Primary nasal influenza infection rewires tissue-scale memory response dynamics.

The nasal mucosa is often the initial site of respiratory viral infection, replication, and transmission. Understanding how infection shapes tissue-scale primary and memory responses is critical for designing mucosal therapeutics and vaccines. We generated a single-cell RNA-sequencing atlas of the murine nasal mucosa, sampling three regions during primary influenza infection and rechallenge. Compositional analysis revealed restricted infection to the respiratory mucosa with stepwise changes in immune and epithelial cell subsets and states. We identified and characterized a rare subset of Krt13+ nasal immune-interacting floor epithelial (KNIIFE) cells, which concurrently increased with tissue-resident memory T (TRM)-like cells. Proportionality analysis, cell-cell communication inference, and microscopy underscored the CXCL16-CXCR6 axis between KNIIFE and TRM cells. Secondary influenza challenge induced accelerated and coordinated myeloid and lymphoid responses without epithelial proliferation. Together, this atlas serves as a reference for viral infection in the upper respiratory tract and highlights the efficacy of local coordinated memory responses.

Primary nasal viral infection rewires the tissue-scale memory response.

The nasal mucosa is frequently the initial site of respiratory viral infection, replication, and transmission. Recent work has started to clarify the independent responses of epithelial, myeloid, and lymphoid cells to viral infection in the nasal mucosa, but their spatiotemporal coordination and relative contributions remain unclear. Furthermore, understanding whether and how primary infection shapes tissue-scale memory responses to secondary challenge is critical for the rational design of nasal-targeting therapeutics and vaccines. Here, we generated a single-cell RNA-sequencing (scRNA-seq) atlas of the murine nasal mucosa sampling three distinct regions before and during primary and secondary influenza infection. Primary infection was largely restricted to respiratory mucosa and induced stepwise changes in cell type, subset, and state composition over time. Type I Interferon (IFN)-responsive neutrophils appeared 2 days post infection (dpi) and preceded transient IFN-responsive/cycling epithelial cell responses 5 dpi, which coincided with broader antiviral monocyte and NK cell accumulation. By 8 dpi, monocyte-derived macrophages (MDMs) expressing Cxcl9 and Cxcl16 arose alongside effector cytotoxic CD8 and Ifng-expressing CD4 T cells. Following viral clearance (14 dpi), rare, previously undescribed Krt13+ nasal immune-interacting floor epithelial (KNIIFE) cells expressing multiple genes with immune communication potential increased concurrently with tissue-resident memory T (TRM)-like cells and early IgG+/IgA+ plasmablasts. Proportionality analysis coupled with cell-cell communication inference, alongside validation by in situ microscopy, underscored the CXCL16-CXCR6 signaling axis between MDMs and effector CD8 T cells 8dpi and KNIIFE cells and TRM cells 14 dpi. Secondary influenza challenge with a homologous or heterologous strain administered 60 dpi induced an accelerated and coordinated myeloid and lymphoid response without epithelial proliferation, illustrating how tissue-scale memory to natural infection engages both myeloid and lymphoid cells to reduce epithelial regenerative burden. Together, this atlas serves as a reference for viral infection in the upper respiratory tract and highlights the efficacy of local coordinated memory responses upon rechallenge.

Implementation Costs of Technology-Enhanced Transitional Palliative Care for Rural Caregivers.

OBJECTIVES: Compared to urban family caregivers (FCG), rural FCG experience greater burdens accessing coordinated care for their loved ones during and after hospitalization. The impact of technology-enhanced transitional palliative care (TPC) on caregiver outcomes is currently being evaluated in a randomized control trial. This study evaluates resource use and health system costs of this FCG-focused TPC intervention and potential Medicare reimbursement mechanisms. METHODS: Rural caregivers of hospitalized patients were randomized into an 8-week intervention consisting of video visits conducted by a registered nurse certified in palliative care, supplemented with phone calls and texts (n = 215), or attentional control. Labor costs were estimated for a registered nurse and compared to scenario analyses using a nurse practitioner or social worker wages. Medicare reimbursement scenarios included Transitional Care Management (TCM) and Chronic Care Management (CCM) CPT codes. RESULTS: In the base case, TPC cost was $395 per FCG facilitated by a registered nurse, compared to $337 and $585 if facilitated by a social worker or nurse practitioner, respectively. Mean Medicare reimbursement in the TCM-only scenario was $322 and $260 for high or moderate complexity patients, respectively. Reimbursement in the CCM only scenario was $348 and $274 for complex and non-complex patients, respectively. Reimbursement in the TCM+CCM scenario was $496 and $397, for high/complex and moderate/non-complex patients, respectively. CONCLUSION: TPC is a feasible, low cost and sustainable strategy to enhance FCG support in rural areas. Potential reimbursement mechanisms are available to offset the costs to the health system for providing transitional palliative care to caregivers of patients recently hospitalized.

