RESUMO
BACKGROUND: The electronic health record is expected to improve the quality and efficiency of health care. Many novel functionalities have been introduced in order to improve medical decision making and communication between health care personnel. There is however limited evidence on whether these new functionalities are useful. The aim of our study was to investigate how well the electronic health record system supports physicians in performing basic clinical tasks. METHODS: Physicians of three prominent Norwegian hospitals participated in the survey. They were asked, in an online questionnaire, how well the hospital's electronic health record system DIPS supported 49 clinical tasks as well as how satisfied they were with the system in general, including the technical performance. Two hundred and eight of 402 physicians (52%) submitted a completely answered questionnaire. RESULTS: Seventy-two percent of the physicians had their work interrupted or delayed because the electronic health record hangs or crashes at least once a week, while 22% had experienced this problem daily. Fifty-three percent of the physicians indicated that the electronic health record is cumbersome to use and adds to their workload. The majority of physicians were satisfied with managing tests, e.g., requesting laboratory tests, reading test results and managing radiological investigations and electrocardiograms. Physicians were less satisfied with managing referrals. There was high satisfaction with some of the decision support functionalities available for prescribing drugs. This includes drug interaction alerts and drug allergy warnings, which are displayed automatically. However, physicians were less satisfied with other aspects of prescribing drugs, including getting an overview of the ongoing drug therapy. CONCLUSIONS: In the survey physicians asked for improvements of certain electronic health record functionalities like medication, clinical workflow support including planning and better overviews. In addition, there is apparently a need to focus on system stability, number of logins, reliability and better instructions on available electronic health record features. Considerable development is needed in current electronic health record systems to improve usefulness and satisfaction.
Assuntos
Atitude do Pessoal de Saúde , Registros Eletrônicos de Saúde , Corpo Clínico Hospitalar , Fluxo de Trabalho , Atitude Frente aos Computadores , Sistemas de Apoio a Decisões Clínicas , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Masculino , Noruega , Inquéritos e Questionários , Interface Usuário-Computador , Carga de TrabalhoRESUMO
Malignant melanoma is the most lethal form of skin cancer, with a high propensity to metastasize to the brain. More than 60% of melanomas have the BRAFV600E mutation, which activates the mitogen-activated protein kinase (MAPK) pathway [1]. In addition, increased PI3K (phosphoinositide 3-kinase) pathway activity has been demonstrated, through the loss of activity of the tumor suppressor gene, PTEN [2]. Here, we treated two melanoma brain metastasis cell lines, H1_DL2, harboring a BRAFV600E mutation and PTEN loss, and H3, harboring WT (wild-type) BRAF and PTEN loss, with the MAPK (BRAF) inhibitor vemurafenib and the PI3K pathway associated mTOR inhibitor temsirolimus. Combined use of the drugs inhibited tumor cell growth and proliferation in vitro in H1_DL2 cells, compared to single drug treatment. Treatment was less effective in the H3 cells. Furthermore, a strong inhibitory effect on the viability of H1_DL2 cells, when grown as 3D multicellular spheroids, was seen. The treatment inhibited the expression of pERK1/2 and reduced the expression of pAKT and p-mTOR in H1_DL2 cells, confirming that the MAPK and PI3K pathways were inhibited after drug treatment. Microarray experiments followed by principal component analysis (PCA) mapping showed distinct gene clustering after treatment, and cell cycle checkpoint regulators were affected. Global gene analysis indicated that functions related to cell survival and invasion were influenced by combined treatment. In conclusion, we demonstrate for the first time that combined therapy with vemurafenib and temsirolimus is effective on melanoma brain metastasis cells in vitro. The presented results highlight the potential of combined treatment to overcome treatment resistance that may develop after vemurafenib treatment of melanomas.
Assuntos
Antineoplásicos/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Indóis/farmacologia , Indóis/uso terapêutico , Melanoma/metabolismo , Melanoma/patologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , VemurafenibRESUMO
Brain metastasis is associated with a particular poor prognosis. Novel insight into the brain metastatic process is therefore warranted. Several preclinical models of brain tumor metastasis have been developed during the last 60 years, and they have in part revealed some of the mechanisms underlying the metastatic process. This review discusses mechanisms of brain metastasis with a key focus of the development of animal model systems. This includes the use of rodent, syngeneic brain metastasis models (spontaneous, chemically induced and genetically engineered models) and human xenotransplantation models (ectopic inoculation and orthotopic models). Current information indicates that none of these fully reflect tumor development seen in patients with metastatic disease. The various model systems used, however, have provided important insight into specific mechanisms of the metastatic process related to the brain. By combining the knowledge obtained from animal models, new important information on the molecular mechanisms behind metastasis will be obtained, leading to the future development of new therapeutic strategies.
Assuntos
Neoplasias Encefálicas/secundário , Modelos Animais de Doenças , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Humanos , Camundongos , RatosRESUMO
Biologic and therapeutic advances in melanoma brain metastasis are hampered by the paucity of reproducible and predictive animal models. In this work, we developed a robust model of brain metastasis that empowers quantitative tracking of cellular dissemination and tumor progression. Human melanoma cells labeled with superparamagnetic iron oxide nanoparticles (SPION) were injected into the left cardiac ventricle of mice and visualized by MRI. We showed that SPION exposure did not affect viability, growth, or migration in multiple cell lines across several in vitro assays. Moreover, labeling did not impose changes in cell-cycle distribution or apoptosis. In vivo, several SPION-positive cell lines displayed similar cerebral imaging and histologic features. MRI-based automated quantification of labeled cells in the brain showed a sigmoid association between metastasis frequency and doses of inoculated cells. Validation of this fully automated quantification showed a strong correlation with manual signal registration (r(2) = 0.921, P < 0.001) and incidence of brain metastases (r(2) = 0.708, P < 0.001). Metastasis formation resembled the pattern seen in humans and was unaffected by SPION labeling (histology; tumor count, P = 0.686; survival, P = 0.547). In summary, we present here a highly reproducible animal model that can improve the predictive value of mechanistic and therapeutic studies of melanoma brain metastasis.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Rastreamento de Células , Nanopartículas de Magnetita , Melanoma/diagnóstico , Melanoma/patologia , Animais , Apoptose , Transporte Biológico , Neoplasias Encefálicas/mortalidade , Ciclo Celular , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Sobrevivência Celular , Citoplasma/metabolismo , Modelos Animais de Doenças , Feminino , Compostos Férricos/química , Humanos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/química , Melanoma/mortalidade , Camundongos , Coloração e Rotulagem , Fatores de Tempo , Carga Tumoral , CicatrizaçãoRESUMO
Animal modeling for primary brain tumors has undergone constant development over the last 60 years, and significant improvements have been made recently with the establishment of highly invasive glioblastoma models. In this review we discuss the advantages and pitfalls of model development, focusing on chemically induced models, various xenogeneic grafts of human cell lines, including stem cell-like cell lines and biopsy spheroids. We then discuss the development of numerous genetically engineered models available to study mechanisms of tumor initiation and progression. At present it is clear that none of the current animal models fully reflects human gliomas. Yet, the various model systems have provided important insight into specific mechanisms of tumor development. In particular, it is anticipated that a combined comprehensive knowledge of the various models currently available will provide important new knowledge on target identification and the validation and development of new therapeutic strategies.