Plasma ctDNA enables early detection of temozolomide resistance mutations in glioma.

Background: Liquid biopsy based on circulating tumor DNA (ctDNA) is a novel tool in clinical oncology, however, its use has been limited in glioma to date, due to low levels of ctDNA. In this study, we aimed to demonstrate that sequencing techniques optimized for liquid biopsy in glioma patients can detect ctDNA in plasma with high sensitivity and with potential clinical utility. Methods: We investigated 10 glioma patients with tumor tissue available from at least 2 surgical operations, who had 49 longitudinally collected plasma samples available for analysis. Plasma samples were sequenced with CAPP-seq (AVENIO) and tissue samples with TSO500. Results: Glioma-derived ctDNA mutations were detected in 93.8% of plasma samples. 25% of all mutations detected were observed in plasma only. Mutations of the mismatch repair (MMR) genes MSH2 and MSH6 were the most frequent circulating gene alterations seen after temozolomide treatment and were frequently observed to appear in plasma prior to their appearance in tumor tissue at the time of surgery for recurrence. Conclusions: This pilot study suggests that plasma ctDNA in glioma is feasible and may provide sensitive and complementary information to tissue biopsy. Furthermore, plasma ctDNA detection of new MMR gene mutations not present in the initial tissue biopsy may provide an early indication of the development of chemotherapy resistance. Additional clinical validation in larger cohorts is needed.

Human biomonitoring and toxicokinetics as key building blocks for next generation risk assessment.

Human health risk assessment is historically built upon animal testing, often following Organisation for Economic Co-operation and Development (OECD) test guidelines and exposure assessments. Using combinations of human relevant in vitro models, chemical analysis and computational (in silico) approaches bring advantages compared to animal studies. These include a greater focus on the human species and on molecular mechanisms and kinetics, identification of Adverse Outcome Pathways and downstream Key Events as well as the possibility of addressing susceptible populations and additional endpoints. Much of the advancement and progress made in the Next Generation Risk Assessment (NGRA) have been primarily focused on new approach methodologies (NAMs) and physiologically based kinetic (PBK) modelling without incorporating human biomonitoring (HBM). The integration of toxicokinetics (TK) and PBK modelling is an essential component of NGRA. PBK models are essential for describing in quantitative terms the TK processes with a focus on the effective dose at the expected target site. Furthermore, the need for PBK models is amplified by the increasing scientific and regulatory interest in aggregate and cumulative exposure as well as interactions of chemicals in mixtures. Since incorporating HBM data strengthens approaches and reduces uncertainties in risk assessment, here we elaborate on the integrated use of TK, PBK modelling and HBM in chemical risk assessment highlighting opportunities as well as challenges and limitations. Examples are provided where HBM and TK/PBK modelling can be used in both exposure assessment and hazard characterization shifting from external exposure and animal dose/response assays to animal-free, internal exposure-based NGRA.

"Deficiency in ELF4, X-Linked": a Monogenic Disease Entity Resembling Behçet's Syndrome and Inflammatory Bowel Disease.

Defining monogenic drivers of autoinflammatory syndromes elucidates mechanisms of disease in patients with these inborn errors of immunity and can facilitate targeted therapeutic interventions. Here, we describe a cohort of patients with a Behçet's- and inflammatory bowel disease (IBD)-like disorder termed "deficiency in ELF4, X-linked" (DEX) affecting males with loss-of-function variants in the ELF4 transcription factor gene located on the X chromosome. An international cohort of fourteen DEX patients was assessed to identify unifying clinical manifestations and diagnostic criteria as well as collate findings informing therapeutic responses. DEX patients exhibit a heterogeneous clinical phenotype including weight loss, oral and gastrointestinal aphthous ulcers, fevers, skin inflammation, gastrointestinal symptoms, arthritis, arthralgia, and myalgia, with findings of increased inflammatory markers, anemia, neutrophilic leukocytosis, thrombocytosis, intermittently low natural killer and class-switched memory B cells, and increased inflammatory cytokines in the serum. Patients have been predominantly treated with anti-inflammatory agents, with the majority of DEX patients treated with biologics targeting TNFα.

