A Quality Improvement Initiative to Reduce Hospitalizations for Low-risk Diabetic Ketoacidosis.

BACKGROUND AND OBJECTIVES: Children with established type 1 diabetes (T1D) who present to the emergency department (ED) with mild diabetic ketoacidosis (DKA) are often hospitalized, although outpatient management may be appropriate. Our aim was to reduce hospitalization rates for children with established T1D presenting to our ED with mild DKA who were considered low risk for progression of illness. METHODS: We conducted a quality improvement initiative between January 1, 2012, and December 31, 2018 among children and young adults ≤21 years of age with established T1D presenting to our tertiary care ED with low-risk DKA. Children transferred to our institution were excluded. DKA severity was classified as low, medium, or high risk on the basis of laboratory and clinical criteria. Our quality improvement initiative consisted of development and implementation of an evidence-based treatment guideline after review by a multidisciplinary team. Our primary outcome was hospitalization rate, and our balancing measure was 3-day ED revisits. Statistical process control methods were used to evaluate outcome changes. RESULTS: We identified 165 patients presenting with low-risk DKA. The baseline preimplementation hospitalization rate was 74% (95% confidence interval 64%-82%), and after implementation, this decreased to 55% (95% confidence interval 42%-67%) (-19%; P = .011). The postimplementation hospitalization rate revealed special cause variation. One patient in the postimplementation period returned to the ED within 3 days but did not have DKA and was not hospitalized. CONCLUSIONS: Hospitalization rates for children and young adults presenting to the ED with low-risk DKA can be safely reduced without an increase in ED revisits.

Phosphorothioate analogues of alkyl lysophosphatidic acid as LPA3 receptor-selective agonists.

The metabolically stabilized LPA analogue 1-oleoyl-2-O-methyl-rac-glycerophosphorothioate (OMPT) was recently shown to be a potent subtype-selective agonist for LPA3, a G-protein-coupled receptor (GPCR) in the endothelial differentiation gene (EDG) family. Further stabilization was achieved by replacing the sn-1 O-acyl group with an O-alkyl ether. A new synthetic route for the enantiospecific synthesis of the resulting alkyl LPA phosphorothioate analogues is described. The pharmacological properties of the alkyl OMPT analogues were characterized for subtype-specific agonist activity using Ca2+-mobilization assays in RH7777 cells expressing the individual EDG family LPA receptors. Alkyl OMPT analogues induced cell migration in cancer cells mediated through LPA1. Alkyl OMPT analogues also activated Ca2+ release through LPA2 activation but with less potency than sn-1-oleoyl LPA. In contrast, alkyl OMPT analogues were potent LPA3 agonists. The alkyl OMPTs 1 and 3 induced cell proliferation at submicromolar concentrations in 10T 1/2 fibroblasts. Interestingly, the absolute configuration of the sn-2 methoxy group of the alkyl OMPT analogues was not recognized by any of the LPA receptors in the EDG family. By using a reporter gene assay for the LPA-activated nuclear transcription factor PPARgamma, we demonstrated that phosphorothioate diesters have agonist activity that is independent of their ligand properties at the LPA-activated GPCRs. The availability of new alkyl LPA analogues expands the scope of structure-activity studies and will further refine the molecular nature of ligand-receptor interactions for this class of GPCRs.