ObjectiveMorbidity and mortality in Rheumatoid Arthritis (RA) is partly mitigated by maintaining immune and hematologic homeostasis. Identification of those at risk is challenging. Red cell distribution width (RDW) and absolute lymphocyte count (ALC) associate with cardiovascular disease (CVD) and mortality in the general population, and with disease activity in RA. How these parameters relate to inflammation and mortality in RA were investigated.MethodsIn a retrospective single VA-Rheumatology Clinic cohort of 327 RA patients treated with methotrexate (MTX)+/-TNF-blocker we evaluated RDW and ALC before and during therapy, and in relation to subsequent mortality. Findings were validated in a national VA cohort (n=13,914). In a subset of patients and controls we evaluated inflammatory markers.ResultsIn the local cohort, High RDW and Low ALC prior to MTX treatment each associated with subsequent mortality over 10 years (p<0.001 and p=0.004). The highest mortality was observed in those with both high-RDW and low ALC. This remained after adjusting for age and co-morbidities, and was validated in the national RA cohort. In the immunology cohort, soluble and cellular inflammatory markers were higher in RA than controls, ALC correlated with plasma TNFR2, NK/Monocyte-HLADR-MFI, and CD4CM/CD8CMHLADR/CD38%, while RDW associated with CD4%/CD8% and CD4EM/CD4TE HLADR/CD38%. MTX initiation was followed by an increase in RDW and decrease in ALC. TNF-blocker therapy added to MTX resulted in an increase in ALC.ConclusionRDW and ALC before DMARD therapy associate with biomarkers of monocyte/macrophage inflammation and subsequent mortality. Mechanistic linkage between TNF signaling and lymphopenia here warrants further investigation.

Background: Hepatitis-C virus (HCV) chronic infection can lead to cirrhosis, hepatocellular carcinoma (HCC), end-stage liver disease, cardiovascular disease (CVD), and mortality. Transient Elastography (TE) is used to non-invasively assess fibrosis. Whether immune monitoring provides additive prognostic value is not established. Increased red-cell distribution width (RDW) and decreased absolute lymphocyte count (ALC) predict mortality in those without liver disease. Whether these relationships remain during HCV infection is unknown.  Materials and Methods: A retrospective cohort of 1,715 single-site VA Liver Clinic patients receiving Transient Elastography (TE) 2014-2019 to evaluate HCV-associated liver damage were evaluated for RDW and ALC in relation to traditional parameters of cardiovascular risk, liver health, development of HCC, and mortality. Results: The cohort was 97% male, 55% African American, 26% with diabetes mellitus, 67% with hypertension, and 66% with tobacco use. After TE, 3% were subsequently diagnosed with HCC, and 12% (n=208) died. Most deaths (n=189) were due to non-liver causes. The TE score associated with prevalent CVD positively correlated with atherosclerotic cardiovascular disease (ASCVD) 10-Year Risk Score, age, RDW, and negatively correlated with ALC. Patients with anisocytosis (RDW above 14%) or lymphopenia (ALC level under 1.2x109/L) had greater subsequent all-cause mortality, even after adjusting for age, TE score, and comorbidities. TE score, and to a modest degree RDW, were associated with subsequent liver-associated mortality, while TE score, RDW, and ALC were each independently associated with non-liver cause of death. Conclusion: Widely available mortality calculators generally require multiple pieces of clinical information. RDW and ALC, parameters collected on a single laboratory test that is commonly performed, prior to HCV therapy may be pragmatic markers of long-term risk of mortality.

Background: Among nursing home residents, for whom age and frailty can blunt febrile responses to illness, the temperature used to define fever can influence the clinical recognition of COVID-19 symptoms. To assess the potential for differences in the definition of fever to characterize nursing home residents with COVID-19 infections as symptomatic, pre-symptomatic, or asymptomatic, we conducted a retrospective study on a national cohort of Department of Veterans Affairs (VA) Community Living Center (CLC) residents tested for SARS-CoV-2.Methods: Residents with positive SARS-CoV-2 tests were classified as asymptomatic if they did not experience any symptoms, and as symptomatic or presymptomatic if the experienced a fever (>100.4 F) before or following a positive SARS-CoV-2 test, respectively. All-cause 30-day mortality was assessed as was the influence of a lower temperature threshold (>99.0 F) on classification of residents with positive SARS-CoV-2 tests.Results: From March 2020 through November 2020, VA CLCs tested 11,908 residents for SARS-CoV-2 using RT-PCR, with a positivity of rate of 13% (1557). Among residents with positive tests and using >100.4 F, 321 (21%) were symptomatic, 425 (27%) were pre-symptomatic, and 811 (52%) were asymptomatic. All-cause 30-day mortality among residents with symptomatic and pre-symptomatic COVID-19 infections was 24% and 26%, respectively, while those with an asymptomatic infection had mortality rates similar to residents with negative SAR-CoV-2 tests (10% and 5%, respectively). Using >99.0 F would have increased the number of residents categorized as symptomatic at the time of testing from 321 to 773. Conclusions: All-cause 30-day mortality was similar among VA CLC residents with symptomatic or pre-symptomatic COVID-19 infection, and lowerThe findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of the VA or of the U.S. Government.

BACKGROUND Data describing antibiotic use in U.S. nursing homes remain limited. We report antibiotic use among skilled nursing facility residents from 29 U.S. nursing homes and assessed correlations between antibiotics prescribed to residents in skilled care and nursing home characteristics. DESIGN Retrospective cohort study. SETTING Twenty‐nine U.S. nursing homes in the same healthcare corporation. PARTICIPANTS Residents receiving skilled care in 2016. MEASUREMENTS We used pharmacy invoice and nursing home census data to calculate the days of antibiotic therapy per 1,000 days of skilled care (1,000 DOSC), the rate of antibiotic starts per 1,000 DOSC, the length of antibiotic therapy, and the average antibiotic spectrum index. We also assessed correlations between antibiotic use and nursing home characteristics. RESULTS Antibiotics accounted for an average of 9.6% (±0.6%) of systemic medications prescribed among residents receiving skilled care. On average, 26.8% (±2.9%) of antibiotics were intravenous. Fluoroquinolones were prescribed at the highest rates (19% across all facilities), followed by beta‐lactam/beta‐lactamase inhibitors (11%), first‐ and second‐generation cephalosporins, sulfonamides, and oral tetracyclines (each at 9%). Both the proportion of residents using enrolled in Medicare and number of unique prescribers responsible for systemic prescriptions positively correlated with the rate of antibiotic starts. CONCLUSIONS Our study demonstrates that pharmacy invoices represent a useful and preexisting source of data for assessing antibiotic prescriptions among individuals receiving skilled nursing care. The correlation between the number of unique prescribers and antibiotic starts suggests that prescribers are central to efforts to improve antibiotic use in nursing homes.