Equity-Mobilizing Partnerships in Community (EMPaCT): Co-Designing Patient Engagement to Promote Health Equity.

Equity-Mobilizing Partnerships in Community (EMPaCT) is a novel approach to patient engagement that centres diverse lived experiences and promotes equity-oriented and inclusive partnerships. As an independent community table, EMPaCT is made up primarily of patients/diverse members of community. Researchers and other decision makers come to this table with their projects to learn how to make their project more inclusive and equitable. In this paper, we detail how we used participatory co-design to define, build and grow EMPaCT as an innovative and scalable patient partnership model that promotes bottom-up action for health equity.

Development and Application of a Semi quantitative Scoring Method for Ultrastructural Assessment of Acute Stress in Pancreatic Islets.

BACKGROUND: Pancreas and islet transplantation outcomes are negatively impacted by injury to the endocrine cells from acute stress during donor death, organ procurement, processing, and transplant procedures. Here, we report a novel electron microscopy scoring system, the Newcastle Pancreas Endocrine Stress Score (NPESS). METHODS: NPESS was adapted and expanded from our previously validated method for scoring pancreatic exocrine acinar cells, yielding a 4-point scale (0-3) classifying ultrastructural pathology in endocrine cell nuclei, mitochondria, endoplasmic reticulum, cytoplasmic vacuolization, and secretory granule depletion, with a maximum additive score of 15. We applied NPESS in a cohort of deceased organ donors after brainstem (DBD) and circulatory (DCD) death with a wide range of cold ischemic times (3.6-35.9 h) including 3 donors with type 1 and 3 with type 2 diabetes to assess islets in situ (n = 30) in addition to pancreata (n = 3) pre- and postislet isolation. RESULTS: In DBD pancreata, NPESS correlated with cold ischemic time (head: r = 0.55; P = 0.02) and mirrored exocrine score (r = 0.48; P = 0.01). When stratified by endocrine phenotype, cells with granules of heterogeneous morphology had higher scores than α, ß, and δ cells (P < 0.0001). Cells of mixed endocrine-exocrine morphology were observed in association with increased NPESS (P = 0.02). Islet isolation was associated with improved NPESS (in situ: 8.39 ± 0.77 [Mean ± SD]; postisolation: 5.44 ± 0.31; P = 0.04). CONCLUSIONS: NPESS provides a robust method for semiquantitative scoring of subcellular ultrastructural changes in human pancreatic endocrine cells in situ and following islet isolation with utility for unbiased evaluation of acute stress in organ transplantation research.

The Sociotechnical Ethics of Digital Health: A Critique and Extension of Approaches From Bioethics.

The widespread adoption of digital technologies raises important ethical issues in health care and public health. In our view, understanding these ethical issues demands a perspective that looks beyond the technology itself to include the sociotechnical system in which it is situated. In this sense, a sociotechnical system refers to the broader collection of material devices, interpersonal relationships, organizational policies, corporate contracts, and government regulations that shape the ways in which digital health technologies are adopted and used. Bioethical approaches to the assessment of digital health technologies are typically confined to ethical issues raised by features of the technology itself. We suggest that an ethical perspective confined to functions of the technology is insufficient to assess the broader impact of the adoption of technologies on the care environment and the broader health-related ecosystem of which it is a part. In this paper we review existing approaches to the bioethics of digital health, and draw on concepts from design ethics and science & technology studies (STS) to critique a narrow view of the bioethics of digital health. We then describe the sociotechnical system produced by digital health technologies when adopted in health care environments, and outline the various considerations that demand attention for a comprehensive ethical analysis of digital health technologies in this broad perspective. We conclude by outlining the importance of social justice for ethical analysis from a sociotechnical perspective.

Risk stratification for coronary artery disease in multi-ethnic populations: Are there broader considerations for cost efficiency?

Coronary artery disease (CAD) screening and diagnosis are core cardiac specialty services. From symptoms, autopsy correlations supported reductions in coronary blood flow and dynamic epicardial and microcirculatory coronaries artery disease as etiologies. While angina remains a clinical diagnosis, most cases require correlation with a diagnostic modality. At the onset of the evidence building process much research, now factored into guidelines were conducted among population and demographics that were homogenous and often prior to newer technologies being available. Today we see a more diverse multi-ethnic population whose characteristics and risks may not consistently match the populations from which guideline evidence is derived. While it would seem very unlikely that for the majority, scientific arguments against guidelines would differ, however from a translational perspective, there will be populations who differ and importantly there are cost-efficacy questions, e.g., the most suitable first-line tests or what parameters equate to an adequate test. This article reviews non-invasive diagnosis of CAD within the context of multi-ethnic patient populations.

Impact of Socioeconomic Status on Clinical Outcomes in Patients With ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Low socioeconomic status (SES) has been previously shown to be associated with worse cardiovascular outcomes. However, unlike in Australia, many of these studies have been performed in countries without universal healthcare where SES may be expected to have a greater impact on care and outcomes. We sought to determine whether there is an association between SES and baseline characteristics, clinical outcomes and use of secondary prevention therapy in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: We prospectively collected data on 5665 consecutive ST-segment-elevation myocardial infarction PCI patients between 2005 and 2015 from 6 government-funded hospitals participating in a multicenter registry. Patients were categorized into SES quintiles using the Index of Relative Socioeconomic Disadvantage system, a score allocated to each residential postcode based on factors like income, educational level, and employment status by the Australian Bureau of Statistics. In our study, lower SES patients were more likely to have diabetes mellitus, smoke, and initially present to a non-PCI capable hospital (all P≤0.01). Among primary PCI patients, the median time to reperfusion was slightly higher in lower SES groups (211 [144-337] versus 193 [145-285] minutes, P<0.001). Drug-eluting stent use was higher in the higher SES groups ( P<0.001). At 12 months after PCI, lower SES patients had higher rates of ongoing smoking and lower use of guideline-recommended secondary prevention therapy (both P<0.01). Despite these differences, SES group was not found to be an independent predictor of 12-month major adverse cardiovascular events. CONCLUSIONS: Lower SES patients have more comorbidities and experienced slightly longer reperfusion times but otherwise similar care. Despite these baseline differences, clinical outcomes after ST-segment-elevation myocardial infarction PCI were similar regardless of SES.

Cell biology assessment of glucokinase mutations V62M and G72R in pancreatic beta-cells: evidence for cellular instability of catalytic activity.

Mutations in the glucokinase (GK) gene cause defects in blood glucose homeostasis. In some cases (V62M and G72R), the phenotype cannot be explained by altered enzyme kinetics or protein instability. We used transient and stable expression of green fluorescent protein (GFP) GK chimaeras in MIN6 beta-cells to study the phenotype defect of V62M and G72R. GK activity in lysates of MIN6 cell lines stably expressing wild-type or mutant GFP GK showed the expected affinity for glucose and response to pharmacological activators, indicating the expression of catalytically active enzymes. MIN6 cells stably expressing GFP V62M or GFP G72R had a lower GK activity-to-GK immunoreactivity ratio and GK activity-to-GK mRNA ratio but not GK immunoreactivity-to-GK mRNA ratio than wild-type GFP GK. Heterologous expression of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2/FDP2) in cell lines increased GK activity for wild-type GK and V62M but not for G72R, whereas expression of liver GK regulatory protein (GKRP) increased GK activity for wild type but not V62M or G72R. Lack of interaction of these mutants with GKRP was also evident in hepatocyte transfections from the lack of nuclear accumulation. These results suggest that cellular loss of GK catalytic activity rather than impaired translation or enhanced protein degradation may account for the hyperglycemia in subjects with V62M and G72R mutations.