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1.
ACS Nano ; 13(6): 6670-6688, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31117376

RESUMO

To dissect therapeutic mechanisms of transplanted stem cells and develop exosome-based nanotherapeutics in treating autoimmune and neurodegenerative diseases, we assessed the effect of exosomes secreted from human mesenchymal stem cells (MSCs) in treating multiple sclerosis using an experimental autoimmune encephalomyelitis (EAE) mouse model. We found that intravenous administration of exosomes produced by MSCs stimulated by IFNγ (IFNγ-Exo) (i) reduced the mean clinical score of EAE mice compared to PBS control, (ii) reduced demyelination, (iii) decreased neuroinflammation, and (iv) upregulated the number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) within the spinal cords of EAE mice. Co-culture of IFNγ-Exo with activated peripheral blood mononuclear cells (PBMCs) cells in vitro reduced PBMC proliferation and levels of pro-inflammatory Th1 and Th17 cytokines including IL-6, IL-12p70, IL-17AF, and IL-22 yet increased levels of immunosuppressive cytokine indoleamine 2,3-dioxygenase. IFNγ-Exo could also induce Tregs in vitro in a murine splenocyte culture, likely mediated by a third-party accessory cell type. Further, IFNγ-Exo characterization by deep RNA sequencing suggested that IFNγ-Exo contains anti-inflammatory RNAs, where their inactivation partially hindered the exosomes potential to induce Tregs. Furthermore, we found that IFNγ-Exo harbors multiple anti-inflammatory and neuroprotective proteins. These results not only shed light on stem cell therapeutic mechanisms but also provide evidence that MSC-derived exosomes can potentially serve as cell-free therapies in creating a tolerogenic immune response to treat autoimmune and central nervous system disorders.

2.
Cell Commun Signal ; 17(1): 25, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885218

RESUMO

BACKGROUND: Flavokawain B (FKB) has been identified from kava root extracts as a potent apoptosis inducer for inhibiting the growth of various cancer cell lines, including prostate cancer. However, the molecular targets of FKB in prostate cancer cells remain unknown. METHODS: An in vitro NEDD8 Initiation Conjugation Assay was used to evaluate the neddylation inhibitory activity of FKB. Molecular docking and a cellular thermal shift assay were performed to assess the direct interaction between FKB and the NEDD8 activating enzyme (NAE) complex. Protein neddylation, ubiqutination, stability and expression in cells were assessed with immunoprecipitation and Western blotting methods using specific antibodies. Deletion and site specific mutants and siRNAs were used to evaluate deep mechanisms by which FKB induces Skp2 degradation. Cell growth inhibition and apoptosis induction were measured by MTT, ELISA and Western blotting methods. RESULTS: FKB inhibits NEDD8 conjugations to both Cullin1 and Ubc12 in prostate cancer cell lines and Ubc12 neddylation in an in vitro assay. Molecular docking study and a cellular thermal shift assay reveal that FKB interacts with the regulatory subunit (i.e. APP-BP1) of the NAE. In addition, FKB causes Skp2 degradation in an ubiquitin and proteasome dependent manner. Overexpression of dominant-negative cullin1 (1-452), K720R mutant (the neddylation site) Cullin1 or the F-box deleted Skp2 that losses its binding to the Skp1/Cullin1 complex causes the resistance to FKB-induced Skp2 degradation, whereas siRNA knock-down of Cdh1, a known E3 ligase of Skp2 for targeted degradation, didn't attenuate the effect of FKB on Skp2 degradation. These results suggest that degradation of Skp2 by FKB is involved in a functional Cullin1. Furthermore, proteasome inhibitors Bortezomib and MG132 transcriptionally down-regulate the expression of Skp2, and their combinations with FKB result in enhanced inhibitory effects on the growth of prostate cancer cell lines via synergistic down-regulation of Skp2 and up-regulation of p27/Kip1 and p21/WAF1 protein expression. FKB also selectively inhibits the growth of RB deficient cells with high expression of Skp2. CONCLUSION: These findings provide a rationale for further investigating combination of FKB and Bortezomib for treatment of RB deficient, castration-resistant prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Bortezomib/farmacologia , Flavonoides/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Proteínas Quinases Associadas a Fase S/metabolismo , Antígenos CD/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Bortezomib/uso terapêutico , Caderinas/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteínas Culina/metabolismo , Flavonoides/uso terapêutico , Humanos , Leupeptinas/farmacologia , Leupeptinas/uso terapêutico , Masculino , Proteína NEDD8/metabolismo , Células PC-3 , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo
3.
Eur J Med Chem ; 157: 50-61, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30075402

