Receipt of rheumatology care and lupus-specific labs among young adults with systemic lupus erythematosus: A US Medicare retention in care cohort study.

OBJECTIVE: In systemic lupus erythematosus, poor disease outcomes occur in young adults, patients identifying as Black or Hispanic, and socioeconomically disadvantaged patients. These identities and social factors differentially shape care access and quality that contribute to lupus health disparities in the US. Thus, our objective was to measure markers of care access and quality, including rheumatology visits (longitudinal care retention) and lupus-specific serology testing, by race and ethnicity, neighborhood disadvantage, and geographic context. METHODS: This cohort study used a geo-linked 20% national sample of young adult Medicare beneficiaries (ages 18-35) with lupus-coded encounters and a 1-year assessment period. Retention in lupus care required a rheumatology visit in each 6-month period, and serology testing required ≥1 complement or dsDNA antibody test within the year. Multivariable logistic regression models were fit for visit-based retention and serology testing to determine associations with race and ethnicity, neighborhood disadvantage, and geography. RESULTS: Among 1,036 young adults with lupus, 39% saw a rheumatologist every 6 months and 28% had serology testing. White beneficiaries from the least disadvantaged quintile of neighborhoods had higher visit-based retention than other beneficiaries (64% vs 30%-60%). Serology testing decreased with increasing neighborhood disadvantage quintile (aOR 0.80; 95% CI 0.71, 0.90) and in the Midwest (aOR 0.46; 0.30, 0.71). CONCLUSION: Disparities in care, measured by rheumatology visits and serology testing, exist by neighborhood disadvantage, race and ethnicity, and region among young adults with lupus, despite uniform Medicare coverage. Findings support evaluating lupus care quality measures and their impact on US lupus outcomes.

Association of rurality and identifying as black with receipt of specialty care among patients hospitalized with a diabetic foot ulcer: a Medicare cohort study.

INTRODUCTION: Rural patients with diabetic foot ulcers, especially those identifying as black, face increased risk of major amputation. Specialty care can reduce this risk. However, care disparities might beget outcome disparities. We aimed to determine whether a smaller proportion of rural patients, particularly those identifying as black, receive specialty care compared with the national proportion. RESEARCH DESIGN AND METHODS: This 100% national retrospective cohort examined Medicare beneficiaries hospitalized with diabetic foot ulcers (2013-2014). We report observed differences in specialty care, including: endocrinology, infectious disease, orthopedic surgery, plastic surgery, podiatry, or vascular surgery. We used logistic regression to examine possible intersectionality between rurality and race, controlling for sociodemographics, comorbidities, and ulcer severity and including an interaction term between rurality and identifying as black. RESULTS: Overall, 32.15% (n=124 487) of patients hospitalized with a diabetic foot ulcer received specialty care. Among rural patients (n=13 100), the proportion decreased to 29.57%. For patients identifying as black (n=21 649), the proportion was 33.08%. Among rural patients identifying as black (n=1239), 26.23% received specialty care. This was >5 absolute percentage points less than the overall cohort. The adjusted OR for receiving specialty care among rural versus urban patients identifying as black was 0.61 (95% CI 0.53 to 0.71), which was lower than that for rural versus urban patients identifying as white (aOR 0.85, 95% CI 0.80 to 0.89). This metric supported a role for intersectionality between rurality and identifying as black. CONCLUSIONS: A smaller proportion of rural patients, particularly those identifying as black, received specialty care when hospitalized with a diabetic foot ulcer compared with the overall cohort. This might contribute to known disparities in major amputations. Future studies are needed to determine causality.

Association of Race, Ethnicity, and Rurality With Major Leg Amputation or Death Among Medicare Beneficiaries Hospitalized With Diabetic Foot Ulcers.

Importance: Patients identifying as Black and those living in rural and disadvantaged neighborhoods are at increased risk of major (above-ankle) leg amputations owing to diabetic foot ulcers. Intersectionality emphasizes that the disparities faced by multiply marginalized people (eg, rural US individuals identifying as Black) are greater than the sum of each individual disparity. Objective: To assess whether intersecting identities of Black race, ethnicity, rural residence, or living in a disadvantaged neighborhood are associated with increased risk in major leg amputation or death among Medicare beneficiaries hospitalized with diabetic foot ulcers. Design, Setting, and Participants: This retrospective cohort study used 2013-2014 data from the US National Medicare Claims Data Database on all adult Medicare patients hospitalized with a diabetic foot ulcer. Statistical analysis was conducted from August 1 to October 27, 2021. Exposures: Race was categorized using Research Triangle Institute variables. Rurality was assigned using Rural-Urban Commuting Area codes. Residents of disadvantaged neighborhoods comprised those living in neighborhoods at or above the national 80th percentile Area Deprivation Index. Main Outcomes and Measures: Major leg amputation or death during hospitalization or within 30 days of hospital discharge. Logistic regression was used to explore interactions among race, ethnicity, rurality, and neighborhood disadvantage, controlling for sociodemographic characteristics, comorbidities, and ulcer severity. Results: The cohort included 124 487 patients, with a mean (SD) age of 71.5 (13.0) years, of whom 71 286 (57.3%) were men, 13 100 (10.5%) were rural, and 21 649 (17.4%) identified as Black. Overall, 17.6% of the cohort (n = 21 919), 18.3% of rural patients (2402 of 13 100), and 21.9% of patients identifying as Black (4732 of 21 649) underwent major leg amputation or died. Among 1239 rural patients identifying as Black, this proportion was 28.0% (n = 347). This proportion exceeded the expected excess for rural patients (18.3% - 17.6% = 0.7%) plus those identifying as Black (21.9% - 17.6% = 4.3%) by more than 2-fold (28.0% - 17.6% = 10.4% vs 0.7% + 4.3% = 5.0%). The adjusted predicted probability of major leg amputation or death remained high at 24.7% (95% CI, 22.4%-26.9%), with a significant interaction between race and rurality. Conclusions and Relevance: Rural patients identifying as Black had a more than 10% absolute increased risk of major leg amputation or death compared with the overall cohort. This study suggests that racial and rural disparities interacted, amplifying risk. Findings support using an intersectionality lens to investigate and address disparities in major leg amputation and mortality for patients with diabetic foot ulcers.

Directed evolution of aminoglycoside phosphotransferase (3') type IIIa variants that inactivate amikacin but impose significant fitness costs.

The rules that govern adaptive protein evolution remain incompletely understood. Aminoglycoside aminotransferase (3') type IIIa (hereafter abbreviated APH(3')-IIIa) is a good model enzyme because it inactivates kanamycin efficiently; it recognizes other aminoglycoside antibiotics, including amikacin, but not nearly as well. Here we direct the evolution of APH(3')-IIIa variants with increased activity against amikacin. After four rounds of random mutation and selection in Escherichia coli, the minimum inhibitory concentration of amikacin rose from 18 micrograms/mL (wild-type enzyme) to over 1200 micrograms/mL (clone 4.1). The artificially evolved 4.1 APH(3')-IIIa variant exhibited 19-fold greater catalytic efficiency (k cat/K M) than did the wild-type enzyme in reactions with amikacin. E. coli expressing the evolved 4.1 APH(3')-IIIa also exhibited a four-fold decrease in fitness (as measured by counting colony forming units in liquid cultures with the same optical density) compared with isogenic cells expressing the wild-type protein under non-selective conditions. We speculate that these fitness costs, in combination with the prevalence of other amikacin-modifying enzymes, hinder the evolution of APH(3')-IIIa in clinical settings.