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OBJECTIVE: Physicians vary in their computed tomography (CT) scan usage. It remains unclear how physician gender relates to clinical practice or patient outcomes. The aim of this study was to assess the association between physician gender and decision to order head CT scans for older emergency patients who had fallen. METHODS: This was a secondary analysis of a prospective observational cohort study conducted in 11 hospital emergency departments (EDs) in Canada and the United States. The primary study enrolled patients who were 65 years and older who presented to the ED after a fall. The analysis evaluated treating physician gender adjusted for multiple clinical variables. Primary analysis used a hierarchical logistic regression model to evaluate the association between treating physician gender and the patient receiving a head CT scan. Secondary analysis reported the adjusted odds ratio (OR) for diagnosing intracranial bleeding by physician gender. RESULTS: There were 3663 patients and 256 physicians included in the primary analysis. In the adjusted analysis, women physicians were no more likely to order a head CT than men (OR 1.26, 95% confidence interval 0.98-1.61). In the secondary analysis of 2294 patients who received a head CT, physician gender was not associated with finding a clinically important intracranial bleed. CONCLUSIONS: There was no significant association between physician gender and ordering head CT scans for older emergency patients who had fallen. For patients where CT scans were ordered, there was no significant relationship between physician gender and the diagnosis of clinically important intracranial bleeding.
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STUDY OBJECTIVE: Computed tomography pulmonary angiogram (CTPA) is overused during pulmonary embolism (PE) testing in the emergency department (ED), whereas prediction rules and D-dimer are underused. We report the adherence, clinical benefit, and safety of a D-dimer-only strategy to guide need for PE imaging in the ED. METHODS: This was a prospective multicenter implementation study in 2 EDs with historical and external controls. Patients with suspected PE underwent D-dimer testing and imaging (CTPA or ventilation-perfusion scan) when D-dimer levels were 500 ng/mL or more. PE was ruled out if D-dimer was less than 500 ng/mL or with negative imaging. The primary implementation outcome was the proportion of patients tested for PE in adherence with the pathway. The primary clinical benefit outcome was the proportion of patients tested for PE who received pulmonary imaging. The primary safety outcome was diagnosis of PE in the 30 days following negative PE testing postimplementation. RESULTS: Between January 2018 and June 2021, 16,155 patients were tested for PE, including 33.4% postimplementation, 30.7% preimplementation, and 35.9% in an external control site. Adherence with the D-dimer-only pathway was 97.6% (adjusted odds ratio (aOR) post- versus preimplementation 5.26 (95% confidence interval 1.70 to 16.26). There was no effect on the proportion undergoing PE imaging. Imaging yield increased aOR 4.89 (1.17 to 20.53). Two cases of PE (0.04%; 0.01% to 0.16%) were diagnosed within 30 days. CONCLUSION: In this Canadian ED study, the uptake of a D-dimer-only PE testing strategy was high. Implementation was associated with higher imaging yield and a D-dimer level of less than 500 ng/mL safely excluded PE.
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STUDY OBJECTIVE: Since Canada eased pandemic restrictions, emergency departments have experienced record levels of patient attendance, wait times, bed blocking, and crowding. The aim of this study was to report Canadian emergency physician burnout rates compared with the same physicians in 2020 and to describe how emergency medicine work has affected emergency physician well-being. METHODS: This longitudinal study on Canadian emergency physician wellness enrolled participants in April 2020. In September 2022, participants were invited to a follow-up survey consisting of the Maslach Burnout Inventory and an optional free-text explanation of their experience. The primary outcomes were emotional exhaustion and depersonalization levels, which were compared with the Maslach Burnout Inventory survey conducted at the end of 2020. A thematic analysis identified common stressors, challenges, emotions, and responses among participants. RESULTS: The response rate to the 2022 survey was 381 (62%) of 615 between September 28 and October 28, 2022, representing all provinces or territories in Canada (except Yukon). The median participant age was 42 years. In total, 49% were men, and 93% were staff physicians with a median of 12 years of work experience. 59% of respondents reported high emotional exhaustion, and 64% reported high depersonalization. Burnout levels in 2022 were significantly higher compared with 2020. Prevalent themes included a broken health care system, a lack of societal support, and systemic workplace challenges leading to physician distress and loss of physicians from the emergency workforce. CONCLUSION: We found very high burnout levels in emergency physician respondents that have increased since 2020.
