Medical Students' Diagnostic Accuracy and Treatment Plans.

Physician-mentored patient rounds (PMPR) were used to assess diagnostic accuracy and treatment plans of preclinical medical students. During 4 PMPR sessions, students gathered patient history, observed a physical exam, analyzed diagnostic tests, and developed treatment plans for a patient with chronic obstructive pulmonary disease. Of 470 students, 99.4% correctly diagnosed the patient. Nearly 78% prescribed long-acting beta-agonists or long-acting muscarinic antagonists. Most included appropriate pharmacologic treatments. Only 47% included smoking cessation in their treatment.

Status of Entrustable Professional Activities (EPA) Implementation at Colleges of Osteopathic Medicine in the United States and Future Considerations.

CONTEXT: Competency-based medical education, developmental milestones for residency training, and the single graduate medical education (GME) accreditation system have emerged over the last decade, necessitating new ways to adequately prepare graduates to meet new standards in proficiency, including the 13 Core Entrustable Professional Activities (EPA) for Entering Residency. The American Association of Colleges of Osteopathic Medicine (AACOM) Entrustable Professional Activities (EPA) steering committee has implemented an information-gathering process to provide suggestions for supporting a variety of EPA-related implementation efforts at colleges of osteopathic medicine (COMs) across the country. OBJECTIVE: To review the status of EPA implementation at COMs nationally. METHODS: An explanatory mixed-methods design was used to guide information gathering and synthesis of a 41-question survey and interview feedback; the overarching premise of this design was to use qualitative data to build upon initial quantitative findings. This survey was delivered electronically through a link emailed to liaisons at each main, branch, and satellite campus of the 47 schools within the AACOM institutional database. After survey administration, follow-up structured interviews were conducted according to an 18-question script with a purposive sample of 16 institutions with EPA implementation levels ranging from "moderate implementation with reporting" to "full implementation with reporting." Post-interview, the interview notes were analyzed and results were aggregated for comparison with the original survey findings. RESULTS: Of the 47 schools surveyed, 42 responded (89.4%). To maintain uniformity in data coding and analysis, 36 of 47 (76.6%) of COMs with independently submitted survey responses were retained in the review. The majority of those respondents (23 of 36; 64%) indicated that their institution was above "somewhat knowledgeable" toward "expert" regarding knowledge of EPAs, but 23 (64%) also indicated "no confidence" or "somewhat confident" regarding EPA implementation. Postinterview results showed that the majority of schools were equally distributed across the "foundational implementation" (10; 28%), "slight implementation" (11; 31%), and "moderate implementation" (11, 31%) categories, with a few schools indicating "no implementation" (2; 5%) or "progressive implementation" (2; 5%). CONCLUSION: The results of this review indicate that most osteopathic medical schools are at the early stages of EPA implementation, with emphasis varying by program year in terms of the specific EPAs addressed. Many schools appear engaged in curricular change efforts that will support the advancement of EPA use within their institutions. Faculty development was identified as a continued critical need for a majority of institutions.

Physician-Mentored Patient Rounds to Observe and Assess Entrustable Professional Activities 1 and 2 in Preclinical Medical Students.

CONTEXT: Thirteen entrustable professional activities (EPAs) for entering residency were created to aid medical educators as they prepare preclinical students for their residency and to assess student readiness for residency. The A.T. Still University Kirksville College of Osteopathic Medicine (ATSU-KCOM) developed a program called physician-mentored patient rounds (PMPR), which focuses on EPA 1 and EPA 2. OBJECTIVE: To determine whether PMPRs could be used to assess expected behaviors of EPA 1 (gather a history and perform a physical examination) and EPA 2 (prioritize a differential diagnosis after a clinical encounter). METHODS: The PMPR sessions at ATSU-KCOM take place over several weeks (30-minute sessions per week), during which students gather a patient's history (sessions 1 and 2), observe a physical examination by the physician mentor (session 2), analyze diagnostic test results (session 3), and formulate a treatment plan (session 4). The PMPRs in this study used a real patient with confirmed chronic obstructive pulmonary disease (COPD). This study did not include the session-4 treatment plan. Between sessions, students completed an assignment to further demonstrate their behaviors as expected in the EPAs. Student responses were analyzed and summarized for physician feedback in the subsequent PMPR session. Students' diagnostic accuracy was measured at the conclusion of each session. RESULTS: A total of 516 students were included in the study. The PMPR weekly attendance was high (453-475). Although history gathering in the large-group setting was disorderly, diagnostic accuracy over the 3-session period improved. After history taking, 411 students (86.5%) included COPD in the differential diagnosis. A smaller number, 235 students (49.5%), listed COPD as the most likely diagnosis. After the physical examination, 439 included COPD in the differential diagnosis, and 385 listed COPD as the most likely diagnosis. After analysis of diagnostic test results, 468 students listed COPD as the most likely diagnosis. CONCLUSION: Physician-mentored patient rounds seem to be an effective means to assess preclinical students' expected behaviors as described in EPA 1 and EPA 2.

