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Background: During the coronavirus disease 2019 (COVID-19) pandemic, there was a marked increase in alcohol consumption. COVID-19 superimposed on underlying liver disease notably worsens the outcome of many forms of liver injury. The goal of a current pilot study was to test the dual exposure of alcohol and COVID-19 infection in an experimental animal model of alcohol-associated liver disease (ALD)., Methods: After 4 weeks of ethanol (EtOH) feeding, C57BL/6 male mice received SARS-CoV-2 (SARS2-N501Y MA30 ) intranasally at 3 × 10 2 , 1 × 10 3 , 3 × 10 3 , and 1 × 10 4 plaque-forming units (PFU). Mice were then weighed/monitored daily for morbidity/mortality for 10 days while continuing EtOH consumption. Markers of liver inflammation, injury, and intestinal barrier integrity were evaluated., Results: A similar gradual weight loss was observed in all inoculated mice (slightly less in the 3 × 10 2 group) up to post-infection day 4. Greater mortality was observed in mice receiving the highest viral dose at days 3 and 4 post-infection. The majority of the surviving mice subjected to EtOH and inoculated with 3 × 10 3 or 1 × 10 4 PFU rapidly lost 25% of their body weight and were euthanized on post-infection day 4. Analysis of liver health in animals that survived to the end of the experiment exhibited no significant changes in hepatic steatosis but had a limited increase in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at all viral doses versus EtOH alone. However, the 1 × 10 4 PFU viral dose exacerbated EtOH-induced hepatic inflammation characterized by elevated levels of several pro-inflammatory cytokines, including Il-6 and Tnf-α. There was limited effect of viral infection on the intestine., Conclusions: SARS-CoV-2 infection caused a dose-dependent negative impact on body weight and survival in mice fed EtOH. This pilot study suggests that early mortality observed after high-dose SARS-CoV-2 challenge could be due, in part, to hepatic dysfunction following chronic EtOH feeding., (© 2025 Research Society on Alcohol.)

Background : While frailty is a well-established predictor of overall mortality among patients with metastatic non-small cell lung cancer (mNSCLC), its association with patient-reported outcomes is not well-characterized. The goal of this study was to examine the association between an electronic frailty index (eFI) score and patient-reported outcome measures along with prognostic awareness among patients with mNSCLC receiving immunotherapy. Methods : In a cross-sectional study, patients with mNSCLC who were on immunotherapy completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) and the National Cancer Institute Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). We utilized bivariate analyses to compare quality of life, symptoms, supportive services, and prognostic awareness among 3 groups defined by e-frailty status. Results : Sixty patients (mean age 62.5 years, 75% Caucasian, 60% women) participated. Most patients were pre-frail (68%), with 13% being frail and 18% non-frail. Pre-frail and frail patients had significantly lower physical function scores (mean 83.9 fit vs 74.8 pre-frail vs 60.0 frail, P = .04) and higher rates of self-reported pain (75% frail vs 41.5% pre-frail vs 18.2% fit; P = .04) compared to non-frail patients. We found no differences in palliative referral rates. Conclusion : Pre-frail and frail mNSCLC patients identified by the eFI have higher rates of pain and physical functional impairments than non-frail patients. These findings highlight the importance of emphasizing preventive interventions targeting social needs, functional limitations, and pain management, especially among pre-frail patients to reduce further decline., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Having a family member hospitalized in the intensive care unit (ICU) can be a stressful experience for family members, encompassing both psychological and spiritual distress. With over 5 million ICU admissions annually in the United States, it is imperative to enhance the experiences and coping mechanisms of ICU family members. In particularly challenging situations, some family members even face psychological effects known as post-intensive care syndrome-family, which includes anxiety, depression, and posttraumatic stress. The distress may be worsened when patients and families experience poor communication or medical care, which has been shown to be more common among minoritized populations including Black and Hispanic patients and families. Family members' emotional and spiritual distress also has an effect on the medical decisions they make for the patient. While research has delved into the impact of spiritual care for ICU family members, further investigation is still needed to determine the most effective approaches for delivering such care. This narrative review will describe a conceptual model aimed at guiding future research in this endeavor. The model proposes that chaplains provide emotional, spiritual, and information support to ICU family members. This affects both their ICU experience, decision making, and outcomes for the patient and family. This process is also affected by characteristics of the family such as race, ethnicity, and economic status. This model helps identify gaps in research, including the need for randomized trials of spiritual care that identify mechanisms underlying outcomes and demonstrate impact of spiritual care, and consider race, ethnicity, and other characteristics.