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Esgotamento Profissional , Serviço Hospitalar de Emergência , Médicos , Humanos , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Canadá/epidemiologia , Masculino , Estudos Longitudinais , Feminino , Adulto , Médicos/psicologia , Médicos/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Pessoa de Meia-Idade , Medicina de Emergência , Inquéritos e QuestionáriosRESUMO
RhoU is an atypical member of the Rho family of small G-proteins, which has N- and C-terminal extensions compared to the classic Rho GTPases RhoA, Rac1 and Cdc42, and associates with membranes through C-terminal palmitoylation rather than prenylation. RhoU mRNA expression is upregulated in prostate cancer and is considered a marker for disease progression. Here, we show that RhoU overexpression in prostate cancer cells increases cell migration and invasion. To identify RhoU targets that contribute to its function, we found that RhoU homodimerizes in cells. We map the region involved in this interaction to the C-terminal extension and show that C-terminal palmitoylation is required for self-association. Expression of the isolated C-terminal extension reduces RhoU-induced activation of p21-activated kinases (PAKs), which are known downstream targets for RhoU, and induces cell morphological changes consistent with inhibiting RhoU function. Our results show for the first time that the activity of a Rho family member is stimulated by self-association, and this is important for its activity.
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Neoplasias da Próstata , Proteínas rho de Ligação ao GTP , Humanos , Masculino , Proteína cdc42 de Ligação ao GTP/genética , Proteína cdc42 de Ligação ao GTP/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: Ground-level falls are common among older adults and are the most frequent cause of traumatic intracranial bleeding. The aim of this study was to derive a clinical decision rule that safely excludes clinically important intracranial bleeding in older adults who present to the emergency department after a fall, without the need for a computed tomography (CT) scan of the head. METHODS: This prospective cohort study in 11 emergency departments in Canada and the United States enrolled patients aged 65 years or older who presented after falling from standing on level ground, off a chair or toilet seat, or out of bed. We collected data on 17 potential predictor variables. The primary outcome was the diagnosis of clinically important intracranial bleeding within 42 days of the index emergency department visit. An independent adjudication committee, blinded to baseline data, determined the primary outcome. We derived a clinical decision rule using logistic regression. RESULTS: The cohort included 4308 participants, with a median age of 83 years; 2770 (64%) were female, 1119 (26%) took anticoagulant medication and 1567 (36%) took antiplatelet medication. Of the participants, 139 (3.2%) received a diagnosis of clinically important intracranial bleeding. We developed a decision rule indicating that no head CT is required if there is no history of head injury on falling; no amnesia of the fall; no new abnormality on neurologic examination; and the Clinical Frailty Scale score is less than 5. Rule sensitivity was 98.6% (95% confidence interval [CI] 94.9%-99.6%), specificity was 20.3% (95% CI 19.1%-21.5%) and negative predictive value was 99.8% (95% CI 99.2%-99.9%). INTERPRETATION: We derived a Falls Decision Rule, which requires external validation, followed by clinical impact assessment. Trial registration: ClinicalTrials. gov, no. NCT03745755.
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Traumatismos Craniocerebrais , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Traumatismos Craniocerebrais/diagnóstico por imagem , Serviço Hospitalar de Emergência , Hemorragias Intracranianas/diagnóstico por imagem , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
In 2020, almost overnight, the paradigm for healthcare interactions changed in Ontario. To limit person-to-person transmission of COVID-19, the norm of in-person interactions shifted to virtual care. While this shift was part of broader public health measures and an acknowledgment of patient and societal concerns, it also represented a change in care modalities that had the potential to affect the quality of care provided, as well as short- and long-term patient outcomes. While public policy decisions were being made to moderate the use of virtual care at the end of the declared pandemic, a thorough analysis of short-term patient outcomes was needed to quantify the impact of virtual care on the population of Ontario.