Effect of a Spiritual Care Training Program to Build Knowledge, Competence, Confidence and Self-awareness Among Australian Health and Aged Care Staff: An Exploratory Study.

The aim of this study was to evaluate a new spiritual care training program with health and aged care staff. A four-module program was delivered to 44 participants at a large Catholic health and aged care provider in Australia. Pre, post and 6 week follow-up surveys were administered and included measures of spiritual care competency, confidence, perspectives of spirituality and spiritual care, spiritual well-being, and satisfaction. Paired sample t-tests showed total scores of participants' spiritual well-being, spiritual care competency and confidence significantly improved following the training and were largely maintained at follow-up. Perspectives on spirituality and spiritual care did not significantly change over time.

Australian Patient Preferences for Discussing Spiritual Issues in the Hospital Setting: An Exploratory Mixed Methods Study.

While there is high patient acceptance for clinical staff discussing issues regarding spirituality with hospital inpatients, it is not clear which staff member patients prefer for these discussions. This unique exploratory study investigated inpatient preferences regarding which staff member should raise the topic of spirituality. A cross-sectional survey was conducted with inpatients at six hospitals in Sydney, Australia (n = 897), with a subset invited to participate in qualitative interviews (n = 41). Pastoral care staff (32.9%) were the preferred staff members with whom to discuss spiritual issues, followed by doctors (22.4%). Qualitative findings indicated that individual characteristics of the staff member are more important than their role.

Factors influencing occupational exposure to pyrethroids and glyphosate: An analysis of urinary biomarkers in Malaysia, Uganda and the United Kingdom.

BACKGROUND: Long-term exposure to pesticides is often assessed using semi-quantitative models. To improve these models, a better understanding of how occupational factors determine exposure (e.g., as estimated by biomonitoring) would be valuable. METHODS: Urine samples were collected from pesticide applicators in Malaysia, Uganda, and the UK during mixing/application days (and also during non-application days in Uganda). Samples were collected pre- and post-activity on the same day and analysed for biomarkers of active ingredients (AIs), including synthetic pyrethroids (via the metabolite 3-phenoxybenzoic acid [3-PBA]) and glyphosate, as well as creatinine. We performed multilevel Tobit regression models for each study to assess the relationship between exposure modifying factors (e.g., mixing/application of AI, duration of activity, personal protective equipment [PPE]) and urinary biomarkers of exposure. RESULTS: From the Malaysia, Uganda, and UK studies, 81, 84, and 106 study participants provided 162, 384 and 212 urine samples, respectively. Pyrethroid use on the sampling day was most common in Malaysia (n = 38; 47%), and glyphosate use was most prevalent in the UK (n = 93; 88%). Median pre- and post-activity 3-PBA concentrations were similar, with higher median concentrations post-compared to pre-activity for glyphosate samples in the UK (1.7 to 0.5 µg/L) and Uganda (7.6 to 0.8 µg/L) (glyphosate was not used in the Malaysia study). There was evidence from individual studies that higher urinary biomarker concentrations were associated with mixing/application of the AI on the day of urine sampling, longer duration of mixing/application, lower PPE protection, and less education/literacy, but no factor was consistently associated with exposure across biomarkers in the three studies. CONCLUSIONS: Our results suggest a need for AI-specific interpretation of exposure modifying factors as the relevance of exposure routes, levels of detection, and farming systems/practices may be very context and AI-specific.

A dataset of small-mammal detections in West Africa and their associated micro-organisms.

Rodents, a globally distributed and ecologically important mammalian order, serve as hosts for various zoonotic pathogens. However, sampling of rodents and their pathogens suffers from taxonomic and spatial biases. This affects consolidated databases, such as IUCN and GBIF, limiting inference regarding the spillover hazard of zoonotic pathogens into human populations. Here, we synthesised data from 127 rodent trapping studies conducted in 14 West African countries between 1964 and 2022. We combined occurrence data with pathogen screening results to produce a dataset containing detection/non-detection data for 65,628 individual small mammals identified to the species level from at least 1,611 trapping sites. We also included 32 microorganisms, identified to the species or genus levels, that are known or potential pathogens. The dataset is formatted to Darwin Core Standard with associated metadata. This dataset can mitigate spatial and taxonomic biases of current databases, improving understanding of rodent-associated zoonotic pathogen spillover across West Africa.

