ABSTRACT
BACKGROUND: Pandemics create challenges for medical centers, which call for innovative adaptations to care for patients during the unusually high census, to distribute stress and work hours among providers, to reduce the likelihood of transmission to health care workers, and to maximize resource utilization. METHODS: We describe a multidisciplinary vascular access team's development to improve frontline providers' workflow by placing central venous and arterial catheters. Herein we describe the development, organization, and processes resulting in the rapid formation and deployment of this team, reporting on notable clinical issues encountered, which might serve as a basis for future quality improvement and investigation. We describe a retrospective, single-center descriptive study in a large, quaternary academic medical center in a major city. The COVID-19 vascular access team included physicians with specialized experience in placing invasive catheters and whose usual clinical schedule had been lessened through deferment of elective cases. The target population included patients with confirmed or suspected COVID-19 in the medical ICU (MICU) needing invasive catheter placement. The line team placed all invasive catheters on patients in the MICU with suspected or confirmed COVID-19. RESULTS AND CONCLUSIONS: Primary data collected were the number and type of catheters placed, time of team member exposure to potentially infected patients, and any complications over the first three weeks. Secondary outcomes pertained to workflow enhancement and quality improvement. 145 invasive catheters were placed on 67 patients. Of these 67 patients, 90% received arterial catheters, 64% central venous catheters, and 25% hemodialysis catheters. None of the central venous catheterizations or hemodialysis catheters were associated with early complications. Arterial line malfunction due to thrombosis was the most frequent complication. Division of labor through specialized expert procedural teams is feasible during a pandemic and offloads frontline providers while potentially conferring safety benefits.
Subject(s)
COVID-19 , Catheterization, Central Venous , Central Venous Catheters , Catheterization, Central Venous/adverse effects , Catheterization, Central Venous/methods , Critical Illness , Humans , Pandemics , Retrospective StudiesABSTRACT
Many health systems are engaging in pay-for-performance agreements with payers that focus primarily on improving ambulatory preventive screenings. These also are referred to as gaps in care. Gaps in care are typically measured by the Healthcare Effectiveness Data and Information Set measures of health care quality. To address gaps in care effectively, the physician-led Gaps in Care program at Northwell Health works to improve processes related to measurement, data attribution, patient outreach, and patient engagement. Following a structured framework to address patient gaps in care is a successful strategy for accomplishing complex value-based care delivery.
Subject(s)
Physicians , Reimbursement, Incentive , Delivery of Health Care , Humans , Quality of Health CareABSTRACT
Antiangiogenic agents have been widely investigated in combination with standard chemotherapy or targeted cancer agents for better management of advanced cancers. Therapeutic agents that concurrently inhibit epidermal growth factor receptor and other angiokinases could be useful alternatives to combination therapies for epidermal growth factor receptor-dependent cancers. Here, we report the synthesis of an indole derivative of pazopanib using a bioisosteric replacement strategy, which was designated MKP101. MKP101 inhibited not only the epidermal growth factor receptor with an IC50 value of 43 nM but also inhibited angiokinases as potently as pazopanib. In addition, MKP101 effectively inhibited vascular endothelial growth factor-induced endothelial proliferation, tube formation, migration of human umbilical vein endothelial cells and proliferation of HCC827, an epidermal growth factor receptor-addicted cancer cell line. A docking model of MKP101 and the kinase domain of the epidermal growth factor receptor was generated to predict its binding mode, and validated by synthesizing and evaluating MKP101 derivatives. Additionally, a study of structure-activity relationships of indolylamino or indolyloxy pyrimidine analogues derived from MKP101 demonstrated that selectivity for epidermal growth factor receptor and other angiokinases, especially vascular endothelial growth factor receptor 2 depends on the position of substituents on pyrimidine and the type of link between pyrimidine and the indole moiety. We believe that this study could provide a basis for developing angiokinase inhibitors having high affinity for the epidermal growth factor receptor, from the pyrimidine scaffold.
Subject(s)
Angiogenesis Inhibitors/pharmacology , ErbB Receptors/antagonists & inhibitors , Indoles/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein Kinases/metabolism , Pyrimidines/pharmacology , Angiogenesis Inhibitors/chemical synthesis , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/therapeutic use , Carcinoma, Non-Small-Cell Lung/pathology , Cell Proliferation/drug effects , ErbB Receptors/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Indazoles , Indoles/chemical synthesis , Indoles/chemistry , Indoles/therapeutic use , Inhibitory Concentration 50 , Lung Neoplasms/pathology , Molecular Docking Simulation , Neovascularization, Pathologic/drug therapy , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Pyrimidines/therapeutic use , Structure-Activity Relationship , Sulfonamides/chemistry , Sulfonamides/pharmacology , Vascular Endothelial Growth Factor A/pharmacologyABSTRACT
Takeda G-protein-coupled receptor 5 (TGR5) is a promising molecular target for metabolic diseases. A series of 4-(2,5-dichlorophenoxy)pyrimidine and cyclopropylmalonamide derivatives were synthesized as potent agonists of TGR5 based on a bioisosteric replacement strategy. Several compounds exhibited improved potency, compared to a reference compound with a pyridine scaffold. The pharmacokinetic profile of the representative compound 18 was considered moderate.
Subject(s)
Cytochrome P-450 Enzyme Inhibitors/pharmacology , Cytochrome P-450 Enzyme System/metabolism , Drug Discovery , Malonates/pharmacology , Pyrimidines/pharmacology , Receptors, G-Protein-Coupled/agonists , Animals , Biological Availability , Cytochrome P-450 Enzyme Inhibitors/administration & dosage , Cytochrome P-450 Enzyme Inhibitors/chemistry , Dose-Response Relationship, Drug , HEK293 Cells , Humans , Malonates/administration & dosage , Malonates/chemistry , Mice , Mice, Inbred ICR , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Microsomes, Liver/metabolism , Molecular Structure , Pyrimidines/administration & dosage , Pyrimidines/chemistry , Structure-Activity RelationshipABSTRACT
ExoU is a potent virulence factor of Pseudomonas aeruginosa and is considered a potential therapeutic target. In order to discover novel ExoU inhibitors, we screened an in-house chemical library utilizing a yeast-based screening system. Some sulfonamides displayed significant activity without nonspecific cytotoxicity. We describe a series of sulfonamides as novel ExoU inhibitors, along with a brief structure-activity relationship.