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COVID-19 , Humanos , COVID-19/epidemiologia , Ontário/epidemiologia , Pandemias , Saúde Pública , Política PúblicaRESUMO
BACKGROUND AND IMPORTANCE: The Canadian Association of Emergency Physicians atrial fibrillation (AF) checklist advises that emergency physicians initiate anticoagulation therapy for patients with AF or flutter who are CHADS65 positive. OBJECTIVES: The aim was to compare anticoagulation initiation rates between patients treated with and without an anticoagulation assessment pathway (the SAFE pathway). DESIGN: This was a retrospective cohort study. SETTINGS AND PARTICIPANTS: All emergency department patients were discharged home with a diagnosis of AF between June 2018 and May 2020 at two Canadian emergency departments. INTERVENTION: The SAFE pathway is a hard copy form which allows emergency physicians to document contraindications to anticoagulation, the positive components of the CHADS65 score, and details how to prescribe anticoagulation. OUTCOME MEASURES AND ANALYSIS: Trained researchers abstracted data on the use of the SAFE pathway by the presence or absence of the completed, scanned pathway in the electronic medical chart. The exposure of interest was use of this pathway. Patients were followed forward in time for 90 days by electronic medical record review to document stroke, transient ischemic attack, arterial embolism and major bleeding events. All events were independently adjudicated. Adjusted odds ratios were calculated to compare outcomes between those managed with and without the SAFE pathway. RESULTS: In total, 766 patients were included, of whom 264 were already taking anticoagulation, 166 were CHADS65 negative and 65 had a contraindication to anticoagulation, leaving 271 patients eligible for anticoagulation prescription. Among the 271 eligible patients, 137/166 managed with the SAFE pathway were initiated on anticoagulation and 24/105 managed without the SAFE pathway started anticoagulation (adjusted odds ratio 25.9; 13.1-51.2). There was no statistically significant difference in the 90-day rate of stroke or bleeding. CONCLUSION: Use of the SAFE pathway was associated with a higher rate of anticoagulation prescription.
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Anticoagulantes , Fibrilação Atrial , Prescrições de Medicamentos , Humanos , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Canadá , Estudos Retrospectivos , Prescrições de Medicamentos/estatística & dados numéricos , Serviço Hospitalar de Emergência , Padrões de Prática Médica , Medição de Risco , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease and its influence on drug-induced liver injury (DILI) is not fully understood. We investigated whether NAFLD can influence acetaminophen (APAP [N-acetyl-p-aminophenol])-induced hepatotoxicity in a diet-induced obese (DIO) mouse model of NAFLD. The male C57BL/6NTac DIO mice, fed a high-fat diet for more than 12 weeks, developed obesity, hyperinsulinemia, impaired glucose tolerance, and hepatomegaly with hepatic steatosis, similar to human NAFLD. In the acute toxicity study after a single dose of APAP (150 mg/kg), compared with control lean mice, the DIO mice had decreased serum transaminase levels and less severe hepatocellular injury. The DIO mice also had altered expression of genes related to APAP metabolism. Chronic APAP exposure for 26 weeks did not predispose the DIO mice with NAFLD to more severe hepatotoxicity compared with the lean mice. These results suggested that the C57BL/6NTac DIO mouse model appears to be more tolerant to APAP-induced hepatotoxicity than lean mice, potentially related to altered xenobiotic metabolizing capacity in the fatty liver. Further mechanistic studies with APAP and other drugs in NAFLD animal models are necessary to investigate the mechanism of altered susceptibility to intrinsic DILI in some human NAFLD patients.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Acetaminofen/toxicidade , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Dieta , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , ObesidadeRESUMO
The downregulation of Pleckstrin Homology-Like Domain family A member 1 (PHLDA1) expression mediates resistance to targeted therapies in receptor tyrosine kinase-driven cancers. The restoration and maintenance of PHLDA1 levels in cancer cells thus constitutes a potential strategy to circumvent resistance to inhibitors of receptor tyrosine kinases. Through a pharmacological approach, we identify the inhibition of MAPK signalling as a crucial step in PHLDA1 downregulation. Further ChIP-qPCR analysis revealed that MEK1/2 inhibition produces significant epigenetic changes at the PHLDA1 locus, specifically a decrease in the activatory marks H3Kme3 and H3K27ac. In line with this, we show that treatment with the clinically relevant class I histone deacetylase (HDAC) inhibitor 4SC-202 restores PHLDA1 expression in lapatinib-resistant human epidermal growth factor receptor-2 (HER2)+ breast cancer cells. Critically, we show that when given in combination, 4SC-202 and lapatinib exert synergistic effects on 2D cell proliferation and colony formation capacity. We therefore propose that co-treatment with 4SC-202 may prolong the clinical efficacy of lapatinib in HER2+ breast cancer patients.
