Implications of Race Adjustment in Lung-Function Equations.

BACKGROUND: Adjustment for race is discouraged in lung-function testing, but the implications of adopting race-neutral equations have not been comprehensively quantified. METHODS: We obtained longitudinal data from 369,077 participants in the National Health and Nutrition Examination Survey, U.K. Biobank, the Multi-Ethnic Study of Atherosclerosis, and the Organ Procurement and Transplantation Network. Using these data, we compared the race-based 2012 Global Lung Function Initiative (GLI-2012) equations with race-neutral equations introduced in 2022 (GLI-Global). Evaluated outcomes included national projections of clinical, occupational, and financial reclassifications; individual lung-allocation scores for transplantation priority; and concordance statistics (C statistics) for clinical prediction tasks. RESULTS: Among the 249 million persons in the United States between 6 and 79 years of age who are able to produce high-quality spirometric results, the use of GLI-Global equations may reclassify ventilatory impairment for 12.5 million persons, medical impairment ratings for 8.16 million, occupational eligibility for 2.28 million, grading of chronic obstructive pulmonary disease for 2.05 million, and military disability compensation for 413,000. These potential changes differed according to race; for example, classifications of nonobstructive ventilatory impairment may change dramatically, increasing 141% (95% confidence interval [CI], 113 to 169) among Black persons and decreasing 69% (95% CI, 63 to 74) among White persons. Annual disability payments may increase by more than $1 billion among Black veterans and decrease by $0.5 billion among White veterans. GLI-2012 and GLI-Global equations had similar discriminative accuracy with regard to respiratory symptoms, health care utilization, new-onset disease, death from any cause, death related to respiratory disease, and death among persons on a transplant waiting list, with differences in C statistics ranging from -0.008 to 0.011. CONCLUSIONS: The use of race-based and race-neutral equations generated similarly accurate predictions of respiratory outcomes but assigned different disease classifications, occupational eligibility, and disability compensation for millions of persons, with effects diverging according to race. (Funded by the National Heart Lung and Blood Institute and the National Institute of Environmental Health Sciences.).

Demographic Representation Among Speakers and Program Committee Members at the IDWeek Conference, 2013-2021.

BACKGROUND: In 2016, the IDWeek program committee was charged with ensuring gender equity in speaker sessions. Whether this charge also resulted in more opportunities for historically underrepresented speakers is unknown. METHODS: We conducted a retrospective analysis of trends in the demographic composition of IDWeek speakers and program committee members between 2013 and 2021. We used descriptive statistics to summarize data, χ2 tests to compare speaker demographics between 2013-2016 (before 2016) and 2017-2021 (after 2016), and Cochran-Armitage tests for trend. Each speaker slot was considered an independent event. RESULTS: A total of 5482 speaker slots were filled by 3389 individuals from 2013 to 2021. There was a linear increase in female speakers from 38.6% in 2013 to 58.4% in 2021 (P < .001). The proportion of white speakers decreased overall from 84.9% in 2013 to 63.5% in 2021. Compared with white speakers, more slots were filled by Asian speakers after 2016 versus before 2016 (20.1% vs 14.8%, respectively; P < .001). Program committee members from 2013-2021 were >80% non-Hispanic white; <5% of committee members identified as black, American Indian, Alaska Native, Native Hawaiian, Pacific Islander, or Hispanic. More program committee slots were filled by women after 2016 than before 2016 (52.7% vs 33.9%; P = .004). CONCLUSIONS: Intentional consideration of gender equity by the program committee was associated with equitable gender representation of invited speakers at IDWeek after 2016. Gradually, the proportions of IDWeek speakers from historically excluded racial/ethnic approached their respective proportions in the IDSA membership. White speakers remained overrepresented relative to membership proportions until 2021, and gaps in program committee racial/ethnic demographic representation highlights opportunities for continued inclusion, diversity, access, and equity at IDWeek.

Structural vulnerability among patients with HIV and SARS-CoV-2 Co-infection: descriptive case series from the U.S. Midwest.

HIV and COVID-19 disproportionately impact marginalized populations, especially racial and ethnic minorities. This descriptive case series from an HIV clinic in the U.S. Midwest explores the sociodemographic and clinical characteristics of 37 individuals with HIV and SARS-CoV-2 co-infection. All 37 had suppressed viral loads prior to diagnosis with COVID-19, and all 37 survived. Relative to our overall HIV clinic population, over twice as many Hispanic patients, three times as many undocumented patients, and four times as many refugee patients contracted COVID-19, highlighting the structural vulnerability of these sub-populations.

