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As medicine is moving toward performance and outcome-based payment and is transitioning away from productivity-based systems, value is now being appraised in healthcare through "performance measures." Over the past few decades, assessment of clinical performance in health care has been essential in ensuring safe and cost-effective patient care. The Centers for Medicare & Medicaid Services is further driving this change with measurable, outcomes-based national payer incentive payment systems. With the continually evolving requirements in health care reform focused on value-based care, there is a growing concern that clinicians, particularly dermatologists, may not understand the scientific rationale of health care quality measurement. As such, in order to help dermatologists understand the health care measurement science landscape to empower them to engage in the performance measure development and implementation process, the first article in this 2-part continuing medical education series reviews the value equation, historic and evolving policy issues, and the American Academy of Dermatology's approach to performance measurement development to provide the required foundational knowledge for performance measure developers.
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Medicare , Qualidade da Assistência à Saúde , Idoso , Humanos , Estados Unidos , Atenção à Saúde , Reforma dos Serviços de Saúde , Instalações de SaúdeRESUMO
Throughout the 21st century, national and local governments, private health sectors, health insurance companies, healthcare professionals, labor unions, and consumers have been striving to develop an effective approach to evaluate, report, and improve the quality of healthcare. As medicine improves and health systems grow to meet patient needs, the performance measurement system of care effectiveness must also evolve. Continual efforts should be undertaken to effectively measure quality of care to create a more informed public, improve health outcomes, and reduce healthcare costs. As such, recent policy reform has necessitated that performance systems be implemented in healthcare, with the "performance measure" being the foundation of the system in which all of healthcare must be actively engaged in to ensure optimal care for patients. The development of performance measures can be highly complex, particularly when creating specialty-specific performance measures. To help dermatologists understand the process of creating dermatology-specific performance measures to engage in creating or implementing performance measures at the local or national levels, this article in the two-part continuing medical education series reviews the types, components, and process of developing, reviewing, and implementing performance measures.
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Dermatologia , Humanos , Atenção à Saúde , Seguro SaúdeRESUMO
Hypoxia is associated with resistance to radiotherapy and chemotherapy in malignant gliomas, and it can be imaged by positron emission tomography with 18F-fluoromisonidazole (18F-FMISO). Previous results for patients with brain cancer imaged with 18F-FMISO at a single center before conventional chemoradiotherapy showed that tumor uptake via T/Bmax (tissue SUVmax/blood SUV) and hypoxic volume (HV) was associated with poor survival. However, in a multicenter clinical trial (ACRIN 6684), traditional uptake parameters were not found to be prognostically significant, but tumor SUVpeak did predict survival at 1 year. The present analysis considered both study cohorts to reconcile key differences and examine the potential utility of adding radiomic features as prognostic variables for outcome prediction on the combined cohort of 72 patients with brain cancer (30 University of Washington and 42 ACRIN 6684). We used both 18F-FMISO intensity metrics (T/Bmax, HV, SUV, SUVmax, SUVpeak) and assessed radiomic measures that determined first-order (histogram), second-order, and higher-order radiomic features of 18F-FMISO uptake distributions. A multivariate model was developed that included age, HV, and the intensity of 18F-FMISO uptake. HV and SUVpeak were both independent predictors of outcome for the combined data set (P < .001) and were also found significant in multivariate prognostic models (P < .002 and P < .001, respectively). Further model selection that included radiomic features showed the additional prognostic value for overall survival of specific higher order texture features, leading to an increase in relative risk prediction performance by a further 5%, when added to the multivariate clinical model..
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Neoplasias Encefálicas/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Misonidazol/análogos & derivados , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias de Tecidos Moles/metabolismo , Adulto , Idoso , Feminino , Humanos , Hipóxia/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Misonidazol/administração & dosagem , Prognóstico , Compostos Radiofarmacêuticos/farmacocinética , Neoplasias de Tecidos Moles/patologiaRESUMO
UNLABELLED: Synovial sarcoma generally is associated with poor prognosis. With recent advances in molecular biology, it has become apparent not all synovial sarcomas share the same tumor biology. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for risk assessment in several types of sarcomas. We therefore assessed the clinical value of (18)F-FDG-PET-derived maximum standard uptake value (SUV(max)) for predicting survival in patients with synovial sarcoma. (18)F-FDG-PET was performed in 44 patients with synovial sarcoma before therapy and resection. SUV(max) was calculated for each tumor and then evaluated for prognostic usefulness along with metastasis at presentation, tumor grade, histopathologic subtype, age, gender, postsurgical margins, anatomic location, and tumor size for overall survival and progression-free survival. SUV(max) ranged from 1.2 to 13.0 (median, 4.35). Pretherapy tumor SUV(max) predicted overall survival and progression-free survival. Patients presenting with a SUV(max) greater than 4.35 had a decreased disease-free survival and were therefore at high risk for having local recurrences and metastatic disease. LEVEL OF EVIDENCE: Level I, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.
