High-fat diet consumption negatively influences closed-head traumatic brain injury in a pediatric rodent model.

Traumatic brain injury (TBI) is one of the most common causes of emergency room visits in children, and it is a leading cause of death in juveniles in the United States. Similarly, a high proportion of this population consumes diets that are high in saturated fats, and millions of children are overweight or obese. The goal of the present study was to assess the relationship between diet and TBI on cognitive and cerebrovascular outcomes in juvenile rats. In the current study, groups of juvenile male Long Evans rats were subjected to either mild TBI via the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA) or underwent sham procedures. The animals were provided with either a combination of high-fat diet and a mixture of high-fructose corn syrup (HFD/HFCS) or a standard chow diet (CH) for 9 days prior to injury. Prior to injury, the animals were trained on the Morris water maze for three consecutive days, and they underwent a post-injury trial on the day of the injury. Immediately after TBI, the animals' righting reflexes were tested. Four days post-injury, the animals were euthanized, and brain samples and blood plasma were collected for qRT-PCR, immunohistochemistry, and triglyceride assays. Additional subsets of animals were used to investigate cerebrovascular perfusion using Laser Speckle and perform immunohistochemistry for endothelial cell marker RECA. Following TBI, the righting reflex was significantly increased in TBI rats, irrespective of diet. The TBI worsened the rats' performance in the post-injury trial of the water maze at 3 h, p(injury) < 0.05, but not at 4 days post-injury. Reduced cerebrovascular blood flow using Laser Speckle was demonstrated in the cerebellum, p(injury) < 0.05, but not foci of the cerebral cortices or superior sagittal sinus. Immunoreactive staining for RECA in the cortex and corpus callosum was significantly reduced in HFD/HFCS TBI rats, p < 0.05. qRT-PCR showed significant increases in APOE, CREB1, FCGR2B, IL1B, and IL6, particularly in the hippocampus. The results from this study offer robust evidence that HFD/HFCS negatively influences TBI outcomes with respect to cognition and cerebrovascular perfusion of relevant brain regions in the juvenile rat.

Implementation of Choosing Wisely® Recommendations for Lymph Node Surgery in Male Breast Cancer.

BACKGROUND: The Choosing Wisely® (CW) campaign recommended de-implementation of surgical management of axillary nodes in specified patients. This study aimed to assess trends in the application of CW guidelines for lymph node (LN) surgery in males with breast cancer. METHODS: The National Cancer Database was queried for males diagnosed with breast cancer from 2017 to 2020. Patients were categorized into two cohorts based on CW criteria. Cohort 1 included all T1-2, clinically node-negative patients who underwent breast-conserving therapy and with ≤ 2 positive nodes, and Cohort 2 included all T1-2, node-negative, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative patients aged ≥ 70 years. In Cohort 1, patients who underwent sentinel LN biopsy (SLNB) alone were compared with axillary LN dissection (ALND) or no LN surgery, while in Cohort 2, patients who underwent LN surgery were compared with those with no LN surgery. RESULTS: Of 617 patients who met the criteria for Cohort 1, 73.1% underwent SLNB alone compared with ALND (11.8%) or no LN surgery (15.1%). Those who received SLNB alone were younger (65 vs. 68 vs. 73 years; p < 0.001). The annual proportion of males who underwent SLNB alone remained stable from 2017 to 2020. Overall, 1565 patients met the criteria for Cohort 2, and 84.9% received LN surgery. LN surgery was omitted in older patients (81 vs. 77; p < 0.001). The proportion of elderly males with early-stage breast cancer who underwent LN surgery increased from 2017 to 2020. CONCLUSION: This study demonstrates that CW recommendations are not being routinely applied to males. These findings reinforce the need for additional studies and subsequent recommendations for optimal application of axillary surgery de-implementation for males diagnosed with breast cancer.

Germline BARD1 variants predispose to mesothelioma by impairing DNA repair and calcium signaling.

