Brigid M. Wilson

To improve adult vaccinations rates, we implemented a Virtual Vaccine (ViVa) clinic that provided concise vaccine recommendations for patients with an upcoming primary care visit. Among Veterans ≥50, 36% of patients reviewed by the ViVa clinic received ≥1 of the recommended vaccines, compared to 23% of those in control groups.

Background: Residents in nursing homes are particularly susceptible to pressure injuries and infections with multidrug-resistant organisms (MDROs) due to high colonization rates, frequent healthcare contact, and antibiotic exposure. The Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Skin Care and MDRO Prevention in Long-Term Care (LTC) implemented evidence-based skin care and infection prevention (IP) strategies combined with safety-culture building initiatives to prevent pressure injuries and improve IP practices in U.S. skilled nursing facilities and nursing homes.Methods: Participating facilities in the quality improvement initiative had access to 19 webinars paired with “teachable moments,” brief educational tools designed for distribution to direct-care staff during daily huddles. Implementation advisers supported facilities through monthly coaching calls. Educational content emphasized proper bathing, skin assessment and care, prevention of pathogen transmission, and antibiotic stewardship. Facilities reported hospital transfer rates for a 12-month retrospective baseline period (June 2022–May 2023) and throughout the 18-month implementation period (June 2023–November 2024). Minimum Data Set (MDS) data on pressure injuries and skin conditions were obtained from the Centers for Medicare & Medicaid Services and summarized quarterly. Linear mixed models assessed changes between periods. Facilities also self-reported process measure changes including implementation of IP strategies and practices through monthly surveys.Findings: Among 318 enrolled facilities, 309 (97%) completed the Safety Program. Hospital transfer rates did not change from beginning to end of the program. The percentage of residents with stage 2-4 or unstageable nosocomial unhealed pressure injuries decreased significantly by 0.60 percentage points (95% CI: -0.75 to -0.45, p<0.001). Reductions in overall pressure injury rates were greater among facilities with high engagement compared with facilities with low engagement (-0.90% vs -0.24%; p<0.005). Adoption of several recommended IP strategies and practices, including feedback systems and monitoring of hand hygiene and personal protective equipment compliance, increased significantly during the program.Interpretation: Participation in a national nursing home quality improvement program focused on skin care, infection prevention, and safety culture was associated with reductions in nosocomial pressure injuries and increased adoption of recommended IP practices, but no significant change in hospital transfer rates. Facilities with greater program engagement experienced larger reductions in pressure injury rates, suggesting that active participation may support implementation of practices to improve resident safety in LTC settings.

Background: RSV vaccine effectiveness (VE) has not been described among nursing home (NH) residents, who are at increased risk for severe disease. We report VE of bivalent RSVpreF against laboratory-confirmed RSV infection among NH residents across two seasons, overall and stratified by age and comorbidities.Methods: We conducted a national retrospective cohort study of residents living in Veterans Affairs (VA) NH over two RSV seasons (October 2023–April 2024; October 2024–April 2025), using VA administrative data. The main outcome was laboratory-confirmed RSV infection. Vaccination status classified as a three-level, within-person, time-varying exposure: unvaccinated, vaccinated in current season, or vaccinated in the prior season. VE was calculated as 1 minus the hazard ratio, using Cox proportional hazards models adjusted for resident demographics and RSV season, conditional on calendar month.Findings: We identified 15,078 unique NH residents and 220 laboratory-confirmed RSV infections, of which 29 (13%) occurred among vaccinated residents at a median (IQR) of 189 (84-388) days post-vaccination. Current-season VE was 74% (95% CI: 56–85) and prior-season VE was 60% (95% CI: 28-78). VE declined among residents aged ≥75 years when vaccinated in the prior season from 73% (50–86) to 53% (10–76). Similarly, VE declined modestly among those with cardiopulmonary disease when vaccinated in the prior season from 76% (51–89) to 54% (4–78).Interpretation: In this first RSV vaccine VE study among NH residents, bivalent RSVpreF vaccination was associated with a meaningful reduction in laboratory-confirmed RSV infection risk that persisted across two seasons, with diminished second-season protection for those with advanced age or cardiopulmonary disease. These findings support the use of RSV vaccination as an effective strategy to reduce the RSV disease burden in long-term care settings and indicate subgroups that remain an important target for prevention efforts.

