MICs for each regimen (%fT>MIC). RESULTS: Both regimens led to a sufficiently high %fT>MIC for pathogens with target MICs < 4 mg/L. When higher MICs were targeted, the %fT>MIC of 4 × 1 g meropenem decreased faster than that of 3 × 2 g meropenem. At high MICs of 32 mg/L, both dosing regimens failed to provide appropriate drug concentrations. Renal function was a significant covariate of target attainment. CONCLUSIONS: The results of this study can guide clinicians in their choice of an empirical dosing regimen for meropenem. If pathogens with low MICs (< 4 mg/L) are targeted, both dosing regimens are adequate, whereas more resistant strains require higher doses.

Low Serum Levels of Soluble Receptor Activator of Nuclear Factor κ B Ligand (sRANKL) Are Associated with Metabolic Dysregulation and Predict Long-Term Mortality in Critically Ill Patients.

Soluble receptor activator of nuclear factor κ B ligand (sRANKL) is a member of the tumor necrosis factor receptor superfamily, and therefore, involved in various inflammatory processes. The role of sRANKL in the course of bone remodeling via activation of osteoclasts as well as chronic disease progression has been described extensively. However, the potential functional importance of sRANKL in critically ill or septic patients remained unknown. Therefore, we measured sRANKL serum concentrations in 303 critically ill patients, including 203 patients with sepsis and 100 with non-sepsis critical illness. Results were compared to 99 healthy controls. Strikingly, in critically ill patients sRANKL serum levels were significantly decreased at intensive care unit (ICU) admission (p = 0.011) without differences between sepsis and non-sepsis patients. Inline, sRANKL was correlated with markers of metabolic dysregulation, such as pre-existing diabetes and various adipokines (e.g., adiponectin, leptin receptor). Importantly, overall mortality of critically ill patients in a three-year follow-up was significantly associated with decreased sRANKL serum concentrations at ICU admission (p = 0.038). Therefore, our study suggests sRANKL as a biomarker in critically ill patients which is associated with poor prognosis and overall survival beyond ICU stay.

Association of Serum Calprotectin Concentrations with Mortality in Critically Ill and Septic Patients.

Background: Calprotectin is present in the cytosol of neutrophil granulocytes and released upon activation. Fecal calprotectin is applied in the clinical management of inflammatory bowel disease whereas serum calprotectin has been discussed as a biomarker in inflammatory disorders. However, its long-term prognostic relevance in critical illness remains unclear. Our aim was to investigate serum calprotectin concentrations as a prognostic biomarker in critically ill and septic patients. Methods: Serum calprotectin concentrations were analyzed in 165 critically ill patients (108 with sepsis, 57 without sepsis) included in our observational study. Patients were enrolled upon admission to the medical intensive care unit (ICU) of the RWTH Aachen University Hospital. Calprotectin concentrations were compared to 24 healthy controls and correlated with clinical parameters, therapeutic interventions, and survival. Results: Serum calprotectin concentrations were significantly increased in ICU patients as well as in septic patients compared to respective controls (p < 0.001 for ICU patients and p = 0.001 for septic patients). Lower calprotectin concentrations were measured in patients with comorbidities i.e., coronary artery disease. Calprotectin concentrations strongly correlated with the C-reactive protein (p < 0.001) and were closely associated to parameters of mechanical ventilation (i.a. inspiratory oxygen fraction, FiO2; p < 0.001). The overall survival was significantly impaired in septic patients with high baseline calprotectin concentrations (p = 0.036). However, patients with increasing calprotectin serum concentrations within the first week of ICU admission showed an improved overall survival (p = 0.009). Conclusions: In summary, serum calprotectin concentrations are significantly increased in critically ill patients with sepsis. High calprotectin concentrations at ICU admission predict long-term mortality risk, whereas increasing calprotectin concentrations are associated with a favorable long-term outcome.

Midregional Proadrenomedullin (MRproADM) Serum Levels in Critically Ill Patients Are Associated with Short-Term and Overall Mortality during a Two-Year Follow-Up.

