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1.
Acad Med ; 99(7): 736-740, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38489481

RESUMEN

PROBLEM: Despite increasing recognition of the importance of quality and patient safety in academic medicine, challenges remain with ensuring physician participation in quality assurance and quality improvement efforts, such as lack of compensation and enabling resources. An organizational culture that includes physician leadership and a supportive infrastructure is needed to encourage physician backing of quality and patient safety initiatives. APPROACH: The authors describe the development of a robust quality and patient safety program in the Department of Medicine at The Ottawa Hospital over the past 7 years and highlight how the department changed its organizational culture by prioritizing quality and patient safety and establishing the necessary infrastructure to support this program. Program development was characterized by 4 overarching themes: incentives, administrative structure and physician leadership, training and support, and system enhancements. OUTCOMES: As a result of the program, the department broadly implemented a standardized framework for conducting quality committee meetings and morbidity and mortality rounds and reviewing patient safety incidents and patient experience across its 16 divisions. This has led to 100% departmental compliance on corporate quality assurance metrics each year (e.g., regular multidisciplinary divisional quality committee meetings), along with physician participation in formal quality improvement initiatives that align with larger corporate goals. NEXT STEPS: The authors reflect on lessons learned during the implementation of the program and the essential elements that contributed to its success. Next steps for the program include using a centralized repository of quality and patient safety data, including patient safety incident dashboards, to encourage greater divisional collaboration on quality improvement initiatives and continuous institutional learning over time. Another important avenue will be to create an academic hub for excellence in quality and a formal approach to reward and promote physicians for their quality work.


Asunto(s)
Cultura Organizacional , Seguridad del Paciente , Mejoramiento de la Calidad , Humanos , Seguridad del Paciente/normas , Mejoramiento de la Calidad/organización & administración , Ontario , Desarrollo de Programa/métodos , Liderazgo , Garantía de la Calidad de Atención de Salud
3.
PeerJ ; 9: e11290, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33987001

RESUMEN

Hadrosaurid (duck-billed) dinosaur bonebeds are exceedingly prevalent in upper Cretaceous (Campanian-Maastrichtian) strata from the Midwest of North America (especially Alberta, Canada, and Montana, U.S.A) but are less frequently documented from more northern regions. The Wapiti Formation (Campanian-Maastrichtian) of northwestern Alberta is a largely untapped resource of terrestrial palaeontological information missing from southern Alberta due to the deposition of the marine Bearpaw Formation. In 2018, the Boreal Alberta Dinosaur Project rediscovered the Spring Creek Bonebed, which had been lost since 2002, along the northern bank of the Wapiti River, southwest of Grande Prairie. Earlier excavations and observations of the Spring Creek Bonebed suggested that the site yielded young hadrosaurines. Continued work in 2018 and 2019 recovered ~300 specimens that included a minimum of eight individuals, based on the number of right humeri. The morphology of several recovered cranial elements unequivocally supports lambeosaurine affinities, making the Spring Creek sample the first documented occurrence of lambeosaurines in the Wapiti Formation. The overall size range and histology of the bones found at the site indicate that these animals were uniformly late juveniles, suggesting that age segregation was a life history strategy among hadrosaurids. Given the considerable size attained by the Spring Creek lambeosaurines, they were probably segregated from the breeding population during nesting or caring for young, rather than due to different diet and locomotory requirements. Dynamic aspects of life history, such as age segregation, may well have contributed to the highly diverse and cosmopolitan nature of Late Cretaceous hadrosaurids.