Deterioration of the blood–brain barrier (BBB), including impaired neurovascular uncoupling, contributes to cognitive decline in aging. The BBB is formed principally by brain microvascular endothelial cells (ECs), and ECs throughout the body are enriched for the transcription factor Krüppel-like factor 4 (KLF4). Because KLF4 levels in ECs decrease with age, we tested whether that decline contributes to aging-related BBB deterioration, neurovascular dysfunction, and cognitive impairment. Using EC-specific Klf4 knockout mice (EC-K4KO), we show that loss of EC KLF4 accelerates multiple age-related brain pathologies. Indeed, middle-aged EC-K4KO mice display pathological features that are not normally observed until advanced age, including marked BBB leakage, impaired neurovascular coupling, loss of microvessels, increased oxidative damage, neuroinflammation, neurodegeneration, anxiety-like behavior, and cognitive deficits. Single-cell RNA sequencing of brain vasculature reveals dysregulation of immune response and barrier-related genes in ECs lacking KLF4, indicating that KLF4 maintains brain endothelial homeostasis by constraining proinflammatory and senescence programs at the chromatin level. Together, these results identify loss of EC KLF4 as a key driver of neurovascular decline and age-associated cognitive dysfunction.

Objective: Describe the workload associated with using telehealth to support Antimicrobial Stewardship efforts at Veterans Affairs Medical Centers (VAMCs) without local infectious diseases (ID) expertise. Design: A mixed-methods process assessment to evaluate workload and workflow associated with Videoconference Antimicrobial Stewardship Teams (VASTs). Setting and Participants: Rural VAMC champions paired with ID consultants at geographically distant VAMCs to form VASTs. Methods: Total workload estimates were based on time that champions and ID consultants allocated to VAST activities. Clinical Procedural Terminology (CPT) codes were used to estimate the workloads for clinical encounters. Role-based process maps were developed to understand variation in implementation by VAMC. Results: The average workload that champions and ID consultants allocated to VAST activities was 6.7% (range 1.0%–20.0%) and 8.4% (range 2.0%–12.5%) full-time equivalents (FTEs), respectively. Clinical encounters completed by ID consultants contributed an average of 1.4% (range < 0.01%–2.5%) FTEs to the workload. The average proportion of FTEs required to sustain VASTs was 13.0% (range 3.0%–31.6%). Process maps showed four phases common to each VAST’s workflow: case identification, meeting preparation, team meeting, and documentation. The tasks associated with each phase varied between VASTs. Champions carried out most tasks related to case finding and meeting preparation; the ID consultants completed most documentation tasks. Conclusions: The distribution of tasks within and among the VASTs indicated opportunities to improve workflow efficiency. Investing <12.5% of the FTE allocated to VA Antimicrobial Stewardship programs to support the time of an ID consultant from another VAMC can help rural VAMCs achieve staffing sustainability.

