Measurement of Quality-of-Life Outcomes in Pediatric and Young Adult Patients Treated for Eosinophilic Esophagitis.

Eosinophilic esophagitis is a chronic, immune-mediated esophageal condition that may lead to impairment of quality of life in pediatric and young adult patients. We performed a prospective, cross-sectional study on 40 patients between the ages of 2-21 years with an established diagnosis of eosinophilic esophagitis. The study evaluated physical, emotional, social, and school functioning in patients undergoing treatment with proton pump inhibitors, dietary elimination, or swallowed corticosteroids. There were no statistically significant differences in total or domain-specific quality of life scores between proton pump inhibitors, dietary elimination, and swallowed corticosteroid therapy. Overall, total and domain-specific quality of life were well-preserved in patients with eosinophilic esophagitis, with the highest scores reported in social functioning. There were also no statistically significant associations between clinical, endoscopic, and histologic features and quality-of-life measures.

Meta-analysis of early adolescent self-regulation interventions: Moderation by intervention and outcome type.

INTRODUCTION: Self-regulation has been identified as a highly promising target for interventions promoting broad wellbeing across development; however, there appear to be notable limitations in efficacy for early adolescents in particular. One possible reason is that the emotion regulation needs of youth have not been intentionally targeted in many interventions for this age group. The aim of this study is to advance understanding of how different intervention approaches defined from a clear theoretical model may impact different types of outcomes and with regard to different types of measures. METHODS: We conducted a systematic literature review of four databases using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and identified 33 studies of early adolescents (aged 10-15) using five different intervention approaches that were methodologically rigorous (e.g., randomized controlled trial design with low risk of bias). Studies were conducted predominantly in North America (58%), and Western Europe (30%). RESULTS: A two-level mixed-effects meta-analysis indicated a small but significant overall intervention effect (Hedges g = 0.12). When examined by intervention type, effects were significant only for approaches focusing predominantly on emotion regulation (g = 0.20), which significantly improved behavioral outcomes as well as emotional outcomes. Approaches examining cognitive regulation, parent training, physical activity, and working memory did not differ significantly from zero. Across intervention types, outcomes demonstrated the largest effects for youth report of emotional distress. CONCLUSION: Overall, results suggest that emotion regulation may be a critically important self-regulation mechanism during early adolescence and demonstrates value in the use of applied theoretical frameworks to operationalize intervention approaches and outcomes.

Reduced Cognitive Burden and Increased Focus: A Mixed-methods Study Exploring How Implementing Scribes Impacted Physicians.

BACKGROUND: Understanding how medical scribes impact care delivery can inform decision-makers who must balance the cost of hiring scribes with their contribution to alleviating clinician burden. OBJECTIVE: The objective of this study was to understand how scribes impacted provider efficiency and satisfaction. DESIGN: This was mixed-methods study. PARTICIPANTS: Internal and family medicine clinicians were included. MEASURES: We administered structured surveys and conducted unstructured interviews with clinicians who adopted scribes. We collected average days to close charts and quantity of after-hours clinical work in the 6 months before and after implementation using electronic health record data. We conducted a difference in difference (DID) analysis using a multilevel Poisson regression. RESULTS: Three themes emerged from the interviews: (1) charting time is less after training; (2) clinicians wanted to continue working with scribes; and (3) scribes did not reduce the overall inbox burden. In the 6-month survey, 76% of clinicians endorsed that working with a scribe improved work satisfaction versus 50% at 1 month. After implementation, days to chart closure decreased [DID=0.38 fewer days; 95% confidence interval (CI): -0.61, -0.15] the average minutes worked after hours on clinic days decreased (DID=-11.5 min/d; 95% CI: -13.1, -9.9) as did minutes worked on nonclinical days (DID=-24.9 min/d; 95% CI: -28.1, -21.7). CONCLUSIONS: Working with scribes was associated with reduced time to close charts and reduced time using the electronic health record, markers of efficiency. Increased satisfaction accrued once scribes had experience.

Oral immunotherapy: The answer to peanut allergy?

Peanut and tree-nut allergies have increased dramatically in prevalence, especially in children. Historically, children with food allergies have been treated through strict avoidance of the allergen. Recently, an oral preparation of peanut allergen (Palforzia) was approved for immunotherapy (ie, desensitization) in children 4 to 17 years old. This article reviews oral immunotherapy and its role in children with peanut allergies.

Activity Settings and Daily Routines in Preschool Classrooms: Diverse Experiences in Early Learning Settings for Low-Income Children.

