Abnormal paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies.

OBJECTIVES: Patients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein that protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients. METHODS: A total of 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analysed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes. RESULTS: The arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM-associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes. CONCLUSIONS: The arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favourable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.

Increasing Chlamydia and Gonorrhea Testing for Adolescents in the Pediatric Emergency Department.

OBJECTIVE: Adolescents who use the emergency department are more likely to engage in high-risk sexual activity and are at an increased risk of sexually transmitted infections. We aimed to increase testing for Chlamydia and gonorrhea from 12% to 50% among adolescents presenting to our pediatric emergency department with at-risk chief complaints over 12 months. METHODS: Plan-Do-Study-Act cycles were initiated in July 2020. A multidisciplinary team reviewed preexisting data and developed interventions to increase Chlamydia and gonorrhea testing in teens with at-risk complaints, including genitourinary and behavioral health complaints, and females with abdominal pain. Two categories of interventions were implemented: education and electronic medical record optimization. Process measures were the proportion of patients with a documented sexual history and the proportion of patients tested with a documented confidential phone number. Secondary outcome measures included the weekly number of positive test results and the proportion of patients testing positive who were contacted to arrange treatment. Statistical process control charts were used to examine changes in measures over time. RESULTS: Within 14 months of project initiation, the proportion of at-risk patients tested increased from 12% to 59%. Teen phone number documentation remained unchanged from 23%. Sexual history documentation remained unchanged from 46%. The number of positive test results increased from 1.8 to 3.4 per month, and the proportion of patients testing positive who were contacted to arrange treatment remained unchanged at 83%. CONCLUSIONS: We surpassed our goal and increased the proportion of at-risk patients tested for Chlamydia and gonorrhea to 59%, sustained for 4 months from the last intervention.