Neighborhood Deprivation and Racial/Ethnic Disparities in Human Immunodeficiency Virus Viral Suppression: A Single-center, Cross-sectional Study in the United States Midwest.

Combating disparities is a crucial goal of ongoing efforts to end the human immunodeficiency virus (HIV) epidemic. In a multivariable analysis of a cohort in the Midwestern United States, racial/ethnic disparities in HIV viral suppression were no longer robust after accounting for other sociodemographic factors. Neighborhood deprivation and low income were independently inversely associated with viral suppression.

Astrocytes locally translate transcripts in their peripheral processes.

Local translation in neuronal processes is key to the alteration of synaptic strength necessary for long-term potentiation, learning, and memory. Here, we present evidence that regulated de novo protein synthesis occurs within distal, perisynaptic astrocyte processes. Astrocyte ribosomal proteins are found adjacent to synapses in vivo, and immunofluorescent detection of peptide elongation in acute slices demonstrates robust translation in distal processes. We have also developed a biochemical approach to define candidate transcripts that are locally translated in astrocyte processes. Computational analyses indicate that astrocyte-localized translation is both sequence-dependent and enriched for particular biological functions, such as fatty acid synthesis, and for pathways consistent with known roles for astrocyte processes, such as GABA and glutamate metabolism. These transcripts also include glial regulators of synaptic refinement, such as Sparc Finally, the transcripts contain a disproportionate amount of a binding motif for the quaking RNA binding protein, a sequence we show can significantly regulate mRNA localization and translation in the astrocytes. Overall, our observations raise the possibility that local production of astrocyte proteins may support microscale alterations of adjacent synapses.

Patient with anomalous skin pigmentation expands the phenotype of ARID2 loss-of-function disorder, a SWI/SNF-related intellectual disability.

ARID2 loss-of-function is associated with a rare genetic disorder characterized in 14 reported patients to date. ARID2 encodes a member of the SWItch/sucrose non-fermentable chromatin remodeling complex. Other genes encoding subunits of this complex, such as ARID1A, ARID1B, and SMARCA2, are mutated in association with Coffin-Siris syndrome (CSS) and Nicolaides Baraitser syndrome (NCBRS) phenotypes. Previously reported ARID2 mutations manifested clinically with a CSS-like phenotype including intellectual disability, coarsened facial features, fifth toenail hypoplasia, and other recognizable dysmorphisms. However, heterogeneity exists between previously reported patients with some patients showing more overlapping features with NCBRS. Herein, we present a patient with a novel disease-causing ARID2 loss-of-function mutation. His clinical features included intellectual disability, coarse and dysmorphic facial features, toenail hypoplasia, ADHD, short stature, and delayed development consistent with prior reports. Our patient also presented with previously unreported clinical findings including ophthalmologic involvement, persistent fetal fingertip and toetip pads, and diffuse hyperpigmentary and hypopigmentary changes sparing his face, palms, and soles. The anomalous skin findings are particularly of interest given prior literature outlining the role of ARID2 in melanocyte homeostasis and melanoma. This clinical report and review of the literature is further affirming of the characteristic symptoms and expands the phenotype of this newly described and rare syndrome.

Alcohol Decreases Organic Dust-Stimulated Airway Epithelial TNF-Alpha Through a Nitric Oxide and Protein Kinase-Mediated Inhibition of TACE.

