Reducing emergency department visits utilizing a primary care asthma specialty clinic in a high-risk patient population.

OBJECTIVE: Asthma is a leading cause of pediatric emergency department (ED) use. Optimizing asthma outcomes is a goal of Nationwide Children's Hospital (NCH) and its affiliated Accountable Care Organization. NCH's Primary Care Network, comprised of 12 offices serving a predominantly Medicaid population, sought to determine whether an Asthma Specialty Clinic (ASC) operated within a single primary care office could reduce ED asthma rates and improve quality measures, relative to all other network offices. METHODS: An ASC was piloted with four components: patient monitoring, provider continuity, standardized assessment, and multi-disciplinary education. A registry was established to contact patients at recommended intervals. At extended-length visits, a general pediatrician evaluated patients and a multi-disciplinary team provided education. Novel educational tools were utilized, guideline-based templates recorded and spirometry obtained. ED asthma rate, spirometry utilization, and controller fills by intervention office patients were compared to all other network offices before and after ASC initiation. RESULTS: At baseline, asthma ED visits by intervention and usual care populations were similar (p = 0.43). After, rates were significantly lower for intervention office patients versus usual care office patients (p < 0.001), declining in the intervention population by 26.2%, 25.2%, and 31.8% in 2013, 2014, and 2015, respectively, from 2012 baseline, versus increases of 3.8%, 16.2%, and 9.5% in the usual care population. Spirometry completion, controller fills, and patients with favorable Asthma Medication Ratios significantly increased for intervention office patient relative to the usual care population. CONCLUSIONS: A primary care-based asthma clinic was associated with a significant and sustainable reduction in ED utilization versus usual care. What's new: This study describes a comprehensive, multi-disciplinary, and innovative model for an asthma management program within the medical home that demonstrated a significant reduction in ED visits, an increase in spirometry utilization, and an increase in controller fills in a high-risk asthma population versus comparison group.

Targeted Therapy in Pediatric AML: An Evolving Landscape.

The outcomes associated with pediatric acute myeloid leukemia (AML) have improved over the last few decades, with the implementation of intensive chemotherapy, hematopoietic stem cell transplant, and improved supportive care. However, even with intensive therapy and the use of HSCT, both of which carry significant risks of short- and long-term side effects, approximately 30% of children are not able to be cured. The characterization of AML in pediatrics has evolved over time and it currently involves use of a variety of diagnostic tools, including flow cytometry and comprehensive genomic sequencing. Given the adverse effects of chemotherapy and the need for additional therapeutic options to improve outcomes in these patients, the genomic and molecular architecture is being utilized to inform selection of targeted therapies in pediatric AML. This review provides a summary of current, targeted therapy options in pediatric AML.

Effect of osteopathic manipulative treatment on pulmonary function testing in children with asthma.

CONTEXT: Asthma is a leading cause of pediatric chronic illness, and poor disease control can lead to decreased quality of life and impaired academic performance. Although osteopathic manipulative treatment (OMT) has been shown to have positive effects on pulmonary function in adult patient populations, less is known about its impact in children. OBJECTIVES: To evaluate changes in pulmonary function testing (PFT) in pediatric patients on the same day they received OMT compared with PFT in those who received usual care. METHODS: We recruited patients between the ages of 7-18 years with a diagnosis of asthma who were receiving routine care at a primary care asthma clinic and had undergone baseline spirometry. Patients were excluded if they met any of the following criteria: clinical indication for pre- and postbronchodilator spirometry on the day of their visit, albuterol use in the last 8 hours, oral steroid use in the previous 2 weeks, or diagnosis of asthma exacerbation in the previous 4 weeks. Eligible patients were then randomized to either an OMT or a control group. Patients in the OMT group were treated with rib raising and suboccipital release in addition to standard asthma care, while control group patients received standard care only. A second PFT was performed for patients in both groups at the end of the visit. OMT was performed by multiple osteopathic pediatric residents specifically trained for this study. Change in spirometry results (forced vital capacity [FVC], forced expiration volume in 1 second [FEV1], FVC/FEV1, and forced expiratory flow 25-75%) were then compared. RESULTS: The study population included 58 patients: 31 (53.4%) were assigned to the OMT group and 27 (46.6%) were assigned to the standard of care group. Patients who received OMT had greater improvement in all spirometry values compared to the usual group; however, these changes were not statistically significant. CONCLUSIONS: The benefits of OMT on short term spirometry results in pediatric asthma patients remain unclear.

Targeting AML-associated FLT3 mutations with a type I kinase inhibitor.

Tyrosine kinase domain (TKD) mutations contribute to acquired resistance to FMS-like tyrosine kinase 3 (FLT3) inhibitors used to treat FLT3-mutant acute myeloid leukemia (AML). We report a cocrystal structure of FLT3 with a type I inhibitor, NCGC1481, that retained potent binding and activity against FLT3 TKD and gatekeeper mutations. Relative to the current generation of advanced FLT3 inhibitors, NCGC1481 exhibited superior antileukemic activity against the common, clinically relevant FLT3-mutant AML cells in vitro and in vivo.

Overcoming adaptive therapy resistance in AML by targeting immune response pathways.

Targeted inhibitors to oncogenic kinases demonstrate encouraging clinical responses early in the treatment course; however, most patients will relapse because of target-dependent mechanisms that mitigate enzyme-inhibitor binding or through target-independent mechanisms, such as alternate activation of survival and proliferation pathways, known as adaptive resistance. Here, we describe mechanisms of adaptive resistance in FMS-like receptor tyrosine kinase (FLT3)-mutant acute myeloid leukemia (AML) by examining integrative in-cell kinase and gene regulatory network responses after oncogenic signaling blockade by FLT3 inhibitors (FLT3i). We identified activation of innate immune stress response pathways after treatment of FLT3-mutant AML cells with FLT3i and showed that innate immune pathway activation via the interleukin-1 receptor-associated kinase 1 and 4 (IRAK1/4) complex contributes to adaptive resistance in FLT3-mutant AML cells. To overcome this adaptive resistance mechanism, we developed a small molecule that simultaneously inhibits FLT3 and IRAK1/4 kinases. The multikinase FLT3-IRAK1/4 inhibitor eliminated adaptively resistant FLT3-mutant AML cells in vitro and in vivo and displayed superior efficacy as compared to current targeted FLT3 therapies. These findings uncover a polypharmacologic strategy for overcoming adaptive resistance to therapy in AML by targeting immune stress response pathways.