Background: To support Antimicrobial Stewardship programs (ASPs) as well as the clinical care of patients with infections, we disseminated and implemented a Videoconference Antimicrobial Stewardship Team (VAST) to connect multidisciplinary teams from rural Veterans Affairs (VA) medical centers with geographically distant ID experts. Here, we describe the clinical syndromes discussed and the response to recommendations made during VAST sessions. Methods: Between September 2021 to February 2024, eight ID consultants established VASTs with ten rural VAMCs, holding regularly scheduled videoconference sessions to discuss clinical cases and provide recommendations. Data were collected on patient demographics, clinical syndromes, and recommendations. Acceptance of recommendations within one week of each session was assessed via chart review. Six months after the intervention began, we conducted semi-structured interviews to assess participants’ perceptions of VASTs. Results: VASTs reviewed 626 cases involving 527 unique patients. Among 763 clinical syndromes discussed, the most common were infections of the respiratory (29%) or urinary tract (21%). Overall, VASTs made 973 recommendations, of which 71% were accepted. Of 570 recommendations related to antibiotics, 459 (80%) were accepted. Among 403 other recommendations, 235 (58%) were accepted. Interviews with participants indicated the importance of building trust and strong interpersonal relationships. Conclusions: VASTs effectively supported Antimicrobial Stewardship in rural VA medical centers (VAMCs) without local ID expertise. High acceptance rates, particularly for antibiotic-related recommendations, suggest that telehealth-enabled provider-to-provider models enhance stewardship efforts.

Background: Heart failure (HF) is associated with inflammation, but its specific immunophenotypic characteristics and relevant prognostic relationships are poorly established. Methods: In the HRS (Health and Retirement Study; N=9566), we used multivariable logistic regression, linear regression, and Cox proportional hazard models to describe cross‐sectional relationships between HF, plasma biomarkers, leukocyte levels, lymphocyte subsets enumerated by flow cytometry, and all‐cause survival. We then analyzed real‐world lymphocyte levels, incident HF, and death among outpatients within the US Veterans Affairs Health System (N=38 565). Results: HF was accompanied by elevated inflammatory cytokine levels as well as relative lymphopenia. This lymphopenia was due to marked reduction in the reservoir of naïve CD4+ T cells, whereas total CD8+ T‐cell numbers were not reduced, and the CD4+ effector memory niche was expanded. Importantly, among those without HF, total lymphocytes and naïve CD4+ T cells were each inversely related to aminoterminal pro‐B‐type natriuretic peptide levels and signaled a higher mortality rate. Linkages between lymphocyte deficiency, HF, and survival were robust to adjustment for low physical activity and a variety of inflammatory biomarkers. In the Veterans Affairs system, real‐world lymphopenia (absolute lymphocyte count P P <0.001). Conclusions: HF is associated with total lymphopenia due to a specific deficiency of naïve CD4+ T lymphocytes. Crude lymphopenia among the general ambulatory population can herald incident HF and poor subsequent survival.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen commonly implicated in pneumonia for which vancomycin is often used to cover empirically. Our study examined the impact of a pharmacy-based automatic MRSA polymerase chain reaction (PCR) nares intervention. Methods: We included patients prescribed vancomycin for pneumonia and defined three cohorts: pre-intervention (Cohort 1), post-test implementation (Cohort 2), and post-test implementation with electronic medical record (EMR) enhancements and active stewardship involvement (Cohort 3). The primary outcome was total duration of vancomycin treatment. We performed a desirability of outcome ranking with response adjusted for duration of antibiotic risk (DOOR/RADAR) analysis to prioritize clinical outcomes including adverse events, escalation of care, and death. Results: The median duration of vancomycin therapy decreased between Cohorts 1 and 2 (55 versus 47 hours, p = 0.15), with a greater decrease detected among the subset of Cohort 2 patients from whom the PCR test was actually collected (42 hours, p = 0.035). Duration of therapy was lowest in Cohort 3 (22.3 hours, p < 0.001). In the DOOR/RADAR analysis, no meaningful difference in clinical outcomes was detected between Cohorts 1 and 2 ( p = 0.55). Cohort 3 had substantially better ranked outcomes when compared to Cohorts 1 and 2 ( p < 0.001). Conclusion: Vancomycin treatment duration was shorter in patients after a pharmacy-directed, EMR-based MRSA PCR intervention was implemented, with a greater response after implementation of additional EMR enhancements and active stewardship involvement, improving test collection rate and result response. This study will help inform future interventions pairing automated EMR-based interventions with stewardship team efforts.

