Recent Publications by CFE Educators

Delirium is a neurologic syndrome characterized by inattention and cognitive impairment frequently encountered in medically ill older adults. As a hallmark of age-related brain vulnerability, delirium offers a clinical model to investigate how peripheral immune responses contribute to acute brain dysfunction. Peripheral inflammation is a key trigger of delirium, but the patient-specific immune responses that drive delirium onset and recovery remain poorly understood. This retrospective cohort study of prospectively collected biospecimens examines RNA sequencing from peripheral blood mononuclear cells of adults hospitalized for COVID-19 to better understand patient-specific factors associated with delirium (n = 64). Longitudinal transcriptomic analyses highlight persistent immune dysregulation in delirium, marked by increasing expression trajectories of genes linked to innate immune pathways, including complement activation, cytokine production, and monocyte/macrophage recruitment. Genes involved adaptive immunity showed a declining trajectory over time in patients with delirium. Although corticosteroid treatment suppressed some aspects of immune hyperactivation, aberrant responses contributing to delirium were exacerbated. Delirium resolution was characterized by normalization of key transcripts such as CCL2 and innate immune markers. Novel associations with delirium included transcripts related to stress granule assembly and the T cell regulators DUSP2 and KLF10. Delirium in COVID-19 is associated with distinct and dynamic peripheral immune trajectories that are modulated by corticosteroids. Further understanding these mechanisms has important implications for preventing delirium in older adults. These findings provide novel mechanistic insights with translational relevance for immunomodulatory strategies targeting maladaptive immune responses to prevent or treat delirium in medically ill populations.

BACKGROUND

Chronic opioid use occurs in 25% of individuals with axial spondyloarthritis (axSpA). Whether introduction of tumor necrosis factor inhibitors (TNFi) influenced secular trends in opioid prescription in axSpA is unknown. We examined opioid prescription trends in axSpA, relative to nonsteroidal anti-inflammatory drugs (NSAIDs) and TNFi, using two observational databases.

METHODS

We used data from IQVIA Medical Research Database (IMRD), a UK electronic health records-based database from 2000-2020, and Merative™ MarketScan® (MarketScan), a US administrative claims-based database from 2006-2021. We included adults (18-89 years, IMRD; 18-65 years, MarketScan) with axSpA. We calculated annual prescription rates for opioids, NSAIDs and TNFi (only in MarketScan) and estimated percentage changes in annual prescription rates by medication class using joinpoint regression.

RESULTS

We included 1,689 individuals from IMRD (mean age 47 years; 74% male) and 18,858 individuals from MarketScan (mean age 45 years; 51% male). In IMRD, annual opioid prescription rates decreased by 2.5% (95% CI -9.1,1.9) between 2001-2007, increased by 3.9% (95% CI -3.0, 14.2) between 2007-2016, and decreased by 0.4% (95% CI -11.2, 2.9) between 2016-2020. In MarketScan, annual opioid prescription rates decreased by 1.5% (95% CI -3.0, 2.0) in 2008-2016 and decreased by 8.6% (95% CI -15.2, -5.7) in 2016-2021. TNFi prescriptions increased by 1.8% (95% CI 1.1, 2.5) in 2008-2021.

CONCLUSION

Opioid prescriptions rates remained stable over time in the UK, while they slightly decreased in the US as TNFi uptake increased. These trends may reflect a US nationwide change in guidance for opioid prescriptions issued in 2016.