Adrenomedullin (ADM) is a peptide with pleiotropic effects in systemic inflammation. Its more stable precursor protein midregional proadrenomedullin (MRproADM) can be measured more reliably compared to ADM. Our objective was to investigate the potential role of MRproADM as a diagnostic and prognostic biomarker in critically ill patients at the intensive care unit (ICU). We therefore measured MRproADM in 203 ICU patients and 66 healthy controls. We found that MRproADM levels are significantly increased in critically ill patients as compared to healthy controls. MRproADM levels are significantly increased in patients with sepsis, but its diagnostic value for identifying sepsis is numerically lower than that of established markers (e.g., interleukin-6, C-reactive protein, and procalcitonin). MRproADM levels are closely correlated to endothelial and organ dysfunction, inflammation, and established clinical scores (APACHE II, SOFA, and SAPS2). MRproADM concentrations correlate with vasopressor use but not fluid balance. Increased MRproADM levels (cut - off > 1.4 nmol/L) in critically ill patients are independent predictors of ICU and overall mortality during a follow-up of up to 26 months (OR 3.15 for ICU mortality, 95% CI 1.08-9.20, p = 0.036; OR for overall mortality 2.4, 95% CI 1.12-5.34, p = 0.026). Our study demonstrates the potential of MRproADM serum levels as a prognostic biomarker in critical illness for ICU mortality and long-term survival during follow-up.

Medication safety in a German telemedicine centre: Implementation of a telepharmaceutical expert consultation in addition to existing tele-intensive care unit services.

Introduction: Tele-intensive care unit (tele-ICU) services offer the possibility to provide specialized medical care in remote areas and to improve patient outcomes. The aim of this study was to implement and evaluate an additional telepharmaceutical expert consultation as part of tele-ICU services. Methods: This is a prospective observational study conducted in the telemedicine centre of the University Hospital RWTH Aachen, Germany. Between March and July 2015, all tele-ICU patients of one internal and two remote ICUs received telepharmaceutical consultation. Number and type of drug related problems (DRPs) were identified in a comprehensive medication safety check. Implementation of DRPs was discussed interdisciplinarily by tele-ICU pharmacist, tele-ICU physician and remote ICU physician. Special focus was on drug­drug interactions (DDIs) and dosage adjustment in renal and liver failure. Results: A total of 210 DRPs in 103 patients were identified and discussed. On average, 2.0 (range 0­17) DRPs per patient were found. At least one DRP was found in 62% of patients. Antibacterials for systemic use were most involved in DRPs. A total of 1129 DDI-alerts were generated by ID PHARMA CHECK®. Fifty-six DDIs (5%) were discussed in tele-ICU rounds. The tele-ICU team discussed 28 cases of dosage adjustment in organ failure. Discussion: Telepharmaceutical consultation as part of tele-ICU services was successfully implemented and can improve medication safety. Telemedicine infrastructure provides the possibility to implement guidelines recommending pharmaceutical service in the ICU in remote hospitals not having access to clinical pharmacists. Thus, quality of care can be improved.

Correction to: Central serotonin modulates neural responses to virtual violent actions in emotion regulation networks.

The article "Central serotonin modulates neural responses to virtual violent actions in emotion regulation networks", written by Dhana Wolf, Martin Klasen, Patrick Eisner, Florian D. Zepf, Mikhail Zvyagintsev, Nicola Palomero­Gallagher, René Weber, Albrecht Eisert, Klaus Mathiak was originally published electronically on the publisher's internet portal (currently SpringerLink) on June, 08, 2018 without open access.

Evaluation to improve the quality of medication preparation and administration in pediatric and adult intensive care units.

