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.     

α,ω-Dihydroxy telechelic poly(methyl methacrylate) via β-scission (radical addition-fragmentation) chain transfer polymerisation by macromonomer chain transfer agents,as prepared by catalytic chain transfer polymerisation

α,ω-Dihydroxy telechelic poly(methyl methacrylate) has been prepared by β-scission (radical addition-fragmentation) chain transfer polymerisation. Hydroxyethyl methacrylate dimer macromonomer prepared from catalytic chain transfer polymerisation and isolated as a pure compound is shown to be an efficient chain transfer agent. The mode of chain transfer is via β-scission which results in the dimer breaking in half on addition to a propagating poly(methyl methacrylate) radical terminating the polymerisation and providing a hydroxyethyl methacrylate radical which reinitiates polymerisation. A combination of these two events leads to dihydroxy telechelic products, demonstrated to have a functionality of 2.05 by a combination of NMR and size exclusion chromatography (SEC). The chain transfer coefficients of these methacrylic macromonomers is concentration dependant exhibiting a type of “bootstrap” effect. This ultimately leads to a limiting low molecular weight telechelic product by the use of dimeric β-scission chain transfer agents. A combination of high field NMR and matrix assisted laser desorption time-of-flight mass spectrometry has been utilised to demonstrate the structure of the products. The combination of catalytic chain transfer polymerisation and β-scission chain transfer has been demonstrated to be a powerful tool in the controlled polymerisation of methacrylates by radical methodology.     

Infection with live mycobacteria inhibits in vitro detection of Ia antigen on macrophages

Both antigen-specific and non-specific anergy are common features of disseminated mycobacterial infections, and the pathogenesis of such anergy is as yet not fully understood. To date, most studies have focused on the efferent limb of the immune response, and no detailed information is available on the early macrophage-T cell interaction and its consequence on T cell clonal proliferation. To gain information on this crucial phase of mycobacteriosis, we have conducted studies to evaluate the effect of M. kansasii infection on Ia expression induced by T cell-derived lymphokine and have assessed whether such cells can adequately present either mycobacterial or allogeneic antigens to T cells. In vitro infection of mouse resident peritoneal macrophages with live but not heat-killed M. kansasii resulted in a significantly reduced percentage of cells expressing monoclonal antibody detectable Ia antigen following optimal stimulation with crude lymphokine preparations or recombinant mouse gamma interferon. In parallel experiments, macrophages infected with the mycobacteria were co-cultured with syngeneic in vivo M. kansasii sensitized non-adherent, nylon-wool purified lymph node cells, and lymphoproliferation was measured by [3H]thymidine incorporation. It was shown that in co-cultures with macrophages infected with live M. kansasii, the lymphocyte proliferation was marked even in very low infection ratios. In contrast, the response to heat-killed bacilli was dose dependent, reaching peak levels only in high infection ratios. The ability of infected macrophages to present allogeneic antigens was assessed using the mixed leukocyte reaction. Macrophages infected with heat-killed M. kansasii were able to induce a mixed leukocyte reaction similar to uninfected macrophages whereas macrophages infected with live M. kansasii were unable to stimulate allogeneic T cells. These findings may have implications on immunological disturbances often seen in mycobacterial infections, such as leprosy, in which there can be large numbers of non-toxic viable intracellular bacilli.     

Guidelines for genomic array analysis in acquired haematological neoplastic disorders

Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single‐nucleotide polymorphism‐detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test. However, comprehensive and readable presentation of frequently identified complex genomic profiles remains challenging. To assist diagnostic laboratories, standardization and minimum criteria for clinical interpretation and reporting of acquired genomic abnormalities detected through arrays in neoplastic disorders are presented. © 2016 Wiley Periodicals, Inc.     

Novel vectors for the expression of antibody molecules using variable regions generated by polymerase chain reaction.

A new family of vectors has been produced which facilitates the cloning and expression of immunoglobulin variable regions cloned by polymerase chain reaction (PCR). The vectors are designed to express the cloned variable regions joined to human constant regions and take advantage of priming in the leader sequence so that no amino acid changes will be introduced into the mature antibody molecule. Both the heavy chain and light chain vectors utilize a murine VH promoter provided with an EcoRV restriction site so that the amplified variable regions can be directly cloned into a functional promoter. For the heavy chain an NheI restriction site has been generated at the first two amino acids of CH1 and the cloned leader and variable region are fused directly to the CH1 domain of the constant region. When the leader and variable regions of the light chain were fused directly to C kappa, no expression was observed. Therefore the light chain expression vector was designed with a SalI restriction site for cloning into a splice junction 3' of the variable region; VL then is joined to C kappa by splicing. Both vectors direct the expression of functional, fully assembled immunoglobulin molecules with the expected molecular weight. Use of redundant oligomers to prime the PCR permits the cloning and expression of recombinant antibodies without any prior information as to their sequence and makes it possible to rapidly generate recombinant antibodies from any monoclonal antibody producing cell line.     

ECS produced disruption or facilitation of discriminated active avoidance performance in rats

Two experiments investigated the effect of electroconvulsive shock on the performance of a one-way active avoidance response. In the first experiment it was found that if the response was learned under scopolamine, ECS given prior to relearning failed to produce a deficit. The second experiment demonstrated that ECS facilitated relearning of a response trained to a low criterion level while it disrupted performance of a response trained to a strict criterion. These results support other indications that Deutsch's memory model has predictive value for proactive effects of ECS on relearning (retrieval).