During cycling activities, cyclists often monitor a variety of information such as heart rate, distance, and navigation using a bike-mounted phone or cyclocomputer. In many cases, cyclists also ride on sidewalks or paths that contain pedestrians and other obstructions such as potholes, so monitoring information on a bike-mounted interface can slow the cyclist down or cause accidents and injury. In this article, we present HazARdSnap, an augmented reality-based information delivery approach that improves the ease of access to cycling information and at the same time preserves the user's awareness of hazards. To do so, we implemented real-time outdoor hazard detection using a combination of computer vision and motion and position data from a head mounted display (HMD). We then developed an algorithm that snaps information to detected hazards when they are also viewed so that users can simultaneously view both rendered virtual cycling information and the real-world cues such as depth, position, time to hazard, and speed that are needed to assess and avoid hazards. Results from a study with 24 participants that made use of real-world cycling and virtual hazards showed that both HazARdSnap and forward-fixed augmented reality (AR) user interfaces (UIs) can effectively help cyclists access virtual information without having to look down, which resulted in fewer collisions (51% and 43% reduction compared to baseline, respectively) with virtual hazards.

Within most tissues, the extracellular microenvironment provides mechanical cues that guide cell fate and function. Changes in the extracellular matrix such as aberrant deposition, densification and increased crosslinking are hallmarks of late-stage fibrotic diseases that often lead to organ dysfunction. Biomaterials have been widely used to mimic the mechanical properties of the fibrotic matrix and study cell function. However, the initiation of fibrosis has largely been overlooked, due to the challenges in recapitulating early fibrotic lesions within the native extracellular microenvironment. Using visible light mediated photochemistry, we induced local crosslinking and stiffening of extracellular matrix proteins within ex vivo murine and human tissue. In ex vivo lung tissue of epithelial cell lineage-traced mice, local matrix crosslinking mimicked early fibrotic lesions that increased alveolar epithelial cell spreading, differentiation and extracellular matrix remodeling. However, inhibition of cytoskeletal tension or integrin engagement reduced epithelial cell spreading and differentiation, resulting in alveolar epithelial cell dedifferentiation and reduced extracellular matrix deposition. Our findings emphasize the role of local extracellular matrix crosslinking and remodeling in early-stage tissue fibrosis and have implications for ex vivo disease modeling and applications to other tissues.

Background: There has been a growing interest in integrating social and function-focused care into health care settings. Little is known about what older adults perceive as the needs that impact their lives, and the resources to address patients' social and functional needs often exist outside of traditional health care settings., Methods: Our objective was to understand frail older adults' and community organizations' perspectives on what social and functional needs impact older adults' health, the support they receive, and how organizations and health systems could partner to address these needs. We conducted semi-structured interviews with patients and community-based organizations. Patients were aged 65 years or older, frail (electronic frailty index greater than 0.21), and at an increased geographic risk of unmet social needs (Area Deprivation Index greater than or equal to the 75th percentile). Staff were from organizations that provided social and/or functional resources to older adults. We used an inductive content analysis approach and the constant comparative method to analyze the data and identify themes., Results: We interviewed 23 patients and 28 staff from 22 distinct organizations. We found that social, financial, and functional needs were common and highly intertwined among older adults with frailty, but the support they received at home, from their health care providers, and from community organizations was highly varied., Limitations: Our sample was limited to participants from one county, so the results may not be generalizable to other areas. We only inter-viewed organizations and patients with frailty., Conclusions: Health systems and community organizations have distinct areas of expertise, and purposeful collaboration between them could be important in addressing the needs of frail older adults., Competing Interests: Acknowledgments: All authors listed have contributed sufficiently to the project to be included as authors. Portions of this study were presented at the American Geriatric Society Meeting in May 2022. Funding: Dr. Callahan is supported by the National Institute on Aging of the NIH under Award Number K76AG059986. Dr. Gabbard is supported by the National Institute on Aging of the National Institutes of Health under Award Number K23AG070234. Dr. Palakshappa is sup­ported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K23HL146902. The content is solely the responsibility of the authors and does not necessarily rep­resent the official views of the National Institutes of Health. The fund­ing sources did not have any role in the study design, in the collection, analysis, and interpretation of the data, in the writing of the report, or in the decision to submit the article for publication. DP reports personal fees from WellCare of North Carolina outside of the submitted work. Declaration of interests: The authors declare there is no conflict of interest., (Copyright ©2024 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

