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The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.
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Sobreviventes de Câncer , Neoplasias , American Cancer Society , Dieta , Exercício Físico , Humanos , Neoplasias/terapia , Sobreviventes , Estados Unidos/epidemiologiaRESUMO
The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.
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Exercício Físico/fisiologia , Comportamento Alimentar/fisiologia , Promoção da Saúde/normas , Estilo de Vida Saudável/fisiologia , Neoplasias/prevenção & controle , American Cancer Society , Humanos , Estados UnidosRESUMO
Interspecies differences in locomotor efficiency have been extensively researched, but within-species variation in the metabolic cost of walking and its underlying causes have received much less attention. This is somewhat surprising given the importance of walking energetics to natural selection, and the fact that the mechanical efficiency of striding bipedalism in modern humans is thought to be related in some part to the unique morphology of the human foot. Previous studies of human running have linked specific anatomical traits in the foot to variations in locomotor energetics to provide insight into form-function relationships in human evolution. However, such studies are relatively rare, particularly for walking. In this study, relationships between a range of functional musculoskeletal traits in the human lower limb and the energetics of walking over compliant and noncompliant substrates are examined, with particular focus on the lower limb and foot. Twenty-nine young, healthy individuals walked across three surfaces-a noncompliant laboratory floor, and compliant 6 cm and 13 cm thick foams-at self-selected speeds while oxygen consumption was measured, from which the metabolic cost of transport was calculated. Lower limb lengths, calcaneus lengths, foot shape indices, and maximum isometric plantarflexion torques were also measured and subsequently tested for relationships with metabolic cost over these surfaces using linear regression. It was found that metabolic cost varied considerably between individuals within and across substrate types, but this variation was not statistically related to or explained by variations in musculoskeletal parameters considered to be adaptively important to efficient bipedal locomotion. This therefore provides no supportive evidence that variations in these gross anatomical parameters confer significant advantages to the efficiency of walking, and therefore suggest caution in the use of similar metrics to infer differences in walking energetics in closely related fossil species.
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Metabolismo Energético , Pé/anatomia & histologia , Caminhada , Evolução Biológica , Fenômenos Biomecânicos , Marcha , Humanos , Locomoção , CorridaRESUMO
Musculoskeletal modelling is an important platform on which to study the biomechanics of morphological structures in vertebrates and is widely used in clinical, zoological and palaeontological fields. The popularity of this approach stems from the potential to non-invasively quantify biologically important but difficult-to-measure functional parameters. However, while it is known that model predictions are highly sensitive to input values, it is standard practice to build models by combining musculoskeletal data from different sources resulting in 'generic' models for a given species. At present, there are little quantitative data on how merging disparate anatomical data in models impacts the accuracy of these functional predictions. This issue is addressed herein by quantifying the accuracy of both subject-specific human limb models containing individualised muscle force-generating properties and models built using generic properties from both elderly and young individuals, relative to experimental muscle torques obtained from an isokinetic dynamometer. The results show that subject-specific models predict isokinetic muscle torques to a greater degree of accuracy than generic models at the ankle (root-mean-squared error - 7.9% vs. 49.3% in elderly anatomy-based models), knee (13.2% vs. 57.3%) and hip (21.9% vs. 32.8%). These results have important implications for the choice of musculoskeletal properties in future modelling studies, and the relatively high level of accuracy achieved in the subject-specific models suggests that such models can potentially address questions about inter-subject variations of muscle functions. However, despite relatively high levels of overall accuracy, models built using averaged generic muscle architecture data from young, healthy individuals may lack the resolution and accuracy required to study such differences between individuals, at least in certain circumstances. The results do not wholly discourage the continued use of averaged generic data in musculoskeletal modelling studies but do emphasise the need for to maximise the accuracy of input values if studying intra-species form-function relationships in the musculoskeletal system.