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Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Lapatinib/farmacologia , Lapatinib/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Histona Desacetilases , Quinazolinas/farmacologia , Resistencia a Medicamentos Antineoplásicos , Receptor ErbB-2/metabolismo , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: The pandemic has upended much clinical care, irrevocably changing our health systems and thrusting emergency physicians into a time of great uncertainty and change. This study is a follow-up to a survey that examined the early pandemic experience among Canadian emergency physicians and aimed to qualitatively describe the experiences of these physicians during the global pandemic. The study was conducted at a time when Canadian COVID-19 case numbers were low. METHODS: The investigators engaged in an interview-based study that used an interpretive description analytic technique, sensitised by the principles of phenomenology. One-to-one interviews were conducted, transcribed and then analysed to establish a codebook, which was subsequently grouped into key themes. Results underwent source triangulation (with survey data from a similar period) and investigator-driven audit trail analysis. RESULTS: A total of 16 interviews (11 female, 5 male) were conducted between May and September 2020. The isolated themes on emergency physicians' experiences during the early pandemic included: (1) disruption and loss of emergency department shift work; (2) stress of COVID-19 uncertainty and information bombardment; (3) increased team bonding; (4) greater personal life stress; (5) concern for patients' isolation, miscommunication and disconnection from care; (6) emotional distress. CONCLUSIONS: Canadian emergency physicians experienced emotional and psychological distress during the early COVID-19 pandemic, at a time when COVID-19 prevalence was low. This study's findings could guide future interventions to protect emergency physicians against pandemic-related distress.
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COVID-19 , Médicos , Humanos , Masculino , Feminino , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Canadá/epidemiologia , Médicos/psicologiaRESUMO
STUDY OBJECTIVE: We prospectively assessed the diagnostic accuracy of YEARS and a modified age-adjusted clinical decision rule ("Adjust-Unlikely") for pulmonary embolism (PE) testing in the emergency department. METHODS: This study was conducted in tertiary care Canadian emergency departments. When the D-dimer was <500 ng/ml, PE was excluded. Pulmonary imaging for PE was performed when the D-dimer was ≥500 ng/ml. Patients were followed for 30 days, and PE outcomes were independently adjudicated. Physicians systematically recorded the presence or absence of YEARS items (PE most likely, hemoptysis, signs of deep venous thrombosis) prior to D-dimer testing and imaging. We analyzed the diagnostic accuracy of YEARS and the "Adjust-Unlikely" rule. Age adjustment (age x 10 in those >50 years old) was applied in patients where PE was not the most likely diagnosis and 500 ng/ml threshold when PE was most likely. RESULTS: One thousand seven hundred three patients were included, median age 62 (50, 74), 58% female, PE prevalence 8.0%. YEARS sensitivity for PE diagnosis was 92.6% (87.0, 96.0%) and specificity 45.0% (42.5, 47.5%). Adjust-Unlikely sensitivity was 100.0% (97.2, 100.0%) and specificity 32.4% (30.1, 34.8%). Posttest probability of PE in the group of patients with PE excluded by D-dimer between 500 ng/ml and the adjusted limit was 2.8% (1.6, 5.1%) for YEARS and 0.0% (0.0, 2.6%) for the "Adjust-Unlikely" rule. CONCLUSION: The "Adjust-Unlikely" rule would modestly reduce imaging and identify all cases of PE. YEARS would substantially reduce imaging but miss 1 in 14 cases of PE.
