Mutual information: Measuring nonlinear dependence in longitudinal epidemiological data.

Given a large clinical database of longitudinal patient information including many covariates, it is computationally prohibitive to consider all types of interdependence between patient variables of interest. This challenge motivates the use of mutual information (MI), a statistical summary of data interdependence with appealing properties that make it a suitable alternative or addition to correlation for identifying relationships in data. MI: (i) captures all types of dependence, both linear and nonlinear, (ii) is zero only when random variables are independent, (iii) serves as a measure of relationship strength (similar to but more general than R2), and (iv) is interpreted the same way for numerical and categorical data. Unfortunately, MI typically receives little to no attention in introductory statistics courses and is more difficult than correlation to estimate from data. In this article, we motivate the use of MI in the analyses of epidemiologic data, while providing a general introduction to estimation and interpretation. We illustrate its utility through a retrospective study relating intraoperative heart rate (HR) and mean arterial pressure (MAP). We: (i) show postoperative mortality is associated with decreased MI between HR and MAP and (ii) improve existing postoperative mortality risk assessment by including MI and additional hemodynamic statistics.

Postoperative Acute Kidney Injury by Age and Sex: A Retrospective Cohort Association Study.

BACKGROUND: Acute kidney injury (AKI) after noncardiac surgery is common and has substantial health impact. Preclinical and clinical studies examining the influence of sex on AKI have yielded conflicting results, although they typically do not account for age-related changes. The objective of the study was to determine the association of age and sex groups on postoperative AKI. The authors hypothesized that younger females would display lower risk of postoperative AKI than males of similar age, and the protection would be lost in older females. METHODS: This was a multicenter retrospective cohort study across 46 institutions between 2013 and 2019. Participants included adult inpatients without pre-existing end-stage kidney disease undergoing index major noncardiac, nonkidney/urologic surgeries. The authors' primary exposure was age and sex groups defined as females 50 yr or younger, females older than 50 yr, males 50 yr or younger, and males older than 50 yr. The authors' primary outcome was development of AKI by Kidney Disease-Improving Global Outcomes serum creatinine criteria. Exploratory analyses included associations of ascending age groups and hormone replacement therapy home medications with postoperative AKI. RESULTS: Among 390,382 patients, 25,809 (6.6%) developed postoperative AKI (females 50 yr or younger: 2,190 of 58,585 [3.7%]; females older than 50 yr: 9,320 of 14,4047 [6.5%]; males 50 yr or younger: 3,289 of 55,503 [5.9%]; males older than 50 yr: 11,010 of 132,447 [8.3%]). When adjusted for AKI risk factors, compared to females younger than 50 yr (odds ratio, 1), the odds of AKI were higher in females older than 50 yr (odds ratio, 1.51; 95% CI, 1.43 to 1.59), males younger than 50 yr (odds ratio, 1.90; 95% CI, 1.79 to 2.01), and males older than 50 yr (odds ratio, 2.06; 95% CI, 1.96 to 2.17). CONCLUSIONS: Younger females display a lower odds of postoperative AKI that gradually increases with age. These results suggest that age-related changes in women should be further studied as modifiers of postoperative AKI risk after noncardiac surgery.

The impact of race on utilization of durable left ventricular assist device therapy in patients with advanced heart failure.

BACKGROUND: Heart failure affects >6 million people in the United States alone and is most prevalent in Black patients who suffer the highest mortality risk. Yet prior studies have suggested that Black patients are less likely to receive advanced heart failure therapy. We hypothesized that Black patients would have decreased rates of durable left ventricular assist device (LVAD) implantation within our expansive heart failure program. METHODS: A retrospective single-center cohort study was conducted at a single high-volume academic medical center. Patients between 18 and 85 years admitted with a diagnosis of cardiogenic shock or congestive heart failure between 1, 2013 and 12, 2017 with a left ventricular ejection fraction < 30% and inotropic dependence or need for mechanical circulatory support were included. Patients with contraindications to durable LVAD were excluded. An adjusted logistic regression model for durable LVAD implantation within 90 days of the index admission was used to determine the effect of race on durable LVAD implantation. RESULTS: Among the 702 study patients (60.9% White, 34.1% Black), durable LVAD implantation was performed within 90 days of the index admission in 183 (26%) of the cohort. After multivariate analysis, Black patients were not found to have a statistically significant difference in durable LVAD implantation rates compared to White patients in our study (OR: 0.68 [95% confidence interval: 0.45-1.04; p: .074]). CONCLUSIONS: Black patients in our study did not have a statistically significant difference in the rate of durable LVAD implantation compared with White patients after adjustments were made for age, sex, socioeconomic, and clinical covariates. Larger prospective studies are needed to validate these findings.