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Imagem de Tensor de Difusão , Músculo Esquelético/diagnóstico por imagem , Modelagem Computacional Específica para o Paciente , Adulto , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , TorqueRESUMO
Cancer survivors are often highly motivated to seek information about food choices, physical activity, and dietary supplements to improve their treatment outcomes, quality of life, and overall survival. To address these concerns, the American Cancer Society (ACS) convened a group of experts in nutrition, physical activity, and cancer survivorship to evaluate the scientific evidence and best clinical practices related to optimal nutrition and physical activity after the diagnosis of cancer. This report summarizes their findings and is intended to present health care providers with the best possible information with which to help cancer survivors and their families make informed choices related to nutrition and physical activity. The report discusses nutrition and physical activity guidelines during the continuum of cancer care, briefly highlighting important issues during cancer treatment and for patients with advanced cancer, but focusing largely on the needs of the population of individuals who are disease free or who have stable disease following their recovery from treatment. It also discusses select nutrition and physical activity issues such as body weight, food choices, food safety, and dietary supplements; issues related to selected cancer sites; and common questions about diet, physical activity, and cancer survivorship.
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American Cancer Society , Atividade Motora , Neoplasias/mortalidade , Neoplasias/terapia , Estado Nutricional , Guias de Prática Clínica como Assunto , Suplementos Nutricionais , Humanos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component of B-cell-receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells. METHODS: We conducted a phase 1b-2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma. A total of 85 patients, the majority of whom were considered to have high-risk disease, received ibrutinib orally once daily; 51 received 420 mg, and 34 received 840 mg. RESULTS: Toxic effects were predominantly grade 1 or 2 and included transient diarrhea, fatigue, and upper respiratory tract infection; thus, patients could receive extended treatment with minimal hematologic toxic effects. The overall response rate was the same in the group that received 420 mg and the group that received 840 mg (71%), and an additional 20% and 15% of patients in the respective groups had a partial response with lymphocytosis. The response was independent of clinical and genomic risk factors present before treatment, including advanced-stage disease, the number of previous therapies, and the 17p13.1 deletion. At 26 months, the estimated progression-free survival rate was 75% and the rate of overall survival was 83%. CONCLUSIONS: Ibrutinib was associated with a high frequency of durable remissions in patients with relapsed or refractory CLL and small lymphocytic lymphoma, including patients with high-risk genetic lesions. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01105247.).
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Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adenina/análogos & derivados , Adulto , Tirosina Quinase da Agamaglobulinemia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas , Pirazóis/efeitos adversos , Pirazóis/farmacocinética , Pirazóis/farmacologia , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Recidiva , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND: Not all patients with diffuse large B-cell lymphoma (DLBCL) are candidates for aggressive regimens. (90)Y ibritumomab tiuxetan ((90)Y-IT), an anti-CD20 radionuclide-conjugated antibody, has demonstrated clinical efficacy in DLBCL with a favorable toxicity profile. METHODS: This phase II trial investigated the overall response rate (ORR), event-free survival (EFS), overall survival (OS) and toxicity of treatment with (90)Y-IT (0.4 or 0.3 mCi (90)Y/kg based on platelets) followed by rituximab maintenance therapy in patients with DLBCL not candidates for transplant. RESULTS: 25 patients were enrolled. At best response 8 patients obtained a complete response (CR) and 1 a partial response (ORR 36%). Median EFS was 2.5 months and OS 8.1 months. No patient who obtained CR later relapsed systemically. Two patients were free of disease at the 61- and 100-month follow-ups; 65% had grade 3/4 thrombocytopenia, but no significant bleeding was observed. Grade 3 nonhematologic toxicity occurred in 36%. Patients who had progressed through a rituximab-containing regimen responded poorly. CONCLUSION: The ORR of 36% with (90)Y-IT as salvage therapy for DLBCL while inferior to more aggressive regimens is significant with acceptable toxicity. For a subset of patients not candidates for salvage with autologous transplant, this treatment strategy can produce a durable, long-lasting remission.