We report that ~1.8% of all mesothelioma patients and 4.9% of those younger than 55, carry rare germline variants of the BRCA1 associated RING domain 1 (BARD1) gene that were predicted to be damaging by computational analyses. We conducted functional assays, essential for accurate interpretation of missense variants, in primary fibroblasts that we established in tissue culture from a patient carrying the heterozygous BARD1V523A mutation. We found that these cells had genomic instability, reduced DNA repair, and impaired apoptosis. Investigating the underlying signaling pathways, we found that BARD1 forms a trimeric protein complex with p53 and SERCA2 that regulates calcium signaling and apoptosis. We validated these findings in BARD1-silenced primary human mesothelial cells exposed to asbestos. Our study elucidated mechanisms of BARD1 activity and revealed that heterozygous germline BARD1 mutations favor the development of mesothelioma and increase the susceptibility to asbestos carcinogenesis. These mesotheliomas are significantly less aggressive compared to mesotheliomas in asbestos workers.

A collective agenda: A qualitative study on Exercise is Medicine® On Campus gold-level institutions.

Objective: The Exercise is Medicine® On Campus (EIM-OC) international campaign leverages university resources (e.g., health centers, recreation, and kinesiology departments) to encourage students, faculty, and staff to integrate physical activity into campus culture. This involves evaluating student physical activity levels during health visits and establishing referral systems for exercise prescriptions. EIM-OC allows universities to earn tiered recognition (Gold, Silver, or Bronze) based on their on-campus physical activity promotion and integration. For Gold recognition, schools must incorporate routine physical activity assessments into their health system, ultimately connecting healthcare providers with health/fitness professionals (HFPs, e.g., campus recreation professionals, kinesiology professors). This research worked to uncover pivotal factors driving EIM-OC on-campus collaborations through HFPs' perspectives. Methods: HFPs (n = 11) working full-time at a Gold-level institution (n = 10 in United States) participated. Semi-structured, Zoom-recorded interviews with a generic qualitative research design were completed between June and September 2022. Results: Major thematic findings included the importance of tangible support (e.g., personnel), encounters with both trust and tension cross-campus, positive student development opportunities, and variations in outcome reporting and program evaluation. Faculty and staff emphasized the need for methods to obtain and sustain program funding. Participants also expressed the importance of interdisciplinary collaboration to increase the collective impact of EIM-OC on student health and overall collegiate success. Conclusion: HFPs expanded on their EIM-OC experiences and program sustainment or growth requirements. With increased interdisciplinary collaboration, rigor in outcome reporting, and tangible resources, the collective impact of EIM-OC on student health outcomes and overall collegiate success could be greatly perpetuated.

Low resilience is associated with worse health-related quality of life in caregivers of service members and veterans with traumatic brain injury: a longitudinal study.

PURPOSE: To examine [a] the association of caregiver health-related quality of life (HRQOL) and service member/veteran (SMV) neurobehavioral outcomes with caregiver resilience; [b] longitudinal change in resilience at the group and individual level; and [c] the magnitude of change at the individual level. METHODS: Caregivers (N = 232) of SMVs with traumatic brain injury completed a resilience measure, and 18 caregiver HRQOL and SMV neurobehavioral outcome measures at a baseline evaluation and follow-up evaluation three years later. Caregivers were divided into two resilience groups at baseline and follow-up: [1] Low Resilience (≤ 45 T, baseline n = 99, follow-up n = 93) and [2] High Resilience (> 45 T, baseline n = 133, follow-up n = 139). RESULTS: At baseline and follow-up, significant effects were found between Low and High Resilience groups for the majority of outcome measures. There were no significant differences in resilience from baseline to follow-up at the group-mean level. At the individual level, caregivers were classified into four longitudinal resilience groups: [1] Persistently Low Resilience (Baseline + Follow-up = Low Resilience, n = 60), [2] Reduced Resilience (Baseline = High Resilience + Follow-up = Low Resilience, n = 33), [3] Improved Resilience (Baseline = Low Resilience + Follow-up = High Resilience, n = 39), and [4] Persistently High Resilience (Baseline + Follow-up = High Resilience, n = 100). From baseline to follow-up, approximately a third of the Reduced and Improved Resilience groups reported a meaningful change in resilience (≥ 10 T). Nearly all of the Persistently High and Persistently Low Resilience groups did not report meaningful change in resilience (< 10 T). CONCLUSION: Resilience was not a fixed state for all caregivers. Early intervention may stall the negative caregiving stress-health trajectory and improve caregiver resilience.

The definitions, assessment, and dimensions of cancer-related fatigue: A scoping review.