Performance of a Standardized Clinical Assay for Urinary C-C Motif Chemokine Ligand 14 (CCL14) for Persistent Severe Acute Kidney Injury.

Background: Clinical use of biomarkers requires the development of standardized assays and establishment of cutoffs. Urinary C-C motif chemokine ligand 14 (CCL14) has been validated to predict persistent severe AKI in critically ill patients with established AKI. We now report on the performance of standardized cutoffs using a clinical assay. Methods: A second aim of the multicenter RUBY Study was to establish two cutoffs for the prediction of persistent severe AKI (defined as KDIGO stage 3 AKI for at least 72 consecutive hours). Patients who received renal replacement therapy (RRT) or died before achieving 72 hours in stage 3 AKI were also considered to have reached the end point. Results: A cutoff value for urinary CCL14 of 1.3 ng/ml was determined to achieve high sensitivity (91%; 95% CI, 84% to 96%), and 13 ng/ml achieved high specificity (93%; 95% CI, 89% to 96%). The cutoff of 1.3 ng/ml identifies the majority (91%) of patients who developed persistent severe AKI with a negative predictive value of 92%. The cutoff at 13 ng/ml had a positive predictive value of 72% (with a negative predictive value of 75%). In multivariable adjusted analyses, a CCL14 concentration between 1.3 and 13 ng/ml had an adjusted odds ratio (aOR) of 3.82 (95% CI, 1.73 to 9.12; P=0.001) for the development of persistent severe AKI compared with those with a CCL14 ≤1.3 ng/ml, whereas a CCL14 >13 ng/ml had an aOR of 10.4 (95% CI, 3.89 to 29.9; P<0.001). Conclusions: Using a clinical assay, these standardized cutoffs (1.3 and 13 ng/ml) allow for the identification of patients at high risk for the development of persistent severe AKI. These results have immediate utility in helping to guide AKI patient care and may facilitate future clinical trials.Clinical Trial registry name and registration number: Identification and Validation of Biomarkers of Acute Kidney Injury Recovery, NCT01868724.

Adaptation or Revolution: Telemental Health and Advanced Practice Psychiatric Nursing During COVID-19.

OBJECTIVE: This article will describe the current COVID-19 crisis and the evolving mental health concerns associated with it, discuss how mental health practice has changed, and ways in which psychiatric mental health nurse practitioners (PMHNPs) can adapt and prepare for the future. METHOD: A search of current literature on the COVID-19 crisis, and topics relevant to the mental health components associated with the pandemic are reviewed. Telemental health (TMH) and PMHNP practice are discussed as they relate to the unfolding picture of the viral pandemic. RESULTS: The COVID-19 crisis is having far-reaching implications for mental health treatment and in particular for PMHNPs in practice settings. There have been widespread consequences of the containment measures used for the protection and mitigation of the disease. One such result has been the inability of patients to have face-to-face contact with their providers. The role of TMH has become increasingly important as an adaptation in professional practice. CONCLUSION: Technology has rapidly transformed traditional practice due to the COVID-19 crisis and there is strong evidence that it is well accepted by patients and providers. It is incumbent on PMHNPs to embrace TMH and become educated on best practices and TMH services.

Preoperative Care Assessment of Need Scores Are Associated With Postoperative Mortality and Length of Stay in Veterans Undergoing Knee Replacement.