Entrustable Professional Activities for Entering Residency: Establishing Common Osteopathic Performance Standards in the Transition From Medical School to Residency.

Entrustable professional activities (EPAs) are measurable units of observable professional practice that can be entrusted to an unsupervised trainee. They were first introduced as a method of operationalizing competency-based medical education in graduate medical education. The American Association of Medical Colleges subsequently used EPAs to establish the core skills that medical students must be able to perform before they enter residency training. A recently published guide provides descriptions, guidelines, and rationale for implementing and assessing the core EPAs from an osteopathic approach. These osteopathically informed EPAs can allow schools to more appropriately assess a learner's whole-person approach to a patient, in alignment with the philosophy of the profession. As the single accreditation system for graduate medical education moves forward, it will be critical to integrate EPAs into osteopathic medical education to demonstrate entrustment of medical school graduates. The authors describe the collaborative process used to establish the osteopathic considerations added to EPAs and explores the challenges and opportunities for undergraduate osteopathic medical education.

Comparison of effects of U18666A and enantiomeric U18666A on sterol synthesis and induction of apoptosis.

Treatment of animals or cells with the amphipathic tertiary amine U18666A {3beta-[2-(diethylamino) ethoxy]androst-5-en-17-one} provides models for several human diseases (e.g., cataracts, Niemann-Pick disease, and epilepsy). Although U18666A can inhibit several enzymes in the cholesterol synthesis pathway, we hypothesized that induction of these varied conditions was due to physical effects of the amine rather than to inhibition of specific proteins. To test this possibility we compared the capacity of U18666A and its enantiomer, ent-U18666A, to inhibit net sterol synthesis and induce apoptosis in cultured bovine lens epithelial cells. Nonenantiospecific actions dependent on the physical properties of these mirror image molecules would be identical, but effects dependent upon enantiospecific interactions would be different for the enantiomers. At the same concentrations, both forms of the compound equally inhibited sterol synthesis and induced apoptosis. These observations supported a generalized mechanism of enzyme inhibition such as perturbation of the microenvironment of endoplasmic enzymes and alteration of membrane order, perhaps of the mitochondrial membrane, to explain induction of apoptosis.

Status of caveolin-1 in various membrane domains of the bovine lens.

Recent studies of the distribution and relative concentration of caveolin-1 in fractions of bovine lens epithelial and fiber cells have led to the novel concept that caveolin-1 may largely exist as a peripheral membrane protein in some cells. Caveolin-1 is typically viewed as a scaffolding protein for caveolae in plasma membrane. In this study, membrane from cultured bovine lens epithelial cells and bovine lens fiber cells were divided into urea soluble and insoluble fractions. Cytosolic lipid vesicles were also recovered from the lens epithelial cells. Lipid-raft domains were recovered from fiber cells following treatment with detergents and examined for caveolin and lipid content. Aliquots of all fractions were Western blotted for caveolin-1. Fluorescence microscopy and double immunofluorescence labeling were used to examine the distribution of caveolin-1 in cultured epithelial cells. Electron micrographs revealed an abundance of caveolae in plasma membrane of cultured lens epithelial cells. About 60% of the caveolin-1 in the epithelial-crude membrane was soluble in urea, a characteristic of peripheral membrane proteins. About 30% of the total was urea-insoluble membrane protein that likely supports the structure of caveolae. The remaining caveolin was part of cytosolic lipid vesicles. By contrast, most caveolin in the bovine lens fiber cell membrane was identified as intrinsic protein, being present at relatively low concentrations in caveolae-free lipid raft domains enriched in cholesterol and sphingomyelin. We estimate that these domains occupied 25-30% of the fiber cell membrane surface. Thus, the status of caveolin-1 in lens epithelial cells appears markedly different from that in fiber cells.