Facilitators for increasing dental attendance of people from vulnerable groups: a rapid review of evidence relevant to the UK.

Objective To rapidly review facilitators of access for vulnerable groups and to evaluate their effectiveness.Methods Data sources: MEDLINE via Ovid. Publications in English from 2000. DATA SELECTION: Research involving 'vulnerable groups' relevant to UK health systems, with a primary outcome of increasing attendance. DATA EXTRACTION: One author extracted and tabulated data. These were audited by a second author. DATA SYNTHESIS: A narrative synthesis was produced.Results Data from 31 studies were available for ten vulnerable groups: people with learning, physical or sensory disabilities (n = 8); people experiencing homelessness (n = 6); prisoners (n = 4); asylum-seekers and refugees (n = 3); people living in socioeconomically deprived areas (n = 3); people with severe mental health conditions (n = 2); vulnerable children (n = 2); dependent older people (n = 1); Gypsy, Roma or Traveller groups (n = 1); and people with drug dependency (n = 1). Many facilitators involved organisational reform and more integration of health, social and other services. Other facilitators included: modification of premises; team development and skill-mix use; and awareness of needs and flexible services to meet them. Few studies evaluated effectiveness.Conclusion Although facilitators for access for vulnerable groups have been proposed, there is little evidence to support or refute their effectiveness. Efforts are needed to promote access for vulnerable groups in the UK with evaluation plans embedded.

Self-reported and urinary biomarker-based measures of exposure to glyphosate and mancozeb and sleep problems among smallholder farmers in Uganda.

OBJECTIVE: We aim to showcase the impact of applying eight different self-reported and urinary biomarker-based exposure measures for glyphosate and mancozeb on the association with sleep problems in a study among 253 smallholder farmers in Uganda. METHODS: The questionnaire-based exposure measures included: (1) the number of application days of any pesticide in the last 7 days (never, 1-2; >2 days) and six glyphosate and mancozeb-specific measures: (2) application status over the last 12 months (yes/no), (3) recent application status (never, last 7 days and last 12 months), (4) the number of application days last 12 months, (5) average exposure-intensity scores (EIS) and (6) EIS-weighted number of application days in last 12 months. Based on 384 repeated urinary biomarker concentrations of ethylene thiourea (ETU) and glyphosate from 84 farmers, we also estimated (7) average biomarker concentrations for all 253 farmers. Also in the 84 farmers the measured pre-work and post-work biomarker concentrations were used (8). Multivariable logistic regression models were used to assess the association between the exposure measures and selected Medical Outcomes Study Sleep Scale (MOS-SS) indices (6-item, sleep inadequacy and snoring). RESULTS: We observed positive associations between (1) any pesticide application in the last 7 days with all three MOS-SS indices. Glyphosate application in the last 7 days (3) and mancozeb application in the last 12 months (3) were associated with the 6-item sleep problem index. The estimated average urinary glyphosate concentrations showed an exposure-response association with the 6-item sleep problem index and sleep inadequacy in the same direction as based on self-reported glyphosate application in the last 7 days. In the analysis with the subset of 84 farmers, both measured and modelled post-work urinary glyphosate concentration showed an association with snoring. CONCLUSIONS: Self-reported, estimated average biomarker concentrations and measured urinary biomarker exposure measures of glyphosate and mancozeb showed similar exposure-response associations with sleep outcomes.

A novel COVID-19 program, delivering vaccines throughout rural and remote Australia.