BACKGROUND: Care Assessment of Need (CAN) scores predicting 90-day mortality and hospitalization are automatically computed each week for patients receiving care at Veterans Health Administration facilities. While currently used only by primary care teams for care coordination, we explored their value as a perioperative risk stratification tool before major elective surgery. METHODS: We collected relevant demographic and perioperative data along with perioperative CAN scores for veterans who underwent total knee replacement between July 2014 and December 2015. We examined score distribution, relationships of preoperative CAN 1-year mortality scores with 1-year postoperative mortality and index hospital length of stay (LOS), and patterns of mortality. RESULTS: Among 8206 patients, 1-year mortality was 1.4% (110 patients), and CAN scores exhibited near-normal distribution. Median scores among survivors were significantly higher than those of in nonsurvivors (45 vs 75; P < .001). The Kaplan-Meier curves showed an approximately 4-fold higher rate of death at 1 year in the highest tercile for 1-year mortality CAN scores compared with those with lower scores (2.0% vs 0.5% respectively; P < .001). Locally estimated scatterplot smoothing curves revealed a significant and nonlinear increase in hospital LOS across preoperative CAN scores. CONCLUSIONS: Although designed for ambulatory care use, CAN scores can identify patients at high risk for mortality and extended hospital LOS in an elective surgery population. The CAN scores may prove valuable in supporting informed decision making and preoperative planning in high-risk and vulnerable populations. Further study is needed to confirm the validity of CAN scores and compare them to other more widely used surgical risk calculators.

Preoperative Disability in US Veterans.

Using the 12-item World Health Organization Disability Assessment Schedule (WHODAS-12), we measured the prevalence of disability in all eligible patients during a 4-month period who were presenting for preoperative evaluation at a US Veterans Affairs hospital. Overall disability was at least moderate in more than half of these patients (total n = 472 at Durham, NC). Two of the 6 WHODAS domains, "Getting Around" and "Participation in Society," contributed most to the overall scores-25% and 20%, respectively. Further studies are needed to determine the impact of domain-specific disabilities on postoperative outcomes and to identify potential interventions to address these vulnerabilities.

Design of a Novel Oxygen Therapeutic Using Polymeric Hydrogel Microcapsules Mimicking Red Blood Cells.

The goal of this research was to develop a novel oxygen therapeutic made from a pectin-based hydrogel microcapsule carrier mimicking red blood cells. The study focused on three main criteria for developing the oxygen therapeutic to mimic red blood cells: size (5-10 µm), morphology (biconcave shape), and functionality (encapsulation of oxygen carriers; e.g., hemoglobin (Hb)). The hydrogel carriers were generated via the electrospraying of the pectin-based solution into an oligochitosan crosslinking solution using an electrospinning setup. The pectin-based solution was investigated first to develop the simplest possible formulation for electrospray. Then, Design-Expert® software was used to optimize the production process of the hydrogel microcapsules. The optimal parameters were obtained through the analysis of a total of 17 trials and the microcapsule with the desired morphology and size was successfully prepared under the optimized condition. Fourier transform infrared spectroscopy (FTIR) was used to analyze the chemistry of the microcapsules. Moreover, the encapsulation of Hb into the microcapsule did not adversely affect the microcapsule preparation process, and the encapsulation efficiency was high (99.99%). The produced hydrogel microcapsule system shows great promise for creating a novel oxygen therapeutic.

Preoperative Blood Management Strategy for Elective Hip and Knee Arthroplasty.

To improve quality and outcomes, a preoperative anemia clinic (PAC) was established to screen, evaluate, and manage preoperative anemia. A retrospective review of primary and revision hip and knee arthroplasty patients from August 2013 to September 2017 was conducted. Patients at "high risk" for transfusion were referred to PAC for treatment with iron, erythropoietin, or both based on anemia type. Preoperative anemia clinic referred patients were compared with a 1:3 historic propensity-matched control set of patients to help determine impact of PAC. Forty PAC patients were compared with 120 control patients. Among PAC patients, 26 (63.41%) received iron only, 3 (7.32%) received erythropoietin (EPO) only, and 12 (29.27%) received both. Preoperative hemoglobin significantly increased in the treatment group (median [interquartile range] 10.9 g/dl [10.3-11.2] vs. 12.0 g/dl [11.2-12.7]; p < .001). Four PAC patients (10.00%) received red blood cell transfusions compared with 29 (24.17%) from matched controls (p = .055). In addition, the PAC cohort had higher postoperative nadir hemoglobin levels (mean [SD] 9.7 g/dl [1.31] vs. 8.7 g/dl [1.25]; p < .001). High-risk patients appropriately treated with iron and/or EPO before surgery demonstrate a significant increase in preoperative hemoglobin, trend toward decrease perioperative transfusion, and increased hemoglobin levels postoperatively compared with matched controls.

Erratum to "Quadratus Lumborum Block as Sole, Homeostatic-Preserving Anesthetic for a Patient with Multiple System Atrophy Undergoing Open Inguinal Hernia Repair: A Case Report".

