Faculty Bibliography

BACKGROUND/UNASSIGNED:Effective management of alcohol withdrawal syndrome during hospitalization is paramount to patient safety and quality care. NYC Health + Hospitals initiated a quality improvement project to pilot an electronic health record (EHR) integrated, nurse-driven CIWA-Ar symptom-triggered protocol, including recommendations for medications for alcohol use disorder (MAUD), in medical and surgical units at 3 public hospitals. OBJECTIVE/UNASSIGNED:To describe implementation processes and to report related implementation outcomes (appropriateness, feasibility, and adoption) of the updated CIWA-Ar protocol in a safety net hospital setting. METHODS/UNASSIGNED:NYC Health + Hospitals implemented a standardized CIWA-Ar symptom-triggered, nurse-driven EHR protocol on March 15, 2022. The protocol included order sets, practice advisories, task lists, and reminders for assessments and orders. We measured nursing perspectives on feasibility and appropriateness at 6 months via a survey. We measured provider adoption as the proportion of admissions with a CIWA-Ar protocol ordered among admissions that triggered a recommendation, and MAUD use as the proportion of admissions with a MAUD order during hospitalization among all patients with a protocol ordered. RESULTS/UNASSIGNED:= .249). CONCLUSIONS/UNASSIGNED:The CIWA-Ar protocol was appropriate, feasible, and adopted at NYC public hospitals. Quality improvements to ensure protocol fidelity with benzodiazepine dosing and MAUD prescribing are needed.

The Latino population is at an increased risk of developing dementia. Nurses have been identified as a main source of dementia care support for dementia caregivers. Latino dementia caregivers may have unique challenges due to factors including language barriers and cultural values and expectations. A rapid review was conducted to synthesize the qualitative literature on the experiences of Latino family caregivers of persons living with dementia to support nursing integration of palliative care for Latino family caregivers of persons living with dementia. Fifteen articles were included in this rapid review. Five emergent themes were identified from the included articles: (1) Culture and Caregiving Values; (2) Caregiving Challenges; (3) Health Care System Navigation; (4) Managing Dementia Care Without Formal Supports; and (5) Understanding of Dementia. Latino family caregivers often cited cultural values (eg, familismo) as central to their caregiving identities and balanced their own life and that of their loved one with limited support. This rapid review provides implications for practice, policy, and research that can better support the palliative care needs of Latino family caregivers of persons living with dementia and their caregivers.

Optimizing drug dosing in critically ill patients is complex due to dynamic changes in pharmacokinetics and pharmacodynamics driven by disease-related physiology and interventions such as extracorporeal devices. Inadequate dosing may lead to therapeutic failure, whereas excessive dosing can exceed the patient's physiologic reserve, increasing the risk of adverse effects. As the medication experts on the interprofessional ICU team, critical care pharmacists are uniquely equipped to address the complex pharmacotherapeutic needs of critically ill patients. Key responsibilities include proactive medication management; providing education to clinicians, patients, and families; addressing drug-related questions; guideline development and implementation; and monitoring medication safety and efficacy.

OBJECTIVE:Topical Oxygen therapy (tOT) is a novel treatment method capable of expediting granulation tissue formation in patients with non-healing lower extremity venous leg ulcers (VLUs). tOT provides cyclic oxygen with compression and is able to be administered at home, unlike chamber-based oxygen therapy. Although previous randomized prospective trials have demonstrated effectiveness of tOT in treating ulcers of diabetic etiology, its ability to promote healing in refractory venous ulcers requires additional exploration. Thus, we investigated preliminary outcomes of tOT administration in treatment-resistant VLUs. METHODS:We conducted a single-center retrospective review of treatment outcomes among 31 patients with 32 total extremities with VLUs following longitudinal administration of tOT. All patients received managed Medicaid approval for tOT after each ulcer failed to resolve following multiple alternative therapies, including Unnaboot compression, sclerotherapy, thermal ablation, iliac vein stenting, and debridement. Patient response to tOT was determined by assessing mid-treatment progression of ulcer length and width, in addition to final ulceration status at the conclusion of therapy. Mean treatment length, total ulcer duration, peak ulcer length, and peak ulcer width were determined for each patient and compared between healed and unhealed VLUs. RESULTS:Average age across all individuals was 73±19 years (range 27-99). 14 (45%) patients were male, with a racial breakdown of 18 (58%) White, 5 (16%) Hispanic, 6 (19%) Black, and 2 (6%) Asian patients. Comorbid conditions included hypertension in 31 (100%) patients, hyperlipidemia in 15 (48%), and diabetes in 12 (39%). 4 (13%) patients demonstrated a former history of smoking while 3 (10%) patients were currently using tobacco products during the study period. Total duration across all VLUs was 1075±1004 days. Average duration of tOT was 265±233 days, while average pre-treatment ulcer duration was 718±842 days. Mean ulcer length was 7.6±6.8 cm and mean ulcer width was 5.7±5.0 cm (range 2-24 cm for both). Following tOT administration, 11 (34%) VLUs healed entirely, 9 (28%) ulcers improved but did not completely heal, 8 (25%) remained unchanged, and 4 (13%) worsened despite treatment. Median time to healing among the 11 VLUs which healed completely was 121 days. For ulcers that did not heal, the mean duration of tOT was 333±261 days. No differences were observed in the pretreatment VLU duration (p=0.54), maximum length (p=0.50) or maximum width (p=0.80) of healed versus unhealed VLUs. CONCLUSIONS:20 (62.5%) of the 32 refractory VLUs treated with tOT either decreased in size or healed entirely after failing multiple previous therapies. 3 (27.3%) of the 11 ulcers which healed completely recurred following topical oxygen therapy.