4.
Int J Qual Health Care ; 32(7): 456-463, 2020 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-32696048

RESUMEN

OBJECTIVE: Develop and evaluate a framework for quality improvement which will provide a common approach, terminology and greater likelihood of success in achieving demonstrable and sustained improvement. DESIGN: Descriptive with mixed methods evaluation. SETTING: Tertiary care academic hospital in Ottawa, Canada. PARTICIPANTS: Students enrolled in the Quality and Patient Safety Leadership Executive Program at the local university. METHODS: The quality improvement (QI) framework was developed though comparison and coding of key strengths across four commonly applied quality improvement frameworks. Effectiveness of the framework was evaluated through a satisfaction survey of students who were taught the framework, and independent assessment of student improvement initiatives that followed the QI Framework versus initiatives from a prior year who did not. MAIN OUTCOME MEASURES: Acceptability and effectiveness of the QI Framework. RESULTS: All participants found the QI Framework to be useful and easy to follow. Independent evaluation of improvement initiatives following the QI Framework, as compared to those that did not, scored higher (95% CI: 3.0 ± 0.49) than the projects completed without the QI Framework (95% CI: 2.2 ± 0.30), P value < 0.01. Scores were higher for cohort 2017/18 in all criteria except scaling and spreading, in which there was no change (2015/16 95% CI: 1.2 ± 0.24, 2017/18 95% CI: 1.2 ± 0.38). CONCLUSIONS: The method we have developed is acceptable and helpful to users, and overall application resulted in higher quality initiatives. We believe this method, which we have branded as The Ottawa Hospital Innovation Framework, can be beneficial in healthcare settings for a variety of change initiatives.


Asunto(s)
Liderazgo , Mejoramiento de la Calidad , Canadá , Atención a la Salud , Humanos , Seguridad del Paciente
5.
J Neuroinflammation ; 16(1): 222, 2019 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-31727174

RESUMEN

BACKGROUND: Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1ß (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et al., J Cereb Blood Flow Metab 37:3531-3543, 2017; Hill et al., Lancet Neurol 11:942-950, 2012; Amaro et al., Stroke 47:2874-2876, 2016). METHODS: Transient stroke was induced in mice via one of two methods. One group of mice were subjected to tandem ipsilateral common carotid artery and middle cerebral artery occlusion, while another group underwent the filament-based middle cerebral artery occlusion. We have recently developed an animal model of intra-arterial (IA) drug administration after recanalization (Maniskas et al., J Neurosci Met 240:22-27, 2015). Sub groups of the mice were treated with either saline or Il-1α, wherein the drug was administered either acutely (immediately after surgery) or subacutely (on the third day after stroke). This was followed by behavioral and histological analyses. RESULTS: We now show in the above-mentioned mouse stroke models (transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery occlusion (MCA) occlusion, MCA suture occlusion) that IL-1α is neuroprotective when acutely given either intravenously (IV) or IA at low sub-pathologic doses. Furthermore, while IV administration induces transient hemodynamic side effects without affecting systemic markers of inflammation, IA delivery further improves overall outcomes while eliminating these side effects. Additionally, we show that delayed/subacute IV IL-1α administration ameliorates functional deficit and promotes neurorepair. CONCLUSIONS: Taken together, our present study suggests for the first time that IL-1α could, unexpectedly, be an effective ischemic stroke therapy with a broad therapeutic window.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Interleucina-1alfa/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Interleucina-1alfa/farmacología , Masculino , Ratones , Neuronas/efectos de los fármacos , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Recuperación de la Función/efectos de los fármacos , Accidente Cerebrovascular/patología
6.
Healthc Manage Forum ; 32(5): 266-271, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31238743

RESUMEN

We describe The Ottawa Hospital's (TOH) journey to create a Just Culture. We will describe the concept of a Just Culture, why TOH initiated this transformation, how TOH went about creating the Just Culture, and some of its early impacts. Following two events that called into question our hospital's safety culture, the hospital leadership adopted a deliberate and methodical organization-wide approach to change. These efforts included generating leadership commitment, incorporating the efforts within its corporate strategy, obtaining stakeholder engagement, developing and delivering an education program, and last but not least, efforts to improve safety systems. TOH has attempted to develop an increased focus on safety-for staff, visitors, and patients. The Ottawa Hospital has had demonstrable success throughout this journey as a result of a disciplined effort to create a Just Culture. This work will require ongoing efforts to ensure the culture shift is sustained.