PURPOSE: Cancer-related fatigue (CRF) is challenging to diagnose and manage due to a lack of consensus on its definition and assessment. The objective of this scoping review is to summarize how CRF has been defined and assessed in adult patients with cancer worldwide. METHODS: Four databases (PubMed, Embase, CINAHL Plus, PsycNet) were searched to identify eligible original research articles published in English over a 10-year span (2010-2020); CRF was required to be a primary outcome and described as a dimensional construct. Each review phase was piloted: title and abstract screening, full-text screening, and data extraction. Then, two independent reviewers participated in each review phase, and discrepancies were resolved by a third party. RESULTS: 2923 articles were screened, and 150 were included. Only 68% of articles provided a definition for CRF, of which 90% described CRF as a multidimensional construct, and 41% were identical to the National Comprehensive Cancer Network definition. Studies were primarily conducted in the United States (19%) and the majority employed longitudinal (67%), quantitative (93%), and observational (57%) study designs with sample sizes ≥ 100 people (57%). Participant age and race were often not reported (31% and 82%, respectively). The most common cancer diagnosis and treatment were breast cancer (79%) and chemotherapy (80%; n = 86), respectively. CRF measures were predominantly multidimensional (97%, n = 139), with the Multidimensional Fatigue Inventory (MFI-20) (26%) as the most common CRF measure and "Physical" (76%) as the most common CRF dimension. CONCLUSION: This review confirms the need for a universally agreed-upon definition and standardized assessment battery for CRF.

Potassium-Alkali-Enriched Diet, Hypertension, and Proteinuria following Uninephrectomy.

BACKGROUND: Losing or donating a kidney is associated with risks of developing hypertension and albuminuria. Few studies address mechanisms or interventions. We investigate potential benefits of a K+- alkali-enriched diet and the mechanisms underlying proteinuria. METHODS: Male Sprague Dawley rats were fed either a 2% NaCl + 0.95% KCl diet (HNa-LK) or a 0.74% NaCl + 3% K+-alkali diet (HK-alk) for 3 wk prior to uninephrectomy then maintained on respective diets for 12 wk. Blood pressure (by tail-cuff), urine, blood and kidney proteins were analyzed Pre- and Post-uninephrectomy. RESULTS: Pre-uninephrectomy, HK-alk vs. HNa-LK fed rats exhibited similar blood pressures and plasma [K+], [Na+], but lower proximal (NHE3, NBCe1, NaPi2) and higher distal (NCC, ENaC, pendrin) transporter abundance, a pattern facilitating K+ and HCO3- secretion. Post-uninephrectomy, single nephron GFR rose 50% and Li+ clearance doubled with both diets; in HK-alk vs HNa-LK: the rise in blood pressure was less and ammoniagenesis was lower, abundance of proximal tubule transporters remained lower, ENaC-α fell and NCCp rose consistent with K+ conservation. Post-uninephrectomy, independent of diet, albuminuria increased 8-fold and abundance of endocytic receptors was reduced (megalin by 44%, dab2 by 25-35%) and KIM-1 was increased. CONCLUSIONS: The K-alkali-enriched diet blunted post-uninephrectomy hypertension and facilitated acid clearance by suppressing proximal Na+ transporters and increasing K+ -alkali secretion. Further, uninephrectomy associated proteinuria could be attributed, at least in part, to elevated SNGFR coupled to downregulation of megalin which reduced fractional protein endocytosis and Vmax.

Customizable, biocompatible implants for dorsal nasal augmentation: An in vivo pilot study of eight polylactic acid scaffold designs.

Augmentation of the nasal dorsum often requires implantation of structural material. Existing methods include autologous, cadaveric or alloplastic materials and injectable hydrogels. Each of these options is associated with considerable limitations. There is an ongoing need for precise and versatile implants that produce long-lasting craniofacial augmentation. Four separate polylactic acid (PLA) dorsal nasal implant designs were 3D-printed. Two implants had internal PLA rebar of differing porosities and two were designed as "shells" of differing porosities. Shell designs were implanted without infill or with either minced or zested processed decellularized ovine cartilage infill to serve as a "biologic rebar", yielding eight total treatment groups. Scaffolds were implanted heterotopically on rat dorsa (N = 4 implants per rat) for explant after 3, 6, and 12 months followed by volumetric, histopathologic, and biomechanical analysis. Low porosity implants with either minced cartilage or PLA rebar infill had superior volume retention across all timepoints. Overall, histopathologic and immunohistochemical analysis showed a resolving inflammatory response with an M1/M2 ratio consistently favoring tissue regeneration over the study course. However, xenograft cartilage showed areas of degradation and pro-inflammatory infiltrate contributing to volume and contour loss over time. Biomechanical analysis revealed all constructs had equilibrium and instantaneous moduli higher than human septal cartilage controls. Biocompatible, degradable polymer implants can induce healthy neotissue ingrowth resulting in guided soft tissue augmentation and offer a simple, customizable and clinically-translatable alternative to existing craniofacial soft tissue augmentation materials. PLA-only implants may be superior to combination PLA and xenograft implants due to contour irregularities associated with cartilage degradation.

Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer's Disease and Multiple Sclerosis.

Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's disease (AD) pathology and remyelination. Receptor activation and downstream signaling are explored in vitro, and active dose ranges are determined in vivo based on pharmacodynamic responses from microglia. For mice bearing amyloid-ß (Aß) pathology (PS2APP) or combined Aß and tau pathology (TauPS2APP), chronic TREM2 agonist antibody treatment had limited impact on microglia engagement with pathology, overall pathology burden, or downstream neuronal damage. For mice with demyelinating injuries triggered acutely with lysolecithin, TREM2 agonist antibodies unexpectedly disrupted injury resolution. Likewise, TREM2 agonist antibodies limited myelin recovery for mice experiencing chronic demyelination from cuprizone. We highlight the contributions of dose timing and frequency across models. These results introduce important considerations for future TREM2-targeting approaches.

Overcoming patient reluctance to statin intolerance.

Statin therapy is a cornerstone in the management of dyslipidemia, both in primary and secondary prevention of cardiovascular events. Despite strong guidelines supporting statin use, concerns regarding side effects, particularly musculoskeletal symptoms, contribute to statin intolerance and patient reluctance. While statin intolerance is reported in 5% to 30% of patients, its true prevalence may be overestimated due to the influence of the nocebo effect. Factors associated with higher incidence of statin intolerance include older age, female sex, comorbidities such as diabetes and chronic kidney disease, and concurrent use of medications such as antiarrhythmic agents or calcium channel blockers. Clinical characterization of statin intolerance requires thorough evaluation and exclusion of alternative causes of musculoskeletal symptoms. Strategies to address statin intolerance include reassessing cardiovascular risk, engaging in shared decision-making, statin rechallenge after appropriate washout periods, dosage titration for tolerability, and consideration of alternative therapies when low-density lipoprotein goals cannot be achieved with statins. This review provides an overview of the spectrum of statin intolerance, its clinical assessment, and a systematic approach to caring for a patient with statin intolerance.

Exploring the impact of music on response to ketamine/esketamine: A scoping review.

Music and ketamine are both known to affect therapeutic outcomes, but few studies have investigated their co-administration. This scoping review describes the existing literature on the joint use of music and ketamine-or esketamine (the S(+) enantiomer of ketamine)-in humans. The review considers that extant studies have explored the intersection of ketamine/esketamine and music in healthy volunteers and in patients of various age groups, at different dosages, through different treatment processes, and have varied the sequence of playing music relative to ketamine/esketamine administration. Studies investigating the use of music during ketamine anesthesia are also included in the review because anesthesia and sedation were the early drivers of ketamine use. Studies pertaining to recreational ketamine use were omitted. The review was limited to articles published in the English language but not restricted by publication year. To the best of our knowledge, this scoping review is the first comprehensive exploration of the interplay between music and ketamine/esketamine and offers valuable insights to researchers interested in designing future studies.

Clinical relevance of subthreshold PTSD versus full criteria PTSD following traumatic brain injury in U.S. service members and veterans.

BACKGROUND: The purpose of this cross-sectional study was to examine the influence of subthreshold posttraumatic stress disorder (PTSD) and full PTSD on quality of life following mild traumatic brain injury (mTBI). METHODS: Participants were 734 service members and veterans (SMV) classified into two injury groups: uncomplicated mild TBI (MTBI; n = 596) and injured controls (IC, n = 139). Participants completed a battery of neurobehavioral measures, 12-or-more months post-injury, that included the PTSD Checklist Civilian version, Neurobehavioral Symptom Inventory, and select scales from the TBI-QOL and MPAI. The MTBI group was divided into three PTSD subgroups: No-PTSD (n = 266), Subthreshold PTSD (n = 139), and Full-PTSD (n = 190). RESULTS: There was a linear relationship between PTSD severity and neurobehavioral functioning/quality of life in the MTBI sample. As PTSD severity increased, significantly worse scores were found on 11 of the 12 measures (i.e. , MTBI: Full-PTSD > Sub-PTSD > No-PTSD). When considering the number of clinically elevated scores, a linear relationship between PTSD severity and neurobehavioral functioning/quality of life was again observed in the MTBI sample (e.g., 3-or-more elevated scores: Full-PTSD = 92.1 %, Sub-PTSD = 61.9 %, No-PTSD = 19.9 %). LIMITATIONS: Limitations included the use of a self-report measure to determine diagnostic status that may under/overcount or mischaracterize individuals. CONCLUSION: PTSD symptoms, whether at the level of diagnosable PTSD, or falling short of that because of the intensity or characterization of symptoms, have a significant negative impact on one's quality of life following MTBI. Clinicians' treatment targets should focus on the symptoms that are most troubling for an individual and the individual's perception of quality of life, regardless of the diagnosis itself.