RESUMO

Novel bioactive heterocycles containing a 3,4,5-trimethoxyphenyl fragment as antiproliferative agents by targeting tubulin were synthesized and their preliminary structure activity relationships (SARs) were explored. Among all these chemical agents, 2-(Benzo[d]oxazol-2-ylthio)-N-(4-methoxybenzyl)-N-(3,4,5-trimethoxyphenyl)acetamide (4d) exhibited the potent antiproliferative activity against MGC-803 cells with an IC50 value of 0.45 µM by induction of G2/M pahse arrest and cell apoptosis. In addition, 4d could change the membrane potential (ΔΨ) of the mitochondria against MGC-803 cells. Importantly, 4d acted as a novel tubulin polymerization inhibitor binding to colchicine site with an IC50 value of 3.35 µM.


Assuntos
Antineoplásicos/farmacologia , Compostos Heterocíclicos/farmacologia , Microtúbulos/efeitos dos fármacos , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/química , Humanos , Microtúbulos/metabolismo , Modelos Moleculares , Estrutura Molecular , Polimerização/efeitos dos fármacos , Relação Estrutura-Atividade , Tubulina (Proteína)/efeitos dos fármacos , Tubulina (Proteína)/metabolismo
4.
Curr Pharmacol Rep ; 3(6): 384-395, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30393593

RESUMO

Purpose of review: Rhodiola rosea extracts have been used as a dietary supplement in healthy populations, including athletes, to non-specifically enhance the natural resistance of the body to both physical and behavior stresses for fighting fatigue and depression. We summarize the information with respect to the new pharmacological activities of Rhodiola rosea extracts and its underlying molecular mechanisms in this review article. Recent findings: In addition to its multiplex stress-protective activity, Rhodiola rosea extracts have recently demonstrated its anti-aging, anti-inflammation, immunostimulating, DNA repair and anti-cancer effects in different model systems. Molecular mechanisms of Rhodiola rosea extracts's action have been studied mainly along with one of its bioactive compounds, salidroside. Both Rhodiola rosea extracts and salidroside have contrast molecular mechanisms on cancer and normal physiological functions. For cancer, Rhodiola rosea extracts and salidroside inhibit the mTOR pathway and reduce angiogenesis through down-regulation of the expression of HIF-1α/HIF-2α. For normal physiological functions, Rhodiola rosea extracts and salidroside activate the mTOR pathway, stimulate paracrine function and promote neovascularization by inhibiting PHD3 and stabilizing HIF-1α proteins in skeletal muscles. In contrast to many natural compounds, salidroside is water-soluble and highly bioavailable via oral administration and concentrated in urine by kidney excretion. Summary: Rhodiola rosea extracts and salidroside can impose cellular and systemic benefits similar to the effect of positive lifestyle interventions to normal physiological functions and for anti-cancer. The unique pharmacological properties of Rhodiola rosea extracts or salidroside deserve further investigation for cancer chemoprevention, in particular for human urinary bladder cancer.

5.
Cell Mol Bioeng ; 9(4): 509-529, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28392840

RESUMO

The delivery of therapeutics to the central nervous system (CNS) remains a major challenge in part due to the presence of the blood-brain barrier (BBB). Recently, cell-derived vesicles, particularly exosomes, have emerged as an attractive vehicle for targeting drugs to the brain, but whether or how they cross the BBB remains unclear. Here, we investigated the interactions between exosomes and brain microvascular endothelial cells (BMECs) in vitro under conditions that mimic the healthy and inflamed BBB in vivo. Transwell assays revealed that luciferase-carrying exosomes can cross a BMEC monolayer under stroke-like, inflamed conditions (TNF-α activated) but not under normal conditions. Confocal microscopy showed that exosomes are internalized by BMECs through endocytosis, co-localize with endosomes, in effect primarily utilizing the transcellular route of crossing. Together, these results indicate that cell-derived exosomes can cross the BBB model under stroke-like conditions in vitro. This study encourages further development of engineered exosomes as drug delivery vehicles or tracking tools for treating or monitoring neurological diseases.

