Anesthesia simulators: benefits and limits of experience gained at several European university hospitals]

Simulation has become essential in all situations where reality was too risky, too expensive, difficult to manage or inaccessible. In anaesthesia, the low rate of accidents and incidents, as well as the necessity to assure patient's safety, limit education and training in crisis management. The progress in data processing allowed the development of realistic anaesthesia simulators, associating the usual environment of an operating room, and made possible the simulation of a wide range of events. Most clinical incidents, mishaps, or manipulation errors can be simulated. A video recording allows the focus of attention on human factors. We assessed simulators in three European University hospitals. In Brussels as in Leiden, simulation was mainly used for training in crisis management. In Basel, the complete operating room staff participated in sessions, including also surgical simulation and improvement of communication within the team was one of the main goals. Simulation is valuable for residents' training, as well as continuing medical education, in crisis management and a better understanding of human factors. It remains without risk for the patient, with video possibilities improving the repetition of selected cases. However, its use for evaluation seems to be premature, due to the absence of studies demonstrating the validity and reproducibility of the results gained with simulation. Beyond technical limits which are amended continuously, the development of simulation is hindered by the very high cost of equipment and instructors.     

Alzheimer's disease and Down's syndrome. Some recent etiopathogenic data]

The present status of research clearly demonstrates the occurrence of lesions characteristic of Alzheimer's disease in patients suffering from a Down's syndrome or trisomy 21. The senile plaques appear very early in trisomy 21 (from the age of 20) and are constant after 40 or 45 years. In these two illnesses, the beta-amyloid protein or A4 protein (4.2 kD) leads to deposits in preferential regions of the central nervous system within two compartments: 1) intracellular, contributing to the formation of neurofibrillary tangles and 2) extracellular, making up the amyloid center of senile plaques as well as around the wall of some blood vessels, then corresponding to the amyloid congophilic angiopathies. Unexpectedly, larger proteins including the A4 sequence have been shown to be normally present in several tissues of normal as well as sick individuals and represent possible precursors of the A4 protein. Alzheimer's disease may happen either sporadically or following a familial incidence associated with an autosomic dominant mode of transmission. Moreover, the risk of incidence of trisomy 21 seems to be enhanced for collaterals of Alzheimer's disease patients. Since 1987, the use of molecular biology tools has revealed particularly fruitful. A linkage analysis has been undertaken that showed an association of the putative gene for the familial form of Alzheimer's disease (FAD) with the gene coding for amyloid precursor proteins (APP).(ABSTRACT TRUNCATED AT 250 WORDS)     

Gut oxygenation in sepsis: still a matter of controversy?

Part of Stephan Jakob's exhaustive review paper in the present issue of Critical Care deals with the notion that intestinal cellular energetics are deranged in sepsis, in terms not only of inadequate tissue perfusion but also of impaired mitochondrial respiration and/or coupling (i.e. organ dysfunction in sepsis may occur as a result of 'cytopathic hypoxia'). This suggests that efforts to improve outcome in septic patients by manipulating systemic oxygen delivery and regional blood flow are doomed to failure. That suggestion remains largely speculative, and experimental and clinical results presented here consistently demonstrate that there is still a place for treatment of abnormal perfusion in the context of early severe sepsis and septic shock.     

The endothelium in intensive care

This article reviews the major role that the vascular endothelium plays in pathophysiological processes related to metabolism, vascular function, and blood coagulation. Normally an antithrombotic surface, inflammation activates endothelium to become a prothrombotic and pro-inflammatory interface that is critically involved in multi-organ failure in patients with severe systemic diseases including sepsis. Improving endothelial functions in sepsis is a major therapeutic challenge.     