Background: The Royal Flying Doctor Service of Australia (RFDS) established a unique SARS-CoV-2 vaccination program for vaccinating Australians that live in rural and remote areas. This paper describes the preparation and response phases of the RFDS response. Methods: This study includes vaccinations conducted by the RFDS from 01 January 2021 until 31 December 2021 when vaccines were mandatory for work and social activities. Prior to each clinic, we conducted community consultation to determine site requirements, patient characteristics, expected vaccination numbers, and community transmission rates. Findings: Ninety-five organizations requested support. The majority (n = 60; 63.2%) came from Aboriginal Community Controlled Health Organizations. Following consultation, 360 communities were approved for support. Actual vaccinations exceeded expectations (n = 70,827 vs. 49,407), with a concordance correlation coefficient of 0.88 (95% CI, 0.83, 0.93). Areas that reported healthcare workforce shortages during the preparation phase had the highest population proportion difference between expected and actual vaccinations. Areas that reported high vaccine hesitancy during the preparation phase had fewer than expected vaccines. There was a noticeable increase in vaccination rates in line with community outbreaks and positive polymerase chain reaction cases [r (41) = 0.35, p = 0.021]. Engagement with community leaders prior to clinic deployment was essential to provide a tailored response based on community expectations.

Spirituality is "sometimes just a hug": A conceptual analysis from the perspective of nursing students.

OBJECTIVES: Definitions of spirituality abound; however, the importance of context and need for better understanding within health-care practice has been emphasized. In particular, the understanding of spirituality for nurses has been shown to have an impact both professionally and personally. METHODS: This study used a conceptual analysis to explore the understanding of spirituality by German-speaking nurses in an educational context. RESULTS: A total of 91 nursing students (83.5% female, 16.5% male) took the spiritual care course between January 2022 and January 2023. The majority of participants (n = 63, 69.6%) were in the 26- to 40-year age bracket, 50 (54.9%) identified themselves as Christian, 15 (16.5%) chose other, 12 (13.2%) atheist, 6 (6.6%) humanist or agnostic, and 2 (2.2%) Buddhist. A conceptual analysis of nursing students' written responses to the question "What is spirituality to me?" was conducted. Two overarching categories were identified. The first category was titled "What aspects or characters are linked to spirituality?" and included 5 subcategories: people, life, experience, a sense of security, and capacity. The second category was titled "How is spirituality experienced, practiced and lived?" and included 5 subcategories: sometimes just a hug, to align one's life with that purpose, to be content with myself, conscious attention to oneself, and demarcation from religion. These subcategories were interrelated to one another. SIGNIFICANCE OF RESULTS: These findings have implications for how spirituality is introduced in nursing education.

The oral health of adults attending dental practices in England in 2018: a report of a novel method and findings.

Introduction National surveys of the oral health of adults are conducted decennially. For reasons of feasibility and cost, these only provide accurate information at large geographical areas. To address this, a survey of adults attending dental practices in England was undertaken.Aim To describe and discuss the survey method and findings.Method A clinical examination and questionnaire survey was conducted in a sample of English dental practices.Results Questionnaires (n = 16,572) and clinical examinations (n = 14,270) were completed with patients from 1,173 dental practices. Poorer oral health disproportionately affected older adults and those from more socioeconomically deprived areas. Over one in three from more deprived areas had untreated caries compared with one in five in the less deprived (36.2% vs 19.9%) and impacts of oral problems were nearly three times higher in the more deprived areas (27.9% vs 11.0%). Of those receiving NHS care, 28.7% and 46.2% reported they would struggle/be unable to pay a Band 2 and Band 3 NHS patient charge, respectively.Conclusion It is feasible to undertake a survey of adults in dental practices but care must be taken generalising the findings to the general population and comparing them with other surveys undertaken using different methods.

Differing taxonomic responses of mosquito vectors to anthropogenic land-use change in Latin America and the Caribbean.

Anthropogenic land-use change, such as deforestation and urban development, can affect the emergence and re-emergence of mosquito-borne diseases, e.g., dengue and malaria, by creating more favourable vector habitats. There has been a limited assessment of how mosquito vectors respond to land-use changes, including differential species responses, and the dynamic nature of these responses. Improved understanding could help design effective disease control strategies. We compiled an extensive dataset of 10,244 Aedes and Anopheles mosquito abundance records across multiple land-use types at 632 sites in Latin America and the Caribbean. Using a Bayesian mixed effects modelling framework to account for between-study differences, we compared spatial differences in the abundance and species richness of mosquitoes across multiple land-use types, including agricultural and urban areas. Overall, we found that mosquito responses to anthropogenic land-use change were highly inconsistent, with pronounced responses observed at the genus- and species levels. There were strong declines in Aedes (-26%) and Anopheles (-35%) species richness in urban areas, however certain species such as Aedes aegypti, thrived in response to anthropogenic disturbance. When abundance records were coupled with remotely sensed forest loss data, we detected a strong positive response of dominant and secondary malaria vectors to recent deforestation. This highlights the importance of the temporal dynamics of land-use change in driving disease risk and the value of large synthetic datasets for understanding changing disease risk with environmental change.

