Using simulation for training and to change protocol during the outbreak of severe acute respiratory syndrome

INTRODUCTION: During the 2003 severe acute respiratory syndrome (SARS) crisis, we proposed and tested a new protocol for cardiac arrest in a patient with SARS. The protocol was rapidly and effectively instituted by teamwork training using high-fidelity simulation. METHODS: Phase 1 was a curriculum design of a SARS-specific cardiac arrest protocol in three steps: planning the new protocol, repeated simulations of this protocol in a classroom, and a subsequent simulation of a cardiac arrest on a hospital ward. Phase 2 was the training of 275 healthcare workers (HCWs) using the new protocol. Training involved a seminar, practice in wearing the mandatory personal protection system (PPS), and cardiac arrest simulations with subsequent debriefing. RESULTS: Simulation provided insights that had not been considered in earlier phases of development. For example, a single person can don a PPS worn for the SARS patient in 1 1/2 minutes. However, when multiple members of a cardiac arrest team were dressing simultaneously, the time to don the PPS increased to between 3 1/2 and 5 1/2 minutes. Errors in infection control as well as in medical management of advanced cardiac life support (ACLS) were corrected. CONCLUSION: During the SARS crisis, real-time use of a high-fidelity simulator allowed the training of 275 HCWs in 2 weeks, with debriefing and error management. HCWs were required to manage the SARS cardiac arrest wearing unfamiliar equipment and following a modified ACLS protocol. The insight gained from this experience will be valuable for future infectious disease challenges in critical care

Critical care procedure logging using handheld computers

INTRODUCTION: We conducted this study to evaluate the feasibility of implementing an internet-linked handheld computer procedure logging system in a critical care training program. METHODS: Subspecialty trainees in the Interdepartmental Division of Critical Care at the University of Toronto received and were trained in the use of Palm handheld computers loaded with a customized program for logging critical care procedures. The procedures were entered into the handheld device using checkboxes and drop-down lists, and data were uploaded to a central database via the internet. To evaluate the feasibility of this system, we tracked the utilization of this data collection system. Benefits and disadvantages were assessed through surveys. RESULTS: All 11 trainees successfully uploaded data to the central database, but only six (55%) continued to upload data on a regular basis. The most common reason cited for not using the system pertained to initial technical problems with data uploading. From 1 July 2002 to 30 June 2003, a total of 914 procedures were logged. Significant variability was noted in the number of procedures logged by individual trainees (range 13–242). The database generated by regular users provided potentially useful information to the training program director regarding the scope and location of procedural training among the different rotations and hospitals. CONCLUSION: A handheld computer procedure logging system can be effectively used in a critical care training program. However, user acceptance was not uniform, and continued training and support are required to increase user acceptance. Such a procedure database may provide valuable information that may be used to optimize trainees' educational experience and to document clinical training experience for licensing and accreditation

Switching the cofactor specificity of an imine reductase

Chiral amines have proven to be powerful building blocks for defining new pharmaceutical and agrochemicals due to their high density of structural information. In this light, the reduction of prochiral C=N double bonds is a well-established route in synthetic chemistry due to the easy accessibility of imines from their ketone precursors with the asymmetric addition of hydrogen or a hydride as the key stereo-differentiating step. Recently, we have witnessed remarkable advances in the enzyme-catalyzed asymmetric reduction of imines by NADPH-dependent imine reductases (IREDs).[1,2] Imine reductases were presented that catalyze the asymmetric reduction of various imines and the chemo- and stereoselective reductive amination as a useful method for the preparation of amines derived from aldehydes and ketones.[3,4] Please click Additional Files below to see the full abstract

The critical care management of spontaneous intracranial hemorrhage: a contemporary review

