Inequities in the care of older adults: Identifying education gaps in geriatric medicine fellowship.

The past year amplified inequities in the care of older adults. Milestones focused on social determinants of health (SDOH) are lacking within Geriatric fellowship training. A virtual learning collaborative GERIAtrics Fellows Learning Online And Together (GERI-A-FLOAT) was developed to connect trainees nationwide. To address gaps in education around SDOH, a needs assessment was conducted to inform a curricular thread. A voluntary, anonymous survey was distributed to fellows through a broad network. We sought to understand prior curricula trainees had that were specifically focused on SDOH and older adults. Respondents prioritized topic areas for the curriculum. Seventy-five respondents completed the survey. More than 50% of participants indicated no training on homelessness, immigration, racism, or LGBTQ+ health at any level of medical training, with more than 70% having no training in sexism or care of formerly incarcerated older adults. The most commonly taught concepts were ableism, ageism, and poverty. Respondents prioritized the topic of racism, ageism, and ableism. There is a lack of consistent SDOH curricula pertaining to older adults across all levels of training. This needs assessment is guiding a curricular thread for GERI-A-FLOAT and ideally larger milestones for fellowships. The time is now to prepare future geriatricians to serve as change agents.

An Interactive Workshop on Managing Dysphagia in Older Adults With Dementia.

Introduction: Nearly six million American adults live with dementia, and dysphagia is a common comorbidity impacting their nutrition and quality of life. There is a shortfall in the number of geriatricians available to care for older adults. Thus, primary care physicians should be equipped with the knowledge to adequately care for the geriatric population. Modified diets are routinely prescribed for patients with dementia despite limited evidence that they protect patients from the sequelae of dysphagia and some suggestion of poor side-effect profiles. Methods: We created a onetime, interactive, case-based session to educate medical residents on how to evaluate and treat dementia-associated dysphagia and address the discrepancy between the limited evidence for dietary modifications and their routine use. The session had a mixture of small-group discussion and didactic learning as well as a participatory component during which learners were able to sample thickened liquids. Results: The session was implemented in an established primary care curriculum. Based on survey responses, which were obtained from 15 out of 17 participants, the session significantly improved participants' knowledge of dysphagia-associated dementia and increased their comfort with caring for patients with dysphagia. Discussion: Dementia-associated dysphagia, although an increasingly common clinical problem, remains an underexamined area of medicine. We successfully implemented a session on this topic for internal medicine residents on the primary care track. Limitations included generalizability due to the small number of residents in the course and inability to gather sufficient data to see if knowledge learned was sustained over time.

Coverage and Access for Americans With Chronic Disease Under the Affordable Care Act: A Quasi-Experimental Study.

BACKGROUND: Half of Americans have at least 1 chronic disease. Many in this group, particularly racial/ethnic minorities, lacked insurance coverage and access to care before the Patient Protection and Affordable Care Act (ACA) was enacted. OBJECTIVE: To determine whether the ACA has had an effect on insurance coverage, access to care, and racial/ethnic disparities among adults with chronic disease. DESIGN: Quasi-experimental policy intervention. SETTING: Nationally representative, noninstitutionalized sample in the United States. PATIENTS: 606 277 adults aged 18 to 64 years with a chronic disease. INTERVENTION: Implementation of ACA provisions on 1 January 2014. MEASUREMENTS: Self-reported insurance coverage, having a checkup, having a personal physician, and not having to forgo a needed physician visit because of cost. RESULTS: After the ACA was implemented, insurance coverage increased by 4.9 percentage points (95% CI, 4.4 to 5.4), not having to forgo a physician visit increased by 2.4 percentage points (CI, 1.9 to 2.9), and having a checkup increased by 2.7 percentage points (CI, 2.2 to 3.4). Having a personal physician did not change (0.3 percentage points [CI, -0.2 to 0.8]). All outcomes varied considerably by state, and coverage increased more in states that expanded Medicaid. Although racial/ethnic minorities had greater improvements in some outcomes, approximately 1 in 5 black and 1 in 3 Hispanic persons with a chronic disease continued to lack coverage and access to care after ACA implementation. LIMITATION: The study examined data from only the first year of the ACA's major coverage expansion provisions. CONCLUSION: Although the ACA increased coverage and access for persons with chronic disease, substantial gaps remain, particularly for minorities and those in Medicaid nonexpansion states. PRIMARY FUNDING SOURCE: None.

Determining serpin conformational distributions with single molecule fluorescence.

