ABSTRACT
OBJECTIVES: To describe the rate, timing, and pattern of changes in advance directives (ADs) of do not resuscitate (DNR) and do not hospitalize (DNH) orders among new admissions to nursing homes (NHs). DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: Admissions to all publicly funded NHs in Ontario, Canada, between January 1, 2013, and December 31, 2017. METHODS: Residents were followed until discharged from incident NH stay, death, or were still present at the end of study (December 31, 2019). They were categorized into 3 mutually exclusive baseline composite AD groups: Full Code, DNR Only, and DNR+DNH. We used Poisson regression models to estimate the incidence rate ratios of AD change between different AD groups and different decision makers for personal care, adjusted for baseline clinical and sociodemographic variables. RESULTS: A total of 102,541 NH residents were eligible for inclusion. Residents with at least 1 AD change accounted for 46% of Full Code, 30% of DNR Only, and 25% of DNR+DNH group. Median time to first AD change ranged between 26 and 55 weeks. For Full Code and DNR Only residents, the most frequent change was to an AD 1 level lower in aggressiveness or intervention, whereas for DNR+DNH residents the most frequent change was to DNR Only. About 16% of residents had 2 or more AD changes during their stay. After controlling for covariates, residents with a DNR-only order or DNR+DNH orders at admission and those with a surrogate decision maker were associated with lower AD change rates. CONCLUSIONS AND IMPLICATIONS: Measuring AD adherence rates that are documented only at a particular time often underestimates the dynamics of AD changes during a resident's stay and results in an inaccurate measure of the effectiveness of AD on resident care. There should be more frequent reviews of ADs as they are quite dynamic. Mandatory review after an acute change in a resident's health would ensure that ADs are current.
ABSTRACT
Inappropriate cardiac remodeling and repair after myocardial infarction (MI) predisposes to heart failure. Studies have reported on the potential for lineage negative, steel factor positive (c-kit+) bone marrow-derived hematopoetic stem/progenitor cells (HSPCs) to repair damaged myocardium through neovascularization and myogenesis. However, the precise contribution of the c-kit signaling pathway to the cardiac repair process has yet to be determined. In this study, we sought to directly elucidate the mechanistic contributions of c-kit+ bone marrow-derived hematopoetic stem/progenitor cells in the maintenance and repair of damaged myocardium after MI. Using c-kit-deficient mice, we demonstrate the importance of c-kit signaling in preventing ventricular dilation and hypertrophy, and the maintenance of cardiac function after MI in c-kit-deficient mice. Furthermore, we show phenotypic rescue of cardiac repair after MI of c-kit-deficient mice by bone marrow transplantation of wild-type HSPCs. The transplanted group also had reduced apoptosis and collagen deposition, along with an increase in neovascularization. To better understand the mechanisms underlying this phenotypic rescue, we investigated the gene expression pattern within the infarcted region by using microarray analysis. This analysis suggested activation of inflammatory pathways, specifically natural killer (NK) cell-mediated mobilization after MI in rescued hearts. This finding was confirmed by immunohistology and by using an NK blocker. Thus, our investigation revealed a previously uncharacterized role for c-kit signaling after infarction by mediating bone marrow-derived NK and angiogenic cell mobilization, which contributes to improved remodeling and cardiac function after MI.