OBJECTIVE:To define oncologic outcomes in Veterans in the modern era using a multi-institutional cohort designed to support development and validation of prognostic and predictive biomarkers for oropharyngeal squamous cell carcinoma (OPSCC). METHODS:A retrospective analysis was conducted including adult OPSCC patients treated at one of nine Veterans Affairs Medical Centers between 2000 and 2024; inclusive of 597 HPV-associated and 197 HPV-independent tumors. All patients were treated with curative intent external beam radiotherapy (100%) with (90%) or without concurrent chemotherapy. RESULTS:A total of 894 adult patients (mean age, 64 years; 881 (99.5%) male) were included in the study; 22% of patients self-identified as Black. The estimated 2- and 5-year OS rates for the entire cohort were 71% and 54%, respectively and lagged substantially behind locoregional control (LRC) and distant metastatic control (DMC). For Veterans with HPV-associated OPSCC, LRC and DMC at 5 years were 87% and 87% respectively. The strongest drivers of OS and LRC were T-classification and chemotherapy choice on univariate and multivariate analysis. CONCLUSIONS:Although LRC and DMC rates among Veterans track well with recently completed clinical trial outcomes, OS rates lag substantially suggestive of higher rates of non-cancer-specific mortality. Together, these data suggest that predictive biomarker strategies focused on treatment effectiveness should be predicated on LRC and DMC rather than OS. This multicenter study is the first step in providing a robust dataset capable of developing and optimizing artificial intelligence (AI)-informed prognostic and predictive strategies essential to a precision oncology approach to OPSCC.

BACKGROUND:Genetic determinants of resilience remain poorly defined beyond family studies. OBJECTIVES/OBJECTIVE:The purpose of this study was to perform an unbiased study of individuals with discordance between clinical/genetic risk and atherosclerotic burden to discover novel genetic pathways underpinning atherosclerosis. METHODS:We used 2 genotyped cohorts with well-defined coronary anatomy: PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) (discovery cohort: coronary computed tomography angiography) and CATHGEN (CATHeterization GENetics) (validation cohort: invasive angiography). Resilience was defined as high clinical and polygenic risk of coronary artery disease (CAD), yet without coronary plaque. Resilient individuals were compared to patients with obstructive CAD (oCAD) (stenosis ≥70%) using genome-wide association analyses at variant, gene, and pathway levels. RESULTS:In PROMISE (n = 605), 46 (8%) were resilient and 88 (15%) had oCAD. In CATHGEN (n = 3,236), 127 (4%) were resilient and 1,852 (57%) had oCAD. Clinical risk factors and polygenic risk scores were similar between resilient and oCAD patients in both cohorts. Variant- and gene-level analyses did not yield genome-wide significant signals. Pathway-level analyses identified 4 resilience-associated pathways in PROMISE that replicated in CATHGEN: adipocytokine signaling, fatty acid metabolism, fatty acid degradation, and vascular smooth muscle contraction. CONCLUSIONS:Resilience to CAD-defined as the absence of coronary atherosclerosis despite high clinical and polygenic risk-is present in both lower- (PROMISE) and higher-risk (CATHGEN) cohorts and is linked to protective variants in metabolic and vascular pathways. This unbiased, proof-of-concept approach reveals biologically plausible targets for replication and mechanistic studies in larger imaging-based genetics cohorts.

