South Florida Veterans Affairs Foundation for Research and Education

Caregivers' self-perceived preparedness for caregiving influences care recipients' and caregivers' emotional health, and care recipients' aging in place. Dementia's unique, long, and progressive nature compared to other age-related illnesses, along with associated behavioral symptoms and personality changes, may cause caregivers' preparedness to vary significantly from that of those caring for patients with other chronic conditions. This study aimed to describe and compare specific domains and tasks in which family caregivers of veterans with and without dementia reported wanting to be better prepared. Using the Veterans Affairs' HERO CARE (Home Excellence Resource Outcome Center to Advance, Redefine, and Evaluate Non-Institutional Care) Survey data, we analyzed caregivers' responses to one open-ended question: "Out of all the tasks that you help the veteran with, is there anything specific you would like to be better prepared for?" Response themes were deductively coded into 9 domains, and differences in reported domains between caregivers of care recipients with and without dementia were compared. A total of 732 caregivers were included: 301 (41.1%) caregivers of veterans with dementia and 431 (58.9%) without. Caregivers of veterans with and without dementia, respectively, were similar except in age, being spousal caregivers, working at least part-time, hours of care provision per week, and proportion with a high burden. Veterans with dementia, versus without, were older and had higher frailty and risk scores. Preparedness concerns among caregivers (N=732) included care coordination (n=164, 22.4%), emotional and social support (n=145, 19.8%), advance planning (n=116, 15.8%), nursing and health monitoring (n=94, 12.8%), personal care (n=65, 8.9%), mobility (n=79, 10.8%), household (n=58, 7.9%), caregiver self-care (n=36, 4.9%), and emergent situations (n=28, 3.8%). The commonest tasks caregivers expressed needs for included managing emotional and behavioral symptoms (n=74, 10.1%), recognizing and responding to significant changes in the veterans' condition (n=66, 9.0%), seeking medical information relevant to the veterans' needs (n=54, 7.4%), handling financial and legal matters (n=52, 7.1%), and advocating for services (n=49, 6.7%). Similar proportions of caregivers of veterans with and without dementia reported preparedness needs in all domains and tasks. The preparedness needs of caregivers of veterans with and without dementia were mostly similar in most domains and tasks. The commonest preparedness gaps were in the domains of care coordination, emotional and social support, and advance planning. The findings can inform interventions to prepare all caregivers to support aging in place.

Growth hormone-releasing hormone (GHRH) antagonists exert antitumor functions in different experimental cancers. However, their role in combination with radiotherapy in non-small cell lung cancer (NSCLC) remains unknown. Therefore, we investigated the radiosensitizing effect of GHRH antagonists in NSCLC. A549 and H522 NSCLC cell lines were exposed to ionizing radiation (IR) and GHRH antagonists MIA-602 and MIA-690, either individually or in combination. Cell viability and proliferation were evaluated by MTT, BrdU, flow cytofluorimetry, and clonogenic assays; gene and protein expression, signaling pathways, and apoptosis were analyzed by real-time PCR, Western blot, annexin staining, and caspase-3 assay. GHRH antagonists showed antitumor effects alone and potentiated IR-induced inhibition of cell viability and proliferation. The combination of MIA-690 and IR decreased the expression of GHRH receptor, its oncogenic splice variant 1, and IGF1 mRNA levels. Additionally, cell cycle inhibitors and proapoptotic markers were upregulated, whereas cyclins, oncogenic MYC, and the antiapoptotic protein Bcl-2 were downregulated. Radioresistance was prevented by MIA-690, which also blunted epithelial-mesenchymal transition by enhancing E-cadherin and reducing mesenchymal, oxidative, and proangiogenic effectors. Finally, both MIA-602 and MIA-690 enhanced radiosensitivity in primary human NSCLC cells. These findings highlight the potential of GHRH antagonists as radiosensitizers in NSCLC treatment.

The hypothalamic polypeptide growth hormone-releasing hormone (GHRH) stimulates the secretion of growth hormone (GH) from the pituitary through binding and activation of the pituitary type of GHRH receptor (GHRH-R), which belongs to the family of G protein-coupled receptors with seven potential membrane-spanning domains. Various splice variants of GHRH-R (SV) in human neoplasms and other extrapituitary tissues were demonstrated and their cDNA was sequenced. Among the SVs, splice variant 1 (SV1) possesses the greatest similarity to the full-length GHRH-R and remains functional by eliciting cAMP signaling and mitogenic activity upon stimulation by GHRH. In this review, we briefly discuss the activation, regulation, molecular mechanisms and signaling pathways of GHRH-Rs and their SVs in various tissues and also summarize the expression, biological activities and potential function of GHRH, its analogs and their receptors. A large body of work have extensively studied and evaluated potential clinical applications of agonists and antagonists of GHRH in diverse fields, including oncology, endocrinology, obesity, diabetes, other metabolic dysfunctions, cardiology, immune functions, mood disorders, Alzheimer’s and lung disease, ophthalmology, inflammation, wound healing and other applications. These results strongly support the potential therapeutic use of GHRH analogs in human medicine in the near future.

