Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethyl starch in critically ill patients - a multidisciplinary statement

Introduction: Hydroxyethyl starch (HES) is a commonly used colloid in critically ill patients. However, its safety has been questioned in recent studies and meta-analyses. Methods: We re-evaluated prospective randomised controlled trials (RCT) from four meta-analyses published in 2013 that compared the effect of HES with crystalloids in critically ill patients, focusing on the adherence to 'presumably correct indication'. Regarding the definition of 'presumably correct indication', studies were checked for the following six criteria (maximum six points): short time interval from shock to randomisation (<6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy. Results: Duration of fluid administration ranged from 90 min up to a maximum of 90 days. Four studies considered follow-up until 90-day mortality, three studies 28-/30-day mortality, whereas four studies reported only early mortality. Included studies showed a large heterogeneity of the indication score ranging between 1 and 4 points with a median (25%; 75% quartile) of 4 (2; 4). Conclusions: The most important question, whether or not HES may be harmful when it is limited to immediate haemodynamic stabilisation, cannot be answered yet in the absence of any study sufficiently addressing this question. In order to overcome the limitations of most of the previous studies, we now suggest an algorithm emphasising the strict indication of HES. Additionally, we give a list of suggestions that should be adequately considered in any prospective RCT in the field of acute volume resuscitation in critically ill patients

Emotion regulation through execution, observation, and imagery of emotional movements

According to Damasio’s somatic marker hypothesis, emotions are generated by conveying the current state of the body to the brain through interoceptive and proprioceptive afferent input. The resulting brain activation patterns represent unconscious emotions and correlate with subjective feelings. This proposition implies a corollary that the deliberate control of motor behavior could regulate feelings. We tested this possibility, hypothesizing that engaging in movements associated with a certain emotion would enhance that emotion and/or the corresponding valence. Furthermore, because motor imagery and observation are thought to activate the same mirror-neuron network engaged during motor execution, they might also activate the same emotional processing circuits, leading to similar emotional effects. Therefore, we measured the effects of motor execution, motor imagery and observation of whole-body dynamic expressions of emotions (happiness, sadness, fear) on affective state. All three tasks enhanced the corresponding affective state, indicating their potential to regulate emotions

The effects of hydroxyethyl starch 130/0.4 (6%) on blood loss and use of blood products in major surgery: A pooled analysis of randomized clinical trials

BACKGROUND: The effects of different types of hydroxylethyl starch (HES) on blood coagulation closely depend on their physicochemical properties. HES with lower molar substitution and a lower in vivo molecular weight interferes relatively little with hemostasis and therefore results in lower perioperative blood losses and red blood cell (RBC) transfusion. To test this hypothesis, we analyzed pooled data from all available studies in major surgery comparing 6% HES 130/0.4 and 6% HES 200/0.5 from waxy maize starch. METHODS: Estimated blood loss, drainage loss, calculated blood loss, transfused blood product volumes, and coagulation variables were examined for 24 h after the start of surgery. Groups were compared using analysis of variance, evaluating several covariates. RESULTS: Four-hundred-forty-nine patients from seven clinical trials were analyzed, 228 received HES 130/0.4, and 221 received HES 200/0.5. For HES 130/0.4 patients, when compared to HES 200/0.5 patients, the estimated blood loss was reduced by 404 mL [P = 0.006], drainage loss was 272 mL less [P = 0.009], and calculated RBC loss was 149 mL less [P = 0.003]. RBC transfusion volumes were also lower for HES 130/0.4 by 137 mL [P = 0.004]. In the early postoperative phase, HES 130/0.4 was found to exert significantly less effect on measures of coagulation, especially activated partial thromboplastin time and von Willebrand factor (antigen and ristocetin cofactor), than HES 200/0.5. CONCLUSIONS: Blood loss and transfusion requirements can be significantly reduced in major surgery when using third generation HES 130/0.4 (Voluven®) compared to second generation waxy maize starch HES 200/0.5. Since HES 130/0.4 and HES 200/0.5 were found similar regarding volume efficacy in other studies, HES 130/0.4 is recommended in this clinical setting. © 2008 International Anesthesia Research Society.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Biomarkers of Intergenerational Risk for Depression: A Review of Mechanisms in Longitudinal High-Risk (LHR) Studies

