891 resultados para Comparing Methotrexate


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This study investigated the psychometric properties of the Horizontal and Vertical Individualism and Collectivism Scale (HVIC) and the Auckland Individualism and Collectivism Scale (AICS). The sample consisted of 1,403 working individuals from Switzerland (N = 585) and from South Africa (N = 818). Principal component factor analyses indicated that a two-factor structure replicated well across the two countries for both scales. In addition, the HVIC four-factor structure replicated well across countries, whereas the responsibility dimension of individualism of the AICS replicated poorly. Confirmatory factor analyses provided satisfactory support to the original theoretical models for both the HVIC and the AICS. Equivalence measurement indices indicated that the cross-cultural replicability properties of both instruments are generally acceptable. However, canonical correlations and correlations between the HVIC and AICS dimensions confirm that these two instruments differ in their underlying meaning of the individualism and collectivism constructs, suggesting that these two instruments assess individualism and collectivism differently.

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BACKGROUND: Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. PURPOSE: To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. METHODS: From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. RESULTS: The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. LIMITATIONS: Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. CONCLUSIONS: BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.

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Background/Purpose: Patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) are critical in evaluating RA treatment effects on function and health-related quality of life (HR-QoL). Significant improvement in PROs has been reported in RA studies of biologic agents, including etanercept (ETN), but most studies have been conducted in patients with established disease. In addition to assessing treatment effects in early RA, there is interest in therapeutic strategies that allow dose reduction or withdrawal of biologic therapy (biologic-free) after induction of response. The PRIZE trial is an ongoing, 3-period study to evaluate the efficacy of combined ETN and methotrexate (MTX) therapy in patients with early, moderate-to-severe RA and to assess whether efficacy (remission) can be maintained with ETN dose reduction or biologic-free (Period 2) or drug-free (Period 3). Herein we report PROs associated with ETN 50 mg QW plus MTX (ETN50/MTX) therapy administered for 52 wks in Period 1 (induction) of the PRIZE trial. Methods: In Period 1, MTX- and biologic-naı‥ve patients with early, active RA (symptom onset 12 mo from enrollment; DAS28 _3.2) received open-label ETN50/MTX for 52 wks. The starting dose of MTX was 10 mg QW; at the discretion of the investigator, titration was permitted up to a maximum of 25 mg QW to achieve remission. Corticosteroid boosts were administered to patients not achieving low disease state at wks 13 and 26, unless contraindicated or not tolerated. PROs were assessed using the Health Assessment Questionnaire (HAQ) total score; Patient Acceptable Symptom State (PASS); EuroQol-5 Dimensions (EQ-5D) total index; Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue; Work Instability Scale for Rheumatoid Arthritis (RAWIS); and Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI:RA). Results: A total of 306 patients received treatment in Period 1 (mITT population); 222 (73%) patients completed the period. The majority of patients were female (70%), with a mean age of 50 y, mean DAS28 of 6.0 (median, 6.0), and duration of disease symptoms from onset of 6.5 months (median, 6.3 mo). Significant and clinically meaningful improvements in PROs, including in HAQ, EQ-5D, SF-36, and FACIT-Fatigue, were demonstrated with ETN50/MTX therapy from baseline to the final on therapy visit (Table; P_0.0001). Similar improvements were observed in all dimensions of RA-WIS and WPAI:RA (Table; P_0.0001). Conclusion: Combination therapy with ETN50/MTX for 52 wks in patients with _12 mo of symptomatic, active RA resulted in significant, clinically important improvements in measures of physical function, including normal HAQ (66.6% of patients), HR-QoL, fatigue, and work productivity. These outcomes are consistent with those reported in prior studies in patients with more established disease.

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Effect size indices are indispensable for carrying out meta-analyses and can also be seen as an alternative for making decisions about the effectiveness of a treatment in an individual applied study. The desirable features of the procedures for quantifying the magnitude of intervention effect include educational/clinical meaningfulness, calculus easiness, insensitivity to autocorrelation, low false alarm and low miss rates. Three effect size indices related to visual analysis are compared according to the aforementioned criteria. The comparison is made by means of data sets with known parameters: degree of serial dependence, presence or absence of general trend, changes in level and/or in slope. The percent of nonoverlapping data showed the highest discrimination between data sets with and without intervention effect. In cases when autocorrelation or trend is present, the percentage of data points exceeding the median may be a better option to quantify the effectiveness of a psychological treatment.

