BACKGROUND/OBJECTIVES Although Alzheimer disease and other dementias are life limiting, only a minority of these patients or their proxy decision makers participate in advance care planning. We describe end‐of‐life care preferences and acute care and hospice use in the last 6 months of life for persons enrolled in a comprehensive dementia care management program. DESIGN Observational, retrospective cohort. SETTING Urban, academic medical center. PARTICIPANTS A total of 322 persons enrolled in dementia care management after July 1, 2012, who died before July 1, 2016. INTERVENTION Dementia care comanagement model using nurse practitioners partnered with primary care providers and community organizations to provide comprehensive dementia care, including advance care planning. MEASUREMENTS Advance care preferences, use of Physician Orders for Life Sustaining Treatment (POLST), hospice enrollment, and hospitalizations and emergency department (ED) visits in the last 6 months of life obtained from electronic health record data. RESULTS Nearly all decedents (99.7%, N = 321) had a goals‐of‐care conversation documented (median = 3 conversations; interquartile range = 2‐4 conversations), and 64% had advance care preferences recorded. Among those with recorded preferences, 88% indicated do not resuscitate, 48% limited medical interventions, and 35% chose comfort‐focused care. Most patients (89%) specified limited artificial nutrition, including withholding feeding tubes. Over half (54%) had no hospitalizations or ED visits in the last 6 months of life, and intensive care unit stays were rare (5% of decedents). Overall, 69% died on hospice. Decedents who had completed a POLST were more likely to die in hospice care (74% vs 62%; P = .03) and die at home (70% vs 59%; P = .04). CONCLUSIONS Enrollees in a comprehensive dementia care comanagement program had high engagement in advance care planning, high rates of hospice use, and low acute care utilization near the end of life. Wider implementation of such programs may improve end‐of‐life care for persons with dementia. J Am Geriatr Soc 67:443–448, 2019.
Erythropoietin-producing human hepatocellular carcinoma (Eph) receptor tyrosine kinases (RTKs) regulate a variety of dynamic cellular events, including cell protrusion, migration, proliferation, and cell-fate determination. Small-molecule inhibitors of Eph kinases are valuable tools for dissecting the physiological and pathological roles of Eph. However, there is a lack of small-molecule inhibitors that are selective for individual Eph isoforms due to the high homology within the family. Herein, we report the development of the first potent and specific inhibitors of a single Eph isoform, EphB3. Through structural bioinformatic analysis, we identified a cysteine in the hinge region of the EphB3 kinase domain, a feature that is not shared with any other human kinases. We synthesized and characterized a series of electrophilic quinazolines to target this unique, reactive feature in EphB3. Some of the electrophilic quinazolines selectively and potently inhibited EphB3 both in vitro and in cells. Cocrystal structures of EphB3 in complex with two quinazolines confirmed the covalent linkage between the protein and the inhibitors. A "clickable" version of an optimized inhibitor was created and employed to verify specific target engagement in the whole proteome and to probe the extent and kinetics of target engagement of existing EphB3 inhibitors. Furthermore, we demonstrate that the autophosphorylation of EphB3 within the juxtamembrane region occurs in trans using a specific inhibitor. These exquisitely specific inhibitors will facilitate the dissection of EphB3's role in various biological processes and disease contribution.
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