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Anticorpos Monoclonais Murinos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Radioisótopos de Ítrio/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/química , Antineoplásicos/efeitos adversos , Intervalo Livre de Doença , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Radioimunoterapia , Indução de Remissão , Rituximab , Terapia de Salvação , Taxa de Sobrevida , Trombocitopenia/etiologia , Tomografia Computadorizada por Raios X , Radioisótopos de Ítrio/químicaRESUMO
BACKGROUND: Chemoimmunotherapy has led to improved numbers of patients achieving disease response, and longer overall survival in young patients with chronic lymphocytic leukaemia; however, its application in elderly patients has been restricted by substantial myelosuppression and infection. We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia. METHODS: In our open-label phase 1b/2 trial, we enrolled previously untreated patients at clinical sites in the USA. Eligible patients were aged at least 65 years, and had symptomatic chronic lymphocytic leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28 day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose was discontinued after enrolment had begun because comparable activity of the doses has been shown. The primary endpoint was the safety of the dose-fixed regimen in terms of frequency and severity of adverse events for all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01105247. FINDINGS: Between May 20, 2010, and Dec 18, 2012, we enrolled 29 patients with chronic lymphocytic leukaemia and two patients with small lymphocytic lymphoma. Median age was 71 years (range 65-84), and 23 (74%) patients were at least 70 years old. Toxicity was mainly of mild-to-moderate severity (grade 1-2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%] patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients). 15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient). Three (10%) patients developed grade 3 infections, although no grade 4 or 5 infections occurred. One patient developed grade 3 neutropenia, and one developed grade 4 thrombocytopenia. After a median follow-up of 22.1 months (IQR 18.4-23.2), 22 (71%) of 31 patients achieved an objective response (95% CI 52.0-85.8); four patients (13%) had a complete response, one patient (3%) had a nodular partial response, and 17 (55%) patients had a partial response. INTERPRETATION: The safety and activity of ibrutinib in elderly, previously untreated patients with symptomatic chronic lymphocytic leukaemia, or small lymphocytic lymphoma is encouraging, and merits further investigation in phase 3 trials. FUNDING: Pharmacyclics, Leukemia and Lymphoma Society, D Warren Brown Foundation, Mr and Mrs Michael Thomas, Harry Mangurian Foundation, P50 CA140158 to Prof J C Byrd MD.
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Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adenina/análogos & derivados , Tirosina Quinase da Agamaglobulinemia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Piperidinas , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversosRESUMO
BACKGROUND: A classical example of repeated speciation coupled with ecological diversification is the evolution of 14 closely related species of Darwin's (Galápagos) finches (Thraupidae, Passeriformes). Their adaptive radiation in the Galápagos archipelago took place in the last 2-3 million years and some of the molecular mechanisms that led to their diversification are now being elucidated. Here we report evolutionary analyses of genome of the large ground finch, Geospiza magnirostris. RESULTS: 13,291 protein-coding genes were predicted from a 991.0 Mb G. magnirostris genome assembly. We then defined gene orthology relationships and constructed whole genome alignments between the G. magnirostris and other vertebrate genomes. We estimate that 15% of genomic sequence is functionally constrained between G. magnirostris and zebra finch. Genic evolutionary rate comparisons indicate that similar selective pressures acted along the G. magnirostris and zebra finch lineages suggesting that historical effective population size values have been similar in both lineages. 21 otherwise highly conserved genes were identified that each show evidence for positive selection on amino acid changes in the Darwin's finch lineage. Two of these genes (Igf2r and Pou1f1) have been implicated in beak morphology changes in Darwin's finches. Five of 47 genes showing evidence of positive selection in early passerine evolution have cilia related functions, and may be examples of adaptively evolving reproductive proteins. CONCLUSIONS: These results provide insights into past evolutionary processes that have shaped G. magnirostris genes and its genome, and provide the necessary foundation upon which to build population genomics resources that will shed light on more contemporaneous adaptive and non-adaptive processes that have contributed to the evolution of the Darwin's finches.
