Protocol-directed care in the ICU: Making a future generation of intensivists less knowledgeable?

Background: Clinical protocols are associated with improved patient outcomes; however, they may negatively affect medical education by removing trainees from clinical decision making.Methods: Objective: To study the relationship between critical care training with mechanical ventilation protocols and subsequent knowledge about ventilator management.Design: A retrospective cohort equivalence study linking a national survey of mechanical ventilation protocol availability with knowledge about mechanical ventilation. Exposure to protocols was defined as high intensity if an intensive care unit had 2 or more protocols for at least 3 years and as low intensity if 0 or 1 protocol.Setting: Accredited US pulmonary and critical care fellowship programs.Subjects: First-time examinees of the American Board of Internal Medicine (ABIM) Critical Care Medicine Certification Examination in 2008 and 2009.Intervention: N/A. Outcomes: Knowledge, measured by performance on examination questions specific to mechanical ventilation management, calculated as a mechanical ventilation score using item response theory. The score is standardized to a mean (SD) of 500 (100), and a clinically important difference is defined as 25. Variables included in adjusted analyses were birth country, residency training country, and overall first-attempt score on the ABIM Internal Medicine Certification Examination.Results: The 90 of 129 programs (70%) responded to the survey. Seventy seven programs (86%) had protocols for ventilation liberation, 66 (73%) for sedation management, and 54 (60%) for lung-protective ventilation at the time of the survey. Eighty eight (98%) of these programs had trainees who completed the ABIM Critical Care Medicine Certification Examination, totaling 553 examinees. Of these 88 programs, 27 (31%) had 0 protocols, 19 (22%) had 1 protocol, 24 (27%) had 2 protocols, and 18 (20%) had 3 protocols for at least 3 years. 42 programs (48%) were classified as high intensity and 46 (52%) as low intensity, with 304 trainees (55%) and 249 trainees (45%), respectively. In bi-variable analysis, no difference in mean scores was observed in high-intensity (497; 95% CI, 486-507) vs low-intensity programs (497; 95% CI, 485-509). Mean difference was 0 (95% CI, -16 to 16), with a positive value indicating a higher score in the high-intensity group. In multivariable analyses, no association of training was observed in a high-intensity program with mechanical ventilation score (adjusted mean difference, -5.36; 95% CI, -20.7 to 10.0).Conclusions: Among first-time ABIM Critical Care Medicine Certification Examination examinees, training in a high-intensity ventilator protocol environment compared with a low-intensity environment was not associated with worse performance on examination questions about mechanical ventilation management. © 2012 BioMed Central Ltd

A Bargaining Game Analysis of International Climate Negotiations

Climate negotiations under the United Nations Framework Convention on Climate Change have so far failed to achieve a robust international agreement to reduce greenhouse gas emissions. Game theory has been used to investigate possible climate negotiation solutions and strategies for accomplishing them. Negotiations have been primarily modelled as public goods games such as the Prisoner’s Dilemma, though coordination games or games of conflict have also been used. Many of these models have solutions, in the form of equilibria, corresponding to possible positive outcomes—that is, agreements with the requisite emissions reduction commitments. Other work on large-scale social dilemmas suggests that it should be possible to resolve the climate problem. It therefore seems that equilibrium selection may be a barrier to successful negotiations. Here we use an N-player bargaining game in an agent-based model with learning dynamics to examine the past failures of and future prospects for a robust international climate agreement. The model suggests reasons why the desirable solutions identified in previous game-theoretic models have not yet been accomplished in practice and what mechanisms might be used to achieve these solutions

Mechanisms underlying disorders of consciousness: Bridging gaps to move toward an integrated translational science