Spontaneous intracerebral hemorrhage (ICH), defined as nontraumatic bleeding into the brain parenchyma, is the second most common subtype of stroke, with 5.3 million cases and over 3 million deaths reported worldwide in 2010. Case fatality is extremely high (reaching approximately 60 % at 1 year post event). Only 20 % of patients who survive are independent within 6 months. Factors such as chronic hypertension, cerebral amyloid angiopathy, and anticoagulation are commonly associated with ICH. Chronic arterial hypertension represents the major risk factor for bleeding. The incidence of hypertension-related ICH is decreasing in some regions due to improvements in the treatment of chronic hypertension. Anticoagulant-related ICH (vitamin K antagonists and the newer oral anticoagulant drugs) represents an increasing cause of ICH, currently accounting for more than 15 % of all cases. Although questions regarding the optimal medical and surgical management of ICH still remain, recent clinical trials examining hemostatic therapy, blood pressure control, and hematoma evacuation have advanced our understanding of ICH management. Timely and aggressive management in the acute phase may mitigate secondary brain injury. The initial management should include: initial medical stabilization; rapid, accurate neuroimaging to establish the diagnosis and elucidate an etiology; standardized neurologic assessment to determine baseline severity; prevention of hematoma expansion (blood pressure management and reversal of coagulopathy); consideration of early surgical intervention; and prevention of secondary brain injury. This review aims to provide a clinical approach for the practicing clinician. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1432-0) contains supplementary material, which is available to authorized users

Renal Thrombotic Microangiopathy in Mice with Combined Deletion of Endocytic Recycling Regulators EHD3 and EHD4

Eps15 Homology Domain-containing 3 (EHD3), a member of the EHD protein family that regulates endocytic recycling, is the first protein reported to be specifically expressed in the glomerular endothelium in the kidney; therefore we generated Ehd3–/– mice and assessed renal development and pathology. Ehd3–/– animals showed no overt defects, and exhibited no proteinuria or glomerular pathology. However, as the expression of EHD4, a related family member, was elevated in the glomerular endothelium of Ehd3–/– mice and suggested functional compensation, we generated and analyzed Ehd3–/–; Ehd4–/– mice. These mice were smaller, possessed smaller and paler kidneys, were proteinuric and died between 3–24 weeks of age. Detailed analyses of Ehd3–/–; Ehd4–/– kidneys demonstrated thrombotic microangiopathy (TMA)-like glomerular lesions including thickening and duplication of glomerular basement membrane, endothelial swelling and loss of fenestrations. Other changes included segmental podocyte foot process effacement, mesangial interposition, and abnormal podocytic and mesangial marker expression. The glomerular lesions observed were strikingly similar to those seen in human pre-eclampsia and mouse models of reduced VEGF expression. As altered glomerular endothelial VEGFR2 expression and localization and increased apoptosis was observed in the absence of EHD3 and EHD4, we propose that EHD-mediated endocytic traffic of key surface receptors such as VEGFR2 is essential for physiological control of glomerular function. Furthermore, Ehd3–/–; Ehd4–/– mice provide a unique model to elucidate mechanisms of glomerular endothelial injury which is observed in a wide variety of human renal and extra-renal diseases

Directed Evolution of an Artificial Imine Reductase

Artificial metalloenzymes, resulting from incorporation of a metal cofactor within a host protein, have received increasing attention in the last decade. The directed evolution is presented of an artificial transfer hydrogenase (ATHase) based on the biotin-streptavidin technology using a straightforward procedure allowing screening in cell-free extracts. Two streptavidin isoforms were yielded with improved catalytic activity and selectivity for the reduction of cyclic imines. The evolved ATHases were stable under biphasic catalytic conditions. The X-ray structure analysis reveals that introducing bulky residues within the active site results in flexibility changes of the cofactor, thus increasing exposure of the metal to the protein surface and leading to a reversal of enantioselectivity. This hypothesis was confirmed by a multiscale approach based mostly on molecular dynamics and protein-ligand dockings

Friends and Foes: The Dynamics of Dual Social Structures

This paper investigates the evolutionary dynamics of a dual social structure encompassing collaboration and conflict among corporate actors. We apply and advance structural balance theory to examine the formation of balanced and unbalanced dyadic and triadic structures, and to explore how these dynamics aggregate to shape the emergence of a global network. Our findings are threefold. First, we find that existing collaborative or conflictual relationships between two companies engender future relationships of the same type, but crowd out relationships of the different type. This results in (a) an increased likelihood of the formation of balanced (uniplex) relationships that combine multiple ties of either collaboration or conflict, and (b) a reduced likelihood of the formation of unbalanced (multiplex) relationships that combine collaboration and conflict between the same two firms. Second, we find that network formation is driven not by a pull toward balanced triads, but rather by a pull away from unbalanced triads. Third, we find that the observed micro-level dynamics of dyads and triads affect the structural segregation of the global network into two separate collaborative and conflictual segments of firms. Our empirical analyses used data on strategic partnerships and patent infringement and antitrust lawsuits in biotechnology and pharmaceuticals from 1996 to 2006

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570