Asunto(s)
Hospitales , Cultura Organizacional , Innovación Organizacional , Administración de la Seguridad , Investigación sobre Servicios de Salud , Humanos , Liderazgo , Ontario , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud
7.
ISME J ; 12(9): 2238-2251, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29884827

RESUMEN

Coral reef ecosystems are highly sensitive to microbial activities that result from dissolved organic matter (DOM) enrichment of their surrounding seawater. However, the response to particulate organic matter (POM) enrichment is less studied. In a microcosm experiment, we tested the response of bacterioplankton to a pulse of POM from the mass-spawning of Orbicella franksi coral off the Caribbean coast of Panama. Particulate organic carbon (POC), a proxy measurement for POM, increased by 40-fold in seawater samples collected during spawning; 68% degraded within 66 h. The elevation of multiple hydrolases presumably solubilized the spawn-derived POM into DOM. A carbon budget constructed for the 275 µM of degraded POC showed negligible change to the concentration of dissolved organic carbon (DOC), indicating that the DOM was readily utilized. Fourier transform ion cyclotron resonance mass spectrometry shows that the DOM pool became enriched with heteroatom-containing molecules, a trend that suggests microbial alteration of organic matter. Our sensitivity analysis demonstrates that bacterial carbon demand could have accounted for a large proportion of the POC degradation. Further, using bromodeoxyuridine immunocapture in combination with 454 pyrosequencing of the 16S ribosomal RNA gene, we surmise that actively growing bacterial groups were the primary degraders. We conclude that coral gametes are highly labile to bacteria and that such large capacity for bacterial degradation and alteration of organic matter has implications for coral reef health and coastal marine biogeochemistry.


Asunto(s)
Antozoos/fisiología , Bacterias/metabolismo , Plancton/metabolismo , Agua de Mar/química , Animales , Bacterias/crecimiento & desarrollo , Bacterias/aislamiento & purificación , Carbono/análisis , Arrecifes de Coral , Material Particulado/análisis , Plancton/crecimiento & desarrollo , Plancton/aislamiento & purificación
8.
JCI Insight ; 3(8)2018 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-29669933

RESUMEN

Angiogenesis, new blood vessel formation from preexisting vessels, is critical for solid tumor growth. As such, there have been efforts to inhibit angiogenesis as a means to obstruct tumor growth. However, antiangiogenic therapy faces major challenges to the selective targeting of tumor-associated-vessels, as current antiangiogenic targets also disrupt steady-state vessels. Here, we demonstrate that the developmentally critical transcription factor Etv2 is selectively upregulated in both human and mouse tumor-associated endothelial cells (TAECs) and is required for tumor angiogenesis. Two-photon imaging revealed that Etv2-deficient tumor-associated vasculature remained similar to that of steady-state vessels. Etv2-deficient TAECs displayed decreased Flk1 (also known as Vegfr2) expression, FLK1 activation, and proliferation. Endothelial tube formation, proliferation, and sprouting response to VEGF, but not to FGF2, was reduced in Etv2-deficient ECs. ROS activated Etv2 expression in ECs, and ROS blockade inhibited Etv2 expression in TAECs in vivo. Systemic administration of Etv2 siRNA nanoparticles potently inhibited tumor growth and angiogenesis without cardiovascular side effects. These studies highlight a link among vascular oxidative stress, Etv2 expression, and VEGF response that is critical for tumor angiogenesis. Targeting the ETV2 pathway might offer a unique opportunity for more selective antiangiogenic therapies.


Asunto(s)
Células Endoteliales/metabolismo , Neovascularización Patológica/genética , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/farmacocinética , Animales , Femenino , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Terapia Genética/efectos adversos , Terapia Genética/métodos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Nanopartículas/administración & dosificación , Neovascularización Patológica/terapia , Estrés Oxidativo , ARN Interferente Pequeño/genética , Factores de Transcripción/genética , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
9.
Nat Commun ; 8(1): 1010, 2017 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-29044117

RESUMEN

Effector T cell migration through tissues can enable control of infection or mediate inflammatory damage. Nevertheless, the molecular mechanisms that regulate migration of effector T cells within the interstitial space of inflamed lungs are incompletely understood. Here, we show T cell migration in a mouse model of acute lung injury with two-photon imaging of intact lung tissue. Computational analysis indicates that T cells migrate with an intermittent mode, switching between confined and almost straight migration, guided by lung-associated vasculature. Rho-associated protein kinase (ROCK) is required for both high-speed migration and straight motion. By contrast, inhibition of Gαi signaling with pertussis toxin affects speed but not the intermittent migration of lung-infiltrating T cells. Computational modeling shows that an intermittent migration pattern balances both search area and the duration of contacts between T cells and target cells. These data identify that ROCK-dependent intermittent T cell migration regulates tissue-sampling during acute lung injury.


Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Movimiento Celular , Linfocitos T/metabolismo , Quinasas Asociadas a rho/metabolismo , Lesión Pulmonar Aguda/patología , Algoritmos , Animales , Rastreo Celular/métodos , Femenino , Pulmón/diagnóstico por imagen , Pulmón/metabolismo , Pulmón/patología , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía de Fluorescencia por Excitación Multifotónica
10.
J Clin Invest ; 127(10): 3810-3826, 2017 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-28891817

RESUMEN

The kidney glomerular capillaries are frequent sites of immune complex deposition and subsequent neutrophil accumulation in post-infectious and rapidly progressive glomerulonephritis. However, the mechanisms of neutrophil recruitment remain enigmatic, and there is no targeted therapeutic to avert this proximal event in glomerular inflammation. The uniquely human activating Fc receptor FcγRIIA promotes glomerular neutrophil accumulation and damage in anti-glomerular basement membrane-induced (anti-GBM-induced) glomerulonephritis when expressed on murine neutrophils. Here, we found that neutrophils are directly captured by immobilized IgG antibodies under physiological flow conditions in vitro through FcγRIIA-dependent, Abl/Src tyrosine kinase-mediated F-actin polymerization. Biophysical measurements showed that the lifetime of FcγRIIA-IgG bonds increased under mechanical force in an F-actin-dependent manner, which could enable the capture of neutrophils under physiological flow. Kidney intravital microscopy revealed that circulating neutrophils, which were similar in diameter to glomerular capillaries, abruptly arrested following anti-GBM antibody deposition via neutrophil FcγRIIA and Abl/Src kinases. Accordingly, inhibition of Abl/Src with bosutinib reduced FcγRIIA-mediated glomerular neutrophil accumulation and renal injury in experimental, crescentic anti-GBM nephritis. These data identify a pathway of neutrophil recruitment within glomerular capillaries following IgG deposition that may be targeted by bosutinib to avert glomerular injury.


Asunto(s)
Compuestos de Anilina/farmacología , Glomerulonefritis/inmunología , Inmunoglobulina G/inmunología , Glomérulos Renales/inmunología , Neutrófilos/inmunología , Nitrilos/farmacología , Quinolinas/farmacología , Receptores de IgG/inmunología , Animales , Capilares/inmunología , Capilares/patología , Glomerulonefritis/genética , Glomerulonefritis/patología , Células HL-60 , Humanos , Glomérulos Renales/patología , Ratones , Ratones Noqueados , Neutrófilos/patología , Proteínas Proto-Oncogénicas c-abl/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-abl/genética , Proteínas Proto-Oncogénicas c-abl/inmunología , Receptores de IgG/genética , Familia-src Quinasas/antagonistas & inhibidores , Familia-src Quinasas/inmunología
11.
Cell ; 171(1): 217-228.e13, 2017 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-28890086

RESUMEN

Mammals have evolved neurophysiologic reflexes, such as coughing and scratching, to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases, including asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies markedly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, this study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior.


Asunto(s)
Prurito/inmunología , Células Receptoras Sensoriales/inmunología , Células Receptoras Sensoriales/metabolismo , Transducción de Señal , Enfermedades de la Piel/inmunología , Animales , Ganglios Espinales , Humanos , Interleucina-13/inmunología , Interleucina-4/inmunología , Janus Quinasa 1/metabolismo , Ratones , Ratones Endogámicos C57BL , Prurito/metabolismo , Enfermedades de la Piel/patología
12.
J Neuroimmunol ; 308: 118-130, 2017 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-28501330