AIM: In order to successfully detect, classify, prognosticate, and develop targeted therapies for patients with disorders of consciousness (DOC), it is crucial to improve our mechanistic understanding of how severe brain injuries result in these disorders. METHODS: To address this need, the Curing Coma Campaign convened a Mechanisms Sub-Group of the Coma Science Work Group (CSWG), aiming to identify the most pressing knowledge gaps and the most promising approaches to bridge them. RESULTS: We identified a key conceptual gap in the need to differentiate the neural mechanisms of consciousness per se, from those underpinning connectedness to the environment and behavioral responsiveness. Further, we characterised three fundamental gaps in DOC research: (1) a lack of mechanistic integration between structural brain damage and abnormal brain function in DOC; (2) a lack of translational bridges between micro- and macro-scale neural phenomena; and (3) an incomplete exploration of possible synergies between data-driven and theory-driven approaches. CONCLUSION: In this white paper, we discuss research priorities that would enable us to begin to close these knowledge gaps. We propose that a fundamental step towards this goal will be to combine translational, multi-scale, and multimodal data, with new biomarkers, theory-driven approaches, and computational models, to produce an integrated account of neural mechanisms in DOC. Importantly, we envision that reciprocal interaction between domains will establish a virtuous cycle, leading towards a critical vantage point of integrated knowledge that will enable the advancement of the scientific understanding of DOC and consequently, an improvement of clinical practice

Computational modelling in disorders of consciousness: closing the gap towards personalised models for restoring consciousness

Disorders of consciousness are complex conditions characterised by persistent loss of responsiveness due to brain injury. They present diagnostic challenges and limited options for treatment, and highlight the urgent need for a more thorough understanding of how human consciousness arises from coordinated neural activity. The increasing availability of multimodal neuroimaging data has given rise to a wide range of clinically- and scientifically-motivated modelling efforts, seeking to improve data-driven stratification of patients, to identify causal mechanisms for patient pathophysiology and loss of consciousness more broadly, and to develop simulations as a means of testing in silico potential treatment avenues to restore consciousness. As a dedicated Working Group of clinicians and neuroscientists of the international Curing Coma Campaign, here we provide our framework and vision to understand the diverse statistical and generative computational modelling approaches that are being employed in this fast-growing field. We identify the gaps that exist between the current state-of-the-art in statistical and biophysical computational modelling in human neuroscience, and the aspirational goal of a mature field of modelling disorders of consciousness; which might drive improved treatments and outcomes in the clinic. Finally, we make several recommendations for how the field as a whole can work together to address these challenges

Sphingomyelin Synthases Regulate Protein Trafficking and Secretion

Sphingomyelin synthases (SMS1 and 2) represent a class of enzymes that transfer a phosphocholine moiety from phosphatidylcholine onto ceramide thus producing sphingomyelin and diacylglycerol (DAG). SMS1 localizes at the Golgi while SMS2 localizes both at the Golgi and the plasma membrane. Previous studies from our laboratory showed that modulation of SMS1 and, to a lesser extent, of SMS2 affected the formation of DAG at the Golgi apparatus. As a consequence, down-regulation of SMS1 and SMS2 reduced the localization of the DAG-binding protein, protein kinase D (PKD), to the Golgi. Since PKD recruitment to the Golgi has been implicated in cellular secretion through the trans golgi network (TGN), the effect of down-regulation of SMSs on TGN-to-plasma membrane trafficking was studied. Down regulation of either SMS1 or SMS2 significantly retarded trafficking of the reporter protein vesicular stomatitis virus G protein tagged with GFP (VSVG-GFP) from the TGN to the cell surface. Inhibition of SMSs also induced tubular protrusions from the trans Golgi network reminiscent of inhibited TGN membrane fission. Since a recent study demonstrated the requirement of PKD activity for insulin secretion in beta cells, we tested the function of SMS in this model. Inhibition of SMS significantly reduced insulin secretion in rat INS-1 cells. Taken together these results provide the first direct evidence that both enzymes (SMS1 and 2) are capable of regulating TGN-mediated protein trafficking and secretion, functions that are compatible with PKD being a down-stream target for SMSs in the Golgi

The Persisting Burden of Intracerebral Haemorrhage: Can Effective Treatments Be Found?

Colin Josephson, Rustam Al-Shahi Salman, and colleagues discuss the effectiveness of treatments for intracerebral haemorrhage