This paper examines activity settings and daily classroom routines experienced by 3- and 4-year-old low-income children in public center-based preschool programs, private center-based programs, and family child care homes. Two daily routine profiles were identified using a time-sampling coding procedure: a High Free-Choice pattern in which children spent a majority of their day engaged in child-directed free-choice activity settings combined with relatively low amounts of teacher-directed activity, and a Structured-Balanced pattern in which children spent relatively equal proportions of their day engaged in child-directed free-choice activity settings and teacher-directed small- and whole-group activities. Daily routine profiles were associated with program type and curriculum use but not with measures of process quality. Children in Structured-Balanced classrooms had more opportunities to engage in language and literacy and math activities, whereas children in High Free-Choice classrooms had more opportunities for gross motor and fantasy play. Being in a Structured-Balanced classroom was associated with children's language scores but profiles were not associated with measures of children's math reasoning or socio-emotional behavior. Consideration of teachers' structuring of daily routines represents a valuable way to understand nuances in the provision of learning experiences for young children in the context of current views about developmentally appropriate practice and school readiness.

Copper handling by astrocytes: insights into neurodegenerative diseases.

Copper (Cu) is an essential trace element in the brain that can be toxic at elevated levels. Cu accumulation is a suspected etiology in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and prion-induced disorders. Astrocytes are a proposed depot in the brain for Cu and other metals, including lead (Pb). This article describes the physiological roles of Cu in the central nervous system and in selected neurodegenerative diseases, and reviews evidence that astrocytes accumulate Cu and protect neurons from Cu toxicity. Findings from murine genetic models of Menkes disease and from cell culture models concerning the molecular mechanisms by which astrocytes take up, store, and buffer Cu intracellularly are discussed, as well as potential mechanistic linkages between astrocyte functions in Cu handling and neurodegenerative diseases.

Oral gavage subchronic neurotoxicity and inhalation subchronic immunotoxicity studies of ethylbenzene in the rat.

The potential for neurotoxicological and immunotoxicological effects of ethylbenzene was studied in young adult Crl:CD(SD) rats following 90-day oral (neurotoxicity) or 28-day inhalation (immunotoxicity) exposures. In the neurotoxicity study, ethylbenzene was administered orally via gavage twice daily at 0, 25, 125, or 250 mg/kg per dose (total daily dosages of 0, 50, 250, or 500 mg/kg bwt/day [mg/kg bwt/day]) for 13 weeks and the functional observational battery (FOB), automated tests for motor activity and neuropathological examination were conducted. In the immunotoxicity study, animals were exposed by inhalation to 0, 25, 100, or 500 ppm ethylbenzene (approximately 26, 90, or 342 mg/kg bwt/day as calculated from physiologically based pharmacokinetic modeling). Immunotoxicity was evaluated in female rats using the splenic antibody-forming cell plaque-forming assay in sheep red blood cell sensitized animals. The no-observed-effect level for the oral gavage study was 50mg/kg bwt/day based on increased relative weights of the liver and kidneys in the male rats. The no-observed-adverse-effect level (NOAEL) for adult neurotoxicity was the highest dose tested 500 mg/kg bwt/day. The NOAEL for the immunotoxicity evaluation was the highest tested exposure concentration, 500 ppm (342 mg/kg bwt/day).

Food allergy and eosinophilic esophagitis: learning what to avoid.

Food allergies have increased in prevalence significantly in the past decade and so, apparently, has eosinophilic esophagitis. Although the cause of eosinophilic esophagitis is unknown, allergic responses including food allergies have been implicated. This article reviews both conditions, focusing on how to detect and manage them.

CD11b+ myeloid cells are the key mediators of Th2 cell homing into the airway in allergic inflammation.

STAT6-mediated chemokine production in the lung is required for Th2 lymphocyte and eosinophil homing into the airways in allergic pulmonary inflammation, and thus is a potential therapeutic target in asthma. However, the critical cellular source of STAT6-mediated chemokine production has not been defined. In this study, we demonstrate that STAT6 in bone marrow-derived myeloid cells was sufficient for the production of CCL17, CCL22, CCL11, and CCL24 and for Th2 lymphocyte and eosinophil recruitment into the allergic airway. In contrast, STAT6 in airway-lining cells did not mediate chemokine production or support cellular recruitment. Selective depletion of CD11b(+) myeloid cells in the lung identified these cells as the critical cellular source for the chemokines CCL17 and CCL22. These data reveal that CD11b(+) myeloid cells in the lung help orchestrate the adaptive immune response in asthma, in part, through the production of STAT6-inducible chemokines and the recruitment of Th2 lymphocytes into the airway.

Mode-of-action framework for evaluating the relevance of rodent forestomach tumors in cancer risk assessment.