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Embolia Pulmonar , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Canadá/epidemiologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiologia , Produtos de Degradação da Fibrina e do Fibrinogênio , Serviço Hospitalar de EmergênciaRESUMO
Activated Cdc42-associated kinase (ACK) is an oncogenic nonreceptor tyrosine kinase associated with poor prognosis in several human cancers. ACK promotes proliferation, in part by contributing to the activation of Akt, the major effector of class 1A phosphoinositide 3-kinases (PI3Ks), which transduce signals via membrane phosphoinositol lipids. We now show that ACK also interacts with other key components of class 1A PI3K signaling, the PI3K regulatory subunits. We demonstrate ACK binds to all five PI3K regulatory subunit isoforms and directly phosphorylates p85α, p85ß, p50α, and p55α on Tyr607 (or analogous residues). We found that phosphorylation of p85ß promotes cell proliferation in HEK293T cells. We demonstrate that ACK interacts with p85α exclusively in nuclear-enriched cell fractions, where p85α phosphorylated at Tyr607 (pTyr607) also resides, and identify an interaction between pTyr607 and the N-terminal SH2 domain that supports dimerization of the regulatory subunits. We infer from this that ACK targets p110-independent p85 and further postulate that these regulatory subunit dimers undertake novel nuclear functions underpinning ACK activity. We conclude that these dimers represent a previously undescribed mode of regulation for the class1A PI3K regulatory subunits and potentially reveal additional avenues for therapeutic intervention.
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Fosfatidilinositol 3-Quinases , Proteínas Tirosina Quinases , Núcleo Celular/enzimologia , Células HEK293 , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Multimerização Proteica , Proteínas Tirosina Quinases/metabolismo , Transdução de SinaisRESUMO
Tetrabromobisphenol A (TBBPA), a derivative of BPA, is a ubiquitous environmental contaminant with weak estrogenic properties. In women, uterine fibroids are highly prevalent estrogen-responsive tumors often with excessive accumulation of extracellular matrix (ECM) and may be the target of environmental estrogens. We have found that BPA has profibrotic effects in vitro, in addition to previous reports of the in vivo fibrotic effects of BPA in mouse uterus. However, the role of TBBPA in fibrosis is unclear. To investigate the effects of TBBPA on uterine fibrosis, we developed a 3D human uterine leiomyoma (ht-UtLM) spheroid culture model. Cell proliferation was evaluated in 3D ht-UtLM spheroids following TBBPA (10-6 -200 µM) administration at 48 h. Fibrosis was assessed using a Masson's Trichrome stain and light microscopy at 7 days of TBBPA (10-3 µM) treatment. Differential expression of ECM and fibrosis genes were determined using RT² Profiler™ PCR arrays. Network and pathway analyses were conducted using Ingenuity Pathway Analysis. The activation of pathway proteins was analyzed by a transforming growth factor-beta (TGFB) protein array. We found that TBBPA increased cell proliferation and promoted fibrosis in 3D ht-UtLM spheroids with increased deposition of collagens. TBBPA upregulated the expression of profibrotic genes and corresponding proteins associated with the TGFB pathway. TBBPA activated TGFB signaling through phosphorylation of TGFBR1 and downstream effectors-small mothers against decapentaplegic -2 and -3 proteins (SMAD2 and SMAD3). The 3D ht-UtLM spheroid model is an effective system for studying environmental agents on human uterine fibrosis. TBBPA can promote fibrosis in uterine fibroid through TGFB/SMAD signaling.