Effects of Fronto-Temporal Transcranial Direct Current Stimulation on Auditory Verbal Hallucinations and Resting-State Functional Connectivity of the Left Temporo-Parietal Junction in Patients With Schizophrenia

Auditory verbal hallucinations (AVH) in patients with schizophrenia are associated with abnormal hyperactivity in the left temporo-parietal junction (TPJ) and abnormal connectivity between frontal and temporal areas. Recent findings suggest that fronto-temporal transcranial Direct Current stimulation (tDCS) with the cathode placed over the left TPJ and the anode over the left prefrontal cortex can alleviate treatment-resistant AVH in patients with schizophrenia. However, brain correlates of the AVH reduction are unclear. Here, we investigated the effect of tDCS on the resting-state functional connectivity (rs-FC) of the left TPJ. Twenty-three patients with schizophrenia and treatment-resistant AVH were randomly allocated to receive 10 sessions of active (2 mA, 20min) or sham tDCS (2 sessions/d for 5 d). We compared the rs-FC of the left TPJ between patients before and after they received active or sham tDCS. Relative to sham tDCS, active tDCS significantly reduced AVH as well as the negative symptoms. Active tDCS also reduced rs-FC of the left TPJ with the left anterior insula and the right inferior frontal gyrus and increased rs-FC of the left TPJ with the left angular gyrus, the left dorsolateral prefrontal cortex and the precuneus. The reduction of AVH severity was correlated with the reduction of the rs-FC between the left TPJ and the left anterior insula. These findings suggest that the reduction of AVH induced by tDCS is associated with a modulation of the rs-FC within an AVH-related brain network, including brain areas involved in inner speech production and monitoring.Key words: resting state, brain stimulation, fMRI, temporal cortex     

Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease

Breathing involves a complex interplay between the brainstem automatic network and cortical voluntary command. How these brain regions communicate at rest or during inspiratory loading is unknown. This issue is crucial for several reasons: (i) increased respiratory loading is a major feature of several respiratory diseases, (ii) failure of the voluntary motor and cortical sensory processing drives is among the mechanisms that precede acute respiratory failure, (iii) several cerebral structures involved in responding to inspiratory loading participate in the perception of dyspnea, a distressing symptom in many disease. We studied functional connectivity and Granger causality of the respiratory network in controls and patients with chronic obstructive pulmonary disease (COPD), at rest and during inspiratory loading. Compared with those of controls, the motor cortex area of patients exhibited decreased connectivity with their contralateral counterparts and no connectivity with the brainstem. In the patients, the information flow was reversed at rest with the source of the network shifted from the medulla towards the motor cortex. During inspiratory loading, the system was overwhelmed and the motor cortex became the sink of the network. This major finding may help to understand why some patients with COPD are prone to acute respiratory failure. Network connectivity and causality were related to lung function and illness severity. We validated our connectivity and causality results with a mathematical model of neural network. Our findings suggest a new therapeutic strategy involving the modulation of brain activity to increase motor cortex functional connectivity and improve respiratory muscles performance in patients. Hum Brain Mapp 37:2736–2754, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Cost-effectiveness of activated protein C in real-life clinical practice

Background

Recombinant human activated protein C (rhAPC) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal randomized trial. We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice.

Methods

We conducted a prospective observational study involving adult patients recruited before and after licensure of rhAPC in France. Inclusion criteria were applied according to the label approved in Europe. The expected recruitment bias was controlled by building a sample of patients matched for propensity score. Complete hospitalization costs were quantified using a regression equation involving intensive care units variables. rhAPC acquisition costs were added, assuming that all costs associated with rhAPC were already included in the equation. Cost comparisons were conducted using the nonparametric bootstrap method. Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio.

Results

In the initial cohort (n = 1096), post-license patients were younger, had less co-morbid conditions and had failure of more organs than did pre-license patients (for all: P < 0.0001). In the matched sample (n = 840) the mean age was 62.4 ± 14.9 years, Simplified Acute Physiology Score II was 56.7 ± 18.5, and the number of organ failures was 3.20 ± 0.83. When rhAPC was used, 28-day mortality tended to be reduced (34.1% post-license versus 37.4% pre-license, P = 0.34), bleeding events were more frequent (21.7% versus 13.6%, P = 0.002) and hospital costs were higher (€47,870 versus €36,717, P < 0.05). The incremental cost-effectiveness ratios gained were as follows: €20,278 per life-year gained and €33,797 per quality-adjusted life-year gained. There was a 74.5% probability that rhAPC would be cost-effective if there were willingness to pay €50,000 per life-year gained. The probability was 64.3% if there were willingness to pay €50,000 per quality-adjusted life-year gained.

Conclusion

This study, conducted in matched patient populations, demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay €50,000 per life-year gained is 74.5%.