Angiotensin II Directly Increases Endothelial Calcium and Nitric Oxide in Kidney and Brain Microvessels In Vivo With Reduced Efficacy in Hypertension.

BACKGROUND: The vasoconstrictor effects of angiotensin II via type 1 angiotensin II receptors in vascular smooth muscle cells are well established, but the direct effects of angiotensin II on vascular endothelial cells (VECs) in vivo and the mechanisms how VECs may mitigate angiotensin II-mediated vasoconstriction are not fully understood. The present study aimed to explore the molecular mechanisms and pathophysiological relevance of the direct actions of angiotensin II on VECs in kidney and brain microvessels in vivo. METHODS AND RESULTS: Changes in VEC intracellular calcium ([Ca2+]i) and nitric oxide (NO) production were visualized by intravital multiphoton microscopy of cadherin 5-Salsa6f mice or the endothelial uptake of NO-sensitive dye 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, respectively. Kidney fibrosis by unilateral ureteral obstruction and Ready-to-use adeno-associated virus expressing Mouse Renin 1 gene (Ren1-AAV) hypertension were used as disease models. Acute systemic angiotensin II injections triggered >4-fold increases in VEC [Ca2+]i in brain and kidney resistance arterioles and capillaries that were blocked by pretreatment with the type 1 angiotensin II receptor inhibitor losartan, but not by the type 2 angiotensin II receptor inhibitor PD123319. VEC responded to acute angiotensin II by increased NO production as indicated by >1.5-fold increase in 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate fluorescence intensity. In mice with kidney fibrosis or hypertension, the angiotensin II-induced VEC [Ca2+]i and NO responses were significantly reduced, which was associated with more robust vasoconstrictions, VEC shedding, and microthrombi formation. CONCLUSIONS: The present study directly visualized angiotensin II-induced increases in VEC [Ca2+]i and NO production that serve to counterbalance agonist-induced vasoconstriction and maintain residual organ blood flow. These direct and endothelium-specific angiotensin II effects were blunted in disease conditions and linked to endothelial dysfunction and the development of vascular pathologies.

Leadership academy for excellence in disability services: evaluation of outcomes for state employees.

As the United States' first disability-specific leadership academy in state government, the Leadership Academy for Excellence in Disability Services is a year-long competency-based training experience designed for employees who manage programs that impact the lives of Tennesseans with intellectual and developmental disabilities and their families. The Tennessee Department of Human Resources, in collaboration with the Tennessee Council on Developmental Disabilities, began implementing this program in 2017. The lasting impact of such a training experience on the practices of state employees once they complete the program is not known; this was the aim of the study. A follow-up survey examining graduate perceptions and outcomes was sent to 71 graduates; 48 completed the measure. The results reveal an increase in knowledge of disability service systems and a perceived ability to lead and advocate for others. Leadership competencies deemed most important to graduates' current efforts in state government included developing direct reports, managing diversity, organizational agility, and innovation management. Graduates' written comments cited the variety of subject matter experts, networking opportunities, and small group projects as fundamental in breaking down barriers to cross-agency collaboration in their disability work. The impact of this experience continues to be seen years after completing the leadership academy.

Delineating three-dimensional behavior of uveal melanoma cells under anchorage independent or dependent conditions.

