Patient and Hospital-Level Characteristics Associated with the Use of Do-Not-Resuscitate Orders in Patients Hospitalized for Sepsis

BACKGROUND: Identifying factors associated with do-not-resuscitate (DNR) orders is an informative step in developing strategies to improve their use. As such, a descriptive analysis of the factors associated with the use of DNR orders in the early and late phases of hospitalizations for sepsis was performed. METHODS: A retrospective cohort of adult patients hospitalized for sepsis was identified using a statewide administrative database. DNR orders placed within 24 h of hospitalization (early DNR) and after 24 h of hospitalization (late DNR) were the primary outcome variables. Multivariable logistic regression analysis was used to identify patient, hospital, and healthcare system-related factors associated with the use of early and late DNR orders. RESULTS: Among 77,329 patients hospitalized for sepsis, 27.5 % had a DNR order during their hospitalization. Among the cases with a DNR order, 75.5 % had the order within 24 h of hospitalization. Smaller hospital size and the absence of a teaching program increased the likelihood of an early DNR order being written. Additionally, greater patient age, female gender, White race, more medical comorbidities, Medicare payer status and admission from a skilled nursing facility were all significantly associated with the likelihood of having an early DNR. The strength of association between these factors and the use of late DNR orders was weaker. In contrast, the greater the burden of medical comorbidities, the more likely a patient was to receive a late DNR order. CONCLUSION: Multiple patient, hospital, and healthcare system-related factors are associated with the use of DNR orders in sepsis, many of which appear to be independent of a patient’s clinical status. Over the course of the hospitalization, the burden of medical illness shows a stronger association relative to other variables. The influence of these multi-level factors needs to be recognized in strategies to improve the use of DNR orders. . ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-014-2906-x) contains supplementary material, which is available to authorized users

Amyloid-β-independent regulators of tau pathology in Alzheimer disease

The global epidemic of Alzheimer disease (AD) is worsening, and no approved treatment can revert or arrest progression of this disease. AD pathology is characterized by the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the brain. Genetic data, as well as autopsy and neuroimaging studies in patients with AD, indicate that Aβ plaque deposition precedes cortical tau pathology. Because Aβ accumulation has been considered the initial insult that drives both the accumulation of tau pathology and tau-mediated neurodegeneration in AD, the development of AD therapeutics has focused mostly on removing Aβ from the brain. However, striking preclinical evidence from AD mouse models and patient-derived human induced pluripotent stem cell models indicates that tau pathology can progress independently of Aβ accumulation and arises downstream of genetic risk factors for AD and aberrant metabolic pathways. This Review outlines novel insights from preclinical research that implicate apolipoprotein E, the endocytic system, cholesterol metabolism and microglial activation as Aβ-independent regulators of tau pathology. These factors are discussed in the context of emerging findings from clinical pathology, functional neuroimaging and other approaches in humans. Finally, we discuss the implications of these new insights for current Aβ-targeted strategies and highlight the emergence of novel therapeutic strategies that target processes upstream of both Aβ and tau