Background: Children with acute and chronic illness undergo frequent, painful, and distressing procedures. Objective: This randomized controlled trial was used to evaluate the effectiveness of guided imagery (GI) versus virtual reality (VR) on the procedural pain and state anxiety of children and young adults undergoing unsedated procedures. We explored the role of trait anxiety and pain catastrophizing in intervention response. Methods: Children and young adults were recruited from the hematology, oncology, and blood and marrow transplant clinics at a children’s hospital. Each study participant completed the GI and VR intervention during separate but consecutive unsedated procedures. Self-report measures of pain and anxiety were completed before and after the procedures. Results: A total of 50 participants (median age 13 years) completed both interventions. GI and VR performed similarly in the management of procedural pain. Those with high pain catastrophizing reported experiencing less nervousness about pain during procedures that used VR than those using GI. State anxiety declined pre- to postprocedure in both interventions; however, the decrease reached the level of significance during the VR intervention only. Those with high trait anxiety had less pain during GI. Conclusions: In our sample, VR worked as well as GI to manage the pain and distress associated with common procedures experienced by children with acute or chronic illnesses. Children who are primed for pain based on beliefs about pain or because of their history of chronic pain had a better response to VR. GI was a better intervention for those with high trait anxiety. Trial Registration: ClinicalTrials.gov NCT04892160; https://clinicaltrials.gov/ct2/show/NCT04892160

High doses of acetaminophen (APAP) result in hepatotoxicity that involves metabolic activation of the parent compound, covalent binding of the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI) to liver proteins, and depletion of hepatic glutathione. Impaired fatty acid β-oxidation has been implicated in previous studies of APAP-induced hepatotoxicity. To better understand relationships between toxicity and fatty acid β-oxidation in the liver in APAP toxicity, metabolomic assays for long chain acylcarnitines were examined in relationship to established markers of liver toxicity, oxidative metabolism, and liver regeneration in a time course study in mice. Male B6C3F1 mice were treated with APAP (200 mg/kg IP) or saline and sacrificed at 1, 2, 4, 8, 24 or 48 h after APAP. At 1 h, hepatic glutathione was depleted and APAP protein adducts were markedly increased. Alanine aminotransferase (ALT) levels were elevated at 4 and 8 h, while proliferating cell nuclear antigen (PCNA) expression, indicative of hepatocyte regeneration, was apparent at 24 h and 48 h. Elevations of palmitoyl, oleoyl and myristoyl carnitine were apparent by 2–4 h, concurrent with the onset of Oil Red O staining in liver sections. By 8 h, acylcarnitine levels were below baseline levels and remained low at 24 and 48 h. A partial least squares (PLS) model suggested a direct association of acylcarnitine accumulation in serum to APAP protein adduct and hepatic glutathione levels in mice. Overall, the kinetics of serum acylcarnitines in APAP toxicity in mice followed a biphasic pattern involving early elevation after the metabolism phases of toxicity and later depletion of acylcarnitines.

Objective: Describe anxiety and depressive symptoms in children with juvenile idiopathic arthritis (JIA) using Patient Reported Outcomes Measurement Information System (PROMIS) measures and evaluate potential correlations with disease manifestations.Methods: We performed a cross-sectional study of children with JIA and a parent proxy who completed PROMIS measures on depression, anxiety, stress, and pain. The Childhood Health Assessment Questionnaire (CHAQ) measured mobility, and the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) measured disease activity.Results: Eighty-four patients completed the study. Demographic median values included age (14 yrs), disease duration (4.73 yrs), CHAQ score (0), total active joint count (0), and cJADAS10 (2). Using cJADAS10, 57 patients (70%) had inactive or low disease activity. Mean PROMISt-scores for depressive and anxiety symptoms were lower in children with JIA compared to the reference population (P< 0.0001). Nineteen patients (23%) had moderate to severe symptoms of anxiety and/or depression. Age and CHAQ score (mobility) correlated with depressive symptoms (r= 0.36,P=0.0008 andr= 0.32,P =0.0029, respectively) but not anxiety. Depressive and anxiety symptoms correlated with pain (r= 0.64 andr= 0.47, respectively,P <0.0001) and stress (r= 0.79 andr= 0.75, respectively,P <0.0001) but not with sex, JIA subtype, disease duration, or disease activity.Conclusion: Approximately one-quarter of children with JIA reported moderate to severe symptoms of anxiety and depression. These symptoms are associated with pain and stress, but they are not associated with other disease manifestations. Understanding how mental health symptoms and JIA affect each other is necessary in order to improve patient outcomes and provide well-rounded care.

Gastroesophageal reflux disease (GERD) significantly impacts patient quality of life and is a major risk factor for the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). Proton pump inhibitors (PPIs) are the standard-of-care for GERD and are among the most prescribed drugs in the world, but do not protect against nonacid components of reflux such as pepsin, or prevent reflux-associated carcinogenesis. We recently identified an HIV protease inhibitor amprenavir that inhibits pepsin and demonstrated the antireflux therapeutic potential of its prodrug fosamprenavir in a mouse model of laryngopharyngeal reflux. In this study, we assessed the capacity of amprenavir to protect against esophageal epithelial barrier disruption in vitro and related molecular events, E-cadherin cleavage, and matrix metalloproteinase induction, which are associated with GERD severity and esophageal cancer. Herein, weakly acidified pepsin (though not acid alone) caused cell dissociation accompanied by regulated intramembrane proteolysis of E-cadherin. Soluble E-cadherin responsive matrix metalloproteinases (MMPs) were transcriptionally upregulated 24 h post-treatment. Amprenavir, at serum concentrations achievable given the manufacturer-recommended dose of fosamprenavir, protected against pepsin-induced cell dissociation, E-cadherin cleavage, and MMP induction. These results support a potential therapeutic role for amprenavir in GERD recalcitrant to PPI therapy and for preventing GERD-associated neoplastic changes.