Background: Advance care planning (ACP) is a process that involves patients expressing their personal goals, values, and future medical care preferences. Digital applications may help facilitate this process, though their use in older adults has not been adequately studied., Objective: This pilot study aimed to evaluate the reach, adoption, and usability of Koda Health, a web-based patient-facing ACP platform, among older adults., Methods: Older adults (aged 50 years and older) who had an active Epic MyChart account at an academic health care system in North Carolina were recruited to participate. A total of 2850 electronic invitations were sent through MyChart accounts with an embedded hyperlink to the Koda platform. Participants who agreed to participate were asked to complete pre- and posttest surveys before and after navigating through the Koda Health platform. Primary outcomes were reach, adoption, and System Usability Scale (SUS) scores. Exploratory outcomes included ACP knowledge and readiness., Results: A total of 161 participants enrolled in the study and created an account on the platform (age: mean 63, SD 9.3 years), with 80% (129/161) of these participants going on to complete all steps of the intervention, thereby generating an advance directive. Participants reported minimal difficulty in using the Koda platform, with an overall SUS score of 76.2. Additionally, knowledge of ACP (eg, mean increase from 3.2 to 4.2 on 5-point scale; P<.001) and readiness (eg, mean increase from 2.6 to 3.2 on readiness to discuss ACP with health care provider; P<.001) significantly increased from before to after the intervention., Conclusions: This study demonstrated that the Koda Health platform is feasible, had above-average usability, and improved ACP documentation of preferences in older adults. Our findings indicate that web-based health tools like Koda may help older individuals learn about and feel more comfortable with ACP while potentially facilitating greater engagement in care planning., (© R Lynae Roberts, Katelin D Cherry, Desh P Mohan, Tiffany Statler, Eric Kirkendall, Adam Moses, Jennifer McCraw, Andrew E Brown III, Tatiana Y Fofanova, Jennifer Gabbard. Originally published in JMIR Aging (https://aging.jmir.org).)

Physical QWERTY keyboards are the current standard for performing precision text-entry with extended reality devices. Ideally, there would exist a comparable, self-contained solution that works anywhere, without requiring external keyboards. Unfortunately, when physical keyboards are recreated virtually, we currently lose critical haptic feedback information from the sense of touch, which impedes typing. In this paper, we introduce the MusiKeys Technique, which uses auditory feedback in virtual reality to communicate missing haptic feedback information typists normally receive when using a physical keyboard. To examine this concept, we conducted a user study with 24 participants which encompassed four mid-air virtual keyboards augmented with increasing amounts of feedback information, along with a fifth physical keyboard for reference. Results suggest that providing clicking feedback on key-press and key-release improves typing performance compared to not providing auditory feedback, which is consistent with the literature. We also found that audio can serve as a substitute for information contained in haptic feedback, in that users can accurately perceive the presented information. However, under our specific study conditions, this awareness of the feedback information did not yield significant differences in typing performance. Our results suggest this kind of feedback replacement can be perceived by users but needs more research to tune and improve the specific techniques.