6.
Biomaterials ; 77: 87-97, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26584349

RESUMO

Systemic administration of mesenchymal stem cells (MSCs) affords the potential to ameliorate the symptoms of Multiple Sclerosis (MS) in both preclinical and clinical studies. However, the efficacy of MSC-based therapy for MS likely depends on the number of cells that home to inflamed tissues and on the controlled production of paracrine and immunomodulatory factors. Previously, we reported that engineered MSCs expressing P-selectin glycoprotein ligand-1 (PSGL-1) and Sialyl-Lewis(x) (SLeX) via mRNA transfection facilitated the targeted delivery of anti-inflammatory cytokine interleukin-10 (IL-10) to inflamed ear. Here, we evaluated whether targeted delivery of MSCs with triple PSGL1/SLeX/IL-10 engineering improves therapeutic outcomes in mouse experimental autoimmune encephalomyelitis (EAE), a murine model for human MS. We found PSGL-1/SLeX mRNA transfection significantly enhanced MSC homing to the inflamed spinal cord. This is consistent with results from in vitro flow chamber assays in which PSGL-1/SleX mRNA transfection significantly increased the percentage of rolling and adherent cells on activated brain microvascular endothelial cells, which mimic the inflamed endothelium of blood brain/spinal cord barrier in EAE. In addition, IL-10-transfected MSCs show significant inhibitory activity on the proliferation of CD4(+) T lymphocytes from EAE mice. In vivo treatment with MSCs engineered with PSGL-1/SLeX/IL-10 in EAE mice exhibited a superior therapeutic function over native (unmodified) MSCs, evidenced by significantly improved myelination and decreased lymphocytes infiltration into the white matter of the spinal cord. Our strategy of targeted delivery of performance-enhanced MSCs could potentially be utilized to increase the effectiveness of MSC-based therapy for MS and other central nervous system (CNS) disorders.


Assuntos
Encefalomielite Autoimune Experimental/terapia , Interleucina-10/biossíntese , Glicoproteínas de Membrana/biossíntese , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Animais , Linfócitos T CD4-Positivos/imunologia , Adesão Celular , Movimento Celular , Técnicas de Cocultura , Endotélio Vascular/metabolismo , Vetores Genéticos/genética , Células HL-60 , Humanos , Interleucina-10/genética , Lentivirus/genética , Antígenos CD15/genética , Antígenos CD15/metabolismo , Ativação Linfocitária , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Bainha de Mielina/fisiologia , Ácido N-Acetilneuramínico/metabolismo , Especificidade de Órgãos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas Recombinantes de Fusão/metabolismo , Medula Espinal/patologia , Transfecção
7.
Clin Ther ; 33(11): 1759-1768.e1, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22001358