BACKGROUND: Although rare, uveal melanoma (UM) is a life-threatening malignancy. Understanding its biology is necessary to improve disease outcome. Three-dimensional (3D) in vitro culture methods have emerged as tools that incorporate physical and spatial cues that better mimic tumor biology and in turn deliver more predictive preclinical data. Herein, we comprehensively characterize UM cells under different 3D culture settings as a suitable model to study tumor cell behavior and therapeutic intervention. METHODS: Six UM cell lines were tested in two-dimensional (2D) and 3D-culture conditions. For 3D cultures, we used anchorage-dependent (AD) methods where cells were embedded or seeded on top of basement membrane extracts and anchorage-free (AF) methods where cells were seeded on agarose pre-coated plates, ultra-low attachment plates, and on hanging drops, with or without methylcellulose. Cultures were analyzed for multicellular tumor structures (MCTs) development by phase contrast and confocal imaging, and cell wellbeing was assessed based on viability, membrane integrity, vitality, apoptotic features, and DNA synthesis. Vascular endothelial growth factor (VEGF) production was evaluated under hypoxic conditions for cell function analysis. RESULTS: UM cells cultured following anchorage-free methods developed MCTs shaped as spheres. Regardless of their sizes and degree of compaction, these spheres displayed an outer ring of viable and proliferating cells, and a core with less proliferating and apoptotic cells. In contrast, UM cells maintained under anchorage-dependent conditions established several morphological adaptations. Some remained isolated and rounded, formed multi-size irregular aggregates, or adopted a 2D-like flat appearance. These cells invariably conserved their metabolic activity and conserved melanocytic markers (i.e., expression of Melan A/Mart-1 and HMB45). Notably, under hypoxia, cells maintained under 3D conditions secrete more VEGF compared to cells cultured under 2D conditions. CONCLUSIONS: Under an anchorage-free environment, UM cells form sphere-like MCTs that acquire attributes reminiscent of abnormal vascularized solid tumors. UM cells behavior in anchorage-dependent manner exposed diverse cells populations in response to cues from an enriched extracellular matrix proteins (ECM) environment, highlighting the plasticity of UM cells. This study provides a 3D cell culture platform that is more predictive of the biology of UM. The integration of such platforms to explore mechanisms of ECM-mediated tumor resistance, metastatic abilities, and to test novel therapeutics (i.e., anti-angiogenics and immunomodulators) would benefit UM care.

Informing implementation and dissemination of a specialized primary care medical home for patients with serious mental illness: Clinician and administrator perspectives.

People with serious mental illness (SMI) have lower rates of use of preventative medical services and higher rates of mortality compared to the general population. Research shows that specialized primary care medical homes improve the health care of patients with SMI and are feasible to implement, safe, and more effective than usual care. However, specialized medical homes remain uncommon and model dissemination limited. As part of a controlled trial assessing an SMI-specialized medical home, we examined clinician and administrator perspectives regarding specialized versus mainstream primary care and identified ways to enhance the scale-up of a specialized primary care model for future dissemination. We conducted semistructured interviews with clinicians and administrators at three sites prior to the implementation of an SMI-specialized primary care medical home (n = 26) and at 1-year follow-up (n = 24); one site implemented the intervention, and two sites served as controls. Interviews captured service design features that affected the quality of care provided; contextual factors that supported or impeded medical home implementation; and knowledge, attitudes, and behaviors regarding the care of patients with SMI. Interviews were transcribed and coded. Clinicians and administrators described SMI-specialized primary care medical homes as advancing care coordination and outcomes for patients with SMI. Stakeholders identified elements of a specialized medical home that they viewed as superior to usual care, including having a holistic picture of patients' needs and greater care coordination. However, to enable scale-up, efforts are needed to increase staffing on care teams, develop robust clinician onboarding or training, and ensure close coordination with mental health care providers. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Service needs and neurobehavioral functioning following traumatic brain injury in U.S. military personnel.