Conformational plasticity is key to inhibitory serpin function, and this plasticity gives serpins relatively easy access to alternative, dysfunctional conformations. Thus, a given serpin population may contain both functional and dysfunctional proteins. Single molecule fluorescence (SMF), with its ability to interrogate one fluorescently labeled protein at a time, is a powerful method for elucidating conformational distributions and monitoring how these distributions change over time. SMF and related methods have been particularly valuable for characterizing serpin polymerization. Fluorescence correlation spectroscopy experiments have revealed a second lag phase during in vitro α(1)-antitrypsin polymerization associated with the formation of smaller oligomers that then condense to form longer polymers [Purkayastha, P., Klemke, J. W., Lavender, S., Oyola, R., Cooperman, B. S., and Gai, F. (2005). Alpha 1-antitrypsin polymerization: A fluorescence correlation spectroscopic study. Biochemistry44, 2642-2649.]. SMF studies of in vitro neuroserpin polymerization have confirmed that a monomeric intermediate is required for polymer formation while providing a test of proposed polymerization mechanisms [Chiou, A., Hägglöf, P., Orte, A., Chen, A. Y., Dunne, P. D., Belorgey, D., Karlsson-Li, S., Lomas, D., and Klenerman, D. (2009). Probing neuroserpin polymerization and interaction with amyloid-beta peptides using single molecule fluorescence. Biophys. J.97, 2306-2315.]. SMF has also been used to monitor protease-serpin interactions. Single pair Förster resonance energy transfer studies of covalent protease-serpin complexes suggest that the extent of protease structural disruption in the complex is protease dependent [Liu, L., Mushero, N., Hedstrom, L., and Gershenson, A. (2006). Conformational distributions of protease-serpin complexes: A partially translocated complex. Biochemistry45, 10865-10872.]. SMF techniques are still evolving and the combination of SMF with encapsulation methods has the potential to provide more detailed information on the conformational changes associated with serpin polymerization, protease-serpin complex formation, and serpin folding.

Short-lived protease serpin complexes: partial disruption of the rat trypsin active site.

Serpins inhibit serine proteases by mechanically disrupting the protease active site. The protease first reacts with the serpin's reactive center loop (RCL) to form an acylenzyme. Then the RCL inserts into a beta-sheet in the body of the serpin, translocating the attached protease approximately 70 A and deforming the protease active site, thereby trapping the acylenzyme. Loop insertion (approximately 1 s(-1)) is an order of magnitude slower than hydrolysis of a typical substrate acylenzyme (approximately 50 s(-1)), indicating that the protease is inhibited during translocation. We have previously trapped a partially translocated covalent complex of rat trypsin and alpha1-proteinase inhibitor (EpartI*) resulting from attractive interactions between cationic dyes and anionic rat trypsin. Here, using single pair Förster resonance energy transfer, we demonstrate that EpartI* is a metastable complex that can dissociate to free protease and cleaved serpin (I*) as well as convert to the canonical fully translocated complex EfullI*. The partitioning between these two pathways is pH dependent, with conversion favored at low pH and dissociation favored at high pH. The short lifetime of EpartI* (approximately 3 h at pH 7.4) and the pH dependence of EpartI* dissociation suggest that, unlike in EfullI*, the catalytic triad is intact in EpartI*. These results also demonstrate that interactions between target proteases and the body of the serpin can hinder protease translocation leading to short-lived covalent complexes.

Conformational distributions of protease-serpin complexes: a partially translocated complex.

Serpins regulate serine proteases by forming metastable covalent complexes with their targets. The protease docks with the serpin and cleaves the serpin's reactive center loop (RCL) forming an acylenzyme intermediate. Cleavage triggers insertion of the RCL into beta sheet A, translocating the attached protease approximately 70 A and disrupting the protease active site, trapping the acylenzyme intermediate. Using single-pair Förster resonance energy transfer (spFRET), we have measured the conformational distributions of trypsin and alpha(1)-proteinase inhibitor (alpha(1)PI) covalent complexes. Bovine trypsin (BTryp) complexes display a single set of conformations consistent with the full translocation of BTryp (E(full)I*). However, the range of spFRET efficiencies is large, suggesting that the region around the trypsin label is mobile. Most complexes between alpha(1)PI variants and the more stable rat trypsin (RTryp) also show a single set of conformations, but the conformational distribution is narrower, indicating less disruption of RTryp. Surprisingly, RTryp complexes containing alpha(1)PI labeled at Cys232 with a cationic fluorophore display two equally populated conformations, E(full)I* and a conformation in which RTryp is only partially translocated (E(part)I*). Destabilizing the RTryp active site, by substituting Ala for Ile16, increases the E(full)I* population. Thus, interactions between anionic RTryp and cationic dyes likely exert a restraining force on alpha(1)PI, increasing the energy needed to translocate trypsin, and this force can be counteracted by active site destabilization. These results highlight the role of protease stability in determining the conformational distributions of protease-serpin covalent complexes and show that full translocation is not required for the formation of metastable complexes.