Development and Validation of the Hospital-to-Home-Health Transition Quality (H3TQ) Index: A Novel Measure to Engage Patients and Home Health Providers in Evaluating Hospital-to-Home Care Transition Quality.

BACKGROUND: Patients requiring skilled home health care (HH) after hospitalization are at high risk of adverse events. Human factors engineering (HFE) approaches can be useful for measure development to optimize hospital-to-home transitions. OBJECTIVE: To describe the development, initial psychometric validation, and feasibility of the Hospital-to-Home-Health-Transition Quality (H3TQ) Index to identify patient safety risks. METHODS: Development: A multisite, mixed-methods study at 5 HH agencies in rural and urban sites across the United States. Testing: Prospective H3TQ implementation on older adults' hospital-to-HH transitions. Populations Studied: Older adults and caregivers receiving HH services after hospital discharge, and their HH providers (nurses and rehabilitation therapists). RESULTS: The H3TQ is a 12-item count of hospital-to-HH transitions best practices for safety that we developed through more than 180 hours of observations and more than 80 hours of interviews. The H3TQ demonstrated feasibility of use, stability, construct validity, and concurrent validity when tested on 75 transitions. The vast majority (70%) of hospital-to-HH transitions had at least one safety issue, and HH providers identified more patient safety threats than did patients/caregivers. The most frequently identified issues were unsafe home environments (32%), medication issues (29%), incomplete information (27%), and patients' lack of general understanding of care plans (27%). CONCLUSIONS: The H3TQ is a novel measure to assess the quality of hospital-to-HH transitions and proactively identify transitions issues. Patients, caregivers, and HH providers offered valuable perspectives and should be included in safety reporting. Study findings can guide the design of interventions to optimize quality during the high-risk hospital-to-HH transition.

FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation.

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis.

Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels as well as cardiac imaging abnormalities shortly after SARS-CoV-2 mRNA vaccination. Contrary to early hypotheses, patients did not demonstrate features of hypersensitivity myocarditis, nor did they have exaggerated SARS-CoV-2-specific or neutralizing antibody responses consistent with a hyperimmune humoral mechanism. We additionally found no evidence of cardiac-targeted autoantibodies. Instead, unbiased systematic immune serum profiling revealed elevations in circulating interleukins (IL-1ß, IL-1RA, and IL-15), chemokines (CCL4, CXCL1, and CXCL10), and matrix metalloproteases (MMP1, MMP8, MMP9, and TIMP1). Subsequent deep immune profiling using single-cell RNA and repertoire sequencing of peripheral blood mononuclear cells during acute disease revealed expansion of activated CXCR3+ cytotoxic T cells and NK cells, both phenotypically resembling cytokine-driven killer cells. In addition, patients displayed signatures of inflammatory and profibrotic CCR2+ CD163+ monocytes, coupled with elevated serum-soluble CD163, that may be linked to the late gadolinium enhancement on cardiac MRI, which can persist for months after vaccination. Together, our results demonstrate up-regulation in inflammatory cytokines and corresponding lymphocytes with tissue-damaging capabilities, suggesting a cytokine-dependent pathology, which may further be accompanied by myeloid cell-associated cardiac fibrosis. These findings likely rule out some previously proposed mechanisms of mRNA vaccine--associated myopericarditis and point to new ones with relevance to vaccine development and clinical care.

Using Virtual Home Assistants to Address Vulnerable Adults' Complex Care Needs: An Exploratory Feasibility Study.