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Evolução Molecular , Genômica , Passeriformes/genética , Adaptação Fisiológica , Animais , Genética Populacional , Modelos Genéticos , Passeriformes/fisiologia , Homologia de Sequência do Ácido NucleicoRESUMO
BACKGROUND: Rituximab combined with chemotherapy has improved the survival of previously untreated patients with follicular lymphoma (FL). Nevertheless, many patients neither want nor can tolerate chemotherapy, leading to interest in biological approaches. Epratuzumab is a humanized anti-CD22 monoclonal antibody with efficacy in relapsed FL. Because both rituximab and epratuzumab have single-agent activity in FL, the antibody combination was evaluated as initial treatment of patients with FL. METHODS: Fifty-nine untreated patients with FL received epratuzumab 360 mg/m2 with rituximab 375 mg/m2 weekly for 4 induction doses. This combination was continued as extended induction in weeks 12, 20, 28, and 36. Response assessed by computed tomography was correlated with clinical risk factors, [18F]fluorodeoxyglucose positron emission tomography findings at week 3, Fcγ polymorphisms, immunohistochemical markers, and statin use. RESULTS: Therapy was well-tolerated, with toxicities similar to expected with rituximab monotherapy. Fifty-two (88.2%) evaluable patients responded, including 25 complete responses (42.4%) and 27 partial responses (45.8%). At 3 years follow-up, 60% of patients remain in remission. Follicular Lymphoma International Prognostic Index (FLIPI) risk strongly predicted progression-free survival (P = .022). CONCLUSIONS: The high response rate and prolonged time to progression observed with this antibody combination are comparable to those observed after standard chemoimmunotherapies and further support the development of biologic, nonchemotherapeutic approaches for these patients.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Murinos/administração & dosagem , Imunoterapia/métodos , Linfoma Folicular/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Murinos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Imunoterapia/efeitos adversos , Linfoma Folicular/metabolismo , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Indução de Remissão , Rituximab , Resultado do TratamentoRESUMO
PURPOSE: Bone marrow biopsies (BMB) are performed before/after therapy to confirm complete response (CR) in patients with lymphoma on clinical trials. We sought to establish whether BMB add value in assessing response or predict progression-free survival (PFS) or overall survival (OS) outcomes in follicular lymphoma (FL) subjects in a large, multicenter, multitrial cohort. METHODS: Data were pooled from seven trials of 580 subjects with previously untreated FL through Alliance for Clinical Trials in Oncology (Alliance) and SWOG Cancer Research Network (SWOG) completing enrollment from 2008 to 2016. RESULTS: Only 5/580 (0.9%) had positive baseline BMB, CR on imaging, and subsequent positive BMB (P < .0001). Therefore, BMB were irrelevant to response in 99% of subjects. A sensitivity analysis of 385 FL subjects treated on an Eastern Cooperative Oncology Group study was included. In the Eastern Cooperative Oncology Group cohort, 5/385 (1.3%) had BMB that affected response assessment. Since some subjects do not undergo confirmatory BMB, we performed a landmark survival analysis from first radiologic CR with data from 580 subjects from Alliance and SWOG. Of subjects with CR on imaging (n = 187), PFS and OS were not significantly different among those with negative BMB to confirm CR (n = 47) versus those without repeat BMB (n = 140; PFS: adjusted hazard ratio, 1.10, 95% CI, 0.62 to 1.94, log-rank P = .686; OS: hazard ratio, 0.59, 95% CI, 0.23 to 1.53, log-rank P = .276). CONCLUSION: We conclude that BMB add little value to response assessment in subjects with FL treated on clinical trials and we recommend eliminating BMB from clinical trial requirements. BMB should also be removed from diagnostic guidelines for FL except in scenarios in which it may change management including confirmation of limited stage and assessment of cytopenias. This would reduce cost, patient discomfort, resource utilization, and potentially remove a barrier to trial enrollment.
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Linfoma Folicular , Estados Unidos , Humanos , Linfoma Folicular/tratamento farmacológico , Medula Óssea/patologia , National Cancer Institute (U.S.) , Análise de Sobrevida , BiópsiaRESUMO
Walking on compliant substrates requires more energy than walking on hard substrates but the biomechanical factors that contribute to this increase are debated. Previous studies suggest various causative mechanical factors, including disruption to pendular energy recovery, increased muscle work, decreased muscle efficiency and increased gait variability. We test each of these hypotheses simultaneously by collecting a large kinematic and kinetic dataset of human walking on foams of differing thickness. This allowed us to systematically characterize changes in gait with substrate compliance, and, by combining data with mechanical substrate testing, drive the very first subject-specific computer simulations of human locomotion on compliant substrates to estimate the internal kinetic demands on the musculoskeletal system. Negative changes to pendular energy exchange or ankle mechanics are not supported by our analyses. Instead we find that the mechanistic causes of increased energetic costs on compliant substrates are more complex than captured by any single previous hypothesis. We present a model in which elevated activity and mechanical work by muscles crossing the hip and knee are required to support the changes in joint (greater excursion and maximum flexion) and spatio-temporal kinematics (longer stride lengths, stride times and stance times, and duty factors) on compliant substrates.