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Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Medição de Risco/métodos , Sarcoma Sinovial/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Sarcoma Sinovial/patologia , Análise de SobrevidaRESUMO
Numerous studies have reported the prognostic utility of texture analyses and the effectiveness of radiomics in PET and PET/CT assessment of non-small cell lung cancer (NSCLC). Here we explore the potential, relative to this methodology, of an alternative model-based approach to tumour characterization, which was successfully applied to sarcoma in previous works. The spatial distribution of 3D FDG-PET uptake is evaluated in the spatial referential determined by the best-fitting ellipsoidal pattern, which provides a univariate uptake profile function of the radial position of intratumoral voxels. A group of structural features is extracted from this fit that include two heterogeneity variables and statistical summaries of local metabolic gradients. We demonstrate that these variables capture aspects of tumour metabolism that are separate to those described by conventional texture features. Prognostic model selection is performed in terms of a number of classifiers, including stepwise selection of logistic models, LASSO, random forests and neural networks with respect to two-year survival status. Our results for a cohort of 93 NSCLC patients show that structural variables have significant prognostic potential, and that they may be used in conjunction with texture features in a traditional radiomics sense, towards improved baseline multivariate models of patient overall survival. The statistical significance of these models also demonstrates the relevance of these machine learning classifiers for prognostic variable selection.
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UNLABELLED: (18)F-FDG PET images of tumors often display highly heterogeneous spatial distribution of (18)F-FDG-positive pixels. We proposed that this heterogeneity in (18)F-FDG spatial distribution can be used to predict tumor biologic aggressiveness. This study presents data to support the hypothesis that a new heterogeneity-analysis algorithm applied to (18)F-FDG PET images of tumors in patients is predictive of patient outcome. METHODS: (18)F-FDG PET images from 238 patients with sarcoma were analyzed using a new algorithm for heterogeneity analysis in tumor (18)F-FDG spatial distribution. Patient characteristics, tumor histology, and patient outcome were compared with image analysis results using univariate and multivariate analysis. Cox proportional hazards models were used to further analyze the significance of the data associations. RESULTS: Statistical analyses show that heterogeneity analysis is a strong independent predictor of patient outcome. CONCLUSION: The new (18)F-FDG PET tumor image heterogeneity analysis method is validated for the ability to predict patient outcome in a clinical population of patients with sarcoma. This method can be extended to other PET image datasets in which heterogeneity in tissue uptake of a radiotracer may predict patient outcome.
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Fluordesoxiglucose F18 , Avaliação de Resultados em Cuidados de Saúde/métodos , Medição de Risco/métodos , Sarcoma/diagnóstico por imagem , Sarcoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Pessoa de Meia-Idade , Prevalência , Prognóstico , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Fatores de Risco , Sarcoma/metabolismo , Sensibilidade e Especificidade , Análise de Sobrevida , Taxa de Sobrevida , Estados UnidosRESUMO
Major US corporations and consumer groups are demanding more accountability for their health care expenditures. In response, the federal government, specialty boards, and state medical boards are evaluating ways to implement objective measures of quality. Many dermatologists already choose to participate in quality measurement and improvement activities. More will need to, as recertification and relicensure requirements change. Dermatologists need measures that are specialty-specific, as measures developed for primary care physicians are generally not appropriate for a dermatologic practice.