BACKGROUND: Farm workers in rural areas consume more alcohol than those who reside in urban areas. Occupational exposures such as agricultural work can pose hazards on the respiratory system. It is established that hog barn dust induces inflammation in the airway, including the release of cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8. We have shown that alcohol alters airway epithelial innate defense through changes in both nitric oxide (NO) and cAMP-dependent protein kinase A (PKA). Simultaneous exposure to hog barn dust and alcohol decreases inflammatory mediators, TNF-α, IL-6, and IL-8, in mice. Previously, mice exposed to both alcohol and hog barn dust showed a depleted amount of lymphocytes compared to mice exposed only to hog barn dust. Weakening of the innate immune response could lead to enhanced susceptibility to disease. In addition, mice that were co-exposed to hog barn dust and alcohol also experienced increased mortality. METHODS: Because we recently demonstrated that PKA activation inhibits the TNF-α sheddase, TNF-α-converting enzyme (TACE), we hypothesized that an alcohol-mediated PKA pathway blocks TACE activity and prevents the normative inflammatory response to hog barn dust exposure. To delineate these effects, we used PKA pathway inhibitors (adenylyl cyclase [AC], cAMP, and PKA) to modulate the effects of alcohol on dust-stimulated TNF-α release in the bronchial epithelial cell line, BEAS-2B. Alcohol pretreatment blocked TACE activity and TNF-α release in hog barn dust-treated cells. RESULTS: Alcohol continued to block hog barn dust-mediated TNF-α release in the presence of the particulate AC inhibitor, SQ22,536. The soluble adenylyl cyclase inhibitor, KH7, however, significantly increased the inflammatory response to hog barn dust. phosphodiesterase 4 inhibitors significantly elevated cAMP and enhanced alcohol-mediated inhibition of dust-stimulated TNF-α release. In addition, the NO synthase inhibitor, l-NMMA, also reversed the alcohol-blocking effect on dust-stimulated TNF-α. CONCLUSIONS: These data suggest that alcohol requires a soluble cyclase-generated cAMP-PKA pathway that is dependent upon the action of NO to inhibit TACE and TNF-α release. These findings support our observations that alcohol functions through a dual NO and PKA pathway in bronchial epithelial cells.

Using Critical Pedagogy to Advance Antiracism in Health Professions Education.

This article draws on Paulo Freire's Pedagogy of the Oppressed to model how health professions education can advance health equity. It first introduces 3 well-known frameworks that can be meaningfully applied as critical pedagogy: structural competency, critical race theory, and participatory action research. It then highlights applications of these frameworks that can prepare trainees for reflection and action that motivate health equity.

Health Care Access and Use Among U.S. Children Exposed to Neighborhood Violence.

INTRODUCTION: Neighborhood violence is an adverse childhood experience which impacts millions of U.S. children and is associated with poor health outcomes across the life course. These effects may be mitigated by access to care. Yet, the ways in which exposure to neighborhood violence shapes children's health care access have been understudied. METHODS: This is a cross-sectional analysis of 16,083 children (weighted N=67,214,201) ages 1 to <18 years from the 2019 and 2021 National Health Interview Survey. Guardians were asked about preventive care access, unmet health needs, and health care utilization in the last year. Changes associated with exposure to neighborhood violence were estimated using marginal effects from multivariable logistic regression models adjusted for year, age, sex, race/ethnicity, parental education, family structure, rurality, income, insurance type, insurance discontinuity, and overall reported health. RESULTS: Of 16,083 sample children, 863 (weighted 5.3% [95% CI 4.8-5.7]) reported exposure to neighborhood violence, representing a weighted population of ∼3.5 million. In adjusted analyses, exposure to violence was associated with forgone prescriptions (adjusted difference 1.2 percentage-points (pp) [95%CI 0.1-2.3]; weighted national population impact 42,833 children), trouble paying medical bills (7.7pp [4.4-11.0]; 271,735), delayed medical (1.5pp [0.2-2.9]; 54,063) and mental health care (2.8pp [1.1-4.6]; 98,627), and increased urgent care (4.5pp [0.9-8.1]; 158,246) and emergency department utilization (6.4pp [3.1-9.8]; 227,373). CONCLUSIONS: In this nationally representative study, neighborhood violence exposure among children was associated with unmet health needs and increased acute care utilization. Evidence-based interventions to improve access to care and reduce economic precarity in communities impacted by violence are needed to mitigate downstream physical and mental health consequences.

Performance of ChatGPT and Google Translate for Pediatric Discharge Instruction Translation.