RESUMEN

Viral infections of the central nervous system (CNS) are often associated with blood-brain barrier (BBB) disruption, yet the impact of virus replication and immune cell recruitment on BBB integrity are incompletely understood. Using two-photon microscopy, we demonstrate that Venezuelan equine encephalitis virus (VEEV) strain TC83-GFP, a GFP expressing, attenuated strain with a G3A mutation within the 5' UTR that is associated with increased sensitivity to type I interferons (IFNs), does not directly impact BBB permeability. Following intranasal infection of both wild-type and IFN-induced protein with tetratricopeptide repeats 1 (IFIT1)-deficient mice, which fail to block TC83-specific RNA translation, virus spreads to the olfactory bulb and cortex via migration along axonal tracts of neurons originating from the olfactory neuroepithelium. Global dissemination of virus in the CNS by 2days post-infection (dpi) was associated with increased BBB permeability in the olfactory bulb, but not in the cortex or hindbrain, where permeability only increased after the recruitment of CX3CR1+ and CCR2+ mononuclear cells on 6 dpi, which corresponded with tight junction loss and claudin 5 redistribution. Importantly, despite higher levels of viral replication, similar results were obtained in IFIT1-deficient mice. These findings indicate that TC83 gains CNS access via anterograde axonal migration without directly altering BBB function and that mononuclear and endothelial cell interactions may underlie BBB disruption during alphavirus encephalitis.


Asunto(s)
Infecciones por Alphavirus/patología , Barrera Hematoencefálica/fisiopatología , Encéfalo/metabolismo , Encéfalo/virología , Replicación Viral/fisiología , Complejo 1 de Proteína Adaptadora/genética , Complejo 1 de Proteína Adaptadora/metabolismo , Infecciones por Alphavirus/genética , Animales , Animales Recién Nacidos , Barrera Hematoencefálica/ultraestructura , Barrera Hematoencefálica/virología , Receptor 1 de Quimiocinas CX3C , Permeabilidad Capilar/fisiología , Células Cultivadas , Corteza Cerebral/citología , Cricetinae , Modelos Animales de Enfermedad , Virus de la Encefalitis Equina Venezolana/fisiología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/fisiología , Células Epiteliales/ultraestructura , Células Epiteliales/virología , Regulación de la Expresión Génica/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Receptores de Quimiocina/genética , Receptores de Quimiocina/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Internalización del Virus
13.
J Histochem Cytochem ; 65(3): 139-151, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27881474

RESUMEN

One of the biggest challenges in managing head and neck cancers, especially salivary gland cancers, is the identification of secreted biomarkers of the disease that can be evaluated noninvasively. A relevant source of enriched tumor markers could potentially be found in the tumor secretome. Although numerous studies have evaluated secretomes from various cancers, the influence of the cancer secretome derived from salivary gland cancers on the behavior of normal cells has not yet been elucidated. Our data indicate that secretome derived from salivary gland cancer cells can influence the expression of two potential biomarkers of oral cancer-namely, bone sialoprotein (BSP) and dentin sialoprotein (DSP)-in normal salivary gland cells. Using routine immunohistochemistry, immunofluorescence, and immunoblotting techniques, we demonstrate an enrichment of BSP and DSP in human salivary gland (HSG) cancer tissue, unique localizations of BSP and DSP in HSG cancer cells, and enriched expression of BSP and DSP in normal salivary gland cells exposed to a cancer secretome. The secretome domain of the cancer microenvironment could alter signaling cascades responsible for normal cell proliferation, migration, and invasion, thus enhancing cancer cell survival and the potential for cancer progression. The cancer secretome may be critical in maintaining and stimulating "cancer-ness," thus potentially promoting specific hallmarks of metastasis.


Asunto(s)
Proteínas de la Matriz Extracelular/análisis , Sialoproteína de Unión a Integrina/análisis , Fosfoproteínas/análisis , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/patología , Sialoglicoproteínas/análisis , Línea Celular , Línea Celular Tumoral , Proteínas de la Matriz Extracelular/metabolismo , Humanos , Sialoproteína de Unión a Integrina/metabolismo , Fosfoproteínas/metabolismo , Neoplasias de las Glándulas Salivales/metabolismo , Glándulas Salivales/citología , Glándulas Salivales/metabolismo , Sialoglicoproteínas/metabolismo
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