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Assistência Ambulatorial/normas , Dermatologia/normas , Melanoma/diagnóstico , Médicos/normas , Garantia da Qualidade dos Cuidados de Saúde/métodos , Neoplasias Cutâneas/diagnóstico , Competência Clínica/normas , Dermatologia/educação , Guias como Assunto , Humanos , Melanoma/prevenção & controle , Avaliação de Processos em Cuidados de Saúde , Indicadores de Qualidade em Assistência à Saúde , Neoplasias Cutâneas/prevenção & controle , Sociedades Médicas , Estados UnidosRESUMO
Intratumoral heterogeneity biomarkers derived from positron emission tomography (PET) imaging with fluorodeoxyglucose (FDG) are of interest for a number of cancers, including sarcoma. A range of radiomic texture variables, adapted from general methodologies for image analysis, has shown promise in the setting. In the context of sarcoma, our group introduced an alternative model-based approach to the measurement of heterogeneity. In this approach, the heterogeneity of a tumor is characterized by the extent to which the 3-D FDG uptake pattern deviates from a simple elliptically contoured structure. By using a nonparametric analysis of the uptake profile obtained from this spatial model, a variable assessing the metabolic gradient of the tumor is developed. The work explores the prognostic potential of this new variable in the context of FDG-PET imaging of sarcoma. A mature clinical series involving 197 patients, 88 of whom have complete time-to-death information, is used. Texture variables based on the imaging data are also evaluated in this series and a range of appropriate machine learning methodologies are then used to explore the complementary prognostic roles for structure and texture variables. We conclude that both texture-based and model-based variables can be combined to achieve enhanced prognostic assessments of outcome for patients with sarcoma based on FDG-PET imaging information.
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Blood flow-metabolism mismatch from dynamic positron emission tomography (PET) studies with [Formula: see text]-labeled water ([Formula: see text]) and [Formula: see text]-labeled fluorodeoxyglucose (FDG) has been shown to be a promising diagnostic for locally advanced breast cancer (LABCa) patients. The mismatch measurement involves kinetic analysis with the arterial blood time course (AIF) as an input function. We evaluate the use of a statistical method for AIF extraction (SAIF) in these studies. Fifty three LABCa patients had dynamic PET studies with [Formula: see text] and FDG. For each PET study, two AIFs were recovered, an SAIF extraction and also a manual extraction based on a region of interest placed over the left ventricle (LV-ROI). Blood flow-metabolism mismatch was obtained with each AIF, and kinetic and prognostic reliability comparisons were made. Strong correlations were found between kinetic assessments produced by both AIFs. SAIF AIFs retained the full prognostic value, for pathologic response and overall survival, of LV-ROI AIFs.
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Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial 18F-FDG PET was predictive of time to skeletal-related events (tSRE) and time to progression (TTP). 18F-NaF PET improves bone metastasis detection compared with bone scanning. We prospectively tested 18F-FDG PET and 18F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (MBC). Methods: Patients with bone-dominant MBC were imaged with 18F-FDG PET and 18F-NaF PET before starting new therapy (scan1) and again at a range of times centered around approximately 4 mo later (scan2). Maximum standardized uptake value (SUVmax) and lean body mass adjusted standardized uptake (SULpeak) were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and 18F-FDG PET and 18F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) were also applied. Survival curves for mPERCIST compared response categories of complete response+partial response+stable disease versus progressive disease for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher 18F-FDG SULpeak at scan2 predicted shorter time to tSRE (P = <0.001) and TTP (P = 0.044). Higher 18F-FDG SUVmax at scan2 predicted a shorter time to tSRE (P = <0.001). A multivariable model using 18F-FDG SUVmax of the index lesion at scan1 plus the difference in SUVmax of up to 5 lesions between scans was predictive for tSRE and TTP. Among 24 patients evaluable by 18F-FDG PET mPERCIST, tSRE and TTP were longer in responders (complete response, partial response, or stable disease) than in nonresponders (progressive disease) (P = 0.007, 0.028, respectively), with a trend toward improved survival (P = 0.1). An increase in the uptake between scans of up to 5 lesions by 18F-NaF PET was associated with longer OS (P = 0.027). Conclusion: Changes in 18F-FDG PET parameters during therapy are predictive of tSRE and TTP, but not OS. mPERCIST evaluation in bone lesions may be useful in assessing response to therapy and is worthy of evaluation in multicenter, prospective trials. Serial 18F-NaF PET was associated with OS but was not useful for predicting TTP or tSRE in bone-dominant MBC.
