Updating and Validating the Rheumatic Disease Comorbidity Index to ICD-10-CM

Background/Objective: Comorbidities can contribute to increased risk for mortality and disability in individuals with rheumatoid arthritis (RA)1,2. The Rheumatic Disease Comorbidity Index (RDCI) assesses 11 comorbidities and produces a weighted score (0-9) that accurately predicts several health outcomes3. The RDCI was developed with self-report data and later validated with ICD-9-CM codes collected from administrative data3,4. On October 1, 2015, the U.S. transitioned to ICD-10-CM, resulting in a nearly five-fold increase in the number of codes available to classify conditions5. Our objective was to update the RDCI by translating it into ICD-10-CM. Methods: We defined an ICD-9-CM cohort and an ICD-10-CM cohort using patient data from the Veterans Affairs Rheumatoid Arthritis Registry (VARA). ICD-10-CM codes were generated by converting ICD-9-CM codes using tools that provide suggested crosswalks, and the codes were reviewed by a physician to assess clinical relevance. Comorbidities were collected from national VA administrative data over a two-year period in both cohorts (ICD-9-CM: October 1, 2013 to September 30, 2015; ICD-10-CM: January 1, 2016 to December 31, 2017). Comorbidity frequencies were compared using Cohen’s Kappa, and RDCI scores were compared using Intraclass Correlation Coefficients (ICC). Results: Both the ICD-9-CM cohort (n=1,082) and ICD-10-CM cohort (n=1,446) were predominantly male (ICD-9-CM: 89%; ICD-10-CM: 87%), Caucasian (ICD-9-CM: 76%; ICD-10-CM: 73%), and middle to old-aged (ICD-9-CM: 67.3 ± 10.2 years; ICD-10-CM: 68.2 ± 10.0 years). Prevalence of comorbidities were similar between coding systems, with absolute differences less than 4% (range: 0.28 to 3.91). Myocardial infarction, hypertension, diabetes mellitus, depression, stroke, other cardiovascular, lung disease, and cancer had moderate agreement or higher (range κ: 0.47 to 0.84), while fracture and ulcer/stomach problem had slight and fair agreement, respectively (κ = 0.13; κ = 0.27)6,7. The RDCI scores were 2.95 ± 1.73 (mean ± SD) for the ICD-9-CM cohort and 2.93 ± 1.75 for the ICD-10-CM cohort. RDCI scores had moderate agreement (ICC: 0.71; 95% CI: 0.68-0.74)8 among individuals who were observed during both the ICD-9-CM and ICD-10-CM eras. Conclusion: We have mapped the RDCI from ICD-9-CM to ICD-10-CM codes, generating comparable RDCI scores in a large RA registry. Individual comorbidity agreement varied, with more chronic conditions such as diabetes and hypertension having higher agreement and more acute conditions such as fractures and ulcer/stomach problems having lower agreement. The updated RDCI can be used in clinical outcomes research with ICD-10-CM era patient data.https://digitalcommons.unmc.edu/surp2021/1043/thumbnail.jp

In vitro comparison of Ethanol Metabolism in Precision Cut Liver Slices from C57Bl/6, Balb/c, DBA/2J and 129S1/SvlmJ Mice and with the Aldeyra Product ADX-629

Alcoholic liver disease (ALD) is common consequence of excessive alcohol consumption [1]. When the liver is damaged by the intake of alcohol, repair mechanisms are deployed, which results in fibrosis or scarring of the liver. Development of this disease is due to the byproducts of ethanol metabolism. These byproducts include acetaldehyde from the metabolism of ethanol and malondialdehyde from the breakdown of cell membranes during injury. An Aldeyra product, ADX-629, is a small molecule that acts as a reactive aldehyde species (RASP) inhibitor. ADX-629 covalently binds free aldehydes, thus diminishing excessive RASP levels. To determine the aldehyde scavenging abilities of ADX-629 in attenuating fatty liver disease, precision cut liver slices (PCLS) were exposed to varying concentrations of ADX-629 as well as 25mM of ethanol. PCLS, which provide a novel in vitro/ex vivo experimental model, were then measured for triglyceride levels and supernatants were analyzed for acetaldehyde levels. It was found that ADX-629 reduced the acetaldehyde levels released from PCLS while also decreasing triglyceride levels. ADX-629 offers promising clinical uses such as in the prevention of fatty liver formation in patients with non-alcoholic steatohepatitis and in the treatment of alcoholic patients by preventing oxidative stress caused by the breakdown of ethanol thereby, preventing ALD.https://digitalcommons.unmc.edu/surp2021/1062/thumbnail.jp

CASPASE-12 and Rheumatoid Arthritis in African-Americans

CASPASE-12 (CASP12) has a downregulatory function during infection and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls. Statistical analyses comparing genotype groups were performed using Kruskal–Wallis non-parametric ANOVA with Mann–Whitney U tests and chi-square tests. There was no significant difference in the overall distribution of CASP12 genotypes within AA with RA, but CASP12 homozygous patients had lower baseline joint-narrowing scores. CASP12 homozygosity appears to be a subtle protective factor for some aspects of RA in AA patients

Development of the American College of Rheumatology Electronic Clinical Quality Measures for Gout

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143639/1/acr23500.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143639/2/acr23500-sup-0001-AppendixS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143639/3/acr23500_am.pd

Development of a macromolecular prodrug for the treatment of inflammatory arthritis: mechanisms involved in arthrotropism and sustained therapeutic efficacy.

INTRODUCTION: The purpose of the present manuscript is to test the hypothesis that arthrotropic localization and synovial cell internalization account for the unique capacity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex, a macromolecular prodrug of dexamethasone) to induce sustained amelioration of joint inflammation and inhibition of tissue damage in an animal model of inflammatory arthritis. METHODS: Rats with adjuvant-induced arthritis (AA) were treated with P-Dex, free dexamethasone, saline or HPMA homopolymer. To define the biodistribution of P-Dex, conjugates with different imaging labels were given to AA rats and analyzed. Isolated joint tissues were evaluated by fluorescence-activated cell sorting (FACS) and immunohistochemical staining. Cellular uptake of P-Dex and its effects on apoptosis and production of proinflammatory cytokines were examined using human monocyte-macrophages and fibroblasts. RESULTS: A single systemic administration of P-Dex completely suppressed AA for \u3e20 days. Magnetic resonance imaging demonstrated higher HPMA copolymer influx into the inflamed joints than the normal joints. Immunohistochemistry and FACS analyses of arthritic joints revealed extensive uptake of the polymer conjugate by synovial fibroblasts and myeloid lineage cells. The capacity of P-Dex to suppress inflammation was confirmed in monocyte-macrophage cultures in which P-Dex treatment resulted in suppression of lipopolysaccharide-induced IL-6 and TNFα release. Similarly, TNFα-induced expression of matrix metalloproteinases (MMP1 and MMP3) in synovial fibroblasts from a rheumatoid arthritis patient was suppressed by P-Dex. P-Dex showed no detectable effect on monocyte apoptosis. CONCLUSIONS: P-Dex provides superior and sustained amelioration of AA compared with an equivalent dose of free dexamethasone. The arthrotropism and local retention of P-Dex is attributed to the enhanced vascular permeability in arthritic joints and the internalization of P-Dex by synovial cells. The uptake and processing of P-Dex by macrophages and fibroblasts, and downregulation of proinflammatory mediators, provides an explanation for the sustained anti-inflammatory efficacy of P-Dex in this model of inflammatory arthritis