Reciprocal innovation, a model of sustained, multidirectional exchange in which health strategies are adapted, revisited, and refined across contexts, offers a compelling framework to rethink how implementation science can support global health equity by enabling dynamic, multidirectional learning across different contexts. Drawing on the EXTRA-CVD trial, a nurse-led cardiovascular disease prevention intervention designed to extend the HIV treatment cascade in United States (U.S.) HIV clinics, which adapted strategies informed by implementation research in Kenya and the U.S. Veterans Affairs health system, this perspective examines how reciprocal innovation can begin to emerge within existing research structures, as well as where opportunities for deeper exchange remain limited. We identify four operational domains of reciprocal innovation: care delivery strategies, end-user engagement, research methodologies, and research leadership and partnership. Across these domains, we describe how cross-context learning shaped intervention adaptation and site-level implementation in EXTRA-CVD, as well as missed opportunities where more intentional feedback, shared leadership, and methodological exchange could have strengthened multidirectional learning. Taken together, this work highlights both the potential and the practical challenges of reciprocal innovation in implementation research, emphasizing its role in moving beyond unidirectional knowledge transfer toward iterative, context-responsive learning. By embedding structures for iterative feedback, equity-centered governance, and multidirectional learning systems within research and implementation systems, future global partnerships can foster more inclusive, responsive, and sustainable health interventions.

INTRODUCTION/BACKGROUND:Aldosterone dysregulation (excess aldosterone production at the source within the adrenal glands) in the absence of primary aldosteronism is a complex physiologic driver of uncontrolled hypertension and cardiovascular and kidney outcomes. Understanding the manifestations and burden of aldosterone dysregulation is critical to optimizing treatment and improving outcomes in patients with hypertension. This review examines the prevalence, patient attributes and burden of aldosterone dysregulation, and its impact on patient outcomes. METHODS:A targeted literature review of articles published between 2013 and 2024 was conducted. A patient/population, intervention, comparison, and outcomes framework was used, with a predefined search and selection protocol. Articles focused on primary aldosteronism were excluded unless they also referenced essential hypertension. A screening tool that used methods including artificial intelligence, trained using manual (human) screening, was employed to select relevant articles, which underwent human review to confirm inclusion/exclusion. RESULTS:Initial searches yielded 16,501 unique articles. Following abstract screening, 327 full-text articles were reviewed, yielding 123 relevant articles. Included studies utilized a range of aldosterone-related thresholds and measures to characterize patients with aldosterone dysregulation. Several patient attributes impact aldosterone levels, including age, race, ethnicity, sex, and body mass index. Lifestyle factors such as sodium intake also impact aldosterone, but the effect varies by race and body weight. Long-term excess aldosterone was associated with elevated blood pressure (BP), cardiovascular-kidney-metabolic diseases, and end-organ damage, leading to a greater risk of adverse clinical outcomes and mortality. Further evidence is needed to determine whether these occur independently of BP levels. CONCLUSION/CONCLUSIONS:Excess aldosterone is associated with poor cardiovascular-kidney-metabolic outcomes, including increased morbidity and mortality. Aldosterone dysregulation (excess aldosterone production at the source) is an underlying driver of cardiovascular-kidney-metabolic diseases, which may not be adequately addressed by current antihypertensive therapies.

BACKGROUND:Epigenetic regulators represent a novel strategy to modulate the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). In preclinical models, DNA hypomethylating agents enhance cytotoxic T-cell infiltration, synergize with PD-1 blockade, and improve survival when combined with immune checkpoint blockade. This single-institution, phase II study evaluated the safety, efficacy, and biomarkers of azacitidine plus pembrolizumab in patients with previously treated PDAC. METHODS:Patients with locally advanced or metastatic PDAC after one prior regimen received 50 mg/m2 subcutaneous azacitidine on days 1-5 of a 28-day cycle, starting week 1, and pembrolizumab 200 mg intravenously every 3 weeks starting week 3. Baseline and on-treatment blood and tumor was collected for exploratory biomarker analysis. RESULTS:Thirty-six patients enrolled between October 2017 and September 2021 (median age: 62.5 years); 34 were evaluable for safety; 31 for efficacy. Treatment was generally well-tolerated, with Grade 1-2 fatigue and diarrhea most common AEs. Three patients (9.7%) had a partial response, and the disease control rate was 35.5%. Median progression-free and overall survival was 1.51 and 4.83 months, respectively. Exploratory analysis suggested higher baseline CD8+ T cells and lower tumor Ki-67 was associated with response, whereas low baseline CD8+ T cell and Granzyme B infiltration correlated with higher exponential tumor growth rate. PD-L1 and CD68 expression were not predictive of benefit. CONCLUSION/CONCLUSIONS:Azacitidine plus pembrolizumab demonstrated limited clinical activity in second line, locally advanced or metastatic PDAC. Biomarker analysis suggests higher baseline CD8+ T-cell infiltration and lower proliferative index may identify patients more likely to benefit. (NCT03264404).