Veterans Biomedical Research Institute

71 Background: Men with metastatic prostate cancer (mPC) experience high symptom burden and often require intensive end-of-life care. Inpatient palliative care (IPC) utilization patterns, including the impact of epidural spinal cord compression (ESCC), are incompletely studied. Methods: We used the National Inpatient Sample database (2016–2022) to identify adult mPC hospitalizations with and without IPC using ICD-10 codes. We compared cohort demographics using t-tests and chi-square tests. We performed multivariate logistic models assessing predictors of IPC and mortality with IPC as the exposure, adjusting for age, race, primary payer, income quartile, hospital characteristics, and Elixhauser Comorbidity Index (ECI). We evaluated ESCC as a primary exposure for IPC use and mortality. p <0.05 was considered significant. Results: We identified 93,018 mPC hospitalizations; IPC occurred in 15,633 (16.8%). mPC admissions rose from 12,050 to 14,471 (APC 2.4%; p =0.019). IPC increased numerically from 1,812 to 2,742, without a significant APC. Versus non-IPC, IPC admissions more often involved age ≥60 (92.4% vs 91.4%; p <0.001), urban hospitals (93.6% vs 91.8%; p <0.001), teaching hospitals (76.4% vs 73.8%; p <0.001), higher comorbidity (ECI≥3: 89.2% vs 86.1%; p <0.001), longer LOS (7.33 vs 5.93 days; p <0.001), and higher unadjusted mortality (24.2% vs 3.3%; p <0.001). In adjusted models, higher IPC use was associated with age ≥60 (aOR 1.187; p <0.001), Black vs White race (aOR 1.09; p <0.001), and Medicaid, private insurance, and self-pay vs Medicare (all p <0.001); lower use occurred in the Midwest and West vs Northeast (aOR 0.87 each; p <0.001), rural vs urban hospitals (aOR 0.83; p <0.001), and non-teaching vs teaching hospitals (aOR 0.89; p <0.001). Larger hospitals had higher use (aOR 1.09; p <0.001). Higher comorbidity was associated with lower IPC (ECI Q3 aOR 0.91; p =0.0015; ECI Q4 aOR 0.92; p =0.009). ESCC independently predicted IPC use (aOR 1.17; p <0.001). In the mortality model, IPC was associated with higher in-hospital death (aOR 9.37; p <0.001). Additional mortality associations included age ≥60 (aOR 1.26; p <0.001), Asian/Pacific Islander race (aOR 1.30; p =0.002), private insurance (aOR 1.34; p <0.001), Midwest region (aOR 1.19; p <0.001), rural location (aOR 1.39; p <0.001), non-teaching hospitals (aOR 1.09; p =0.026) and higher ECI (Q3 aOR 1.24; Q4 aOR 1.55; both <0.001). ESCC was associated with lower inpatient mortality (aOR 0.71; p <0.001). Conclusions: IPC was used in ~1 in 6 mPC admissions, increased over time, and varied by age, race, payer, and hospital factors. ESCC was an independent predictor of IPC use, yet it was associated with lower in-hospital mortality. Geographic and institutional disparities may reflect differences in palliative care availability. The observed IPC use aligns with estimates of need among patients with advanced cancer.

Jet fuel inhalation represents one of the most significant exposures among service members; however, health outcomes are unclear, and the processes linking exposures and respiratory effects are undefined. A systematic literature review of human, animal, and mechanistic studies was conducted to assess and synthesize the scientific evidence on the adverse respiratory effects of jet fuel exposure. Animal studies provided moderate evidence that jet fuel inhalation resulted in adverse effects through cytotoxicity, tissue damage, inflammation, airway remodeling, and lung function changes, which was corroborated by mechanistic data. This was further supported by slight epidemiologic evidence that jet fuel exposure is associated with increased respiratory symptoms and disease. Evidence indicates that jet fuel exposure is likely to produce adverse respiratory effects, which may have important implications for exposed service members and veterans.

Traumatic brain injuries (TBI) frequently occur and can lead to lasting negative cognitive, physical, and mental health outcomes. The biological response to even mild TBIs (mTBI) includes well-characterized inflammatory sequelae that start immediately post-injury, remain for weeks, and can develop into long-term systemic inflammation. Studies have shown that TBI influences multiple physiological systems, including the gastrointestinal tract, through bidirectional communication modulated, in part, by the gut microbiome. Brainstem functioning post-TBI, as measured by acoustic startle sensorimotor processing, might play a role in this feedback loop. The current study investigated pre- to post-TBI (lateral fluid percussion injury model) changes in microbial communities and acoustic startle response in male and female rats. That is, the influence of mTBI on gut microbiome and sensorimotor processing was explored to examine: 1) overall and sex-specific differences in the gut microbiome and taxa in response to mTBI; 2) overall and sex-specific differences in sensorimotor processing following mTBI; and 3) associations between the gut microbiome and sensorimotor processing. Results showed mTBI had a limited effect on microbial diversity overall, and the same was observed in males and females independently. Yet, mTBI was associated with differences in 13 genus-level taxa. Further evaluation highlighted that 11 of the 13 genus-level taxa were sex-specific, with several being known to have short-chain fatty acid-producing capabilities. Alterations in sensorimotor processing were identified following mTBI; however, no sex-specific differences were evident. In addition, no associations were observed between sensorimotor processing and the gut microbiome. This study contributes longitudinal and sex-specific findings to the growing body of research examining the diverse effects of mTBI on the brain and gut microbial communities.