RESUMO

BACKGROUND: Traditionally, skin and skin structure infections (SSSIs) have been viewed as having a lower risk of mortality, morbidity, and cost compared with other types of infection. The influence of secondary bacteremia on the medicoeconomic outcomes of patients with SSSIs has not been well described. OBJECTIVE: The goal of this study was to evaluate the impact of bacteremia complicating SSSIs on length of hospital stay and costs. METHODS: This was a retrospective cohort study involving 579 patients with culture-positive SSSIs who were admitted to Barnes-Jewish Hospital, a major academic medical center, between April 1, 2005, and December 31, 2007. The outcomes evaluated in this analysis included hospital mortality, length of stay, hospital costs, and hospital readmission. RESULTS: Secondary bacteremia was present in 277 (47.8%) patients. Hospital mortality was statistically greater among patients with bacteremia (7.9% vs 1.0%; P < 0.001). The unadjusted median length of stay in bacteremic patients was 7.1 days compared with 2.8 days in those without bacteremia (P < 0.001 by log-rank test). This finding correlated with total hospital costs, which were greater in patients with bacteremia (median values: $14,623 vs $5841.50; P < 0.001). In a Cox model controlling for multiple confounders, bacteremia independently correlated with hospital duration (adjusted hazard ratio [HR], 1.820; 95% CI, 1.654-2.003; P < 0.001) and hospital costs (adjusted HR, 1.895; 95% CI, 1.723-2.083; P < 0.001). Hospital readmission within 30 days of discharge was also significantly more common among patients with SSSIs complicated by bacteremia (24.5% vs 12.9%; P < 0.001). CONCLUSIONS: Bacteremia complicating SSSIs occurred in almost 50% of patients infected with gram-positive bacteria in our institution. Beyond its impact on mortality, bacteremia is associated with increased length of stay, hospital costs, and readmission. However, these data are from a single academic medical center and may not be adjusted for all applicable confounders.


Assuntos
Bacteriemia/complicações , Efeitos Psicossociais da Doença , Infecções por Bactérias Gram-Positivas/complicações , Adulto , Idoso , Bacteriemia/economia , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/mortalidade , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Infect Control Hosp Epidemiol ; 32(4): 360-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21460487

RESUMO

OBJECTIVE: To develop and validate a risk prediction model that could identify patients at high risk for Clostridium difficile infection (CDI) before they develop disease. DESIGN AND SETTING: Retrospective cohort study in a tertiary care medical center. PATIENTS: Patients admitted to the hospital for at least 48 hours during the calendar year 2003. METHODS: Data were collected electronically from the hospital's Medical Informatics database and analyzed with logistic regression to determine variables that best predicted patients' risk for development of CDI. Model discrimination and calibration were calculated. The model was bootstrapped 500 times to validate the predictive accuracy. A receiver operating characteristic curve was calculated to evaluate potential risk cutoffs. RESULTS: A total of 35,350 admitted patients, including 329 with CDI, were studied. Variables in the risk prediction model were age, CDI pressure, times admitted to hospital in the previous 60 days, modified Acute Physiology Score, days of treatment with high-risk antibiotics, whether albumin level was low, admission to an intensive care unit, and receipt of laxatives, gastric acid suppressors, or antimotility drugs. The calibration and discrimination of the model were very good to excellent (C index, 0.88; Brier score, 0.009). CONCLUSIONS: The CDI risk prediction model performed well. Further study is needed to determine whether it could be used in a clinical setting to prevent CDI-associated outcomes and reduce costs.


Assuntos
Infecções por Clostridium/epidemiologia , Clostridium difficile , Medição de Risco/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Criança , Feminino , Hospitalização , Humanos , Laxantes/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
9.
Psychiatr Serv ; 62(1): 12-4, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21209293

RESUMO

There is public health interest in the identification and treatment of modifiable cardiometabolic risk factors among patients treated with antipsychotic medications. However, best-practice screening recommendations endorsed by multiple medical organizations have not translated into real-world clinical practice. Quality improvement strategies may help to address the gap between policy and implementation. This column describes the successful implementation of a best-practice glucose screening program in a large network of community mental health centers that was based on Six Sigma and diffusion of innovation theory.


Assuntos
Antipsicóticos/efeitos adversos , Benchmarking , Difusão de Inovações , Hiperglicemia/prevenção & controle , Programas de Rastreamento , Melhoria de Qualidade , Adulto , Glicemia , Serviços Comunitários de Saúde Mental , Redes Comunitárias , Humanos , Hiperglicemia/induzido quimicamente , Estados Unidos
10.
J Hosp Med ; 5(9): 535-40, 2010 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20734456