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BACKGROUND: Gastric banding still represents one of the most widely used bariatric procedures. It provides acceptable weight loss in many patients, but has frequent long-term complications. Because different types of bands may lead to different results, we designed a randomized study to compare the Lapband® with the SAGB®. We hereby report on the long-term results. METHODS: Between December 1998 and June 2002, 180 morbidly obese patients were randomized between Lapband® or SAGB®. Weight loss, long-term morbidity, and need for reoperation were evaluated. RESULTS: Long-term weight loss did not differ between the two bands. Patients who maintained their band had an acceptable long-term weight loss of between 50 and 60 % EBMIL. In both groups, about half the patients developed long-term complications, with about 50 % requiring major redo surgery. There was no difference in the overall rates of long-term complications or failures between the two groups, but patients who had a Lapband® were significantly more prone to develop band slippage/pouch dilatation (13.3 versus 0 %, p < 0,001). CONCLUSIONS: Although in the absence of complication, gastric banding leads to acceptable weight loss; the long-term complication and major reoperation rates are very high independently from the type of band used or on the operative technique. Gastric banding leads to relatively poor overall long-term results and therefore should not be considered the procedure of choice for the treatment of morbid obesity. Patients should be informed of the limited overall weight loss and the very high complication rates.

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Single-trial analysis of human electroencephalography (EEG) has been recently proposed for better understanding the contribution of individual subjects to a group-analysis effect as well as for investigating single-subject mechanisms. Independent Component Analysis (ICA) has been repeatedly applied to concatenated single-trial responses and at a single-subject level in order to extract those components that resemble activities of interest. More recently we have proposed a single-trial method based on topographic maps that determines which voltage configurations are reliably observed at the event-related potential (ERP) level taking advantage of repetitions across trials. Here, we investigated the correspondence between the maps obtained by ICA versus the topographies that we obtained by the single-trial clustering algorithm that best explained the variance of the ERP. To do this, we used exemplar data provided from the EEGLAB website that are based on a dataset from a visual target detection task. We show there to be robust correspondence both at the level of the activation time courses and at the level of voltage configurations of a subset of relevant maps. We additionally show the estimated inverse solution (based on low-resolution electromagnetic tomography) of two corresponding maps occurring at approximately 300 ms post-stimulus onset, as estimated by the two aforementioned approaches. The spatial distribution of the estimated sources significantly correlated and had in common a right parietal activation within Brodmann's Area (BA) 40. Despite their differences in terms of theoretical bases, the consistency between the results of these two approaches shows that their underlying assumptions are indeed compatible.

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This randomized controlled pilot study examined the effects of a silicone net dressing (Mepitel(®)) and a monofilament polyamide woven dressing (SurfaSoft(®)) on the rate of epithelialisation and epidermal maturation, pain, and ease of dressing removal on paediatric donor sites treated with epithelial cell suspension (ReCell(®)). Fifteen children (1-15 years) admitted for acute or reconstructive burns procedures in a tertiary referral hospital in Australia were randomly assigned to the experimental group, Mepitel(®) (n=8) and to the control group, SurfaSoft(®) (n=7). All donor sites were treated with ReCell(®) and covered with the assigned dressing. Measurements of rate of epithelialisation and epidermal maturation, pain, and ease of dressing removal were recorded every two days until the wound was healed. Results showed that there was no difference in the rate of epidermal maturation between the two groups. Less pain and force to remove the dressing was shown in the Mepitel(®) group when compared to SurfaSoft(®). The rate of epithelialisation was found to be an unreliable measure. Although additional research is required to support the results of this study, these results suggest that Mepitel's(®) pliable, self-adhesive and atraumatic properties may improve healing of ReCell(®) treated donor sites with less pain at dressing changes. This pilot study provides a strong base for further research in this area.