Background: Longitudinal research is critical for understanding the biological mechanisms underlying the development of depression. Researchers recruit high-risk cohorts to understand how risk is transmitted from one generation to the next. Biological measurements have been incorporated into these longitudinal high-risk (LHR) studies in order to illuminate mechanistic pathways. Methods: To frame our review, we first present heritability estimates along the gene-byenvironment continuum as a foundation. We then offer a Biomarkers of Intergenerational Risk for Depression (BIRD) model to describe the multiple hits individuals at risk receive and to allow for greater focus on the interactive effects of markers. BIRD allows for the known multifinality of pathways towards depression and considers the context (i.e., environment) in which these mechanisms emerge. Next, we review the extant LHR cohort studies that have assessed central nervous system (electroencephalography (EEG), neuroimaging), endocrine (hypothalamic-pituitary-adrenal axis (HPA)/cortisol), autonomic (startle, heart rate), genetic, sleep, and birth characteristics. Results: Results to date, in conjunction with the proposed model, point towards several pathways of discovery in understanding mechanisms, providing clear direction for future research examining potential endophenotypes. Limitations: Our review is based on relatively narrow inclusion and exclusion criteria. As such, many interesting studies were excluded, but this weakness is offset by strengths such as the increased reliability of findings. Conclusions: Blanket prevention programs are inefficient and plagued by low effect sizes due to low rates of actual conversion to disorder. The inclusion of biomarkers of risk may lead to enhanced program efficiency by targeting those with greatest ris

Results of a consensus meeting on the use of argatroban in patients with heparin-induced thrombocytopenia requiring antithrombotic therapy - a European Perspective.

Argatroban has been introduced as an alternative parenteral anticoagulant for HIT-patients in several European countries in 2005. In 2009 a panel of experts discussed their clinical experience with argatroban balancing risks and benefits of argatroban treatment in managing the highly procoagulant status of HIT-patients. This article summarizes the main conclusions of this round table discussion. An ongoing issue is the appropriate dosing of argatroban in special patient groups. Therefore, dosing recommendations for different HIT-patient groups (ICU patients; non-ICU patients, paediatric patients, and for patients undergoing renal replacement therapies) are summarized in this consensus statement. Because of the strong correlation between argatroban dosing requirements and scores used to characterize the severity of illness (APACHE; SAPS, SOFA) suitable dosing nomograms are given. This consensus statement contributes to clinically relevant information on the appropriate use and monitoring of argatroban based on the current literature, and provides additional information from clinical experience. As the two other approved drugs for HIT, danaparoid and lepirudin are either currently not available due to manufacturing problems (danaparoid) or will be withdrawn from the market in 2012 (lepirudin), this report should guide physicians who have limited experience with argatroban how to use this drug safely in patients with HIT

Smoking history, and not depression, is related to deficits in detection of happy and sad faces

Previous research has demonstrated that chronic cigarette smoking and major depressive disorder (MDD) are each associated with cognitive decrements. Further, these conditions co-occur commonly, though mechanisms in the comorbid condition are poorly understood. There may be distinct, additive, or overlapping factors underlying comorbid cigarette smoking and MDD. The present study investigated the impact of smoking and MDD on executive function and emotion processing. Participants (N=198) were grouped by diagnostic category (MDD and healthy controls, HC) and smoking status (ever-smokers, ES and never-smokers, NS). Participants completed the Facial Emotion Perception Test (FEPT), a measure of emotional processing, and the parametric Go/No-go task (PGNG), a measure of executive function. FEPT performance was analyzed using ANCOVA with accuracy and reaction time as separate dependent variables. Repeated measures MANCOVA was conducted for PGNG with performance measure and task level as dependent variables. Analyses for each task included diagnostic and smoking group as independent variables, and gender was controlled for. Results for FEPT reveal lower overall accuracy was found for ES relative to NS, though MDD did not differ from HC. Post-hoc analyses revealed ES were poorer at identifying happy and sad, but not fearful or angry, faces. For PGNG, poorer performance was observed in MDD relative to HC in response time to Go targets, but there were no differences for ES and NS. Interaction of diagnosis and smoking group was not observed for performance on either task. The results of this study provide preliminary evidence for distinctive cognitive decrements in smokers and individuals with depression