[This corrects the article DOI: 10.1155/2018/7161860.].

Quadratus Lumborum Block as Sole, Homeostatic-Preserving Anesthetic for a Patient with Multiple System Atrophy Undergoing Open Inguinal Hernia Repair: A Case Report.

Quadratus Lumborum (QL) block has been successfully used for different abdominal procedures in the past. Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized mainly by autonomic instability, motor impairment, and cognitive dysfunction. We report a case of a patient with MSA with a history of multiple episodes of unplanned admissions following outpatient minor surgical procedures under general anesthesia scheduled to undergo open inguinal hernia repair. In our patient, QL block was successfully used for surgical anesthesia and it resulted in hemodynamic stability and an opioid-free perioperative course.

HRI-mediated translational repression reduces proteotoxicity and sensitivity to bortezomib in human pancreatic cancer cells.

Human cancer cells display extensive heterogeneity in their sensitivities to the proteasome inhibitor bortezomib (Velcade). The molecular mechanisms underlying this heterogeneity remain unclear, and strategies to overcome resistance are limited. Here, we discover that inherent differences in eIF2α phosphorylation among a panel of ten human pancreatic cancer cell lines significantly impacts bortezomib sensitivity, and implicate the HRI (heme-regulated inhibitor) eIF2α kinase as a novel therapeutic target. Within our panel, we identified a subset of cell lines with defective induction of eIF2α phosphorylation, conferring a high degree of sensitivity to bortezomib. These bortezomib-sensitive cells exhibited impaired translation attenuation followed by toxic accumulation of protein aggregates and reactive oxygen species (ROS), whereas the bortezomib-resistant cell lines displayed increased phosphorylation of eIF2α, decreased translation, few protein aggregates, and minimal ROS production. Importantly, we identified HRI as the primary bortezomib-activated eIF2α kinase, and demonstrated that HRI knockdown promoted cell death in the bortezomib-resistant cells. Overall, our data implicate inducible HRI-mediated phosphorylation of eIF2α as a central cytoprotective mechanism following exposure to bortezomib and provide proof-of-concept for the development of HRI inhibitors to overcome proteasome inhibitor resistance.

Extrema-weighted feature extraction for functional data.

Motivation: Although there is a rich literature on methods for assessing the impact of functional predictors, the focus has been on approaches for dimension reduction that do not suit certain applications. Examples of standard approaches include functional linear models, functional principal components regression and cluster-based approaches, such as latent trajectory analysis. This article is motivated by applications in which the dynamics in a predictor, across times when the value is relatively extreme, are particularly informative about the response. For example, physicians are interested in relating the dynamics of blood pressure changes during surgery to post-surgery adverse outcomes, and it is thought that the dynamics are more important when blood pressure is significantly elevated or lowered. Results: We propose a novel class of extrema-weighted feature (XWF) extraction models. Key components in defining XWFs include the marginal density of the predictor, a function up-weighting values at extreme quantiles of this marginal, and functionals characterizing local dynamics. Algorithms are proposed for fitting of XWF-based regression and classification models, and are compared with current methods for functional predictors in simulations and a blood pressure during surgery application. XWFs find features of intraoperative blood pressure trajectories that are predictive of postoperative mortality. By their nature, most of these features cannot be found by previous methods. Availability and implementation: The R package 'xwf' is available at the CRAN repository: https://cran.r-project.org/package=xwf. Supplementary information: Supplementary data are available at Bioinformatics online.

Effect of A1C and Glucose on Postoperative Mortality in Noncardiac and Cardiac Surgeries.