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Marcha , Caminhada , Humanos , Cinética , Locomoção , Articulação do TornozeloRESUMO
INTRODUCTION: Academic health centers are poised to improve health through their clinical, education, and research missions. However, these missions often operate in silos. The authors explored stakeholder perspectives at diverse institutions to understand challenges and identify alignment strategies. METHODS: Authors used an exploratory qualitative design and thematic analysis approach with data obtained from electronic surveys sent to participants at five U.S. academic health centers (2017-18), with four different types of medical school/health system partnerships. Participants included educators, researchers, system leaders, administrators, clinical providers, resident/fellow physicians, and students. Investigators coded data using constant comparative analysis, met regularly to reconcile uncertainties, and collapsed/combined categories. RESULTS: Of 175 participants invited, 113 completed the survey (65%). Three results categories were identified. First, five higher-order themes emerged related to aligning missions, including (a) shared vision and strategies, (b) alignment of strategy with community needs, (c) tension of economic drivers, (d) coproduction of knowledge, and (e) unifying set of concepts spanning all missions. Second, strategies for each mission were identified, including education (new competencies, instructional methods, recruitment), research (shifting agenda, developing partnerships, operations), and clinical operations (delivery models, focus on patient factors/needs, value-based care, well-being). Lastly, strategies for integrating each dyadic mission pair, including research-education, clinical operations education, and research-clinical operations, were identified. CONCLUSIONS: Academic health centers are at a crossroads in regard to identity and alignment across the tripartite missions. The study's results provide pragmatic strategies to advance the tripartite missions and lead necessary change for improved patient health.
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The epothilones represent a novel group of microtubule stabilization agents that appear to retain activity even in chemotherapy-resistant cell lines and animal models. Because of their ability to overcome chemotherapy resistance, we conducted a phase II study of Ixabepilone in patients with indolent non-Hodgkin lymphoma and mantle cell lymphoma (MCL). Ixabepilone was given at a dose of 25 mg/m(2) weekly for three of four consecutive weeks. Patients were required to have received < or =4 prior chemotherapy regimens, with an interval of at least one month since the last treatment, 3 months from prior rituximab, and 7 d from prior steroids, an absolute neutrophil count >1 x 10(9)/l and a platelet count >50 x 10(9)/l. Dose reductions were allowed. The overall response rate in assessable patients was 27% in this otherwise heavily treated population. One patient with chemotherapy-refractory follicular lymphoma attained a complete remission that lasted approximately 8 months. Three responses were also seen in refractory MCL and one in small lymphocytic lymphoma. The duration of response ranged from 2 to 8 months. Major toxicities included fatigue, myelosuppression and neuropathy. These data suggest that Ixabepilone has activity in chemotherapy-refractory lymphoma.
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Antineoplásicos/uso terapêutico , Epotilonas/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Esquema de Medicação , Eletromiografia , Epotilonas/efeitos adversos , Feminino , Humanos , Linfoma Folicular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neurônios Motores , Condução Nervosa , Recidiva , Indução de Remissão , Células Receptoras Sensoriais , Resultado do TratamentoRESUMO
Mixed methods research is becoming increasingly popular in the health and social science disciplines. The aim of this article is to give an overview of the varieties of mixed methods designs. We begin by situating mixed methods research in the context of a paradigmatic framework which assists a researcher in making decisions concerning the design of their study. Although the most commonly used mixed methods designs are underpinned by positivist/postpositivist assumptions, the combination of qualitative and quantitative methods can be used within any research paradigm.
