ABSTRACT
Skilled nursing facilities (SNFs) are increasingly being called upon to prevent avoidable hospitalizations. Primary care provider (PCP) bedside assessment for change of condition in SNF patients is believed to improve care and reduce unnecessary hospitalizations, but PCPs are not always available on site in an SNF. This study addresses the potential clinical and financial impacts of an after-hours physician coverage service enabled by technology, TripleCare (TC), to prevent avoidable hospitalizations. TC was launched in a 365-bed SNF in Brooklyn, New York, in March 2015. Outcomes were tracked and evaluated for the initial year. Avoided hospitalizations were identified as such by the covering physicians and confirmed by the facility's medical director. Of the 313 patients cared for by the telemedicine-enabled covering physicians during the year of service, 259 (83%) were treated on site, including 91 who avoided hospitalizations as verified by a third party, and 54 were transferred to the hospital. It is estimated that the associated cost savings to Medicare and other payers exceeded $1.55 million, approximately $500,000 of which went to a managed care Medicare payer, in this 1 SNF during this period. Medicare would annually save $500,000 in an average 120-bed facility, or $4167 per bed. Use of a dedicated virtual after-hours physician coverage service in an SNF demonstrated a significant reduction in avoidable hospitalizations.
Subject(s)
After-Hours Care , Hospitalization/statistics & numerical data , Skilled Nursing Facilities , Telemedicine , Adult , Aged , Female , Humans , Male , Middle Aged , New York City , Organizational Case StudiesABSTRACT
Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC isozymes and GSK-3beta. In a cell-based functional assay, 8f and 8i effectively blocked IL-8 release induced by PKC-betaII (IC(50) = 20-25 nM). In cardiovascular safety assessment, representative lead compounds bound to the hERG channel with high affinity, potently inhibited ion current in a patch-clamp experiment, and caused a dose-dependent increase of QT(c) in guinea pigs.
Subject(s)
Indazoles/chemical synthesis , Indoles/chemical synthesis , Maleimides/chemical synthesis , Protein Kinase C/antagonists & inhibitors , Animals , Cell Line , ERG1 Potassium Channel , Ether-A-Go-Go Potassium Channels , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/chemistry , Glycogen Synthase Kinase 3 beta , Guinea Pigs , Humans , Indazoles/pharmacology , Indazoles/toxicity , Indoles/pharmacology , Indoles/toxicity , Interleukin-8/metabolism , Isoenzymes/antagonists & inhibitors , Isoenzymes/chemistry , Long QT Syndrome/chemically induced , Maleimides/pharmacology , Maleimides/toxicity , Models, Molecular , Patch-Clamp Techniques , Potassium Channel Blockers/chemical synthesis , Potassium Channel Blockers/chemistry , Potassium Channel Blockers/pharmacology , Potassium Channels, Voltage-Gated/drug effects , Potassium Channels, Voltage-Gated/metabolism , Protein Kinase C/chemistry , Protein Kinase C beta , Structure-Activity RelationshipABSTRACT
A novel series of acyclic 3-(7-azaindolyl)-4-(aryl/heteroaryl)maleimides was synthesized and evaluated for activity against GSK-3beta and selectivity versus PKC-betaII, as well as a broad panel of protein kinases. Compounds 14 and 17c potently inhibited GSK-3beta (IC(50)=7 and 26 nM, respectively) and exhibited excellent selectivity over PKC-betaII (325 and >385-fold, respectively). Compound 17c was also highly selective against 68 other protein kinases. In a cell-based functional assay, both 14 and 17c effectively increased glycogen synthase activity by inhibiting GSK-3beta.