Abstract We analyzed the HERO CARE survey responses of 2,925 caregiver/Veteran dyads to: 1) describe the extent to which caregivers of older Veterans feel prepared for their caregiving tasks; 2) assess whether caregiver awareness of VA caregiver support resources was associated with feelings of preparedness; and 3) identify impact of caregiver feelings of preparedness and odds of caregiver interest in institutionalization of Veterans care recipients. Caregivers described themselves as, “Not at all prepared,” Somewhat prepared,” or “Very prepared” for their caregiving tasks. We calculated descriptive statistics for Veterans and caregivers and compared them by levels of caregiver preparedness using chi-square tests and t-tests. We then conducted adjusted multivariable logistic regression analyses to assess the association between caregiver preparedness and awareness of VA caregiver support services, and between desire to institutionalize and caregiver preparedness. Caregivers were mostly non-Hispanic white (73.3%), female (83.3%), and ≥ 65 years old (72.8%); 62.6% of caregivers felt very prepared, 34.7% felt somewhat prepared and 2.7% felt not at all prepared. Caregivers who were aware of at least one VA caregiver support resource were 33% more likely to feel very prepared compared to caregivers who were not aware of at least one resource (OR: 1.3; 95% CI: 1.1, 1.6; p<0.01). Caregivers who felt very prepared for caregiving were 39% less likely to have desire to institutionalize compared to caregivers who did not feel very prepared (OR: 0.6; 95% CI: 0.5-0.8; p <0.001). Veteran-caregiver dyads may benefit from increased awareness of VA resources, including ones that support caregivers.

Abstract The Department of Veterans Affairs (VA) is increasing access to Home- and Community-Based Services (HCBS) as an alternative to long-term institutional care (LTIC). Veteran Directed Care (VDC) is a self-directed HCBS program that empowers veterans at risk of LTIC to hire their own care providers. The VA is increasing VDC access by expanding the program to all VA medical centers (VAMCs) nationally. As part of a multi-aim and mixed-method evaluation project examining barriers and facilitators to expanding VDC, qualitative semi-structured interviews were conducted across seven VAMCs in Florida, South Georgia, and Puerto Rico with two groups of veterans who were referred to VDC: those that enrolled in the program (n=2) and those that declined (n=2). We also interviewed family caregivers of veterans in both groups (n=2 each). Interviews were conducted via Microsoft Teams from January-March 2024 and recorded with auto-transcription. Data were analyzed using rapid qualitative analysis techniques. Enrolled veterans and their caregivers pointed to several facilitators including the ease of enrollment; user-friendly management tools; compensation for care; role recognition; the ability to choose their caregiver and schedule; the reliability and trustworthiness of self-selected care providers; and relationships formed. Those who declined to enroll identified several barriers such as the program complexity; burdensome employee management tasks; fear of losing eligibility for other programs and services; and feeling the compensation was inadequate. Interviews are still ongoing. Understanding the veteran and caregiver perspectives on enrollment will inform strategies and mechanisms to support VA’s goal of increasing VDC access and veteran participation.

Abstract BackgroundReceiving sufficient assistance with ADLs/IADLs can support dementia patients’ physical and psychosocial health, as well as aging in place. The Department of Veterans Affairs has prioritized supporting Veterans in aging at place a home when this is their preference. We aimed in the current study to analyze if there are demographic characteristics and/or comorbidities of Veterans with dementia that are predictive of having unmet ADL/IADL needs.MethodIn 2021‐2022 the caregivers of 741 Veterans with dementia completed round one of the HERO CARE survey, a prospective longitudinal panel design survey administered to caregivers and VHA‐enrolled Veterans across five VHA sites, with oversampling of Veterans with higher predicted risk of long‐term institutionalization. 314 of these surveys had sufficient response data for inclusion in the current analysis. Multiple linear regression was used to regress the outcome of combined total score of unmet ADL/IADL needs (minimum = 0, maximum = 15, mean = 4.86, SD = 4.92) on specific demographic characteristics and comorbidities (using Hierarchical Condition Categories) across five models. The model of best fit was identified by AIC.ResultNon‐white/non‐Hispanic race‐ethnicity (β = 3.14, se = 0.64) and having Parkinson’s or Huntington’s diseases (β = 2.718, se = 0.870) were associated with having more unmet ADL/IADL needs at the 5% significance level. Having major depressive, bipolar, and/or paranoid disorders (β = ‐ 1.395, se = 0.656) was associated with having less unmet ADL/IADL needs at the 5% significance level. When controlling for the other predictors, having non‐white/non‐Hispanic race‐ethnicity was associated with an average increase of 3.25 unmet ADLs/IADLs, having Parkinson’s or Huntington’s Disease was associated with an average increase of 2.72 unmet ADLs/IADLs and having major depressive, bipolar, and/or paranoid disorders was associated with a 1.40 decrease in unmet ADLs/IADLs.ConclusionThe Veterans Affairs Healthcare System (VAHS) may have characteristics that support the provision of ADL/IADL assistance for patients who have dementia in conjunction with major depressive, bipolar and/or paranoid disorders. Increased attention to ADL/IADL supports among VAHS patients who have dementia and non‐white/non‐Hispanic race/ethnicity and/or Parkinson’s or Huntington’s diseases may support Veteran health, wellbeing, and aging in place.