Supine hypertension with orthostatic hypotension (SH-OH) represents a paradoxical and challenging form of blood pressure (BP) dysregulation, particularly in patients with autonomic failure such as Parkinson's disease (PD). This is a case of an 85-year-old male veteran with PD and multiple comorbidities, including coronary artery disease, diabetes with neuropathy, obstructive sleep apnea, and chronic kidney disease, who exhibited severe SH-OH characterized by supine systolic BP exceeding 200 mmHg and orthostatic systolic dropping to 110 mmHg. His symptoms included syncope, dizziness, and headaches. Pathophysiology involves autonomic dysfunction with impaired baroreflex, residual sympathetic activity, and dysregulation of the renin-angiotensin-aldosterone system. Management was tailored to address both SH and OH. Nonpharmacologic strategies included head-of-bed elevation, fluid and salt supplementation, compression garments, and continuous positive airway pressure therapy, which also targeted his untreated OSA and helped reduce sympathetic overactivity. Pharmacologic interventions required fine-tuning due to the complex interplay of SH and OH. Fludrocortisone was contraindicated due to a recent upper gastrointestinal bleed. Pyridostigmine was trialed but discontinued after evidence of atrioventricular block. The final regimen involved clonidine and hydralazine at bedtime for SH, along with midodrine timed around daytime activity for OH. This case highlights the nuanced, often counterbalancing management required in SH-OH, especially in elderly patients with neurodegenerative disease and cardiovascular risk. Multimodal therapy, individualized to avoid exacerbating one component while treating the other, remains essential. Further research is needed to optimize care strategies and improve the quality of life in this vulnerable population.

Behavioral pattern separation is a hippocampal-dependent component of episodic memory and a sensitive marker of early cognitive decline. Here we tested whether mild traumatic injury causes loss of pattern separation in the rat and for its prevention by a novel neuroprotective peptide fragment of the human serotonin 2A receptor (SN..8). Lateral fluid percussion was used to induce mild traumatic brain injury in male Sprague- Dawley rats. Rats were trained to distinguish between a stable vs unstable swim platform separated by increasing distances (4.5 vs 3.0 vs 1.5 feet) in a modification to the classic Morris water maze. Peptide SN..8 vs scrambled version of same amino acids (2 mg/kg) was administered via intraperitoneal route (1-, 3- and 5-days) after lateral fluid percussion or sham injury. Rats received three weeks of training and two weeks of testing before injury and were tested again at 2 and 5-weeks after injury. There was a gradient of decreasing incorrect responses to the choice between (stable vs unstable platform) as the platform separation distance was increased from 1.5 to 3.0 to 4.5 feet consistent with behavioral pattern separation. Systemic administration of SN..8 peptide (vs scrambled) peptide was associated with statistically significant lower rate of incorrect responses (at both 4.5 feet and 3.0 feet platform separation) in traumatic brain-injured rats (but not in sham-injured rats) tested at 2-weeks post-injury. Five weeks after injury, the rats had largely recovered and exhibited a much lower overall rate of incorrect responses across both drug and injury subgroups. Introduction of an unstable platform (choice phase of the Morris water maze) at varying distances from the stable platform resulted in behavior having the hallmark of pattern separation. Our data are the first to suggest that systemic administration of (2 mg/kg) SN..8 peptide immediately after mild traumatic brain injury (lateral fluid percussion) appeared to protect against loss of behavioral pattern separation in the rat.

BackgroundSince headache specialists cannot treat all the patients with headache disorders, multidisciplinary teams that include health psychologists are becoming more prevalent. Health psychologists mainly use a form of cognitive-behavioral therapy (CBT), along with biofeedback on occasion, to effectively address patients’ pain and headache disorders. The Veterans Health Administration (VHA) is one setting that routinely includes a health psychologist with advanced training in pain disorders in their pain care to its veterans. The VHA has established Headache Centers of Excellence (HCoE) around the country to provide multidisciplinary treatment for patients with headache disorders, which enables headache specialists to regularly interact with health psychologists.ObjectiveThe study’s objective is to evaluate headache specialists’ views of health psychologists in the treatment of patients with headache disorders.MethodSemi-structured interviews were conducted with headache specialists in academic-based healthcare settings, the community, and VHA HCoE sites. The interviews were audio-recorded and de-identified so they could be transcribed and analyzed using content matrix analysis.ResultsFour themes emerged: headache specialists desired to work with health psychologists and included them as members of multidisciplinary teams; valued health psychologists because they provided non-pharmacological treatments, such as CBT and biofeedback; preferred in-person communication with health psychologists; and used multiple titles when referring to health psychologists.ConclusionHeadache specialists valued health psychologists as providers of behavioral and non-pharmacological treatments and considered them essential members of multidisciplinary teams. Headache specialists should strive to work with a headache psychologist, not just a general health psychologist. By committing to this, headache specialists can foster changes in the quality of care, resource allocation, and training experiences related to health psychologists.

QT延長症候群（LQTS）はイオンチャネルあるいはイオンチャネルに影響を与えるタンパクをコードする遺伝子の遺伝子変異による心筋細胞の再分極異常により，心電図上，QT時間の延長，倒錯型心室頻拍（torsade de pointes）を示し，失神，けいれん，心臓突然死，救命された心停止を主症状とする疾患である．責任遺伝子として17種が報告されているが，見直しが始まっている．主要なタイプはLQT1，LQT2，LQT3の3型である．遺伝子変異が見つかるのは約2,000人に1人，学校心臓検診（心臓検診）でLQTSの診断基準を満たすのは中学1年時で約1,000人に1人である．治療は遺伝型と表現型（症状）との関連に基づいて行われる．生活指導の徹底，薬物療法の改善等によりLQTS, 特に心臓検診で診断されるLQTSの予後は著明に改善されつつある．