Studies have shown that a majority of known human carcinogens also cause cancer in laboratory animals. The converse, however, is not as well established-known animal carcinogens are not equally predictive of human carcinogenicity. A particularly controversial aspect of interspecies extrapolation is application of rodent forestomach tumor data for predicting cancer risk in humans, given that a human counterpart for the rodent forestomach does not exist. Proliferative lesions in the rodent forestomach may result from a combination of factors related to route-specific tissue irritation and/or unnatural dosing regimens and are less likely to be relevant in evaluating human carcinogenic potential, particularly when tumors are exclusive to the forestomach. We review the comparative functional anatomy, physiology, tumor biology, tissue concordance, and historical regulatory practices in the use of forestomach tumors for cancer risk assessment, examining specific chemical examples. We also propose a standardized mode-of-action approach that combines multiple risk characterization criteria, including relevance to human exposure conditions, physiologically based toxicokinetics, genotoxicity, and comparative/mechanistic toxicology. Forestomach tumors associated with chronic irritation of the forestomach epithelium, particularly those induced by repeated oral gavage dosing, should not form the basis for carcinogenic classification or quantitative cancer potency estimates for humans. Genotoxic chemicals and those that cause tumors at multiple sites, at doses at or below the maximum tolerated dose, and in the absence of forestomach irritation, are more likely to be relevant human carcinogens. Cancer risk assessment that utilizes forestomach tumor data should consider relevant human exposures, systemic bioavailability, tissue dosimetry and concordance.

In vitro models for assessing neurotoxicity of mixtures.

Rapid and inexpensive methods are needed to investigate the interactions of complex mixtures. This commentary addresses the use of cell cultures to detect neurotoxicity of simple binary mixtures, which is a first step in the development of such methods. A small number of recent studies from our laboratory are examined. Though such studies are few, they offer guidance for optimizing the value of cell cultures as systems for chemical toxicity screening and mechanistic research. The same issues that apply to in vitro neurotoxicity studies of single agents also apply to the study of mixtures, such as relevance of endpoints tested, biological usefulness and limitations of cell culture models, and relevance of exposures tested. In this commentary we will focus on several aspects of these issues.

Neurotoxicity induced in differentiated SK-N-SH-SY5Y human neuroblastoma cells by organophosphorus compounds.

Organophosphorus (OP) compounds used as insecticides and chemical warfare agents are known to cause potent neurotoxic effects in humans and animals. Organophosphorus-induced delayed neuropathy (OPIDN) is currently thought to result from inhibition of neurotoxic esterase (NTE), but the actual molecular and cellular events leading to the development of OPIDN have not been characterized. This investigation examined the effects of OP compounds on the SY5Y human neuroblastoma cells at the cellular level to further characterize cellular targets of OP neurotoxicity. Mipafox and paraoxon were used as OP models that respectively do and do not induce OPIDN. Mipafox (0.05 mM) significantly decreased neurite length in SY5Y cells differentiated with nerve growth factor (NGF) while paraoxon at the same concentration had no effect when evaluated after each of three 4-day developmental windows during which cells were treated daily with OP or vehicle. In contrast, paraoxon but not mipafox altered intracellular calcium ion levels ([Ca(2+)](i)), as seen in three types of experiments. First, immediately following the addition of a single high concentration of OP to the culture, paraoxon caused a transient increase in [Ca(2+)](i), while mipafox up to 2 mM had no effect. Paraoxon hydrolysis products could also increase intracellular Ca(2+) levels, although the pattern of rise was different than it appeared immediately after paraoxon administration. Second, repeated low-level paraoxon treatment (0.05 mM/day for 4 days) decreased basal [Ca(2+)](i) in NGF-differentiated cells, though mipafox had no effect. Third, carbachol, a muscarinic acetylcholine receptor agonist, transiently increased [Ca(2+)](i) in differentiated cells, an affect attenuated by 4-day pretreatment with paraoxon (0.05 mM/day), but not by pretreatment with mipafox. These results indicate that the decrease in neurite extension that resulted from mipafox treatment was not caused by a disruption of Ca(2+) homeostasis. The effects of OPs that cause or do not cause OPIDN were clearly distinguishable, not only by their effects on neurite length, but also by their effects on Ca(2+) homeostasis in differentiated SY5Y cells.

Reactions to radiocontrast media.

Adverse reactions to radiocontrast media (RCM) occur unexpectedly and may be life-threatening. This article describes an anaphylactoid reaction (AR) in one patient. The term AR refers to a syndrome clinically similar to anaphylaxis, but these reactions are independent of immunoglobulin E antibody-mediated mast cell or basophil degranulation. This article briefly reviews the literature regarding RCMs and types of reactions to RCM. The risk factors for AR to RCM infusions will be discussed along with current concepts of the pathogenesis of RCM-induced ARs. This article also describes the therapeutic management of patients who have had a previous adverse reaction to RCM and provides an approach to patients who have breakthrough reactions despite adequate premedication, but require additional radiographic studies.