Dry eye disorders, including Sjögren's syndrome, constitute a common problem in the aging population, with limited effective therapeutic options available. The cAMP-activated Cl 2 channel cystic fibrosis transmembrane conductance regulator (CFTR) is a major prosecretory channel at the ocular surface. We investigated whether compounds that target CFTR can correct the abnormal tear film in dry eye. Small-molecule activators of human wild-type CFTR identified by highthroughput screening were evaluated in cell culture and in vivo assays, to select compounds that stimulate Cl 2 -driven fluid secretion across the ocular surface in mice. An aminophenyl-1,3,5-triazine, CFTR act -K089, fully activated CFTR in cell cultures with EC 50 ∼250 nM and produced an ∼8.5 mV hyperpolarization in ocular surface potential difference. When delivered topically, CFTR act -K089 doubled basal tear volume for 4 h and had no effect in CF mice. CFTR act -K089 showed sustained tear film bioavailability without detectable systemic absorption. In a mouse model of aqueous-deficient dry eye produced by lacrimal ablation, topical administration of 0.1 nmol CFTR act -K089 3 times daily restored tear volume to basal levels, preventing corneal epithelial disruption when initiated at the time of surgery and reversing it when started after development of dry eye. Our results support the potential utility of CFTR-targeted activators as a novel prosecretory treatment for dry eye.-Flores, A. M., Casey, S. D., Felix, C. M., Phuan, P. W., Verkman, A. S., Levin, M. H. Small-molecule CFTR activators increase tear secretion and prevent experimental dry eye disease.

Sex, race, and insurance status were independently associated with post-arrest care interventions, patient outcomes and treatment at a 24/7 PCI center. More studies are needed to fully understand the causes and implications of these disparities.

IMPORTANCEPhysicians commonly hospitalize patients presenting to the emergency department (ED) with acute pulmonary embolism (PE), despite eligibility for safe outpatient management. Risk stratification using electronic health record-embedded clinical decision support systems can aid physician site-of-care decision-making and increase safe outpatient management. The long-term sustainability of early improvements after the cessation of trial-based, champion-led promotion is uncertain. OBJECTIVE To evaluate the sustainability of recommended site-of-care decision-making support 4 years after initial physician champion-led interventions to increase outpatient management for patients with acute PE. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study was conducted in 21 US community hospitals in an integrated health system. Participants included adult patients presenting to the ED with acute PE. Study sites had participated in an original decision-support intervention trial 4 years prior to the current study period: 10 sites were intervention sites, 11 sites were controls.In that trial, decision support with champion promotion resulted in significantly higher outpatient management at intervention sites compared with controls. After trial completion, all study sites were given continued access to a modified decision-support tool without further champion-led outreach.Data were analyzed from January 2019 to February 2020.EXPOSURES ED treatment with a modified clinical decision support tool. MAIN OUTCOMES AND MEASURESThe main outcome was frequency of outpatient management, defined as discharge home directly from the ED, stratified by the PE Severity Index. The safety measure of outpatient care was 7-day PE-related hospitalization. RESULTSThis study included 1039 patients, including 533 (51.3%) women, with a median (IQR) age of 65 (52-74) years. Nearly half (474 patients [45.6%]) were rated lower risk on the PE Severity Index.Overall, 278 patients (26.8%) were treated as outpatients, with only four 7-day PE-related hospitalizations (1.4%; 95% CI, 0.4%-3.6%). The practice gap in outpatient management created by the earlier trial persisted in the outpatient management for patients with lower risk: 109 of 236 patients (46.2%) at former intervention sites vs 81 of 238 patients (34.0%) at former control sites (difference, 12.2; [95% CI, 3.4-20.9] percentage points; P = .007), with wide interfacility variation (range, 7.1%-47.1%). CONCLUSIONS AND RELEVANCEIn this cohort study, a champion-led, decision-support intervention to increase outpatient management for patients presenting to the ED with acute pulmonary embolism was associated with sustained higher rates of outpatient management 4 years (continued) Key Points Question Were the outcomes associated with a physician championled, electronic health record-embedded clinical decision support intervention for risk-stratifying adults presenting at the emergency department (ED) with acute pulmonary embolism sustained 4 years after initial promotion? Findings In this coh...