Publications by authors named "Alexandria Lewis"

Background: Delirium commonly occurs in older adults following surgery; although its pathophysiology is not fully understood, underlying neurodegeneration is a risk factor.

Objective: Examine the association of preoperative levels of markers of neuronal damage, neurofilament light (NfL) and phosphorylated tau (p-tau), with postoperative delirium.

Methods: Preoperative cerebrospinal fluid (CSF) and plasma were obtained from 158 patients undergoing hip fracture repair and enrolled in the clinical trial "A STrategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients.

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Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe.

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Introduction: Plasma proteomic analyses of unique brain atrophy patterns may illuminate peripheral drivers of neurodegeneration and identify novel biomarkers for predicting clinically relevant outcomes.

Methods: We identified proteomic signatures associated with machine learning-derived aging- and Alzheimer's disease (AD) -related brain atrophy patterns in the Baltimore Longitudinal Study of Aging (n = 815). Using data from five cohorts, we examined whether candidate proteins were associated with AD endophenotypes and long-term dementia risk.

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While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-β (Aβ) progression - a central feature of AD - remains unknown. In the Baltimore Longitudinal Study of Aging, we quantified 942 immunological proteins in plasma and identified 32 (including CAT [catalase], CD36 [CD36 antigen], and KRT19 [keratin 19]) associated with rates of cortical Aβ accumulation measured with positron emission tomography (PET). Longitudinal changes in a subset of candidate proteins also predicted Aβ progression, and the mid- to late-life (20-year) trajectory of one protein, CAT, was associated with late-life Aβ-positive status in the Atherosclerosis Risk in Communities (ARIC) study.

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Background: Although blood-based biomarkers have been identified as cost-effective and scalable alternatives to PET and CSF markers of neurodegenerative disease, little is known about how these biomarkers predict future brain atrophy and cognitive decline in cognitively unimpaired individuals. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether plasma biomarkers of Alzheimer's disease (AD) pathology (amyloid-β [Aβ], phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal brain volume loss and cognitive decline. Additionally, we determined whether sex, APOEε4 status, and plasma amyloid-β status modified these associations.

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Purpose: In August 2022, the Association of Social Work Boards released a long called for pass rate analysis that revealed significant disparities. While many states look to cease the requirement of the Bachelors, Masters, and Advanced Generalist exams in their licensure process, status quo bias leads to hesitancy to remove the requirement of the Clinical exam.

Method: A critical review was undertaken to identify possible alternatives to the current multiple-choice competency-based exam which yielded three assessment formats (oral exams, portfolios, and performance assessment/simulations) and two alternatives (jurisprudence exams and provisional licensure).

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Objectives: Post-operative delirium (POD) affects up to 50% of cardiac surgery patients, with higher incidence in older adults. There is increasing need for screening tools that identify individuals most vulnerable to POD. Here, we examined the relationship between pre-operative olfaction and both incident POD and POD severity in patients undergoing cardiac surgery.

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The choroid plexus (CP) is a vital brain structure essential for cerebrospinal fluid (CSF) production. Moreover, alterations in the CP's structure and function are implicated in molecular conditions and neuropathologies including multiple sclerosis, Alzheimer's disease, and stroke. Our goal is to provide the first characterization of the association between variation in the CP microstructure and macrostructure/volume using advanced magnetic resonance imaging (MRI) methodology, and blood-based biomarkers of Alzheimer's disease (Aß ratio; pTau181), neuroinflammation and neuronal injury (GFAP; NfL).

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Article Synopsis
  • Neurofilament light is a blood biomarker linked to neuroaxonal injury and may indicate the risk of delirium in patients undergoing cardiac surgery.
  • The study found that 44.6% of patients experienced delirium post-surgery, and those with higher baseline levels of neurofilament light were more likely to have delirium.
  • However, the 42% increase in neurofilament light levels from baseline to postoperative day 1 did not correlate with delirium, suggesting only baseline measurements are significant predictors.
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Background: Proteins expressed by brain endothelial cells (BECs), the primary cell type of the blood-brain barrier, may serve as sensitive plasma biomarkers for neurological and neurovascular conditions, including cerebral small vessel disease.

Methods: Using data from the BLSA (Baltimore Longitudinal Study of Aging; n=886; 2009-2020), BEC-enriched proteins were identified among 7268 plasma proteins (measured with SomaScanv4.1) using an automated annotation algorithm that filtered endothelial cell transcripts followed by cross-referencing with BEC-specific transcripts reported in single-cell RNA-sequencing studies.

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(1) Background: Despite the existence of well-established, CSF-based biomarkers such as amyloid-β and phosphorylated-tau, the pathways involved in the pathophysiology of Alzheimer's disease (AD) remain an active area of research. (2) Methods: We measured 3072 proteins in CSF samples of AD-biomarker positive mild cognitive impairment (MCI) participants ( = 38) and controls ( = 48), using the Explore panel of the Olink proximity extension assay (PEA). We performed group comparisons, association studies with diagnosis, age, and APOE ε4 status, overrepresentation analysis (ORA), and gene set enrichment analysis (GSEA) to determine differentially expressed proteins and dysregulated pathways.

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Objective: White matter damage is a feature of Alzheimer's disease, yet little is known about how facets of the Alzheimer's disease process relate to key features of white matter structure. We examined the association of Alzheimer's disease (Aß ratio; pTau181), neuronal injury (NfL), and reactive astrogliosis (GFAP) biomarkers with MRI measures of myelin content and axonal density.