PURPOSE: To determine the type, frequency, and factors associated with medication preparation and administration errors in adult intensive care units (ICUs) and neonatal ICUs (NICUs)/pediatric ICUs (PICUs). PATIENTS AND METHODS: We conducted a prospective direct observation study in an adult ICU and NICU/PICU in a tertiary university hospital. Between June 2012 and June 2013, a clinical pharmacist and medical student observed the nursing care staff on weekdays during the preparation and administration of intravenous drugs. We analyzed the frequency and type of preparation and administration errors and factors associated with errors. RESULTS: Six hundred and three preparations in the adult ICU and 281 in the NICU/PICU were observed. Three hundred and eighty-five errors occurred in the adult ICU and 38 in the NICU/PICU. There were 5,040 and 2,514 error opportunities, with overall error rates of 7.6% and 1.5%, respectively. The total opportunities for error meant each single step of preparation and administration that was relevant for the drug. Most errors applied to the category "uniform mixing" (adult ICU: n=227, 59%; NICU/PICU: n=14, 37%). The multivariate logistic regression results showed a significantly different influence of the "preparation type" for the adult ICU compared with the NICU/PICU with regard to the occurrence of an error. Preparations for adult patients of the LCD type (liquid concentrate with diluent into syringe or infusion bag) were more often associated with errors than the P (powder in a glass vial that must be reconstituted and diluted if necessary), P=0.012, and LC (liquid concentrate into syringe), P=0.002 type. CONCLUSION: "Uniform mixing" was the most erroneous preparation step in intravenous drug preparations in two ICUs. Improvement of nurse training and the preparation of prefilled syringes in the pharmacy might reduce errors and improve the quality and safety of drug therapy.

Exogenous testosterone and the monoamine-oxidase A polymorphism influence anger, aggression and neural responses to provocation in males.

Testosterone and the monoamine oxidase-A (MAOA) polymorphism are potential neuromodulators for aggression. By acting on similar brain circuits, they might interactively influence human behavior. The current study investigates the causal role of testosterone on aggression-related brain activity and the potential interaction with the MAOA polymorphism. In a double-blind process, 93 healthy males received a testosterone or placebo gel. In an fMRI session, participants performed a Taylor aggression paradigm in which they received provoking feedback and could afterwards decide how aggressively they would react. Testosterone and cortisol levels as well as subjective anger were assessed prior and after the task. Circulating testosterone levels were higher in carriers of the long compared to the short MAOA allele. An interaction of the MAOA polymorphism and testosterone administration was identified in the cuneus, where short allele carriers in the placebo group showed diminished activity in the decision period. Task-related anger was significantly higher in this group. Overall, a mesocorticolimbic network was implicated in processing of high versus low provoking feedback, and core hubs of the default mode network were implicated in the subsequent decision after high versus low provocation. Testosterone administration increased activation in this network. The data provides evidence for an interaction of the MAOA polymorphism and exogenous testosterone on anger and suggests that interactive effects on the brain signal could underlie differential emotional reactivity. The increased default mode activation in the testosterone group suggests an enhanced engagement of social cognition related regions possibly supporting responsivity towards social provocation. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

Central serotonin modulates neural responses to virtual violent actions in emotion regulation networks.

Disruptions in the cortico-limbic emotion regulation networks have been linked to depression, anxiety, impulsivity, and aggression. Altered transmission of the central nervous serotonin (5-HT) contributes to dysfunctions in the cognitive control of emotions. To date, studies relating to pharmaco-fMRI challenging of the 5-HT system have focused on emotion processing for facial expressions. We investigated effects of a single-dose selective 5-HT reuptake inhibitor (escitalopram) on emotion regulation during virtual violence. For this purpose, 38 male participants played a violent video game during fMRI scanning. The SSRI reduced neural responses to violent actions in right-hemispheric inferior frontal gyrus and medial prefrontal cortex encompassing the anterior cingulate cortex (ACC), but not to non-violent actions. Within the ACC, the drug effect differentiated areas with high inhibitory 5-HT1A receptor density (subgenual s25) from those with a lower density (pregenual p32, p24). This finding links functional responses during virtual violent actions with 5-HT neurotransmission in emotion regulation networks, underpinning the ecological validity of the 5-HT model in aggressive behavior. Available 5-HT receptor density data suggest that this SSRI effect is only observable when inhibitory and excitatory 5-HT receptors are balanced. The observed early functional changes may impact patient groups receiving SSRI treatment.