RESUMO
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.
Assuntos
Plantão Médico , Hospitalização/estatística & dados numéricos , Instituições de Cuidados Especializados de Enfermagem , Telemedicina , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Estudos de Casos OrganizacionaisRESUMO
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.
Assuntos
Indazóis/síntese química , Indóis/síntese química , Maleimidas/síntese química , Proteína Quinase C/antagonistas & inibidores , Animais , Linhagem Celular , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/química , Glicogênio Sintase Quinase 3 beta , Cobaias , Humanos , Indazóis/farmacologia , Indazóis/toxicidade , Indóis/farmacologia , Indóis/toxicidade , Interleucina-8/metabolismo , Isoenzimas/antagonistas & inibidores , Isoenzimas/química , Síndrome do QT Longo/induzido quimicamente , Maleimidas/farmacologia , Maleimidas/toxicidade , Modelos Moleculares , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/síntese química , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Proteína Quinase C/química , Proteína Quinase C beta , Relação Estrutura-AtividadeRESUMO
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.