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Fibrose/induzido quimicamente , Fibrose/metabolismo , Leiomioma/induzido quimicamente , Bifenil Polibromatos/administração & dosagem , Fator de Crescimento Transformador beta/metabolismo , Neoplasias Uterinas/induzido quimicamente , Neoplasias Uterinas/metabolismo , Técnicas de Cultura de Células em Três Dimensões/métodos , Proliferação de Células/efeitos dos fármacos , Estrogênios/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Humanos , Leiomioma/metabolismo , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Introduction: Chronic Chagasic cardiomyopathy (CCC), caused by the protozoan Trypanosoma cruzi, is the most severe manifestation of Chagas disease.CCC is characterized by cardiac inflammation and fibrosis caused by a persistent inflammatory response. Following infection, macrophages secrete inflammatory mediators such as IL-1ß, IL-6, and TNF-α to control parasitemia. Although this response contains parasite infection, it causes damage to the heart tissue. Thus, the use of immunomodulators is a rational alternative to CCC. Rho-associated kinase (ROCK) 1 and 2 are RhoA-activated serine/threonine kinases that regulate the actomyosin cytoskeleton. Both ROCKs have been implicated in the polarization of macrophages towards an M1 (pro-inflammatory) phenotype. Statins are FDA-approved lipid-lowering drugs that reduce RhoA signaling by inhibiting geranylgeranyl pyrophosphate (GGPP) synthesis. This work aims to identify the effect of statins on U937 macrophage polarization and cardiac tissue inflammation and its relationship with ROCK activity during T. cruzi infection. Methods: PMA-induced, wild-type, GFP-, CA-ROCK1- and CA-ROCK2-expressing U937 macrophages were incubated with atorvastatin, or the inhibitors Y-27632, JSH-23, TAK-242, or C3 exoenzyme incubated with or without T. cruzi trypomastigotes for 30 min to evaluate the activity of ROCK and the M1 and M2 cytokine expression and secretion profiling. Also, ROCK activity was determined in T. cruzi-infected, BALB/c mice hearts. Results: In this study, we demonstrate for the first time in macrophages that incubation with T. cruzi leads to ROCK activation via the TLR4 pathway, which triggers NF-κB activation. Inhibition of ROCKs by Y-27632 prevents NF-κB activation and the expression and secretion of M1 markers, as does treatment with atorvastatin. Furthermore, we show that the effect of atorvastatin on the NF-kB pathway and cytokine secretion is mediated by ROCK. Finally, statin treatment decreased ROCK activation and expression, and the pro-inflammatory cytokine production, promoting anti-inflammatory cytokine expression in chronic chagasic mice hearts. Conclusion: These results suggest that the statin modulation of the inflammatory response due to ROCK inhibition is a potential pharmacological strategy to prevent cardiac inflammation in CCC.
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Cardiomiopatias , Doença de Chagas , Inibidores de Hidroximetilglutaril-CoA Redutases , Trypanosoma cruzi , Humanos , Animais , Camundongos , Trypanosoma cruzi/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Quinases Associadas a rho/metabolismo , NF-kappa B/metabolismo , Atorvastatina/farmacologia , Células U937 , Macrófagos/metabolismo , Doença de Chagas/genética , Citocinas/metabolismo , Cardiomiopatias/metabolismo , Inflamação/metabolismoRESUMO
Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using serial measurements while incorporating absolute concentration changes for MI or death following ED presentation. We sought to determine the diagnostic estimates of these three algorithms and if one was superior in two different Canadian ED patient cohorts with serial hsTnI measurements. An undifferentiated ED population (Cohort-1) and an ED population with symptoms suggestive of acute coronary syndrome (ACS; Cohort-2) were clinically managed with non-hsTn testing with the hsTnI testing performed in real-time with physicians blinded to these results (i.e., hsTnI not reported). The three algorithms evaluated were the European Society of Cardiology (ESC), the High-STEACS pathway, and the COMPASS-MI algorithm. The diagnostic estimates were derived for each algorithm for the 30-day MI/death outcome for the rule-out and rule-in arm in each cohort and compared to proposed diagnostic benchmarks (i.e., sensitivity ≥ 99.0% and specificity ≥ 90.0%) with 95% confidence intervals (CI). In Cohort-1 (n = 2966 patients, 15.3% had outcome) and Cohort-2 (n = 935 patients, 15.6% had outcome), the algorithm that obtained the highest sensitivity (97.8%; 95% CI: 96.0-98.9 and 98.6%; 95% CI: 95.1-99.8, respectively) in both cohorts was COMPASS-MI. Only Cohort-2 with both the ESC and COMPASS-MI algorithms exceeded the specificity benchmark (97.0%; 95% CI: 95.5-98.0 and 96.7%; 95% CI: 95.2-97.8, respectively). Patient selection for serial hsTnI testing will affect specificity estimates, with no algorithm achieving a sensitivity ≥ 99% for 30-day MI or death.