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BACKGROUND: The need for an integrated view of data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed biological association networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). METHODS: Seven cell lines representative of different types of cancer, including colon cancer (HT29 and Caco2), breast cancer (MCF-7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. Genes deregulated in common between the different cancer cell lines served to generate biological association networks using the Pathway Architect software. RESULTS: Dikkopf homolog-1 (DKK1) is a highly interconnected node in the network generated with genes in common between the two colon cancer cell lines, and functional validations of this target using small interfering RNAs (siRNAs) showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of genes differentially expressed in the two breast cancer cell lines. siRNA treatment against UGT1A also showed an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was overexpressed among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. CONCLUSIONS: Biological association networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using siRNA technology against these three genes showed chemosensitization toward MTX.

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Background: Methotrexate is a chemotherapeutic agent used to treat a variety of cancers. However, the occurrence of resistance limits its effectiveness. Cytochrome c in its reduced state is less capable of triggering the apoptotic cascade. Thus, we set up to study the relationship among redox state of cytochrome c, apoptosis and the development of resistance to methotrexate in MCF7 human breast cancer cells. Results: Cell incubation with cytochrome c-reducing agents, such as tetramethylphenylenediamine, ascorbate or reduced glutathione, decreased the mortality and apoptosis triggered by methotrexate. Conversely, depletion of glutathione increased the apoptotic action of methotrexate, showing an involvement of cytochrome c redox state in methotrexateinduced apoptosis. Methotrexate-resistant MCF7 cells showed increased levels of endogenous reduced glutathione and a higher capability to reduce exogenous cytochrome c. Using functional genomics we detected the overexpression of GSTM1 and GSTM4 in methotrexate-resistant MCF7 breast cancer cells, and determined that methotrexate was susceptible of glutathionylation by GSTs. The inhibition of these GSTM isoforms caused an increase in methotrexate cytotoxicity in sensitive and resistant cells. Conclusions: We conclude that overexpression of specific GSTMs, GSTM1 and GSTM4, together with increased endogenous reduced glutathione levels help to maintain a more reduced state of cytochrome c which, in turn, would decrease apoptosis, thus contributing to methotrexate resistance in human MCF7 breast cancer cells.

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PURPOSE: To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. PATIENTS AND METHODS: Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. RESULTS: Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). CONCLUSION: Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.

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OBJECTIVE: To compare interval breast cancer rates (ICR) between a biennial organized screening programme in Norway and annual opportunistic screening in North Carolina (NC) for different conceptualizations of interval cancer. SETTING: Two regions with different screening practices and performance. METHODS: 620,145 subsequent screens (1996-2002) performed in women aged 50-69 and 1280 interval cancers were analysed. Various definitions and quantification methods for interval cancers were compared. RESULTS: ICR for one year follow-up were lower in Norway compared with NC both when the rate was based on all screens (0.54 versus 1.29 per 1000 screens), negative final assessments (0.54 versus 1.29 per 1000 screens), and negative screening assessments (0.53 versus 1.28 per 1000 screens). The rate of ductal carcinoma in situ was significantly lower in Norway than in NC for cases diagnosed in both the first and second year after screening. The distributions of histopathological tumour size and lymph node involvement in invasive cases did not differ between the two regions for interval cancers diagnosed during the first year after screening. In contrast, in the second year after screening, tumour characteristics remained stable in Norway but became prognostically more favorable in NC. CONCLUSION: Even when applying a common set of definitions of interval cancer, the ICR was lower in Norway than in NC. Different definitions of interval cancer did not influence the ICR within Norway or NC. Organization of screening and screening performance might be major contributors to the differences in ICR between Norway and NC.

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Recently, several anonymization algorithms have appeared for privacy preservation on graphs. Some of them are based on random-ization techniques and on k-anonymity concepts. We can use both of them to obtain an anonymized graph with a given k-anonymity value. In this paper we compare algorithms based on both techniques in orderto obtain an anonymized graph with a desired k-anonymity value. We want to analyze the complexity of these methods to generate anonymized graphs and the quality of the resulting graphs.