Harnessing technology has been proposed as one strategy to meet the social and health needs of older adults who prefer to age in place, but solutions remain elusive. In the current study, we evaluated the feasibility of using voice-activated virtual home assistants (VHAs; i.e., Amazon Echo "Alexa" devices) with older adults participating in the Program for All-Inclusive Care of the Elderly (PACE) over 4 months. Study methods included process evaluations, tracking participants' VHA use, and qualitative feedback from PACE participants and staff. The most common VHA activities were voice-activated smart lighting and asking for information. Participants infrequently used VHA activities that could promote physical or cognitive function (e.g., chair yoga, word recall game). Participants enjoyed using the VHAs, and PACE staff were enthusiastic about the potential for VHAs to facilitate aging in place and provided recommendations to increase participants' use of functional health activities. [Journal of Gerontological Nursing, 49(6), 33-40.].

Nelson syndrome and perinatal challenges: A case report and systematic review of the literature.

Nelson syndrome is a rare and potentially life-threatening complication of treatment with total bilateral adrenalectomy for women with Cushing disease. A successful term pregnancy following fertility treatment in a patient with Nelson syndrome is presented. Our study provides guidance in the prenatal and intrapartum management of this condition. A case report and a systematic review of 14 papers describing 50 pregnancies are presented. An electronic database search included Medline (1946 to September 2022), Embase (1980 to September 2022), Cochrane Library, and UKOSS. A small number of pregnancies in women with Nelson syndrome are reported in literature, but there are no guidelines. Some authors detail the prenatal care provided to their patients. Four studies report prenatal monitoring with visual field checks and two report monitoring with X-rays. Five studies report the use of parenteral hydrocortisone at the time of delivery. Where described, women delivered appropriately grown newborns at term, with timing and mode of delivery dictated by obstetric indications. Preconception counseling and optimization of maternal health status improve pregnancy outcomes in women with Nelson syndrome. Multidisciplinary review in a combined obstetric-endocrine prenatal clinic is ideal. Awareness about potential complications during pregnancy and the postnatal period is crucial in providing optimal care to the mother and baby.

Testing the stability of a family resilience model at 2 and 5 years after traumatic brain injury or spinal cord injury: A longitudinal study.

BACKGROUND: Recent studies have tested models of resilience and caregiver adjustment in individuals with traumatic brain injury (TBI) or spinal cord injury (SCI). Few studies have examined the role of adaptive variables over time. OBJECTIVE: Conduct a longitudinal study to test a model of caregiver resilience with caregiver outcomes at 2- and 5-years post-injury. METHOD: Caregivers of relatives with TBI or SCI were surveyed at 2 years (Time 1) and 5 years (Time 2) post-injury. Stability of the resilience model across the 2 time-points was tested using structural equation modeling with multi-group analysis. Measures included resilience related variables (Connor-Davidson Resilience Scale, General Self-Efficacy Scale, Herth Hope Scale, Social Support Survey) and outcome variables (Caregiver Burden Scale, General Health Questionnaire-28, Medical Outcome Study Short Form -36 [SF-36] and Positive and Negative Affect Scale). RESULTS: In total, 100 caregivers were surveyed at both 2 and 5 years (TBI =77, SCI =23). Scores for resilience (Time 1, 75.9 SD 10.6; Time 2, 71.5 SD 12.6) and self-efficacy (Time 1, 32.51 SD 3.85; Time 2, 31.66 SD 4.28) showed significant minor declines, with other variables remaining stable. The resilience model for the pooled responses (Time 1+ Time 2) demonstrated a good fit (Goodness of Fit Index [GFI] = 0.971; Incremental Fit Index [IFI] = 0.986; Tucker-Lewis Index [TLI] = 0.971; Comparative Fit Index [CFI] = 0.985 and Root Mean Square Error of Approximation [RMSEA] = 0.051). Multi-group analysis then compared Time 1 to Time 2 responses and found that a variant (compared to invariant) model best fitted the data, with social support having stronger associations with mental health and positive affect at Time 2 than Time 1. Hope reduced from Time 1 to Time 2. CONCLUSIONS: The model suggests that resilience-related variables can play an important role in positive caregiver adjustment over time.