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INTRODUCTION: Falling on level ground is now the most common cause of traumatic intracranial bleeding worldwide. Older adults frequently present to the emergency department (ED) after falling. It can be challenging for clinicians to determine who requires brain imaging to rule out traumatic intracranial bleeding, and often head injury decision rules do not apply to older adults who fall. The goal of our study is to derive a clinical decision rule, which will identify older adults who present to the ED after a fall who do not have clinically important intracranial bleeding. METHODS AND ANALYSIS: This is a prospective cohort study enrolling patients aged 65 years or older, who present to the ED of 11 hospitals in Canada and the USA within 48 hours of having a fall. Patients are included if they fall on level ground, off a chair, toilet seat or out of bed. The primary outcome is the diagnosis of clinically important intracranial bleeding within 42 days of the index ED visit. An independent adjudication committee will determine the primary outcome, blinded to all other data. We are collecting data on 17 potential predictor variables. The treating physician completes a study data form at the time of initial assessment, prior to brain imaging. Data extraction is supplemented by an independent, structured electronic medical record review. We will perform binary recursive partitioning using Classification and Regression Trees to derive a clinical decision rule. ETHICS AND DISSEMINATION: The study was initially approved by the Hamilton Integrated Research Ethics Committee and subsequently approved by the research ethics boards governing all participating sites. We will disseminate our results by journal publication, presentation at international meetings and social media. TRIAL REGISTRATION NUMBER: NCT03745755.
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Acidentes por Quedas , Regras de Decisão Clínica , Idoso , Canadá , Serviço Hospitalar de Emergência , Humanos , Estudos ProspectivosRESUMO
BACKGROUND: Most antithrombotic medication users are older adults. Patient-reported outcome measures are commonly used in clinical research on antithrombotic medication, such as the diagnosis of intracranial hemorrhage. OBJECTIVES: To determine the reliability of patient-reported intracranial hemorrhage, anticoagulant and platelet aggregation inhibitor use in the older adult population. PATIENTS/METHODS: We conducted a secondary analysis of a prospective, observational cohort study of older adults who presented to the emergency department with a fall. The primary outcome was diagnosis of intracranial bleeding. We compared patient-reported intracranial bleeding to structured chart review with adjudication. We also compared patient-reported use of antiplatelet and anticoagulant medication to physician-reported medication use supplemented with structured chart review. We calculated the diagnostic accuracy of the patient-reported outcomes using our comparators as the reference standard. RESULTS: Exact agreement for patient-reported intracranial bleeds was 95%, with a Cohen's kappa of 0.30 (95% confidence interval [CI], 0.15-0.45). The sensitivity was 36.7% (95% CI, 20.6%-56.1%) and specificity 97.2% (95% CI, 95.8%-98.1%). For anticoagulant medication use, exact agreement was 87%, Cohen's kappa 0.66 (95% CI, 0.63-0.72), sensitivity 84.0% (95% CI, 79.3%-83.8%), and specificity 87.6% (95% CI, 85.1%-89.7%). For antiplatelet medication use, exact agreement was 77%, Cohen's kappa 0.50 (95% CI, 0.44-0.55), sensitivity 68.7% (95% CI, 64.0%-73.1%), and specificity 81.2% (95% CI, 78.0-83.8%). CONCLUSIONS: Patient-reported outcome and exposure data were unreliable in this study. Our findings have a bearing on future research study design.
