Moral Distress at the End of a Life: When Family and Clinicians Do Not Agree on Implantable Cardioverter-Defibrillator Deactivation

A 63-year-old man with end-stage ischemic cardiomyopathy presented with incessant ventricular tachycardia. He had been hospitalized multiple times in the past year for severe heart failure. As he approached end of life and was regularly receiving defibrillator shocks, his care team recommended deactivation of his implantable cardioverter-defibrillator. However, his family did not wish to allow deactivation, reporting a religious obligation to prolong his life, regardless of the risk of suffering. The patient was unable to adequately participate in the decision-making process. An implantable cardioverter-defibrillator can serve to avoid sudden death but may lead to a prolonged death from heart failure. This possibility forces the examination of values regarding prolongation of life, sometimes producing disagreement among stakeholders. Although ethical consensus holds that defibrillator deactivation is legal and ethical, disagreements about life prolongation may complicate decision making. The ethical, technical, and medical complexity involved in this case speaks to the need for clear, prospective communication involving the patient, the patient's family, and members of the care team.     

How Can Health Literacy Influence Outcomes in Heart Failure Patients? Mechanisms and Interventions

Health literacy is discussed in papers from 25 countries where findings suggest that approximately a third up to one half of the people in developed countries have low health literacy. Specifically, health literacy is the mechanism by which individuals obtain and use health information to make health decisions about individual treatments in the home, access care in the community, promote provider–patient interactions, structure self-care, and navigate health care programs both locally and nationally. Further, health literacy is a key determinant of health and a critical dimension for assessing individuals’ needs, and, importantly, their capacity for self-care. Poorer health knowledge/status, more medication errors, costs, and higher rates of morbidity, readmissions, emergency room visits, and mortality among patients with health illiteracy have been demonstrated. Individuals at high risk for low health literacy include the elderly, disabled, Blacks, those with a poverty-level income, some or less high school education, either no insurance or Medicare or Medicaid, and those for whom English is a second language. As a consequence, health literacy is a complex, multifaceted, and evolving construct including aspects of social, psychological, cultural and economic circumstances. The purpose of this paper is to describe the mechanisms and consequences of health illiteracy. Specifically, the prevalence, associated demographics, and models of health literacy are described. The mechanism of health illiteracy’s influence on outcomes in heart failure is proposed. Tools for health literacy assessment are described and compared. Finally, the health outcomes and general interventions to enhance the health outcomes in heart failure are discussed.     

Patterns of Use of Induction Therapy for T2N0 Esophageal Cancer

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Vitamin D Level and Risk of Community-Acquired Pneumonia and Sepsis

Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels is associated with acute infectious illness. The relationship between vitamin D status, measured prior to acute infectious illness, with risk of community-acquired pneumonia (CAP) and sepsis has not been examined. Community-living individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season-matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to hospitalization. Regression models adjusted for diabetes, renal disease, and peripheral vascular disease evaluated the association of 25(OH)D levels with CAP or sepsis risk. A total of 132 CAP patients and controls were 60 ± 17 years, 71% female, and 86% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted odds ratio (OR) 2.57, 95% CI 1.08–6.08) were strongly associated with increased odds of CAP hospitalization. A total of 422 sepsis patients and controls were 65 ± 14 years, 59% female, and 91% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted OR 1.75, 95% CI 1.11–2.77) were associated with increased odds of sepsis hospitalization. Vitamin D status was inversely associated with risk of CAP and sepsis hospitalization in a community-living adult population. Further clinical trials are needed to evaluate whether vitamin D supplementation can reduce risk of infections, including CAP and sepsis.     

Parent–child mathematical interactions: examining self-report and direct observation

Variability in children’s early-learning home environments points to the need to better understand specific mechanisms of early mathematical development. We used a sample of 66 parent–preschool child dyads to describe parent-reported mathematical activities in the home and observed parent–child mathematical activities in a semi-structured play session. Data were examined to better understand the two methods of assessing the context of parent–child interactions related to mathematics. Parents reported engaging in a range of mathematical activities about 3–5 times per week, on average. Results from observed interactions indicated that parents engaged in math content/concept interactions in 32.5% of all observed intervals and children engaged in math content/concept interactions in 24.2% of all observed intervals. Although observed parent and child math content interactions were highly correlated, observed parent and child mathematical interactions were not correlated with parent-reported math activities.     

Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition

Background: Inhibition of acetylcholinesterase (AChE), a biomarker of organophosphorous and carbamate exposure in environmental and occupational human health, has been commonly used to identify potential safety liabilities. So far, many environmental chemicals, including drug candidates, food additives, and industrial chemicals, have not been thoroughly evaluated for their inhibitory effects on AChE activity. AChE inhibitors can have therapeutic applications (e.g., tacrine and donepezil) or neurotoxic consequences (e.g., insecticides and nerve agents).Objectives: The objective of the current study was to identify environmental chemicals that inhibit AChE activity using in vitro and in silico models.Methods: To identify AChE inhibitors rapidly and efficiently, we have screened the Toxicology in the 21st Century (Tox21) 10K compound library in a quantitative high-throughput screening (qHTS) platform by using the homogenous cell-based AChE inhibition assay and enzyme-based AChE inhibition assays (with or without microsomes). AChE inhibitors identified from the primary screening were further tested in monolayer or spheroid formed by SH-SY5Y and neural stem cell models. The inhibition and binding modes of these identified compounds were studied with time-dependent enzyme-based AChE inhibition assay and molecular docking, respectively.Results: A group of known AChE inhibitors, such as donepezil, ambenonium dichloride, and tacrine hydrochloride, as well as many previously unreported AChE inhibitors, such as chelerythrine chloride and cilostazol, were identified in this study. Many of these compounds, such as pyrazophos, phosalone, and triazophos, needed metabolic activation. This study identified both reversible (e.g., donepezil and tacrine) and irreversible inhibitors (e.g., chlorpyrifos and bromophos-ethyl). Molecular docking analyses were performed to explain the relative inhibitory potency of selected compounds.Conclusions: Our tiered qHTS approach allowed us to generate a robust and reliable data set to evaluate large sets of environmental compounds for their AChE inhibitory activity. https://doi.org/10.1289/EHP6993