Objective: To evaluate the impact of implementation of a conditional reflex urine culturing strategy on urine culture rates, antimicrobial use, and clinical outcomes in hospitalized adults. Design: Pre-post quasi-experimental study. Setting: Emergency departments and inpatient units within a large, integrated healthcare system in Northeast Ohio, comprising 10 medical centers. Patients: Adult patients with a urine culture ordered from June 1, 2018, to May 31, 2023. Methods: A system-wide intervention was implemented on June 1, 2020, requiring urinalysis (UA) with pyuria findings to trigger a urine culture order. We compared urine culture rates, antimicrobial use (measured by days of therapy [DOT] and days of antimicrobial spectrum coverage [DASC]), and clinical outcomes between pre-and post-intervention periods. Results: The intervention resulted in an 85.4% reduction in urine culture rates (0.54 vs 3.71 per 100 patient days). Antimicrobial use decreased, with DOT per 100 patient days dropping by 11.5% and DASC/DOT by 16.1%. No significant differences were observed in Clostridioides difficile infection rate, subsequent bloodstream infections with urinary pathogens, or mortality between pre- and post-intervention groups. Conclusions: A conditional reflex urine culturing strategy implemented as part of a diagnostic stewardship framework reduced urine culture and antimicrobial use without adverse clinical outcomes. This highlights the potential of diagnostic stewardship to optimize antimicrobial use in hospitalized adults.

BACKGROUND: FXII (coagulation factor XII) is best known for its roles in the contact and kallikrein-kinin pathways. FXII is converted to FXIIa (activated factor XII) by PKa (plasma kallikrein) or its unique ability to autoactivate on bacterial or other biologic surfaces. In vivo, FXIIa initiates the intrinsic coagulation pathway and promotes inflammation by reciprocal activation of prekallikrein, which cleaves HK (high-molecular-weight kininogen) to liberate bradykinin. CpaA (coagulation targeting metallo-endopeptidase of A baumannii ) is a secreted metalloprotease identified in a human clinical isolate of Acinetobacter baumannii that cleaves FXII at O-linked glycosylated sites, inhibiting contact activation. While CpaA facilitates a modest in vivo fitness advantage in mice, the role of CpaA in human infection remains unclear. As such, the objectives of this study were to characterize the structural details of the interaction between CpaA, FXII, and the KKS (kallikrein-kinin system) and to determine the downstream consequences on thromboinflammatory responses. METHODS: The effect of purified CpaA on the coagulant activity of FXII and the generation of bradykinin was characterized. Neutrophil signaling, flow cytometry, and functional assays were performed to define how CpaA-mediated cleavage of FXII affects innate immune functions. Bacterial killing by human neutrophils was performed with wild-type and mutant A baumannii strains lacking CpaA. RESULTS: We found that CpaA cleaves both FXII zymogen and FXIIa but not beta Factor XII. However, cleavage of FXIIa by CpaA does not significantly inhibit its clotting activity, demonstrating that CpaA does not inactivate FXIIa, but rather prevents activation of zymogen FXII. CpaA also cleaves HK, resulting in reduced kallikrein activation and bradykinin generation. We previously identified that zymogen FXII interacts with the urokinase receptor on neutrophils and upregulates neutrophil activation. Here, we demonstrate that CpaA cleaves neutrophil FXII, resulting in reduced Akt2 phosphorylation, chemotaxis, oxidative burst, and neutrophil extracellular trap formation. Importantly, CpaA decreases the human neutrophil killing efficiency of A baumannii in culture. CONCLUSIONS: These data identify a role for FXII in responding to bacterial infection and suggest that by inhibiting the contact and kallikrein-kinin pathways and impairing neutrophil activation, CpaA may blunt the innate immune response and help prevent the elimination of A baumannii from the human host.