OBJECTIVE: Hemoglobin A1c (A1C) is used in assessment of patients for elective surgeries because hyperglycemia increases risk of adverse events. However, the interplay of A1C, glucose, and surgical outcomes remains unclarified, with often only two of these three factors considered simultaneously. We assessed the association of preoperative A1C with perioperative glucose control and their relationship with 30-day mortality. RESEARCH DESIGN AND METHODS: Retrospective analysis on 431,480 surgeries within the Duke University Health System determined the association of preoperative A1C with perioperative glucose (averaged over the first 3 postoperative days) and 30-day mortality among 6,684 noncardiac and 6,393 cardiac surgeries with A1C and glucose measurements. A generalized additive model was used, enabling nonlinear relationships. RESULTS: A1C and glucose were strongly associated. Glucose and mortality were positively associated for noncardiac cases: 1.0% mortality at mean glucose of 100 mg/dL and 1.6% at mean glucose of 200 mg/dL. For cardiac procedures, there was a striking U-shaped relationship between glucose and mortality, ranging from 4.5% at 100 mg/dL to a nadir of 1.5% at 140 mg/dL and rising again to 6.9% at 200 mg/dL. A1C and 30-day mortality were not associated when controlling for glucose in noncardiac or cardiac procedures. CONCLUSIONS: Although A1C is positively associated with perioperative glucose, it is not associated with increased 30-day mortality after controlling for glucose. Perioperative glucose predicts 30-day mortality, linearly in noncardiac and nonlinearly in cardiac procedures. This confirms that perioperative glucose control is related to surgical outcomes but that A1C, reflecting antecedent glycemia, is a less useful predictor.

Unique Practice, Unique Place: Exploring Two Assertive Community Treatment Teams in Maine.

Assertive Community Treatment (ACT) is a model of care that provides comprehensive community-based psychiatric care for persons with serious mental illness. This model has been widely documented and has shown to be an evidence-based model of care for reducing hospitalizations for this targeted population. Critical ingredients of the ACT model are the holistic nature of their services, a team based approach to treatment and nurses who assist with illness management, medication monitoring, and provider collaboration. Although the model remains strong there are clear differences between urban and rural teams. This article describes present day practice in two disparate ACT programs in urban and rural Maine. It offers a new perspective on the evolving and innovative program of services that treat those with serious mental illness along with a review of literature pertinent to the ACT model and future recommendations for nursing practice. The success and longevity of these two ACT programs are testament to the quality of care and commitment of staff that work with seriously mentally ill consumers. Integrative care models such as these community-based treatment teams and nursing driven interventions are prime elements of this successful model.

Temporal Trends in Difficult and Failed Tracheal Intubation in a Regional Community Anesthetic Practice.

BACKGROUND: When tracheal intubation is difficult or unachievable before surgery or during an emergent resuscitation, this is a critical safety event. Consensus algorithms and airway devices have been introduced in hopes of reducing such occurrences. However, evidence of improved safety in clinical practice related to their introduction is lacking. Therefore, we selected a large perioperative database spanning 2002 to 2015 to look for changes in annual rates of difficult and failed tracheal intubation. METHODS: Difficult (more than three attempts) and failed (unsuccessful, requiring awakening or surgical tracheostomy) intubation rates in patients 18 yr and older were compared between the early and late periods (pre- vs. post-January 2009) and by annual rate join-point analysis. Primary findings from a large, urban hospital were compared with combined observations from 15 smaller facilities. RESULTS: Analysis of 421,581 procedures identified fourfold reductions in both event rates between the early and late periods (difficult: 6.6 of 1,000 vs. 1.6 of 1,000, P < 0.0001; failed: 0.2 of 1,000 vs. 0.06 of 1,000, P < 0.0001), with join-point analysis identifying two significant change points (2006, P = 0.02; 2010, P = 0.03) including a pre-2006 stable period, a steep drop between 2006 and 2010, and gradual decline after 2010. Data from 15 affiliated practices (442,428 procedures) demonstrated similar reductions. CONCLUSIONS: In this retrospective assessment spanning 14 yr (2002 to 2015), difficult and failed intubation rates by skilled providers declined significantly at both an urban hospital and a network of smaller affiliated practices. Further investigations are required to validate these findings in other data sets and more clearly identify factors associated with their occurrence as clues to future airway management advancements. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B635.

Autophagy is required for crizotinib-induced apoptosis in MET-amplified gastric cancer cells.

MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner. We then used chemical and molecular approaches to inhibit autophagy in order to define its role in cell death. The clinically available inhibitor of autophagy, chloroquine, or RNAi-mediated knockdown of two obligate components of the autophagy pathway (ATG5 and ATG7) blocked cell death induced by crizotinib or RNAi-mediated knockdown of MET, and mechanistic studies localized the effects of autophagy to cytochrome c release from the mitochondria. Overall, the data reveal a novel relationship between autophagy and apoptosis in gastric cancer cells exposed to MET inhibitors. The observations suggest that autophagy inhibitors should not be used to enhance the effects of MET inhibitors in gastric cancer patients.