BACKGROUND AND OBJECTIVES: Patients who speak languages other than English face barriers to equitable healthcare delivery. Machine translation systems, including emerging large language models, have the potential to expand access to translation services, but their merits and limitations in clinical practice remain poorly defined. We aimed to assess the performance of Google Translate and ChatGPT for multilingual translation of pediatric discharge instructions. METHODS: Twenty standardized discharge instructions for pediatric conditions were translated into Spanish, Brazilian Portuguese, and Haitian Creole by professional translation services, Google Translate and ChatGPT-4.0, and evaluated for adequacy (preserved information), fluency (grammatical correctness), meaning (preserved connotation), and severity (clinical harm), along with assessment of overall preference. Domain-level ratings and preferred translation source were summarized with descriptive statistics and compared with professional translations. RESULTS: Google Translate and ChatGPT demonstrated similar domain-level ratings to professional translations for Spanish and Portuguese. For Haitian Creole, compared with both Google Translate and ChatGPT, professional translations demonstrated significantly greater adequacy, fluency meaning, and severity scores. ChatGPT (33.3%, P < .001) and Google Translate (23.3%, P = .024) contained more potentially clinically significant errors (severity score ≤3) for Haitian Creole than professional translations (8.3%). Professional Haitian Creole (48.3%) and Portuguese (43.3%), but not Spanish (15%), translations were most frequently preferred among translation sources. CONCLUSIONS: Machine translation platforms have comparable performance to professional translations for Spanish and Portuguese but shortcomings in quality, accuracy, and preference persist for Haitian Creole. Diverse multilingual training data are needed, along with regulations ensuring safe and equitable applications of machine translation in clinical practice.

Health Care Access and Use Among Children & Adolescents Exposed to Parental Incarceration-United States, 2019.

OBJECTIVE: The United States has the highest incarceration rate in the world, with spillover impacts on 5 million children with an incarcerated parent. Children exposed to parental incarceration (PI) have suboptimal health care access, use, and outcomes in adulthood compared to their peers. However, little is known about their access and utilization during childhood. We evaluated relationships between PI and health care use and access throughout childhood and adolescence. METHODS: We analyzed the nationally representative 2019 National Health Interview Survey Child Sample to examine cross-sectional associations between exposure to incarceration of a residential caregiver, access to care, and health care use among children aged 2-17. Respondents were asked about measures of preventive care access, unmet needs due to cost, and acute care use over the last year. We estimated changes associated with PI exposure using multiple logistic regression models adjusted for age, sex, race, ethnicity, parental education, family structure, rurality, income, insurance status, and disability. RESULTS: Of 7405 sample individuals, 467 (weighted 6.2% [95% CI 5.5-6.9]) were exposed to PI. In adjusted analyses to produce national estimates, exposure to PI was associated with an additional 2.2 million children lacking a usual source of care, 2 million with forgone dental care needs, 1.2 million with delayed mental health care needs, and 865,000 with forgone mental health care needs. CONCLUSIONS: Exposure to PI was associated with worse access to a usual source of care and unmet dental and mental health care needs. Our findings highlight the need for early intervention by demonstrating that these barriers emerge during childhood and adolescence.

Access to a novel first-line single-tablet HIV antiretroviral regimen in Affordable Care Act Marketplace plans, 2018-2020.

BACKGROUND: A pillar of the United States' Ending the HIV Epidemic (EHE) initiative is to rapidly provide antiretroviral therapy (ART) in order to achieve HIV viral suppression. However, insurance benefit design can impede ART access. The primary objective of this study is to understand how Affordable Care Act (ACA) Marketplace qualified health plan (QHP) formularies responded to two new ART single tablet regimens (STRs): dolutegravir/abacavir/lamivudine (DTG/ABC/3TC; approved in 2014) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; approved in 2018). METHODS: We conducted a descriptive study of individual and small group QHPs to assess coverage, cost sharing (coinsurance vs. copay), specialty tiering, prior authorization, and out-of-pocket (OOP) costs for DTG/ABC/3TC and BIC/FTC/TAF. All individual and small group QHPs offered in state ACA Marketplaces from 2018-2020 were identified using plan-level formulary data from Ideon linked to end-of-year data from Robert Wood Johnson Foundation's Individual Market Health Insurance Exchange (HIX). RESULTS: For 2018, 2019, and 2020, respectively, we identified 19,533, 17,007, and 21,547 QHPs. While DTG/ABC/3TC coverage was above 91% from 2018-2020, BIC/FTC/TAF coverage improved from 60 to 86%. Coverage of BIC/FTC/TAF improved in EHE priority jurisdictions from 73 to 90% driven by increased coverage with coinsurance. Although BIC/FTC/TAF had a higher wholesale acquisition cost than DTG/ABC/3TC, monthly OOP cost trends differed regionally in the Midwest but did not differ by EHE priority jurisdiction status. CONCLUSIONS: QHP coverage of STRs is heterogeneous across the US. While coverage of BIC/FTC/TAF increased over time, many QHPs in EHE priority jurisdictions required coinsurance. Access to new ART regimens may be slowed by delayed QHP coverage and benefit design.