RESUMO

OBJECTIVE: Inappropriate empiric therapy worsens outcomes in certain healthcare-associated infections (HCAI). We studied the association of inappropriate empiric therapy with outcomes in patients with HCA complicated skin and skin structure infections (cSSSI). DESIGN: A single-center retrospective cohort study. PATIENTS: Hospitalized with a culture-positive cSSSI. MEASUREMENTS: We defined HCA-cSSSI as having ≥1 of these risk factors: (1) recent hospitalization, (2) recent antibiotics, (3) hemodialysis, (4) transfer from a nursing home, and inappropriate treatment as no antimicrobial therapy active against the pathogen(s) within 24 hours of obtaining culture specimen. We performed descriptive and multivariate statistics to compute the impact of inappropriate empiric therapy on outcomes. Hospital length of stay (LOS) served as primary and mortality as secondary outcomes. RESULTS: Of the 717 patients with culture-positive cSSSI, 527 (73.5%) had HCAI, of whom 405 (76.9%) received appropriate treatment. A higher proportion of those receiving inappropriate than appropriate treatment had a decubitus ulcer (29.5% vs. 10.9%, P < 0.001), a device-associated infection (42.6% vs. 28.6%, P = 0.004), or bacteremia (68.9% vs. 57.8%, P = 0.028). The frequency of methicillin-resistant Staphylococcus aureus (MRSA) did not differ between the groups. The low overall unadjusted mortality rate did not vary based on initial treatment. In a multivariable analysis adjusting for potential confounders inappropriate therapy had an attributable increase in hospital LOS of 1.8 days (95% CI, 1.4-2.3). CONCLUSION: Similar to other populations with HCAI, HCA-cSSSI patients are likely to receive inappropriate empiric therapy for their infection. This early exposure is associated with a significant prolongation of the hospitalization by nearly 2 days.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar , Hospitalização , Dermatopatias Bacterianas/tratamento farmacológico , Idoso , Protocolos Clínicos , Estudos de Coortes , Feminino , Humanos , Tempo de Internação , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Missouri/epidemiologia , Estudos Retrospectivos , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/mortalidade , Resultado do Tratamento
11.
Surg Infect (Larchmt) ; 11(2): 169-76, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20201688

RESUMO

BACKGROUND: Soft-tissue infections traditionally have been viewed as carrying a lower risk of death than other types of infection such as pneumonia, blood stream, and intra-abdominal. The influence of secondary bacteremia on the outcomes of patients with soft-tissue infections is not well described. OBJECTIVES: To describe the risk factors for bacteremia among patients admitted to an urban medical center with soft-tissue infections and the influence of bacteremia on outcomes. METHODS: A retrospective cohort study of 717 patients with culture-positive non-necrotizing soft-tissue infections admitted between April 1, 2005, and December 31, 2007. RESULTS: Bacteremia was present in 52% of the patients. Increasing age, previous hospitalization, decubitus or lower-extremity ulcers, device-related soft-tissue infection, and polymicrobial infection were independent predictors of bacteremia. Intensive care unit admission (adjusted odds ratio [AOR] 3.57; 95% confidence interval [CI] 2.17, 5.86), lower-extremity ulcer (AOR 3.43; 95% CI 2.07, 5.70), and bacteremia (AOR 6.37; 95% CI 3.34, 12.12) were independent predictors of in-hospital death. When patients with device-related soft-tissue infections were excluded, the rate of secondary bacteremia was 37.6% (201/535), and it remained an independent predictor of in-hospital death. CONCLUSIONS: The occurrence of bacteremia in soft-tissue infections is associated with a greater risk of death. Health care providers should be aware of the risk factors for bacteremia in patients with soft-tissue infections in order to provide more appropriate initial antimicrobial therapy and to ascertain its presence as a prognostic indicator.


Assuntos
Bacteriemia/mortalidade , Infecções Bacterianas/mortalidade , Infecções dos Tecidos Moles/complicações , Infecções dos Tecidos Moles/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Infecções Bacterianas/microbiologia , Estudos de Coortes , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
12.
Infect Control Hosp Epidemiol ; 30(12): 1203-10, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19848604

