Characterization and quantitation of the circulating forms of serum transferrin receptor using domain-specific antibodies

To characterize the nature of the immunoreactive transferrin receptor in human serum, antisera were developed to peptide sequences of the extracellular domain of human transferrin receptor between amino acids 107 and 120 and the intracellular domain between amino acids 40 and 54. Antisera against the extracellular domain exhibited reactivity against both purified intact receptor and immunopurified circulating receptor, whereas antisera against the intracellular domain reacted only with intact receptor. Using competitive binding enzyme-linked immunosorbent assays, transferrin receptor in ultracentrifuged sera from normal subjects and patients with sickle cell anemia could be detected with antisera against the extracellular but not the intracellular domain. When the pellet obtained by ultracentrifugation of these sera was assayed after solubilization in 1% teric (polyoxyethylene-9-lauryl ether), only 0.6% of total serum receptor was detected in normal subjects and 3.8% in subjects with sickle cell disease. Roughly equal amounts of this pelleted immunoactivity were detected with antibodies against the extracellular and intracellular domains. These results indicate that less than 1% of transferrin receptor in normal human sera is intact receptor consistent with an exosomal origin and that virtually all circulating transferrin receptor is in the form of a truncated extracellular domain.     

Trust in government and support for governmental regulation: the case of electronic health records

Background

This paper presents results from a public engagement effort in Nebraska, USA, which measured public opinions about governmental involvement in encouraging the use of electronic health records (EHRs).

Objective

We examine the role of trust in government in contributing to public support for government involvement in the development of EHR technologies. We hypothesize that trust in government will lead to support for federal and state governmental encouragement of the use of EHRs among doctors and insurance companies. Further, because individual experiences with health‐care professionals will reduce perceptions of risk, we expect that support for governmental involvement will be tempered by greater personal experience with the health‐care industry.

Design and Results

Examining a small survey of individuals on the issue, we find general support for both of our hypotheses. The findings suggest that trust in government does have a positive relationship with support for government involvement in the policy domain, but that the frequency of personal experiences with health‐care providers reduces the extent to which the public supports governmental involvement in the development of EHR technology.

Discussion and Conclusion

This inquiry contributes to our understanding of public attitudes towards government involvement in EHRs in the United States specifically and contributes to social science examining links between trust in government and support for governmental activity in the emerging policy domain regarding electronic health records systems.     

Rationing Limited Healthcare Resources in the COVID-19 Era and Beyond: Ethical Considerations Regarding Older Adults

Coronavirus disease 2019 (COVID-19) continues to impact older adults disproportionately with respect to serious consequences ranging from severe illness and hospitalization to increased mortality risk. Concurrently, concerns about potential shortages of healthcare professionals and health supplies to address these issues have focused attention on how these resources are ultimately allocated and used. Some strategies, for example, misguidedly use age as an arbitrary criterion that disfavors older adults in resource allocation decisions. This is a companion article to the American Geriatrics Society (AGS) position statement, “Resource Allocation Strategies and Age-Related Considerations in the COVID-19 Era and Beyond.” It is intended to inform stakeholders including hospitals, health systems, and policymakers about ethical considerations that should be considered when developing strategies for allocation of scarce resources during an emergency involving older adults. This review presents the legal and ethical background for the position statement and discusses these issues that informed the development of the AGS positions: (1) age as a determining factor, (2) age as a tiebreaker, (3) criteria with a differential impact on older adults, (4) individual choices and advance directives, (5) racial/ethnic disparities and resource allocation, and (6) scoring systems and their impact on older adults. It also considers the role of advance directives as expressions of individual preferences in pandemics. J Am Geriatr Soc 68:1143–1149, 2020.     

Validating administratively derived frailty scores for use in Veterans Health Administration emergency departments

Objectives

Frailty is a clinical syndrome characterized by decreased physiologic reserve that diminishes the ability to respond to stressors such as acute illness. Veterans Health Administration (VA) emergency departments (ED) are the primary venue of care for Veterans with acute illness and represent key sites for frailty recognition. As questionnaire-based frailty instruments can be cumbersome to implement in the ED, we examined two administratively derived frailty scores for use among VA ED patients.

Methods

This national retrospective cohort study included all VA ED visits (2017–2020). We evaluated two administratively derived scores: the Care Assessment Needs (CAN) score and the VA Frailty Index (VA-FI). We categorized all ED visits across four frailty groups and examined associations with outcomes of 30-day and 90-day hospitalization and 30-day, 90-day, and 1-year mortality. We used logistic regression to assess the model performance of the CAN score and the VA-FI.

Results

The cohort included 9,213,571 ED visits. With the CAN score, 28.7% of the cohort were classified as severely frail; by VA-FI, 13.2% were severely frail. All outcome rates increased with progressive frailty (p-values for all comparisons < 0.001). For example, for 1-year mortality based on the CAN score frailty was determined as: robust, 1.4%; prefrail, 3.4%; moderately frail, 7.0%; and severely frail, 20.2%. Similarly, for 90-day hospitalization based on VA-FI, frailty was determined as prefrail, 8.3%; mildly frail, 15.3%; moderately frail, 29.5%; and severely frail, 55.4%. The c-statistics for CAN score models were higher than for VA-FI models across all outcomes (e.g., 1-year mortality, 0.721 vs. 0.659).

Conclusions

Frailty was common among VA ED patients. Increased frailty, whether measured by CAN score or VA-FI, was strongly associated with hospitalization and mortality and both can be used in the ED to identify Veterans at high risk for adverse outcomes. Having an effective automatic score in VA EDs to identify frail Veterans may allow for better targeting of scarce resources.     

Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study

In an effort to determine what clinically useful information regarding left ventricular diastolic function can be inferred noninvasively with pulsed wave Doppler echocardiography, mitral flow velocity patterns and measured variables were correlated with hemodynamic findings in 70 patients: 30 with coronary artery disease, 20 with idiopathic congestive cardiomyopathy, 14 with a restrictive myocardial process and 6 without significant cardiac disease. The effect of sudden changes in hemodynamics on the mitral flow velocity pattern was also investigated in a subgroup of patients who had simultaneous recording of mitral flow velocity and left ventricular pressure before and after left ventriculography. Mitral flow velocity recordings from 30 healthy adults served as a reference group. This analysis suggests that 1) the majority of patients with these cardiac disorders demonstrate abnormal mitral flow velocity patterns or variables; 2) markedly different flow velocity patterns can be seen in patients with impaired left ventricular relaxation; 3) the different mitral patterns appear to relate more to myocardial function and hemodynamic status than to the type of disease process present; 4) certain mitral patterns suggest different filling pressures and rates of early diastolic left ventricular filling; 5) an increase in left atrial pressure can "normalize" an abnormal mitral flow velocity pattern and "mask" a left ventricular relaxation abnormality; and 6) the different patterns appear to represent a dynamic continuum with the potential to change from one to another as a result of disease progression, medical therapy or sudden changes in hemodynamics. It is concluded that, despite the indirect method of estimation and certain limitations, mitral flow velocity recordings have clinical potential in assessing left ventricular diastolic function that merits further investigation.