Latent topic discovery of clinical concepts from hospital discharge summaries of a heterogeneous patient cohort

Patients in critical care often exhibit complex disease patterns. A fundamental challenge in clinical research is to identify clinical features that may be characteristic of adverse patient outcomes. In this work, we propose a data-driven approach for phenotype discovery of patients in critical care. We used Hierarchical Dirichlet Process (HDP) as a non-parametric topic modeling technique to automatically discover the latent "topic" structure of diseases, symptoms, and findings documented in hospital discharge summaries. We show that the latent topic structure can be used to reveal phenotypic patterns of diseases and symptoms shared across subgroups of a patient cohort, and may contain prognostic value in stratifying patients' post hospital discharge mortality risks. Using discharge summaries of a large patient cohort from the MIMIC II database, we evaluate the clinical utility of the discovered topic structure in identifying patients who are at high risk of mortality within one year post hospital discharge. We demonstrate that the learned topic structure has statistically significant associations with mortality post hospital discharge, and may provide valuable insights in defining new feature sets for predicting patient outcomes.National Institutes of Health (U.S.) (Grant R01-EB001659)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01GM104987

Methods of Blood Pressure Measurement in the ICU*

OBJECTIVE:: Minimal clinical research has investigated the significance of different blood pressure monitoring techniques in the ICU and whether systolic vs. mean blood pressures should be targeted in therapeutic protocols and in defining clinical study cohorts. The objectives of this study are to compare real-world invasive arterial blood pressure with noninvasive blood pressure, and to determine if differences between the two techniques have clinical implications. DESIGN:: We conducted a retrospective study comparing invasive arterial blood pressure and noninvasive blood pressure measurements using a large ICU database. We performed pairwise comparison between concurrent measures of invasive arterial blood pressure and noninvasive blood pressure. We studied the association of systolic and mean invasive arterial blood pressure and noninvasive blood pressure with acute kidney injury, and with ICU mortality. SETTING:: Adult intensive care units at a tertiary care hospital. PATIENTS:: Adult patients admitted to intensive care units between 2001 and 2007. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Pairwise analysis of 27,022 simultaneously measured invasive arterial blood pressure/noninvasive blood pressure pairs indicated that noninvasive blood pressure overestimated systolic invasive arterial blood pressure during hypotension. Analysis of acute kidney injury and ICU mortality involved 1,633 and 4,957 patients, respectively. Our results indicated that hypotensive systolic noninvasive blood pressure readings were associated with a higher acute kidney injury prevalence (p = 0.008) and ICU mortality (p < 0.001) than systolic invasive arterial blood pressure in the same range (≤70 mm Hg). Noninvasive blood pressure and invasive arterial blood pressure mean arterial pressures showed better agreement; acute kidney injury prevalence (p = 0.28) and ICU mortality (p = 0.76) associated with hypotensive mean arterial pressure readings (≤60 mm Hg) were independent of measurement technique. CONCLUSIONS:: Clinically significant discrepancies exist between invasive and noninvasive systolic blood pressure measurements during hypotension. Mean blood pressure from both techniques may be interpreted in a consistent manner in assessing patients' prognosis. Our results suggest that mean rather than systolic blood pressure is the pre ferred metric in the ICU to guide therapy.National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01EB001659

Phenotyping hypotensive patients in critical care using hospital discharge summaries

Among critically-ill patients, hypotension represents a failure in compensatory mechanisms and may lead to organ hypoperfusion and failure. In this work, we adopt a datadriven approach for phenotype discovery and visualization of patient similarity and cohort structure in the intensive care unit (ICU). We used Hierarchical Dirichlet Process (HDP) as a non-parametric topic modeling technique to automatically learn a d-dimensional feature representation of patients that captures the latent 'topic' structure of diseases, symptoms, medications, and findings documented in hospital discharge summaries. We then used the t-Distributed Stochastic Neighbor Embedding (t-SNE) algorithm to convert the d-dimensional latent structure learned from HDP into a matrix of pairwise similarities for visualizing patient similarity and cohort structure. Using discharge summaries of a large patient cohort from the MIMIC II database, we evaluated the clinical utility of the discovered topic structure in phenotyping critically-ill patients who experienced hypotensive episodes. Our results indicate that the approach is able to reveal clinically interpretable clustering structure within our cohort and may potentially provide valuable insights to better understand the association between disease phenotypes and outcomes.National Institutes of Health (U.S.) (Grant R01-EB017205)National Institutes of Health (U.S.) (Grant R01-EB001659)National Institutes of Health (U.S.) (Grant R01GM104987

Myosin light chain kinase binding to a unique site on F-actin revealed by three-dimensional image reconstruction

Ca2+–calmodulin-dependent phosphorylation of myosin regulatory light chains by the catalytic COOH-terminal half of myosin light chain kinase (MLCK) activates myosin II in smooth and nonmuscle cells. In addition, MLCK binds to thin filaments in situ and F-actin in vitro via a specific repeat motif in its NH2 terminus at a stoichiometry of one MLCK per three actin monomers. We have investigated the structural basis of MLCK–actin interactions by negative staining and helical reconstruction. F-actin was decorated with a peptide containing the NH2-terminal 147 residues of MLCK (MLCK-147) that binds to F-actin with high affinity. MLCK-147 caused formation of F-actin rafts, and single filaments within rafts were used for structural analysis. Three-dimensional reconstructions showed MLCK density on the extreme periphery of subdomain-1 of each actin monomer forming a bridge to the periphery of subdomain-4 of the azimuthally adjacent actin. Fitting the reconstruction to the atomic model of F-actin revealed interaction of MLCK-147 close to the COOH terminus of the first actin and near residues 228–232 of the second. This unique location enables MLCK to bind to actin without interfering with the binding of any other key actin-binding proteins, including myosin, tropomyosin, caldesmon, and calponin

