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2.
J Gen Intern Med ; 36(5): 1310-1318, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33564947

RESUMO

BACKGROUND: The evolving COVID-19 pandemic has and continues to present a threat to health system capacity. Rapidly expanding an existing acute care physician workforce is critical to pandemic response planning in large urban academic health systems. INTERVENTION: The Medical Emergency-Pandemic Operations Command (MEOC)-a multi-specialty team of physicians, operational leaders, and support staff within an academic Department of Medicine in Calgary, Canada-partnered with its provincial health system to rapidly develop a comprehensive, scalable pandemic physician workforce plan for non-ventilated inpatients with COVID-19 across multiple hospitals. The MEOC Pandemic Plan comprised seven components, each with unique structure and processes. METHODS: In this manuscript, we describe MEOC's Pandemic Plan that was designed and implemented from March to May 2020 and re-escalated in October 2020. We report on the plan's structure and process, early implementation outcomes, and unforeseen challenges. Data sources included MEOC documents, health system, public health, and physician engagement implementation data. KEY RESULTS: From March 5 to October 26, 2020, 427 patients were admitted to COVID-19 units in Calgary hospitals. In the initial implementation period (March-May 2020), MEOC communications reached over 2500 physicians, leading to 1446 physicians volunteering to provide care on COVID-19 units. Of these, 234 physicians signed up for hospital shifts, and 227 physicians received in-person personal protective equipment simulation training. Ninety-three physicians were deployed on COVID-19 units at four large acute care hospitals. The resurgence of cases in September 2020 has prompted re-escalation including re-activation of COVID-19 units. CONCLUSIONS: MEOC leveraged an academic health system partnership to rapidly design, implement, and refine a comprehensive, scalable COVID-19 acute care physician workforce plan whose components are readily applicable across jurisdictions or healthcare crises. This description may guide other institutions responding to COVID-19 and future health emergencies.


Assuntos
COVID-19 , Médicos , Canadá , Humanos , Pandemias , SARS-CoV-2 , Recursos Humanos
3.
Bioorg Chem ; 103: 104128, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745761

RESUMO

A set of 4-(R2-imino)-3-mercapto-5-(R1)-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and growth inhibition cytotoxicity. Noticeably, the compounds designed to be nitrofurantoin mimics were the most potent anti-neoplastic agents.


Assuntos
Antineoplásicos/farmacologia , Inibidores do Crescimento/farmacologia , Iminas/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Triazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores do Crescimento/síntese química , Inibidores do Crescimento/química , Iminas/síntese química , Iminas/química , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
6.
Org Lett ; 20(6): 1481-1482, 2018 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-29544253
7.
Org Lett ; 17(12): 2867-9, 2015 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-26087893
8.
Bioorg Med Chem Lett ; 20(19): 5847-52, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20727752

RESUMO

Initial high throughput screening efforts identified highly potent and selective kappa opioid receptor antagonist 3 (κ IC(50)=77 nM; µ:κ and δ:κ IC(50) ratios>400) which lacked CNS exposure in vivo. Modification of this scaffold resulted in development of a series of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides showing potent and selectivity κ antagonism as well as good brain exposure. Analog 6c (κ IC(50)=20 nM; µ:κ=36, δ:κ=415) was also shown to reverse κ-agonist induced rat diuresis in vivo.


Assuntos
Benzamidas/química , Receptores Opioides kappa/antagonistas & inibidores , Tropanos/química , Animais , Benzamidas/síntese química , Benzamidas/farmacocinética , Linhagem Celular Tumoral , Diurese/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ensaios de Triagem em Larga Escala , Humanos , Microssomos Hepáticos/metabolismo , Ratos , Receptores Opioides kappa/metabolismo , Relação Estrutura-Atividade , Tropanos/síntese química , Tropanos/farmacocinética
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