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Pesquisa em Enfermagem/métodos , Projetos de Pesquisa , Atitude do Pessoal de Saúde , Viés , Coleta de Dados/métodos , Interpretação Estatística de Dados , Humanos , Pesquisa em Enfermagem/normas , Filosofia em Enfermagem , Pesquisa Qualitativa , Reprodutibilidade dos Testes , Pesquisadores/psicologiaRESUMO
Nursing practices are subject to intersecting and competing discourses, which give them different, sometimes contradictory, meanings. In this article, using a case of intimate bodily care, we explore the workings of these discourses in a nursing student's account of her first experience of bathing an elderly woman. In particular we were interested in how different meanings of nursing "care" figure into the student's story. Through our analysis, we realized that a range of contradictions and tensions structured the student's experience. These contradictions were primarily produced by a collision between two discourses: the student's commonsense way of understanding the intimacy of such an act (liberal humanist discourse) and the impersonal approach characteristic of institutionalized care (scientific medical discourse). This collision caused distress and confusion, such that the student became almost as vulnerable as her patient. We argue that this type of detailed analysis of a nursing student's experience may increase our understanding of the discursive struggles that occur for students during their shifting between classrooms and clinical sites, between theory and practice, in the process of becoming professionals. Understanding these struggles and the relationships of power that produce both nursing student and patient as "vulnerable bodies" is important for nurse educators because they offer opportunities for intervention in the shaping of nursing professionals.
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Adaptação Psicológica , Atitude do Pessoal de Saúde , Banhos , Estudantes de Enfermagem/psicologia , Adulto , Idoso , Banhos/enfermagem , Banhos/psicologia , Competência Clínica , Bacharelado em Enfermagem , Empatia , Feminino , Pesar , Corpo Humano , Humanismo , Humanos , Narração , Nova Zelândia , Papel do Profissional de Enfermagem/psicologia , Relações Enfermeiro-Paciente , Pesquisa Metodológica em Enfermagem , Filosofia em Enfermagem , Poder Psicológico , Autoeficácia , Justiça Social , Valores Sociais , Tabu , TatoRESUMO
Methodologies abound in the field of health and social science research, making a confusing terrain for new researchers. In this article, we offer order out of confusion. Drawing on our work as postgraduate teachers, we outline a paradigm framework which proposes that methodologies are similar or different because of their underlying assumptions and values. We identify four major paradigms, explain the distinctive assumptions which underpin them, and show how each figures the researcher and the researcher-researched relationship. Along the way, we place a variety of methodologies into their paradigm of origin and offer some illustrative examples of health research.
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Pesquisa Metodológica em Enfermagem/organização & administração , Viés , Humanos , Relações Interprofissionais , Relações Pesquisador-SujeitoRESUMO
Internal controls are the methods and procedures used by any business to prevent or detect errors, safeguard assets (especially cash) from being misappropriated, and encourage staff adherence to prescribed managerial policies. Internal controls in a medical practice differ depending on the size and complexity of the practice. The key, however, is that they prevent or detect errors and efforts to circumvent the established policies and procedures of the organization. How good are the internal controls in your group practice? This article identifies ten questions you should use to evaluate your risk of asset misappropriation.
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Auditoria Financeira , Prática de Grupo/economia , Administração da Prática Médica/economia , Documentação , Eficiência Organizacional , Prática de Grupo/normas , Seleção de Pessoal , Estados UnidosRESUMO
PURPOSE: Concerns regarding neurocognitive toxicity of whole-brain radiotherapy (WBRT) have motivated development of alternative, dose-intensive chemotherapeutic strategies as consolidation in primary CNS lymphoma (PCNSL). We performed a multicenter study of high-dose consolidation, without WBRT, in PCNSL. Objectives were to determine: one, rate of complete response (CR) after remission induction therapy with methotrexate, temozolomide, and rituximab (MT-R); two, feasibility of a two-step approach using high-dose consolidation with etoposide plus cytarabine (EA); three, progression-free survival (PFS); and four, correlation between clinical and molecular prognostic factors and outcome. PATIENTS AND METHODS: Forty-four patients with newly diagnosed PCNSL were treated with induction MT-R, and patients who achieved CR received EA consolidation. We performed a prospective analysis of molecular prognostic biomarkers in PCNSL in the setting of a clinical trial. RESULTS: The rate of CR to MT-R was 66%. The overall 2-year PFS was 0.57, with median follow-up of 4.9 years. The 2-year time to progression was 0.59, and for patients who completed consolidation, it was 0.77. Patients age > 60 years did as well as younger patients, and the most significant clinical prognostic variable was treatment delay. High BCL6 expression correlated with shorter survival. CONCLUSION: CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT. On the basis of these encouraging results, an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this randomized trial in PCNSL, in which neither arm involves WBRT.