RESUMO

OBJECTIVE: Healthcare-associated infections are likely to be caused by drug-resistant and possibly mixed organisms and to be treated with inappropriate antibiotics. Because prompt appropriate treatment is associated with better outcomes, we studied the epidemiology of healthcare-associated complicated skin and skin-structure infections (cSSSIs). PATIENTS: Persons hospitalized with cSSSI and a positive culture result. METHODS: We conducted a single-center retrospective cohort study from April 2006 through December 2007. We differentiated healthcare-associated from community-acquired cSSSIs by at least 1 of the following risk factors: (1) recent hospitalization, (2) recent antibiotics, (3) hemodialysis, and (4) transfer from a nursing home. Inappropriate treatment was defined as no antimicrobial therapy with activity against the offending pathogen(s) within 24 hours after collection of a culture specimen. Mixed infections were those caused by both a gram-positive and a gram-negative organism. RESULTS: Among 717 hospitalized patients with cSSSI, 527 (73.5%) had healthcare-associated cSSSI. Gram-negative organisms were more common (relative risk, 1.24 [95% confidence interval, 1.14-1.35) and inappropriate treatment trended toward being more common (odds ratio, 1.29 [95% confidence interval, 0.85-1.95]) in healthcare-associated cSSSI than in community-acquired cSSSI. Mixed cSSSIs occurred in 10.6% of patients with healthcare-associated cSSSI and 6.3% of those with community-acquired cSSSI (P = .082) and were more likely to be treated inappropriately than to be nonmixed infections (odds ratio, 2.42 [95% confidence interval, 1.43-4.10]). Both median length of hospital stay (6.2 vs 2.9 days; P < .001) and mortality rate (6.6% vs 1.1%; P = .003) were significantly higher for healthcare-associated cSSSI than community-acquired cSSSI. CONCLUSIONS: Healthcare-associated cSSSIs are common and are likely to be caused by gram-negative organisms. Mixed infections carry a >2-fold greater risk of inappropriate treatment. Healthcare-associated cSSSIs are associated with increased mortality and prolonged length of hospital stay, compared with community-acquired cSSSIs.


Assuntos
Infecção Hospitalar/epidemiologia , Dermatopatias Bacterianas/epidemiologia , Adulto , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Hospitalização , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Resultado do Tratamento
13.
AMIA Annu Symp Proc ; : 1076, 2007 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-18694174

RESUMO

We administered a knowledge and attitudes questionnaire regarding a technology assisted pharmacist mediated academic detailing intervention designed to improve physician adherence to coronary heart disease (CHD) secondary-prevention guidelines. Questionnaires were administered in two settings: an academic hospital and a community hospital. More knowledgeable physicians reported being more likely to prescribe a pharmacists' recommended medication and to agree that lipid profiles should be automatically performed for inpatients with elevated troponin.


Assuntos
Competência Clínica , Doença das Coronárias/prevenção & controle , Fidelidade a Diretrizes , Centros Médicos Acadêmicos , Atitude do Pessoal de Saúde , Feminino , Hospitais Comunitários , Humanos , Masculino , Médicos , Guias de Prática Clínica como Assunto , Inquéritos e Questionários
14.
AMIA Annu Symp Proc ; : 1062, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17238681

RESUMO

As awareness of medical errors increases, innovative solutions are required to address these errors so that healthcare providers can be proactive rather than reactive. The development of an enterprise-wide voluntary incident reporting application will provide a mechanism to organize and prioritize resources toward correction of processes that could endanger patients.


Assuntos
Erros Médicos/prevenção & controle , Aplicações da Informática Médica , Gestão de Riscos , Humanos , Gestão de Riscos/normas , Interface Usuário-Computador , Vocabulário Controlado
15.
AMIA Annu Symp Proc ; : 1079, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16779366

RESUMO

BJC Healthcare is conducting a randomized controlled study to evaluate the impact of a technology-assisted pharmacist intervention on physicians' adherence to national coronary heart disease (CHD) prevention guidelines. We surveyed physicians to assess their knowledge of the guidelines and attitudes toward pharmacist-mediated interventions.


Assuntos
Competência Clínica , Doença das Coronárias/prevenção & controle , Guias de Prática Clínica como Assunto , Atitude do Pessoal de Saúde , Fidelidade a Diretrizes , Humanos , Médicos , Inquéritos e Questionários
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