Methods: Among cognitively normal participants in the BLSA and GESTALT studies who received MRI measures of myelin content (defined by myelin water fraction [MWF]) and axonal density (defined by neurite density index [NDI]), we quantified plasma levels of Aβ , Aβ , pTau181, NfL, and GFAP.

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Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen empirically covered in pulmonary infections. Limited studies evaluate the relationship between the MRSA PCR nasal swab assays and clinically diagnosed ventilator-associated pneumonia (VAP), lung abscess, and empyema. This retrospective, single-center study included 161 patients, which aimed to validate the clinical utility of MRSA PCR nasal swabs in VAP, lung abscess, and empyema through sensitivity, specificity, positive predictive value (PPV), and negative predicative value (NPV) analysis.

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Although liver dysfunction has been implicated in Alzheimer's disease (AD), it remains unknown how liver disease may influence the trajectory of brain and cognitive changes in older adults. We related self-reported liver disease to longitudinal measures of brain structure and cognition, as well as baseline measures of plasma AD/neurodegeneration biomarkers in the Baltimore Longitudinal Study of Aging. Liver disease was identified using ICD-9 classification codes.

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Background And Objectives: Although an infectious etiology of Alzheimer disease (AD) has received renewed attention with a particular focus on herpes viruses, the longitudinal effects of symptomatic herpes virus (sHHV) infection on brain structure and cognition remain poorly understood, as does the effect of sHHV on AD/neurodegeneration biomarkers.

Methods: We used a longitudinal, community-based cohort to characterize the association of sHHV diagnoses with changes in 3 T MRI brain volume and cognitive performance. In addition, we related sHHV to cross-sectional differences in plasma biomarkers of AD (β-amyloid [Aβ]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neurodegeneration (neurofilament light [NfL]).

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Background: Neurofilament light is a marker of neuronal injury and can be measured in blood. Postoperative increases in neurofilament light have been associated with delirium after noncardiac surgery. However, few studies have examined the association of neurofilament light changes with postdischarge cognition in cardiac surgery patients, who are at highest risk for neuronal injury and cognitive decline.

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Background And Objectives: The assessment of biomarkers in selecting patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery has been limited to small cohort studies and those with limited follow-up. We assessed the potential for CSF biomarkers in predicting immediate response to CSF tap test (TT) and long-term response after shunt surgery.

Methods: CSF was obtained from patients with iNPH referred for CSF TT after baseline assessment of cognition and gait.

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Disulfide analogs of the alcohol sobriety medication disulfiram (Antabuse®) were evaluated for antimicrobial activity. Structure-activity relationship analyses of MIC data obtained for methicillin-resistant Staphylococcus aureus (MRSA) and other pathogenic organisms revealed correlations between the lipophilicity and bulkiness of the substituents. Analogs conferring optimal anti-MRSA activity contained S-octyl disulfides and either N,N-dimethyl- or N-pyrrolidine dithiocarbamate substituents.

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Background: There is a need to adopt evidence-based approaches to discharge planning in the skilled nursing facility (SNF) short stay population.

Purpose: This article describes implementation of the Reengineered Discharge (RED) process in SNFs and makes recommendations for its future implementation.

Methods: The methods included a pre- and postanalysis of an 18-month RED implementation with a contemporaneous comparison of 4 Midwestern SNFs randomly assigned to 2 different RED implementation strategies.

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Article Synopsis
  • The article recommends adapting hospital-based RED (Reengineered Discharge) processes for use in skilled nursing facilities (SNFs) to enhance patient discharge outcomes.
  • Key adaptations include engaging family/caregivers early in the discharge plan, ensuring quick reconnection to primary care providers, and educating patients about their health conditions and medications upon discharge.
  • Limitations such as reduced staff capacity and corporate policies hinder some RED components' implementation, but adapting these transitional care processes can help prevent discharge issues in SNFs.
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Article Synopsis
  • Epstein-Barr virus (EBV), discovered over 50 years ago, is linked to various diseases, particularly B-cell lymphomas, showing its role in tumor development.
  • Recent advancements in high-throughput next-generation sequencing and mouse models have enhanced our understanding of how EBV contributes to cancer at a molecular level.
  • The review discusses recent progress in understanding EBV-related B-cell lymphomas, covering aspects like transcription regulation, chromosome changes, in vivo studies, and treatment approaches for these viral-associated cancers.
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Interprofessional collaboration is the foundation of hospice service delivery. In the United States, hospice agencies are required to regularly convene interprofessional meetings during which teams review plans of care for the patients and families they serve. A small body of research suggests that team functioning could be significantly enhanced in hospice interprofessional meetings; however, systematic investigation of this possibility has been limited to date.

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Background: In the United States, hospice agencies are required to convene interdisciplinary group (IDG) meetings no less frequently than every 15 days to review patients' care plans. Challenges associated with information sharing during these meetings can impede efficiency and frustrate attendees.

Objectives: We sought to examine information sharing in the context of hospice IDG meetings as a first step toward developing an informatics tool to support interdisciplinary collaboration in this setting.

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Background: Researchers have identified important gender differences in the experience of caring for a family member or friend living with advanced disease; however, trends suggest that these differences may be diminishing over time in response to changing gender roles. In addition, while many studies have found caregiving experiences and outcomes to be poorer among female caregivers, noteworthy exceptions exist.

Objective: The primary aim of this exploratory study was to determine how, if at all, current day caregiving at end of life varies by gender.

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