Graft-versus-host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ system that is often affected in GVHD is the eyes. Ocular GVHD (oGVHD) may involve various structures within the eye including the lacrimal glands, eyelids, conjunctiva, cornea, and nasolacrimal ducts, and is a source of morbidity in patients with GVHD. Common presenting features of GVHD overlap with dry eye disease (DED), including decreased tear production, epithelial disruption, and Meibomian gland dysfunction (MGD). In this review, we aim to compare oGVHD and DED to better understand the similarities and differences between the conditions, with a focus on pathophysiology, risk factors, clinical features, and treatments.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness associated with a constellation of other symptoms. While the most common symptom is unrelenting fatigue, many individuals also report suffering from rhinitis, dry eyes and a sore throat. Mucin proteins are responsible for contributing to the formation of mucosal membranes throughout the body. These mucosal pathways contribute to the body’s defense mechanisms involving pathogenic onset. When compromised by pathogens the epithelium releases numerous cytokines and enters a prolonged state of inflammation to eradicate any particular infection. Based on genetic analysis, and computational theory and modeling we hypothesize that mucin protein dysfunction may contribute to ME/CFS symptoms due to the inability to form adequate mucosal layers throughout the body, especially in the ocular and otolaryngological pathways leading to low grade chronic inflammation and the exacerbation of symptoms.

To examine ocular symptoms and signs of veterans with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis, ME/CFS symptoms, and controls. This was a prospective, cross-sectional study of 124 South Florida veterans in active duty during the Gulf War era. Participants were recruited at an ophthalmology clinic at the Miami Veterans Affairs Hospital and evaluated for a diagnosis of ME/CFS, or symptoms of ME/CFS (intermediate fatigue, IF) using the Canadian Consensus criteria. Ocular symptoms were assessed via standardised questionnaires and signs via comprehensive slit lamp examination. Inflammatory blood markers were analysed and compared across groups. Mean age was 55.1 ± 4.7 years, 88.7% identified as male, 58.1% as White, and 39.5% as Hispanic. Ocular symptoms were more severe in the ME/CFS (n = 32) and IF (n = 48) groups compared to controls (n = 44) across dry eye (DE; Ocular Surface Disease Index [OSDI]: 48.9 ± 22.3 vs. 38.8 ± 23.3 vs. 19.1 ± 17.8, p < 0.001; 5 item Dry Eye Questionnaire [DEQ-5]: 10.8 ± 3.9 vs. 10.0 ± 4.6 vs. 6.6 ± 4.2, p < 0.001) and pain-specific questionnaires (Numerical Rating Scale 1-10 [NRS] right now: 2.4 ± 2.8 vs. 2.4 ± 2.9 vs 0.9 ± 1.5; p = 0.007; Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 23.0 ± 18.6 vs. 19.8 ± 19.1 vs. 6.5 ± 9.0, p < 0.001). Ocular surface parameters and blood markers of inflammation were generally similar across groups. Individuals with ME/CFS report increased ocular pain but similar DE signs, suggesting that mechanisms beyond the ocular surface contribute to symptoms.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, complex multi-organ illness characterized by unexplained debilitating fatigue and post-exertional malaise (PEM), which is defined as a worsening of symptoms following even minor physical or mental exertion. Our study aimed to evaluate transcriptomic changes in ME/CFS female patients undergoing an exercise challenge intended to precipitate PEM. Our time points (baseline before exercise challenge, the point of maximal exertion, and after an exercise challenge) allowed for the exploration of the transcriptomic response to exercise and recovery in female patients with ME/CFS, as compared to healthy controls (HCs). Under maximal exertion, ME/CFS patients did not show significant changes in gene expression, while HCs demonstrated altered functional gene networks related to signaling and integral functions of their immune cells. During the recovery period (commonly during onset of PEM), female ME/CFS patients showed dysregulated immune signaling pathways and dysfunctional cellular responses to stress. The unique functional pathways identified provide a foundation for future research efforts into the disease, as well as for potential targeted treatment options.