Background: Risk stratification and population management strategies are critical for providing effective and equitable care for the growing population of older adults in the USA. Both frailty and neighborhood disadvantage are constructs that independently identify populations with higher healthcare utilization and risk of adverse outcomes., Objective: To examine the joint association of these factors on acute healthcare utilization using two pragmatic measures based on structured data available in the electronic health record (EHR)., Design: In this retrospective observational study, we used EHR data to identify patients aged ≥ 65 years at Atrium Health Wake Forest Baptist on January 1, 2019, who were attributed to affiliated Accountable Care Organizations. Frailty was categorized through an EHR-derived electronic Frailty Index (eFI), while neighborhood disadvantage was quantified through linkage to the area deprivation index (ADI). We used a recurrent time-to-event model within a Cox proportional hazards framework to examine the joint association of eFI and ADI categories with healthcare utilization comprising emergency visits, observation stays, and inpatient hospitalizations over one year of follow-up., Key Results: We identified a cohort of 47,566 older adults (median age = 73, 60% female, 12% Black). There was an interaction between frailty and area disadvantage (P = 0.023). Each factor was associated with utilization across categories of the other. The magnitude of frailty's association was larger than living in a disadvantaged area. The highest-risk group comprised frail adults living in areas of high disadvantage (HR 3.23, 95% CI 2.99-3.49; P < 0.001). We observed additive effects between frailty and living in areas of mid- (RERI 0.29; 95% CI 0.13-0.45; P < 0.001) and high (RERI 0.62, 95% CI 0.41-0.83; P < 0.001) neighborhood disadvantage., Conclusions: Considering both frailty and neighborhood disadvantage may assist healthcare organizations in effectively risk-stratifying vulnerable older adults and informing population management strategies. These constructs can be readily assessed at-scale using routinely collected structured EHR data., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

The growing number of people living with dementia (PLWD) requires a coordinated clinical response to deliver pragmatic, evidence-based interventions in frontline care settings. However, infrastructure to support such a response is lacking. Moreover, there are too few researchers conducting rigorous embedded pragmatic clinical trials (ePCTs) to make the vision of high quality, widely accessible dementia care a reality. National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's disease and Related Dementias Clinical Trials (IMPACT) Collaboratory seeks to improve the pipeline of early career researchers qualified to lead ePCTs by funding career development awards. Even with support from the Collaboratory, awardees face practical and methodological challenges to success, recently exacerbated by the COVID-19 pandemic. We first describe the training opportunities and support network for the IMPACT CDA recipients. This report then describes the unique career development challenges faced by early-career researchers involved in ePCTs for dementia care. Topics addressed include challenges in establishing a laboratory, academic promotion, mentoring and professional development, and work-life balance. Concrete suggestions to address these challenges are offered for early-career investigators, their mentors, and their supporting institutions. While some of these challenges are faced by researchers in other fields, this report seeks to provide a roadmap for expanding the work of the IMPACT Collaboratory and initiating future efforts to recruit, train, and retain talented early-career researchers involved in ePCTs for dementia care., (© 2023 The American Geriatrics Society.)