RESUMO
BACKGROUND: Atrial fibrillation increases the risk of stroke, which can be mitigated by anticoagulant prescription. We evaluated local emergency physician anticoagulation practice for patients discharged from the emergency department with atrial fibrillation, along with 90-day incidence of stroke and major bleeding. METHODS: This was a health record review of patients diagnosed with new onset atrial fibrillation in two emergency departments between 2014 and 2017. We collected data on CHADS65 scores, contraindications to direct oral anticoagulant (DOAC) prescription and initiation of anticoagulation in the ED. Patient charts were reviewed for the diagnosis of stroke, transient ischemic attack (TIA), systemic embolism or major bleeding within 90 days. RESULTS: We identified 399 patients, median age 68 (IQR 57-79), 213 (53%) male. Only 299/399 patients had an indication for anticoagulation (CHADS65-positive). Of these 299, 27 had a contraindication to or were already prescribed anticoagulation. 45/272 (17%, 95% confidence interval 12-22%) patients eligible for initiation of anticoagulation left the emergency department with a prescription for anticoagulation. During 90-day follow-up, seven patients had stroke or TIA. Four stroke/TIA patients had been eligible to start an anticoagulant but were not started, two left the emergency department with prescriptions for an anticoagulant and one patient had a contraindication to initiating anticoagulation in the emergency department. There were no major bleeding episodes. CONCLUSION: Few eligible patients were prescribed anticoagulation and the 90-day stroke rate was high. Physicians should become familiar with the CAEP Acute AF Best Practices Checklist AF which offers guidance on anticoagulation prescription.
RéSUMé: CONTEXTE: La fibrillation auriculaire augmente le risque d'accident vasculaire cérébral, qui peut être atténué par la prescription d'anticoagulants. Nous avons évalué la pratique d'anticoagulation des médecins d'urgence locaux pour les patients sortis du service d'urgence avec la fibrillation auriculaire, ainsi que l'incidence sur 90 jours d'AVC et des saignements majeurss. MéTHODES: Il s'agissait d'un examen du dossier de santé des patients diagnostiqués avec une nouvelle apparition de la fibrillation auriculaire dans deux services d'urgence entre 2014 et 2017. Nous avons recueilli des données sur les scores CHADS65, les contre-indications à la prescription d'anticoagulants oraux directs (AOD) et l'initiation de l'anticoagulation au service des urgences. Les fiches des patients ont été revues pour le diagnostic d'AVC, d'accident ischémique transitoire (AIT), d'embolie systémique d'hémorragie majeure dans les 90 jours. RéSULTATS: Nous avons identifié 399 patients, d'âge médian 68 (IQR 57-79), 213 (53 %) hommes. Seuls 299/399 patients avaient une indication d'anticoagulation (CHADS65 positif). Sur ces 299, 27 présentaient une contre-indication ou se voyaient déjà prescrire une anticoagulation. 45/272 (17 %, 95 % intervalle de confiance de 12 % à 22 %) patients éligibles pour l'initiation de l'anticoagulation ont quitté avec une prescription d'anticoagulation. Au cours du suivi de 90 jours, sept patients ont eu un accident vasculaire cérébral ou un AIT. Quatre patients ayant subi un AVC / AIT étaient éligibles pour commencer un anticoagulant mais qui n'ont pas été commencés, deux ont quitté le service des urgences avec des ordonnances d'un anticoagulant et un patient avait une contre-indication à l'initiation de l'anticoagulation au service des urgences. Il n'y a pas eu d'épisodes d'hémorragie majeure. CONCLUSION: Peu de patients éligibles se sont vu prescrire une anticoagulation et le taux d'AVC durant les 90 jours était élevé. Les médecins doivent se familiariser avec la liste de contrôle des meilleures pratiques pour la CAEP FA aiguë qui offre des conseils sur la prescription des anticoagulations.