Patient Factors Associated With Biased Language in Nightly Resident Verbal Handoff.

This cross-sectional study uses audio recordings of resident handoff of inpatient general medicine and general pediatrics teams to measure the extent of stigmatizing language and describes associations between patient factors and biased language in handoffs.

Cost-Effectiveness of a Homeless Care Transition Program: Durham Homeless Care Transitions.

BACKGROUND Transitional care and medical respite programs provide assistance to people experiencing homelessness as they move from acute care into community settings. These programs can address issues that may fall outside the reach of traditional medical care yet have a profound impact on the health of vulnerable populations. This article focuses on the cost-effectiveness of the Durham Homeless Care Transitions (DHCT) program.METHOD This intervention study of the DHCT program uses a comparison group of people experiencing homelessness who were referred but did not participate. Encounter-level data, aggregated by quarterly segments of charges and reimbursements, were abstracted for all persons referred. Descriptive statistics were computed and models of charges and reimbursements were created using ordinary least squares (OLS) regression to compare utilization for 12 months pre- and post-referral.RESULTS Patients referred to the DHCT program (N = 485) were primarily non-Hispanic Black (62.5%), male (68.4%), uninsured (35.5%), and had an average of 5.3 chronic conditions and an average age of 50.0 years (SD = 11.3). There was variability among charges and reimbursement based on health care visit type but a negative association between treatment and charges, indicating that being part of the DHCT program led to lower charges post-referral.LIMITATIONS The study is limited by lack of access to line-item details of charges, reimbursement, and payer mix.CONCLUSION There is evidence of benefit to patients from transitional care and medical respite programs that does not substantially increase the overall societal cost of care; however, health systems commonly require evidence of cost savings and benefit as a return on investment.

Comparing Palliative Care Knowledge in Metropolitan and Nonmetropolitan Areas of the United States: Results from a National Survey.

Background: Despite recent growth in access to specialty palliative care (PC) services, awareness of PC by patients and caregivers is limited and misconceptions about PC persist. Identifying gaps in PC knowledge may help inform initiatives that seek to reduce inequities in access to PC in rural areas. Objective: We compared knowledge of PC in metropolitan and nonmetropolitan areas of the United States using a nationally representative sample of U.S. adults. Design: We used data from the 2018 Health Information National Trends Survey (HINTS) 5 Cycle 2 to compare prevalence and predictors of PC knowledge and misconceptions in nonmetropolitan and metropolitan areas as defined by the 2013 Urban-Rural Classification (URC) Scheme for Counties. We estimated the association between nonmetro status and knowledge of PC, adjusted for respondent characteristics, using multivariable logistic regression. Results: More respondents reported that they had never heard of PC in nonmetro (78.8%) than metro (70.1%) areas (p < 0.05). Controlling for other factors, nonmetro residence was associated with a 41% lower odds of PC knowledge (odds ratio [OR] = 0.59; 95% confidence interval [CI] = 0.37-0.94), and Hispanic respondents also demonstrated significantly lower odds of PC knowledge conditional on rural status (OR = 0.47; CI = 0.27-0.83). Misconceptions about PC were high in both metro and nonmetro areas. Conclusion: Awareness of PC was lower in rural and micropolitan areas compared with metropolitan areas, suggesting the need for tailored educational strategies. The reduced awareness of PC among Hispanic respondents regardless of rural status raises concerns about equitable access to PC services for this population.