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Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Progressão da Doença , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Compostos RadiofarmacêuticosRESUMO
UNLABELLED: We investigated the effects of maternal docosahexanoic acid (DHA) supplementation on pups' auditory startle responses and the composition of brain myelin. METHODS: Timed-pregnant rats were fed throughout pregnancy and lactation diets that contained 0, 0.3, 0.7 or 3% of total fatty acids as DHA. Milk was collected from culled pups' stomachs on postnatal day (PND) 3, latency of the auditory startle reflex was measured on PND 15, and pups were killed and brains collected on PND 24. RESULTS: Higher levels of DHA in maternal diet were reflected in milk and in pups' myelin. The latency of the auditory startle response was significantly longer in offspring of dams fed higher levels of DHA. There was a positive correlation between the myelin content of DHA and the latency of the startle response (p = 0.044), and a negative correlation between the myelin content of DHA and the myelin content of cholesterol (p = 0.005). CONCLUSION: High levels of maternal DHA intake alter the lipid composition of rat pup myelin, and are associated with longer latencies of the auditory startle response--a myelin-dependent electrophysiologic response.
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Animais Recém-Nascidos/fisiologia , Dieta , Ácidos Docosa-Hexaenoicos/administração & dosagem , Bainha de Mielina/química , Prenhez , Efeitos Tardios da Exposição Pré-Natal , Reflexo de Sobressalto/efeitos dos fármacos , Estimulação Acústica , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/metabolismo , Colesterol/análise , Ácidos Docosa-Hexaenoicos/análise , Ácidos Docosa-Hexaenoicos/farmacologia , Feminino , Leite/química , Bainha de Mielina/efeitos dos fármacos , Gravidez , Ratos , Tempo de Reação/efeitos dos fármacosRESUMO
PURPOSE: Advanced head and neck cancer shows hypoxia that results in biological changes to make the tumor cells more aggressive and less responsive to treatment resulting in poor survival. [F-18] fluoromisonidazole (FMISO) positron emission tomography (PET) has the ability to noninvasively quantify regional hypoxia. We investigated the prognostic effect of pretherapy FMISO-PET on survival in head and neck cancer. EXPERIMENTAL DESIGN: Seventy-three patients with head and neck cancer had pretherapy FMISO-PET and 53 also had fluorodeoxyglucose (FDG) PET under a research protocol from April 1994 to April 2004. RESULTS: Significant hypoxia was identified in 58 patients (79%). The mean FMISO tumor/bloodmax (T/Bmax) was 1.6 and the mean hypoxic volume (HV) was 40.2 mL. There were 28 deaths in the follow-up period. Mean FDG standard uptake value (SUV)max was 10.8. The median time for follow-up was 72 weeks. In a univariate analysis, T/Bmax (P=0.002), HV (P=0.04), and the presence of nodes (P=0.01) were strong independent predictors. In a multivariate analysis, including FDG SUVmax, no variable was predictive at P<0.05. When FDG SUVmax was removed from the model (resulting in n=73 with 28 events), nodal status and T/Bmax (or HV) were both highly predictive (P=0.02, 0.006 for node and T/Bmax, respectively; P=0.02 and 0.001 for node and HV, respectively). CONCLUSIONS: Pretherapy FMISO uptake shows a strong trend to be an independent prognostic measure in head and neck cancer.
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Hipóxia Celular , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Misonidazol/análogos & derivados , Tomografia por Emissão de Pósitrons/métodos , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/secundário , Fluordesoxiglucose F18 , Seguimentos , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Análise de SobrevidaRESUMO
PURPOSE: Factorial designs may be proposed to test extra questions within a clinical trial. A common approach to sample size and analysis for factorial trials assumes no statistical interactions and does not adjust for multiple testing. This investigation considered the trade-off between potential gains from testing more questions with fewer patients versus how often a factorial trial might arrive at an incorrect conclusion. METHODS: A simulation study of a 2 x 2 design (observation v chemotherapy v radiation therapy v the combination) was performed under various conditions, including effect of one, both, or neither treatment and absence or presence of statistical interaction (effect of one treatment differed according to the presence of the other). Three analysis approaches were investigated, one assuming no interaction, a second testing first for interaction, and the third testing for interaction as well as adjusting for multiple testing. The approaches were compared with respect to the probability of selecting the correct treatment arm. RESULTS: No one approach was superior. Testing for interaction was beneficial in some settings but detrimental in others. Under some scenarios, the factorial design improved efficiency, but under others, all three approaches resulted in poor probability of selecting the correct treatment arm at the end of the trial. CONCLUSION: Extra efficiency is possible, but it is difficult to predict when favorable conditions exist. If a factorial design is used, potential efficiency gains should be weighed against potential loss of power to arrive at the correct conclusion under possible scenarios of interest.
