Evaluating rescuer performance in response to opioid overdose in a community setting: Evidence for medically appropriate process measures.

Overdose education and naloxone distribution (OEND) programs are widely accepted to reduce opioid overdose deaths. However, there is currently no validated instrument to evaluate the skills of learners completing these programs. Such an instrument could provide feedback to OEND instructors and allow researchers to compare different educational curricula. The aim of this study was to identify medically appropriate process measures with which to populate a simulation-based evaluation tool. Researchers conducted interviews with 17 content experts, including healthcare providers and OEND instructors from south-central Appalachia, to collect detailed descriptions of the skills taught in OEND programs. Researchers used three cycles of open coding, thematic analysis, and consulted currently available medical guidelines to identify thematic occurrences in qualitative data. There was consensus among content experts that the appropriate nature and sequence of potentially lifesaving actions during an opioid overdose is dependent on clinical presentation. Isolated respiratory depression requires a distinct response compared to opioid-associated cardiac arrest. To accommodate these different clinical presentations, raters populated an evaluation instrument with the detailed descriptions of overdose response skills, such as naloxone administration, rescue breathing, and chest compressions. Detailed descriptions of skills are essential to the development of an accurate and reliable scoring instrument. Furthermore, evaluation instruments, such as the one developed from this study, require a comprehensive validity argument. In future work, the authors will integrate the evaluation instrument in high-fidelity simulations, which are safe and controlled environments to study trainees' application of hands-on skills, and conduct formative assessments.

Designing healthcare for human use: Human factors and practical considerations for the translational process.

In recent years, the focus of implementation science (IS) shifted to emphasize the influence of contextual factors on intervention adaptations in clinical, community, and corporate settings. Each of these settings represent a unique work system with varying contexts that influence human capabilities, needs, and performance (otherwise known as "human factors"). The ease of human interaction with a work system or an intervention is imperative to IS outcomes, particularly adoption, implementation, and maintenance. Both scientific approaches consider the "big picture" when designing interventions for users and stakeholders to improve work and health outcomes. IS and human factors are therefore complementary in nature. In this paper, the authors will (1) provide perspective on the synergistic relationship between human factors and IS using two illustrative and applied cases and (2) outline practical considerations for human factors-based strategies to identify contextual factors that influence intervention adoption, implementation, and maintenance dimensions of the RE-AIM framework. This article expands on recent research that developed user- and human-centered design strategies for IS scientists to use. However, defining the complementary relationship between IS and human factors is a necessary and valuable step in maximizing the effectiveness of IS to transform healthcare. While IS can complement practitioners' identification of intervention adaptations, human interaction is a process in the work system often overlooked throughout implementation. Further work is needed to address the influence that organizational endorsement and trust have on intervention adaptations and their translation into the work system.

Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding.

Numerous epidemiological studies have shown a significantly higher risk for development of Alzheimer's disease (AD) in patients affected by type 2 diabetes (T2D), but the molecular mechanism responsible for this association is presently unknown. Both diseases are considered protein misfolding disorders associated with the accumulation of protein aggregates; amyloid-beta (Aß) and tau in the brain during AD, and islet amyloid polypeptide (IAPP) in pancreatic islets in T2D. Formation and accumulation of these proteins follows a seeding-nucleation model, where a misfolded aggregate or 'seed' promotes the rapid misfolding and aggregation of the native protein. Our underlying hypothesis is that misfolded IAPP produced in T2D potentiates AD pathology by cross-seeding Aß, providing a molecular explanation for the link between these diseases. Here, we examined how misfolded IAPP affects Aß aggregation and AD pathology in vitro and in vivo. We observed that addition of IAPP seeds accelerates Aß aggregation in vitro in a seeding-like manner and the resulting fibrils are composed of both peptides. Transgenic animals expressing both human proteins exhibited exacerbated AD-like pathology compared with AD transgenic mice or AD transgenic animals with type 1 diabetes (T1D). Remarkably, IAPP colocalized with amyloid plaques in brain parenchymal deposits, suggesting that these peptides may directly interact and aggravate the disease. Furthermore, inoculation of pancreatic IAPP aggregates into the brains of AD transgenic mice resulted in more severe AD pathology and significantly greater memory impairments than untreated animals. These data provide a proof-of-concept for a new disease mechanism involving the interaction of misfolded proteins through cross-seeding events which may contribute to accelerate or exacerbate disease pathogenesis. Our findings could shed light on understanding the linkage between T2D and AD, two of the most prevalent protein misfolding disorders.