Reevaluating 30-day head ultrasound screening for preterm infants in the era of decreasing periventricular leukomalacia.

OBJECTIVE: Neonatal brain injury is a potentially devastating cause of neurodevelopmental impairment. There is no consensus, however, on the appropriate timing and frequency of routine head ultrasound (HUS) screening for such injuries. We evaluated the diagnostic utility of routine HUS screening at 30 days of life ("late HUS") for detecting severe intraventricular hemorrhage (IVH) or cystic periventricular leukomalacia (c-PVL) in preterm infants with a negative HUS before 14 days of life ("early HUS"). METHODS: Single-center retrospective cohort analysis of infants born at ≤ 32 weeks gestational age (GA) admitted to the University of Nebraska Medical Center NICU from 2011-2018. Demographics, HUS and MRI diagnoses were abstracted from clinical records. Fisher's exact test and t-test assessed associations between categorical and continuous variable, respectively. RESULTS: 205 infants were included-120 very preterm (28-32 weeks GA) and 85 extremely preterm (<28 weeks GA). Negative predictive value of early HUS for predicting any clinically significant anomalies (severe IVH or c-PVL) on late HUS was 100% for extremely and 99.2% for very preterm infants. Term-equivalent MRI detected previously undiagnosed c-PVL in 16.7% of the 24 patients that received MRI; all infants with new c-PVL on MRI had severe IVH on early HUS. CONCLUSION: Following negative early HUS, late HUS detected significant new abnormalities in one infant. These data suggest that in a unit with low prevalence of c-PVL, 30-day HUS may have limited clinical utility following negative screening. In infants with abnormal early HUS, clinicians should consider obtaining term-equivalent MRI screening to detect c-PVL.

Design and Evaluation of a Novel Health Security, Infectious Diseases, Health Systems Science, and Service Learning Course During the COVID-19 Pandemic.

During the COVID-19 pandemic, academic health centers suspended clinical clerkships for students. A need emerged for innovative virtual curricula to continue fostering professional competencies. In March 2020, a multidisciplinary team from the University of Nebraska Medical Center had 2 weeks to create a course on the impact of infectious diseases that addressed the COVID-19 pandemic in real time for upper-level medical and physician assistant students. Content addressing social determinants of health, medical ethics, population health, service learning, health security, and emergency preparedness were interwoven throughout the course to emphasize critical roles during a pandemic. In total, 320 students were invited to complete the survey on knowledge gained and attitudes about the course objectives and materials and 139 responded (response rate 43%). Students documented over 8,000 total hours of service learning; many created nonprofit organizations, aligned their initiatives with health systems efforts, and partnered with community-based organizations. Thematic analysis of qualitative evaluations revealed that learners found the greatest value in the emphasis on social determinants of health, bioethics, and service learning. The use of predeveloped, asynchronous e-modules were widely noted as the least effective aspect of the course. The COVID-19 pandemic introduced substantial challenges in medical education but also provided trainees with an unprecedented opportunity to learn from real-world emergency preparedness and public health responses. The University of Nebraska Medical Center plans to create a health security elective that includes traditional competencies for emergency preparedness and interrogates the social and structural vulnerabilities that drive disproportionately worse outcomes among marginalized communities. With further evaluation, many components of the curriculum could be broadly scaled to meet the increasing need for more public health and health security medical education.

Activity-dependent translation dynamically alters the proteome of the perisynaptic astrocyte process.

Within eukaryotic cells, translation is regulated independent of transcription, enabling nuanced, localized, and rapid responses to stimuli. Neurons respond transcriptionally and translationally to synaptic activity. Although transcriptional responses are documented in astrocytes, here we test whether astrocytes have programmed translational responses. We show that seizure activity rapidly changes the transcripts on astrocyte ribosomes, some predicted to be downstream of BDNF signaling. In acute slices, we quantify the extent to which cues of neuronal activity activate translation in astrocytes and show that this translational response requires the presence of neurons, indicating that the response is non-cell autonomous. We also show that this induction of new translation extends into the periphery of astrocytes. Finally, synaptic proteomics show that new translation is required for changes that occur in perisynaptic astrocyte protein composition after fear conditioning. Regulation of translation in astrocytes by neuronal activity suggests an additional mechanism by which astrocytes may dynamically modulate nervous system functioning.