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Ensaios Clínicos como Assunto/métodos , Neoplasias/terapia , Projetos de Pesquisa , Ensaios Clínicos como Assunto/estatística & dados numéricos , Interpretação Estatística de Dados , Humanos , Tamanho da Amostra , Estatística como Assunto/métodosRESUMO
To describe the varied presenting signs and symptoms in pediatric patients with pheochromocytoma, a retrospective chart review of the presenting signs and symptoms and subsequent clinical course of patients who presented to the Pediatric ICU following surgical excision of a pheochromocytoma was undertaken. The cohort of 7 patients (5 boys, 2 girls) ranged in age from 4 to 16 years. Two patients were hypertensive at initial presentation, and the other 5 developed hypertension after their initial presentation. The initial presenting signs and symptoms were related to the central nervous system (CNS) in 6 of the patients (5 with an acute alteration in mental status and 1 with visual disturbances). Two patients presented with congestive heart failure. Other signs and symptoms at the time of initial presentation included sweating, headache, weight loss, heat intolerance, increased thirst and urination, a decline in school activity, and red/puffy hands and feet. The time from the initial presentation until the diagnosis was confirmed was 5 months or more in 4 of the 7 patients. The diagnosis was confirmed by demonstration of elevated urinary catecholamines in all 7 patients, although 2 patients had initial negative urinary levels.
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Neoplasias das Glândulas Suprarrenais/diagnóstico , Feocromocitoma/diagnóstico , Adolescente , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/cirurgia , Catecolaminas/urina , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Cefaleia/etiologia , Insuficiência Cardíaca/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Feocromocitoma/complicações , Feocromocitoma/cirurgia , Estudos Retrospectivos , Sudorese , Síncope/etiologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
UNLABELLED: (18)F-fluoromisonidazole ((18)F-FMISO) is the most widely used PET agent for imaging hypoxia, a condition associated with resistance to tumor therapy. (18)F-FMISO equilibrates in normoxic tissues but is retained under hypoxic conditions because of reduction and binding to macromolecules. A simple tissue-to-blood (TB) ratio is suitable for quantifying hypoxia. A TB ratio threshold of 1.2 or greater is useful in discriminating the hypoxic volume (HV) of tissue; TBmax is the maximum intensity of the hypoxic region and does not invoke a threshold. Because elimination of blood sampling would simplify clinical use, we tested the validity of using imaging regions as a surrogate for blood sampling. METHODS: Patients underwent 20-min (18)F-FMISO scanning during the 90- to 140-min interval after injection with venous blood sampling. Two hundred twenty-three (18)F-FMISO patient studies had detectable surrogate blood regions in the field of view. Quantitative parameters of hypoxia (TBmax, HV) derived from blood samples were compared with values using surrogate blood regions derived from the heart, aorta, or cerebellum. In a subset of brain cancer patients, parameters from blood samples and from the cerebellum were compared for their ability to independently predict outcome. RESULTS: Vascular regions of heart showed the highest correlation to measured blood activity (R(2) = 0.84). For brain studies, cerebellar activity was similarly correlated to blood samples. In brain cancer patients, Kaplan-Meier analysis showed that image-derived reference regions had predictive power nearly identical to parameters derived from blood, thus obviating the need for venous sampling in these patients. CONCLUSION: Simple static analysis of (18)F-FMISO PET captures both the intensity (TBmax) and the spatial extent (HV) of tumor hypoxia. An image-derived region to assess blood activity can be used as a surrogate for blood sampling in quantification of hypoxia.
