Outpatient Advance Care Planning Internal Medicine Resident Curriculum: Valuing Our Patients' Wishes.

BACKGROUND: Although many studies have illustrated the discomfort that resident physicians feel when discussing end-of-life (EOL) issues with their patients, fewer studies have addressed interventions to directly increase medical resident proficiency and comfort in conducting these discussions and for translating these beliefs into a formal advance care plan. OBJECTIVES: We report on an innovative curriculum conducted at The University of Chicago (NorthShore) internal medicine residency to improve residents' proficiency and comfort in leading outpatient advance care planning (ACP) discussions. METHODS: Four educational components were executed. First, residents completed an on-line module introducing ACP and guiding residents to complete their own ACP. Second, residents attended a didactic "How To" lecture given by physicians with expertise in ACP that emphasized ACP communication tools and a video demonstration. Third, residents completed a video-recorded simulation-based ACP discussion with a standardized patient. Finally, residents conducted an ACP outpatient encounter with one of their continuity clinic patients. Expert preceptors directly observed, evaluated, and provided feedback to residents during both patient encounters. Residents were surveyed before and immediately after the curriculum using a nine-variable questionnaire, which assessed the resident's training and comfort with ACP. RESULTS: Sixteen second year residents completed the curriculum and surveys. Precurriculum and post-curriculum mean change on a Likert scale of 1 (uncomfortable) to 5 (very comfortable) was compared using paired t-tests. Results demonstrated statistically significant improvements in the following comfort level variables: eliciting understanding of health and prognosis (pre 3.63 vs. post 4.38, p = 0.035), discussing EOL care based on patient values (pre 3.50 vs. post 4.38, p = 0.008), specifically discussing EOL care based on patient values in the outpatient setting (pre 2.75 vs. post 4.31, p = 0.001) and initiating an advance directive and medical power of attorney (pre 2.56 vs. post 4.19, p < 0.001). CONCLUSION: A multimodality curriculum including self-directed learning, lectures, and practice with simulated and actual outpatients with active reflection and feedback is effective in improving resident comfort level and formal training in ACP. Further research is needed to understand whether these interventions will translate into an increased frequency of discussions with patients about ACP after residency training.

Endoplasmic reticulum stress or mutation of an EF-hand Ca(2+)-binding domain directs the FKBP65 rotamase to an ERAD-based proteolysis.

FKBP65 is an endoplasmic reticulum (ER)-localized chaperone and rotamase, with cargo proteins that include tropoelastin and collagen. In humans, mutations in FKBP65 have recently been shown to cause a form of osteogenesis imperfecta (OI), a brittle bone disease resulting from deficient secretion of mature type I collagen. In this work, we describe the rapid proteolysis of FKBP65 in response to ER stress signals that activate the release of ER Ca(2+) stores. A large-scale screen for stress-induced cellular changes revealed FKBP65 proteins to decrease within 6-12 h of stress activation. Inhibiting IP(3)R-mediated ER Ca(2+) release blocked this response. No other ER-localized chaperone and folding mediators assessed in the study displayed this phenomenon, indicating that this rapid proteolysis of folding mediator is distinctive. Imaging and cellular fractionation confirmed the localization of FKBP65 (72 kDa glycoprotein) to the ER of untreated cells, a rapid decrease in protein levels following ER stress, and the corresponding appearance of a 30-kDa fragment in the cytosol. Inhibition of the proteasome during ER stress revealed an accumulation of FKBP65 in the cytosol, consistent with retrotranslocation and a proteasome-based proteolysis. To assess the role of Ca(2+)-binding EF-hand domains in FKBP65 stability, a recombinant FKBP65-GFP construct was engineered to ablate Ca(2+) binding at each of two EF-hand domains. Cells transfected with the wild-type construct displayed ER localization of the FKBP65-GFP protein and a proteasome-dependent proteolysis in response to ER stress. Recombinant FKBP65-GFP carrying a defect in the EF1 Ca(2+)-binding domain displayed diminished protein in the ER when compared to wild-type FKBP65-GFP. Proteasome inhibition restored mutant protein to levels similar to that of the wild-type FKBP65-GFP. A similar mutation in EF2 did not confer FKBP65 proteolysis. This work supports a model in which stress-induced changes in ER Ca(2+) stores induce the rapid proteolysis of FKBP65, a chaperone and folding mediator of collagen and tropoelastin. The destruction of this protein may identify a cellular strategy for replacement of protein folding machinery following ER stress. The implications for stress-induced changes in the handling of aggregate-prone proteins in the ER-Golgi secretory pathway are discussed. This work was supported by grants from the National Institutes of Health (R15GM065139) and the National Science Foundation (DBI-0452587).