OBJECTIVE: The purpose of this study was to (a) identify the prevalence and barriers of self-reported service needs in a military sample with and without traumatic brain injury (TBI), (b) evaluate the influence of the number of service needs on overall neurobehavioral functioning, and (c) examine the longitudinal trajectories of service needs over time. METHOD: Participants were 941 U.S. service members and veterans (SMVs) prospectively enrolled into four groups: uncomplicated mild TBI (MTBI; n = 455); complicated mild, moderate, severe, and penetrating TBI combined (STBI; n = 164); injured controls (IC, n = 138); and noninjured controls (NIC, n = 184). Participants completed a battery of neurobehavioral measures, as well as a self-reported service need interview, 12 or more month's postinjury. In addition, a longitudinal cohort (n = 553) was included using a subset of participants who had completed two or more evaluations. RESULTS: When examining the total number of self-reported service needs, there was a greater proportion of the MTBI and STBI groups that had a higher number of service needs compared to the NIC and IC groups (p < .001). In the MTBI and STBI groups, as the number of service needs increased, worse scores were found on all neurobehavioral measures. In the longitudinal cohort, the STBI group reported the highest number of service needs that persisted or developed over time (six needs), followed by the MTBI (three needs), IC (one need), and NIC (zero need) groups. CONCLUSIONS: These findings call for the need to enhance the provision of information given to service members and veterans following TBI regarding available services. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Validation of a modified-composite autonomic symptom score (COMPASS-31) as an outcome measure for persistent autonomic symptoms post-concussion: an observational pilot study.

OBJECTIVE: Persistent symptoms post-mild traumatic brain injury (mTBI) includes autonomic dysregulation (AD). The composite autonomic symptoms score, (COMPASS-31), was developed to quantify AD symptom severity in the last year, which limits clinical utility. The primary aim was to determine validity of a modified-COMPASS-31 measuring symptoms in the last month compared to the original, secondarily to compare both original and modified versions to the Neurobehavioral Symptom Inventory (NSI), and tertiarily to detect change post-treatment of the modified-COMPASS-31 compared to NSI and headache intensity (HI). PARTICIPANTS: Thirty-three military personnel with persistent headache post-mTBI. MAIN OUTCOME MEASURES: Total and domain scores for COMPASS-31 (original vs. modified) NSI and HI at baseline. Change in modified-COMPASS-31. NSI, and HI. RESULTS: Baseline COMPASS-31 versions were comparable and highly correlated (r = 0.72, p < 0.001), they were moderately correlated at best to the NSI (r < 0.6), which may suggest differences in measurement metrics. The mean change in modified-COMPASS-31 scores (15.4/100, effect size 0.8) was mild to moderately correlated to the change in HI (r = 0.39) score, but not to NSI (r = 0.28). CONCLUSION: The modified-COMPASS-31 appears to be valid, can measure change of AD symptom severity, and is recommended as an outcome measure.

Prescribing and Acceptance of Medications for Opioid Use Disorder in VA Primary Care: Veteran and Provider Perspectives.

BACKGROUND: Medications to treat opioid use disorder (MOUD) such as buprenorphine/naloxone can effectively treat OUD and reduce opioid-related mortality, but they remain underutilized, especially in non-substance use disorder settings such as primary care (PC). OBJECTIVE: To uncover the factors that can facilitate successful prescribing of MOUD and uptake/acceptance of MOUD by patients in PC settings in the Veterans Health Administration. DESIGN: Semi-structured qualitative telephone interviews with 77 providers (e.g., primary care providers, hospitalists, nurses, addiction psychiatrists) and 22 Veteran patients with experience taking MOUD. Interviews were recorded, transcribed, and analyzed thematically using a combination a priori/inductive approach. KEY RESULTS: Providers and patients shared their general perceptions and experiences with MOUD, including high satisfaction with buprenorphine/naloxone with few side effects and caveats, although some patients reported drawbacks to methadone. Both providers and patients supported the idea of prescribing MOUD in PC settings to prioritize patient comfort and convenience. Providers described individual-level barriers (e.g., time, stigma, perceptions of difficulty level), structural-level barriers (e.g., pharmacy not having medications ready, space for inductions), and organizational-level barriers (e.g., inadequate staff support, lack of nursing protocols) to PC providers prescribing MOUD. Facilitators centered on education and knowledge enhancement, workflow and practice support, patient engagement and patient-provider communication, and leadership and organizational support. The most common barrier faced by patients to starting MOUD was apprehensions about pain, while facilitators focused on personal motivation, encouragement from others, education about MOUD, and optimally timed provider communication strategies. CONCLUSIONS: These findings can help improve provider-, clinic-, and system-level supports for MOUD prescribing across multiple settings, as well as foster communication strategies that can increase patient acceptance of MOUD. They also point to how interprofessional collaboration across service lines and leadership support can facilitate MOUD prescribing among non-addiction providers.

Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries.

Importance: Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In general, in low- and middle-income countries (LMICs), access to these treatments is limited. Objective: To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs. Design, Setting, and Participants: This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024. Main Outcomes and Measures: Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased. Results: A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%). Conclusions and Relevance: In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.