Background: Patient portals can be an innovative and efficient way to engage patients in advance care planning (ACP). However, comprehension and judgment in older adults with cognitive impairment presents several barriers and challenges to engaging in new technology. Our objective was to develop an ACP portal-based tool (ACPVoice) for community-dwelling persons living with cognitive impairment (PLCI) by engaging end-users in the design process. Methods: Two rounds of cognitive interviews were conducted to identify and resolve cognitive issues related to comprehension, judgment, response, and to assess content validity. Purposive sampling was used with the goal of enrolling 15 different participants (five with mild cognitive impairment and five dyads (those with mild dementia and their care partner) in each round to assess respondents' understanding of questions related to advance care planning to be administered via the patient portal. Results: Twenty PLCI (mean age 78.4, 10 females [50%]) and ten care partners (mean age 60.9, 9 females [90%]) completed cognitive interviews between May 2021 and October 2021. The mean Mini-Mental State Examination score for PLCI was 25.6 (SD 2.6). Unclear wording and undefined vague and/or unfamiliar terms were the major issues identified. Revisions to item wording, response options, and instructions were made to improve question comprehension and response as well as navigational ease. Conclusion: Minor changes to the wording, format, and response options substantially improved respondents' ability to interpret the item content of the ACPVoice tool. Dissemination and implementation of the ACPVoice tool could help to engage community-dwelling PLCI in ACP discussions.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic highlighted the importance of understanding patients' goals, values, and medical care preferences given the high morbidity and mortality. We aimed to examine rates of advance care planning (ACP) documentation along with hospital course differences in the absence or presence of ACP among hospitalized patients with COVID-19., Methods: This retrospective cohort study was performed at a single tertiary academic medical center. All adults admitted between March 1, 2020, and June 30, 2020, for COVID-19 were included. Demographics, ACP documentation rates, presence of ACP forms, palliative care consultation (PCC) rates, code status, and hospital outcome data were collected. Data were analyzed with multivariable analysis to identify predictors of ACP documentation., Results: Among 356 patients (mean age 60.0, 153 (43%) female), 97 (27.2%) had documented ACP and 20 (5.6%) had completed ACP forms. In patients with documented ACP, 52.4% (n = 55) de-escalated care to do-not-resuscitate (DNR)-limited or comfort measures. PCC occurred rarely (<8%), but 78% (n = 21) of those consulted de-escalated care. Being admitted to the intensive care unit (ICU) (OR = 11.1, 95% CI = 5.9-21.1), mechanical intubation (OR = 15.8, 95% CI = 7.4-32.1), and discharge location other than home (OR = 11.3, 95% CI = 5.7-22.7) were associated with ACP documentation., Conclusions: This study found low ACP documentation and PCC rates in patients admitted for COVID-19. PCC and completion of ACP were associated with higher rates of care de-escalation. These results support the need for pro-active ACP and PCC for patients admitted for serious illnesses, like COVID-19, to improve goal-informed care.

Background and Objectives: This study describes patients' prognostic awareness and palliative care use in the setting of immunotherapy for metastatic non-small cell lung cancer (mNSCLC). Design: We surveyed 60 mNSCLC patients receiving immunotherapy at a large academic medical center; conducted follow-up interviews with 12 survey participants; and abstracted palliative care use, advance directive completion, and death within a year of survey completion from the medical record. Results: Forty seven percent of patients surveyed thought they would be cured; 83% were not interested in palliative care. Interviews suggested oncologists emphasized therapeutic options when discussing prognosis and that commonly used descriptions of palliative care may exacerbate misperceptions. Only 7% had received outpatient palliative care and 8% had an advance directive a year after the survey; only 16% of the 19 patients who died had received outpatient palliative care. Conclusions: Interventions are needed to facilitate prognostic discussions and outpatient palliative care during immunotherapy. Clinical Trial Registration Number NCT03741868.

Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV, respectively) are mosquito-borne, neuroinvasive human pathogens for which no FDA-approved therapeutic exists. Besides the biothreat posed by these viruses when aerosolized, arthropod transmission presents serious health risks to humans, as demonstrated by the 2019 outbreak of EEE disease in the United States that resulted in 38 confirmed cases, 19 deaths, and neurological effects in survivors. Here, we describe the discovery of a 2-pyrrolidinoquinazolinone scaffold, efficiently synthesized in two to five steps, whose structural optimization resulted in profound antiviral activity. The lead quinazolinone, BDGR-49, potently reduced cellular VEEV and EEEV titers by >7 log at 1 μM and exhibited suitable intravenous and oral pharmacokinetic profiles in BALB/c mice to achieve excellent brain exposure. Outstanding in vivo efficacy was observed in several lethal, subcutaneous infection mouse models using an 8-day dosing regimen. Prophylactically administered BDGR-49 at 25 mg kg -1 per day fully protected against a 10× LD 50 VEEV Trinidad donkey (TrD) challenge in BALB/c mice. Similarly, we observed 70% protection when 10× LD 50 EEEV FL93-939-infected C57BL/6 mice were treated prophylactically with BDGR-49 at 50 mg kg -1 per day. Last, we observed 100% therapeutic efficacy when mice, challenged with 10× LD 50 VEEV TrD, were dosed at 48 hours after infection with BDGR-49 at 25 mg kg -1 per day. Mouse brain viral titers at 96 hours after infection were reduced to values near the limit of detection. Collectively, these results underscore the substantial development potential of a well-tolerated, brain-penetrant lead compound that shows promise in preventing and treating encephalitic alphavirus disease.