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Hipóxia/diagnóstico por imagem , Misonidazol/análogos & derivados , Neoplasias/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Progressão da Doença , Feminino , Coração/diagnóstico por imagem , Humanos , Hipóxia/diagnóstico , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Oxigênio/química , Tomografia por Emissão de Pósitrons/métodos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos , Distribuição Tecidual , Resultado do TratamentoRESUMO
Beta-defensins are cationic peptides produced by epithelial cells that have been proposed to be an important component of immune function at mucosal surfaces. Similarities between mammalian beta-defensins may permit the use of murine models to further define the role of these peptides in innate host defense. Murine beta-defensin-3 (mBD-3) is a peptide that exhibits homology at the gene level to human beta-defensin-2 (hBD-2), one of four beta-defensins identified in man. The purpose of this study was to determine the antimicrobial activity of mBD-3, the tissue distribution of mBD-3 expression, and the effect of gram-negative bacterial infection on mBD-3 expression. Based on the sequence deduced from mBD-3 cDNA, a 40-amino acid peptide was assembled using automated [n-(9-fluorenyl)methoxycarbonyl] solid-phase synthesis. The antimicrobial activity of synthetic mBD-3 was evaluated in microdilution broth assays using bacterial and fungal organisms. mBD-3 mRNA expression was assayed by polymerase chain reaction (PCR) using cDNA derived from a panel of tissues. Expression of mBD-3 was also evaluated in tissues obtained from mice 24 h after intraperitoneal infection with Escherichia coli using reverse transcriptase (RT)-PCR. Synthetic mBD-3 inhibited the growth of E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans at concentrations from 25 to 50 microg/mL. Constitutive expression of mBD-3 mRNA was not consistently found in any organ using RT-PCR. In an E. coli peritonitis model, expression of mBD-3 mRNA was upregulated only in the esophagus and tongue. We conclude that mBD-3 is an inducible peptide with limited tissue expression during E. coli peritonitis. Because it exhibits broad-spectrum antimicrobial activity, this peptide may serve as an innate defense against microbial invasion at specific mucosal surfaces in the mouse.
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beta-Defensinas/biossíntese , Sequência de Aminoácidos , Animais , Antibacterianos , Anti-Infecciosos/farmacologia , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/imunologia , Feminino , Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Sepse/genética , Sepse/imunologia , Staphylococcus aureus/efeitos dos fármacos , Distribuição Tecidual , beta-Defensinas/genética , beta-Defensinas/farmacologiaRESUMO
OBJECTIVE: To investigate the ability of statistical techniques to detect systematic changes in rowing technique during a rowing session and to discriminate between rowers of different abilities with and without back pain. DESIGN: Statistical techniques were applied to kinematic datasets of elite level rowers, in order to construct an empirical model of the rowing stroke. BACKGROUND: The size and complexity of datasets generated by biomechanical kinematics evaluations has led to opportunities for analysing pathology whilst introducing substantial challenges for statistical analysis. METHODS: Spinal motion and load output of 18 International and National standard competitive rowers were monitored during ergometer rowing sessions. International rower data were used to construct an empirical model of this activity. Linear stroke models were derived using principal components and a generalized cross-validation procedure. Performance characteristics of the identified models were calculated for all rowing groups. The stroke model was applied to distinguishing pattern variations within and between rowers. A multivariate logistic regression analysis was carried out to examine the relationship between stroke model parameters on the incidence of low back pain. RESULTS: 90% of the variability in the data was explained by the first three principal component variables. Stroke models with three basis functions were selected for each variable. The models performed well on the National rowers, providing validation of the models. A 2-variable model showed a significant difference between the rowing stroke characteristics of rowers with and without low back pain (P<0.01). CONCLUSIONS: A parsimonious collection of empirical models effectively describes motion and load characteristics of ergometer rowing. Patterns in rowing technique are found to be strongly associated with the incidence lower back pain. RELEVANCE: Empirical statistical models can be used to track changes in rowing technique, and discriminate between different rowing groups. This may impact rowing training, and rehabilitation.