Resilience to loss and chronic grief: A prospective study from preloss to 18-months postloss

The vast majority of bereavement research is conducted after a loss has occurred. Thus, knowledge of the divergent trajectories of grieving or their antecedent predictors is lacking. This study gathered prospective data on 205 individuals several years prior to the death of their spouse and at 6- and 18-months postloss. Five core bereavement patterns were identified: common grief, chronic grief, chronic depression, improvement during bereavement, and resilience. Common grief was relatively infrequent, and the resilient pattern most frequent. The authors tested key hypotheses in the literature pertaining to chronic grief and resilience by identifying the preloss predictors of each pattern. Chronic grief was associated with preloss dependency and resilience with preloss acceptance of death and belief in a just world. The death of a spouse is generally assumed to be one of the most stressful experiences that people encounter during the course of their lives (Holmes &amp; Rahe, 1967). However, there are marked individual differences in how much and for how long people grieve (Bonanno &amp; Kaltman, 1999, 2001; Wortman &amp; Silver, 1989, 2001). In addition to what is assumed to be the typical or common reaction, an initial increase in depression that gradually subsides over time, several other patterns of grief have been discussed in the literature. These include prolonged or chronic grieving, the noticeable absence of grief symptoms, and delayed grief responses. Social and personality psychologists have become increasingly interested in these different trajectories, and how they compare with those observed for other marital transitions and othe

Collective Traumas and the Development of Leader Values: A Currently Omitted, but Increasingly Urgent, Research Area

The number of worldwide traumatic events is significant, yet the literature pays little attention to their implications for leader development. This article calls for a consideration of how collective trauma such as genocide and the Holocaust can shape the values of leaders, who are second- and third-generation descendants. Drawing on research on the transgenerational transmission of collective trauma and leader values, we show how collective trauma resides in (1) cultural rituals and artifacts, (2) community events and commemorations, and (3) family narratives is transmitted to leader descendants through at least three channels: social learning, social identity, and psychodynamics. We also offer propositions that recommend ways in which the transmission of these repositories can shape certain leader values that guide leader behaviors. Our conceptual review suggests that the transmission of collective trauma on leader development and leader values remains under-researched, offering prospects for new research and learning on the origins and seeds of leader development

Proton-pump inhibitor use is associated with low serum magnesium concentrations

Although case reports link proton-pump inhibitor (PPI) use and hypomagnesemia, no large-scale studies have been conducted. Here we examined the serum magnesium concentration and the likelihood of hypomagnesemia ( < 1.6 mg/dl) with a history of PPI or histamine-2 receptor antagonist used to reduce gastric acid, or use of neither among 11,490 consecutive adult admissions to an intensive care unit of a tertiary medical center. Of these, 2632 patients reported PPI use prior to admission, while 657 patients were using a histamine-2 receptor antagon ist. PPI use was associated with 0.012 mg/dl lower adjusted serum magnesium concentration compared to users of no acid-suppressive medications, but this effect was restricted to those patients taking diuretics. Among the 3286 patients concurrently on diuretics, PPI use was associated with a significant increase of hypomagnesemia (odds ratio 1.54) and 0.028 mg/dl lower serum magnesium concentration. Among those not using diuretics, PPI use was not associated with serum magnesium levels. Histamine-2 receptor antagonist use was not significantly associated with magnesium concentration without or with diuretic use. The use of PPI was not associated with serum phosphate concentration regardless of diuretic use. Thus, we verify case reports of the association between PPI use and hypomagnesemia in those concurrently taking diuretics. Hence, serum magnesium concentrations should be followed in susceptible individuals on chronic PPI therapy.National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant 2R01 EB001659

Effects of a strategy to improve offender assessment practices: Staff perceptions of implementation outcomes

Background: This implementation study examined the impact of an organizational process improvement intervention (OPII) on a continuum of evidence based practices related to assessment and community reentry of drug-involved offenders: Measurement/Instrumentation, Case Plan Integration, Conveyance/Utility, and Service Activation/Delivery. Methods: To assess implementation outcomes (staff perceptions of evidence-based assessment practices), a survey was administered to correctional and treatment staff (n = 1509) at 21 sites randomly assigned to an Early- or Delayed-Start condition. Hierarchical linear models with repeated measures were used to examine changes in evidence-based assessment practices over time, and organizational characteristics were examined as covariates to control for differences across the 21 research sites. Results: Results demonstrated significant intervention and sustainability effects for three of the four assessment domains examined, although stronger effects were obtained for intra- than inter-agency outcomes. No significant effects were found for Conveyance/Utility. Conclusions: Implementation interventions such as the OPII represent an important tool to enhance the use of evidence-based assessment practices in large and diverse correctional systems. Intra-agency assessment activities that were more directly under the control of correctional agencies were implemented most effectively. Activities in domains that required cross-systems collaboration were not as successfully implemented, although longer follow-up periods might afford detection of stronger effects