Immunomagnetic capture of lens membrane fractions containing steroid binding protein.

This study describes the use of magnetic Dynabeads to purify microsomes from a crude microsomal fraction. A 28 kDa membrane-associated protein is proposed to mediate the binding of progesterone and other steroid hormones to ocular lens membranes and the rapid-nongenomic actions of these steroids. The subcellular location of this membrane steroid binding protein (MSBP) was probed by capture of organelles containing MSBP by magnetic beads displaying an antibody to a cytoplasmic domain of the protein. The beads were exposed to a crude microsomal fraction from lens epithelia. Western blotting was used to identify captured organelles and confirm the presence of MSBP. Microsomes and trace fiber cell plasma membrane were captured. Microsomes contained the 28 kDa MSBP. Lens fiber cell membrane contained a 55 kDa immunoreactive protein. The role of this serendipitously recognized protein in binding of steroids is unknown.

Distribution of caveolin-1 in bovine lens and redistribution in cultured bovine lens epithelial cells upon confluence.

The distribution of caveolin-1 in the lens and lens epithelial cells was determined to assess possible roles in cholesterol trafficking, cell to cell communication and signal transduction. Bovine lenses and cultured bovine lens epithelial cells (BLEC) were divided into subcellular fractions and the distribution of proteins recognized by three different caveolin-1 antibodies determined. The immunolocalization of caveolin-1 in the lens epithelium and in subconfluent and confluent cultured BLEC was probed by fluorescence microscopy and laser scanning confocal microscopy. EGF induced phosphorylation of caveolin-1 was detected by Western blotting with an anti-phosphotyrosine antibody to immunoprecipitated caveolin-1 from BLEC and human cancer cells. Monomeric caveolin-1 of about 26 kDa was detected in the epithelial cell membrane of cultured BLEC and fresh epithelia and in the plasma membrane fraction of lens cortical fiber cells. Caveolin-1 of cultured BLEC redistributed from the cytoplasm to plasma membrane as the cells proceeded from subconfluent to confluent states. The apparent abundance of caveolin-1 in cortical fiber cell plasma membrane is consistent with possible roles in distribution of lens membrane cholesterol and membrane structure. The presence of caveolin-1 in the plasma membrane of epithelial cells at - but not before - confluency is consistent with a role of caveolin-1 in cell to cell communications. EGF stimulated phosphorylation of caveolin-1 in human A431 cells but not lens cells.

Discordant expression of the sterol pathway in lens underlies simvastatin-induced cataracts in Chbb: Thom rats.

Simvastatin rapidly induced cataracts in young Chbb:Thom (CT) but not Sprague Dawley (SD) or Hilltop Wistar (HW) rats. Oral treatment for 14 but not 7 days committed CT rat lenses to cataract formation. The cholesterol to phospholipid molar ratio in lenses of treated CT rats was unchanged. Differences between strains in serum and ocular humor levels of simvastatin acid poorly correlated with susceptibility to cataracts. No significant differences were found between rat strains in the capacity of simvastatin acid to inhibit lens-basal sterol synthesis. Prolonged treatment with simvastatin comparably elevated HMG-CoA reductase protein and enzyme activity in lenses of both cataract resistant and sensitive strains. However, in contrast to SD and HW rats, where sterol synthesis was markedly increased, sterol synthesis in CT rat lenses remained at baseline. Discordant expression of sterol synthesis in CT rats may be due to inadequate upregulation of lens HMG-CoA synthase. HMG-CoA synthase protein levels, and to a much lesser extent mRNA levels, increased in lens cortex of SD but not CT rats. Because upregulation of the sterol pathway may result in increased formation of isoprene-derived anti-inflammatory substances, failure to upregulate the pathway in CT rat lenses may reflect an attenuated compensatory response to injury that resulted in cataracts.