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Modelos Estatísticos , Análise de Componente Principal , Coluna Vertebral/fisiologia , Esportes/fisiologia , Fenômenos Biomecânicos , Humanos , Dor Lombar/fisiopatologiaRESUMO
BACKGROUND: Our previous research investigated the ability of [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging results to predict outcome in patients with sarcoma. Tumor uptake of FDG before and after neoadjuvant chemotherapy was predictive of patient outcome. With this background, a prospective clinical study was designed to assess whether tumor FDG uptake levels in the middle of neoadjuvant chemotherapy added additional prognostic information to pre-therapy imaging data. METHODS: Sixty-five patients with either bone or soft-tissue sarcoma were treated with neoadjuvant-based chemotherapy according to the standard clinical practice for each tumor group. All patients had FDG PET studies before therapy, mid-therapy (after two cycles of chemotherapy), and before resection. Tumor FDG uptake (SUVmax, the maximum standardized uptake value) at each imaging time point, tumor type (bone or soft-tissue sarcoma), tumor size, and histopathologic grade were recorded for each patient. The time from the pre-therapy FDG PET study to events of local tumor recurrence, metastasis, or death were extracted from the clinical records for comparison with the imaging data. Univariate and multivariate analyses of the imaging and clinical data were performed. RESULTS: Univariate and multivariate data analyses showed that the difference (measured as the percentage reduction) between the pre-therapy and mid-therapy maximum tumor uptake values added prognostic value to patient outcome predictions independently of other patient variables. CONCLUSIONS: The utility of a tumor pre-therapy FDG PET scan as a biomarker for the outcome of patients with sarcoma was strengthened by a mid-therapy scan to evaluate the interim treatment response.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Sarcoma/diagnóstico por imagem , Sarcoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Análise de Variância , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Análise Multivariada , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Sarcoma/mortalidade , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/cirurgia , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: To support the adoption of guideline concordant care by primary care practices, the New York Diabetes Coalition (NYDC) promoted use of an electronic diabetes registry and developed an interactive educational module on using the registry and improving patient communication. The NYDC hypothesized that use of a registry with immediate feedback would achieve measurable and clinically meaningful improvement in the proportion of patients at goal for diabetes health metrics. RESEARCH DESIGN AND METHODS: In 2006-2007, the NYDC recruited 7 small to midsized primary care practices to implement the registry and to receive education and coaching on registry use, practice work flow, and patient engagement. The patient cohort included those with 2 or more visits with a diagnosis of diabetes within a 12-month period. Each patient's health measure status (at goal, above goal, not recorded) was assessed quarterly for hemoglobin A1C , low-density lipoprotein (LDL), and blood pressure (BP), and most recent A1C value was noted. A cohort analysis was performed using random effects regression models to assess the impact of the registry over time for each diabetes health metric. RESULTS: After controlling for variability between sites, with each subsequent quarter during the registry period patients were 1.4 times more likely to have A1C ≤ 9, almost twice (OR = 1.8) as likely to have LDL < 100, and 1.3 times more likely to have BP < 140/90. These improvements in compliance were statistically significant. Average A1C also improved over time, though this did not reach statistical significance. DISCUSSION: Utilizing a Web-based registry and interactive education, the project demonstrated improved patient outcomes, as well as the feasibility of collecting aggregate data from unrelated, independent practices.
Assuntos
Diabetes Mellitus/terapia , Educação de Pacientes como Assunto/métodos , Indicadores de Qualidade em Assistência à Saúde , Sistema de Registros , Estudos de Coortes , Coalizão em Cuidados de Saúde , Humanos , Internet , Cidade de Nova Iorque , Aceitação pelo Paciente de Cuidados de Saúde , Atenção Primária à Saúde/métodos , Sistema de Registros/estatística & dados numéricos , Fatores de TempoRESUMO
OBJECTIVE: Leiomyosarcoma, a malignant neoplasm of smooth muscle, accounts for 7% of the sarcomas. Patients with leiomyosarcoma tumors have an average survival of 5 years. These tumors, which are derived from mesenchymal tissues, are difficult to diagnose, and treatment options remain controversial. The relatively rare incidence of this soft tissue sarcoma subtype has limited the number of patients available for studies and research. This study examines whether the imaging characteristics of positron emission tomography (PET) with radiolabeled fluorodeoxyglucose (FDG) provide a reliable, noninvasive means to predict tumor behavior in patients with leiomyosarcomas. METHODS: [18F]-FDG-PET was performed on the tumors of participating patients before the neoadjuvant chemotherapy or resection, and a maximum tumor standard uptake value (SUVmax) was calculated. RESULTS: The SUVmax was correlated with tumor grade (P=0.001) and tumor size as greatest dimension (P=0.004). Analysis of these data indicated the potential effectiveness of FDG-PET imaging in predicting tumor grade. CONCLUSION: In leiomyosarcoma, the SUVmax from FDG-PET is a likely predictor of tumor behavior. The results of this study suggest that a large (by greatest dimension) intermediate grade tumor is expected to have the same predicted outcome as a high-grade tumor and should be treated in the same manner, as they share the same prognosis by definition of tumor grade. Improvements made in the clinical treatment of leiomyosarcomas by use of FDG-PET imaging data may lead to an increase in patient survival.