LLERGIC RHINITIS AFFECTS approximately 20% to 40% of the US population. 1 Currently, 2 forms of specific immunotherapy (subcutaneous immunotherapy and sublingual immunotherapy) are used clinically in the United States. Considerable interest has emerged in sublingual immunotherapy, which involves placement of the allergen under the tongue for local absorption to desensitize the allergic individual over an extended treatment period to diminish allergic symptoms. Compared with subcutaneous immunotherapy, sublingual immunotherapy is easy to administer, does not involve administration of injections, and may be administered at home, avoiding the inconvenience of office visits. The opportunity for home-based therapy makes it potentially suitable for use in medically underserved areas. In 1996, a World Health Organization Task Force on Immunotherapy cited the For editorial comment see p 1297. CME available online at www.jamanetworkcme.com and questions on p 1299.

Purpose BRAF is frequently activated by gene fusion or point mutation in pilocytic astrocytoma, the most common pediatric brain tumor. We investigated the functional effect of constitutive BRAF activation in normal human neural stem and progenitor cells to determine its role in tumor induction in the brain. Experimental Design The constitutively active BRAFV600E allele was introduced into human neurospheres, and its effects on MAPK (mitogen-activated protein kinase) signaling, proliferation, soft agarose colony formation, stem cell phenotype, and induction of cellular senescence were assayed. Immunohistochemistry was used to examine p16INK4a levels in pilocytic astrocytoma. Results BRAFV600E expression initially strongly promoted colony formation but did not lead to significantly increased proliferation. BRAFV600E-expressing cells subsequently stopped proliferating and induced markers of oncogene-induced senescence including acidic β-galactosidase, PAI-1, and p16INK4a whereas controls did not. Onset of senescence was associated with decreased expression of neural stem cell markers including SOX2. Primary pilocytic astrocytoma cultures also showed induction of acidic β-galactosidase activity. Immunohistochemical examination of 66 pilocytic astrocytomas revealed p16INK4a immunoreactivity in the majority of cases, but patients with tumors negative for p16INK4a had significantly shorter overall survival. Conclusions BRAF activation in human neural stem and progenitor cells initially promotes clonogenic growth in soft agarose, suggesting partial cellular transformation, but oncogene-induced senescence subsequently limits proliferation. Induction of senescence by BRAF may help explain the low-grade pathobiology of pilocytic astrocytoma, whereas worse clinical outcomes associated with tumors lacking p16INK4a expression could reflect failure to induce senescence or an escape from oncogene-induced senescence.

BACKGROUND AND OBJECTIVE: Subcutaneous immunotherapy (SCIT) is approved in the United States for the treatment of pediatric asthma and rhinitis; sublingual immunotherapy (SLIT) does not have regulatory approval but is used in clinical practice. The objective of this study was to systematically review the evidence regarding the efficacy and safety of SCIT and SLIT for the treatment of pediatric asthma and allergic rhinoconjunctivitis. METHODS:Two independent reviewers selected articles for inclusion, extracted data, and graded the strength of evidence for each clinical outcome. All studies were randomized controlled trials of children with allergic asthma or rhinoconjunctivitis treated with SCIT or an aqueous formulation of SLIT. Data sources were Medline, Embase, LILACS, CENTRAL, and the Cochrane Central Register of Controlled Trials through May 2012. RESULTS:In 13 trials, 920 children received SCIT or usual care; in 18 studies, 1583 children received SLIT or usual care. Three studies compared SCIT with SLIT head-to-head in 135 children. The strength of evidence is moderate that SCIT improves asthma and rhinitis symptoms and low that SCIT improves conjunctivitis symptoms and asthma medication scores. Strength of evidence is high that SLIT improves asthma symptoms and moderate that SLIT improves rhinitis and conjunctivitis symptoms and decreases medication usage. The evidence is low to support SCIT over SLIT for improving asthma or rhinitis symptoms or medication usage. Local reactions were frequent with SCIT and SLIT. There was 1 report of anaphylaxis with SCIT.CONCLUSIONS: Evidence supports the efficacy of both SCIT and SLIT for the treatment of asthma and rhinitis in children. Pediatrics

Generally moderate to strong evidence supports the effectiveness of SCIT for treatment of allergic rhinitis and asthma, particularly with single-allergen immunotherapy regimens. Adverse reactions to SCIT are common, but no deaths were reported in the included studies.

Key strategies for engaging patients in medication safety are education and medication reconciliation. Patient engagement levels were generally low, as defined by a novel framework for determining levels of patient engagement. As more patient engagement studies are conducted, this framework should be evaluated for associations with patient outcomes.

IMPORTANCE Although children with low socioeconomic status (SES) have increased risk for sleep-disordered breathing (SDB), their access to subspecialty care is often limited. Polysomnography (PSG) is the gold standard diagnostic test used to characterize SDB and diagnose obstructive sleep apnea; however, it is unknown whether SES impacts timeliness of obtaining PSG and surgical treatment with adenotonsillectomy (AT).OBJECTIVE To evaluate the impact of SES on the timing of PSG, surgery with AT, and loss to follow-up for children with SDB. DESIGN, SETTING, AND PARTICIPANTSRetrospective cohort analysis conducted in tertiary outpatient pediatric otolaryngology clinics among patients newly evaluated for SDB over a 3-month period who did not have prior PSG ordered and had a minimum of 1-year follow-up. MAIN OUTCOMES AND MEASURES Public insurance (Medical Assistance [MA]) was used as a proxy for low SES. Demographics and disposition between groups were compared using t tests and χ 2 analysis. Logistic regression adjusting for disposition and insurance was used to predict loss to follow-up. Days to PSG and days to AT were evaluated using the Kaplan-Meier estimator, and the log-rank test was used to compare distribution of time to events between insurance groups.RESULTS A total of 136 children (without PSG) were evaluated for SDB over the course of 3 months; 62 (45.6%) had MA. CONCLUSIONS AND RELEVANCE Children with public insurance experienced longer intervals from initial evaluation to PSG or surgery. Almost half of patients with PSG requested were lost to follow-up, regardless of SES. These findings suggest that PSG may be a deterrent for definitive care for all children, and particularly for children with public insurance or low SES. This study emphasizes the need to understand factors contributing to disparities surrounding delay in care with PSG and surgery for children with SDB.

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A novel coronavirus disease, named coronavirus disease 2019 or COVID-19, which sparked an outbreak in Wuhan, China in December 2019, is now a pandemic. The rapid spread of this disease from one to more than 155 regions worldwide in 2.5 months highlights the need for better preparation to manage a pandemic. In this commentary, we describe how Human Factors and Ergonomics (HFE) can contribute to the COVID-19 pandemic response. Specifically, we provide an example of how HFE methodologies informed workflow redesigns implemented as part of COVID-19 pandemic preparations in an academic pediatric ambulatory clinic. We then identify key mechanisms and areas where HFE can contribute to and improve the effectiveness of a pandemic response: Just-in-time (JIT) training development, adapting workflows and processes, restructuring teams and tasks, developing effective mechanisms and tools for communication, engaging patient and families to follow the recommended practices (e.g., social distancing, revised hospital visitation policies), identifying and mitigating barriers to implementation of plans, and learning from failures and successes to improve both the current and future pandemic responses. We recommend integrating HFE approaches and tools across health care systems, state health organizations, and the Centers for Disease Control and Prevention (CDC) as they confront this pandemic.