Automated tracking of level of consciousness and delirium in critical illness using deep learning

Over- and under-sedation are common in the ICU, and contribute to poor ICU outcomes including delirium. Behavioral assessments, such as Richmond Agitation-Sedation Scale (RASS) for monitoring levels of sedation and Confusion Assessment Method for the ICU (CAM-ICU) for detecting signs of delirium, are often used. As an alternative, brain monitoring with electroencephalography (EEG) has been proposed in the operating room, but is challenging to implement in ICU due to the differences between critical illness and elective surgery, as well as the duration of sedation. Here we present a deep learning model based on a combination of convolutional and recurrent neural networks that automatically tracks both the level of consciousness and delirium using frontal EEG signals in the ICU. For level of consciousness, the system achieves a median accuracy of 70% when allowing prediction to be within one RASS level difference across all patients, which is comparable or higher than the median technician-nurse agreement at 59%. For delirium, the system achieves an AUC of 0.80 with 69% sensitivity and 83% specificity at the optimal operating point. The results show it is feasible to continuously track level of consciousness and delirium in the ICU

Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p> Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p> Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p> Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p&gt

The international phase 4 validation study of the EORTC QLQ-SWB32: a stand-alone measure of spiritual wellbeing (SWB) for people receiving palliative care for cancer

The EORTC Quality of Life (QL) Group has just completed the final phase (field-testing and validation) of an international project to develop a stand-alone measure of spiritual wellbeing (SWB) for palliative cancer patients. Participants (n= 451) - from 14 countries on four continents; 54% female; 188 Christian, 50 Muslim, 156 with no religion - completed a provisional 36-item measure of SWB plus the EORTC QLQ-C15-PAL (PAL), then took part in a structured debriefing interview. All items showed good score distribution across response categories. We assessed scale structure using Principal Component Analysis and Rasch analysis, and explored construct validity, and convergent/divergent validity with the PAL. Twenty-two items in four scoring scales (Relationship with Self, Relationships with Others, Relationship with Something Greater, and Existential) explained 53% of the variance. The measure also includes a global SWB item and nine other items. Scores on the PAL global QL item and Emotional Functioning scale weakly-moderately correlated with scores on the global SWB item and two of the four SWB scales. This new validated 32-item SWB measure addresses a distinct aspect of QL, and is now available for use in research and clinical practice, with a role as both a measurement and an intervention tool

Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto

<p>Abstract</p> <p>Background</p> <p>Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS.</p> <p>Methods</p> <p>Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak.</p> <p>Results</p> <p>There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak.</p> <p>Conclusion</p> <p>Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.</p

Multiparticle azimuthal correlations for extracting event-by-event elliptic and triangular flow in Au + Au collisions at sNN =200 GeV

We present measurements of elliptic and triangular azimuthal anisotropy of charged particles detected at forward rapidity 1&lt;|η|&lt;3 in Au + Au collisions at sNN=200 GeV, as a function of centrality. The multiparticle cumulant technique is used to obtain the elliptic flow coefficients v2{2},v2{4},v2{6}, and v2{8}, and triangular flow coefficients v3{2} and v3{4}. Using the small-variance limit, we estimate the mean and variance of the event-by-event v2 distribution from v2{2} and v2{4}. In a complementary analysis, we also use a folding procedure to study the distributions of v2 and v3 directly, extracting both the mean and variance. Implications for initial geometrical fluctuations and their translation into the final-state momentum distributions are discussed

Pseudorapidity Dependence of Particle Production and Elliptic Flow in Asymmetric Nuclear Collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200 GeV.

Asymmetric nuclear collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200  GeV provide an excellent laboratory for understanding particle production, as well as exploring interactions among these particles after their initial creation in the collision. We present measurements of charged hadron production dN_{ch}/dη in all such collision systems over a broad pseudorapidity range and as a function of collision multiplicity. A simple wounded quark model is remarkably successful at describing the full data set. We also measure the elliptic flow v_{2} over a similarly broad pseudorapidity range. These measurements provide key constraints on models of particle emission and their translation into flow

Production of π0 and η mesons in Cu+Au collisions at sNN =200 GeV

Production of π0 and η mesons has been measured at midrapidity in Cu+Au collisions at sNN=200GeV. Measurements were performed in π0(η)→γγ decay channel in the 1(2)-20GeV/c transverse momentum range. A strong suppression is observed for π0 and η meson production at high transverse momentum in central Cu+Au collisions relative to the p+p results scaled by the number of nucleon-nucleon collisions. In central collisions the suppression is similar to Au+Au with comparable nuclear overlap. The η/π0 ratio measured as a function of transverse momentum is consistent with mT-scaling parametrization down to pT=2GeV/c, its asymptotic value is constant and consistent with Au+Au and p+p and does not show any significant dependence on collision centrality. Similar results were obtained in hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions as well as in e+e- collisions in a range of collision energies sNN=3-1800 GeV. This suggests that the quark-gluon-plasma medium produced in Cu+Cu collisions either does not affect the jet fragmentation into light mesons or it affects the π0 and η the same way

Adamantyl Ethanone Pyridyl Derivatives: Potent and Selective Inhibitors of Human 11β-Hydroxysteroid Dehydrogenase Type 1

Elevated levels of active glucocorticoids have been implicated in the development of several phenotypes of metabolic syndrome, such as type 2 diabetes and obesity. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyses the intracellular conversion of inactive cortisone to cortisol. Selective 11β-HSD1 inhibitors have shown beneficial effects in various conditions, including diabetes, dyslipidemia and obesity. A series of adamantyl ethanone pyridyl derivatives has been identified, providing potent and selective inhibitors of human 11β-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11β-HSD1 and are selective for this isoform, with no activity against 11β-HSD2 and 17β-HSD1. Structure–activity relationship studies reveal that an unsubstituted pyridine tethered to an adamantyl ethanone motif through an ether or sulfoxide linker provides a suitable pharmacophore for activity. The most potent inhibitors have IC50 values around 34–48 nm against human 11β-HSD1, display reasonable metabolic stability in human liver microsomes, and weak inhibition of key human CYP450 enzymes

The Biology of the Cytolethal Distending Toxins

The cytolethal distending toxins (CDTs), produced by a variety of Gram-negative pathogenic bacteria, are the first bacterial genotoxins described, since they cause DNA damage in the target cells. CDT is an A-B2 toxin, where the CdtA and CdtC subunits are required to mediate the binding on the surface of the target cells, allowing internalization of the active CdtB subunit, which is functionally homologous to the mammalian deoxyribonuclease I. The nature of the surface receptor is still poorly characterized, however binding of CDT requires intact lipid rafts, and its internalization occurs via dynamin-dependent endocytosis. The toxin is retrograde transported through the Golgi complex and the endoplasmic reticulum, and subsequently translocated into the nuclear compartment, where it exerts the toxic activity. Cellular intoxication induces DNA damage and activation of the DNA damage responses, which results in arrest of the target cells in the G1 and/or G2 phases of the cell cycle and activation of DNA repair mechanisms. Cells that fail to repair the damage will senesce or undergo apoptosis. This review will focus on the well-characterized aspects of the CDT biology and discuss the questions that still remain unanswered