234 resultados para results
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Background Sunburn and sun bed use increase risk of malignant melanoma, the incidence of which continues to rise.
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Background: When cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim. Methods: COIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1·162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448. Findings: 1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15·8 months (IQR 9·4—26·1) in arm A and 14·4 months (8·0—24·7) in arm C (hazard ratio [HR] 1·084, 80% CI 1·008—1·165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19·6 months (13·0—28·1) in arm A and 18·0 months (12·1—29·3) in arm C (HR 1·087, 0·986—1·198). The upper limits of CIs for HRs in both analyses were greater than the predefined non-inferiority boundary. Preplanned subgroup analyses in the per-protocol population showed that a raised baseline platelet count, defined as 400 000 per µL or higher (271 [28%] of 978 patients), was associated with poor survival with intermittent chemotherapy: the HR for comparison of arm C and arm A in patients with a normal platelet count was 0·96 (95% CI 0·80—1·15, p=0·66), versus 1·54 (1·17—2·03, p=0·0018) in patients with a raised platelet count (p=0·0027 for interaction). In the per-protocol population, more patients on continuous than on intermittent treatment had grade 3 or worse haematological toxic effects (72 [15%] vs 60 [12%]), whereas nausea and vomiting were more common on intermittent treatment (11 [2%] vs 43 [8%]). Grade 3 or worse peripheral neuropathy (126 [27%] vs 25 [5%]) and hand—foot syndrome (21 [4%] vs 15 [3%]) were more frequent on continuous than on intermittent treatment. Interpretation: Although this trial did not show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival, chemotherapy-free intervals remain a treatment option for some patients with advanced colorectal cancer, offering reduced time on chemotherapy, reduced cumulative toxic effects, and improved quality of life. Subgroup analyses suggest that patients with normal baseline platelet counts could gain the benefits of intermittent chemotherapy without detriment in survival, whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy and should not receive a treatment break.
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Background: Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005.
Subjects and Methods: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests.
Results: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P <. 001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P <. 001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P <. 001).
Conclusion: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective. © The Author 2011. Published by Oxford University Press. All rights reserved.
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We have conducted a sensitive 3mm observation toward the shocked region, Lynds 1157 B1, which is an interaction spot between a molecular outflow and its ambient gas. We have successfully detected the CH3CHO, HCOOCH3, and HCOOH lines, as well as the CH2DOH line. The abundances of these molecules relative to CH3OH are found to be lower than those in the low-mass star-forming core, IRAS 16293-2422. Since these molecules are thought to evaporate from grain mantles, the observational results mean that complex molecules are less abundant in grain mantles residing in the ambient cloud surrounding a prestellar/protostellar core. Instead, efficient formation of the complex organic species and deuterated species should take place in a prestellar/protostellar core. The present result verifies the importance of an unbiased line survey of this source.
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1 Activation of human platelets by thrombin is mediated by the proteolytic cleavage of two G-protein coupled protease-activated receptors, PAR-1 and PAR-4. However, thrombin also binds specifically to the platelet surface glycoprotein GPIb. It has been claimed that thrombin can induce aggregation of platelets via a novel GPIb-mediated pathway, which is independent of PAR activation and fibrinogen binding to alpha(IIb)beta(3) integrin, but dependent upon polymerizing fibrin and the generation of intracellular signals.
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BACKGROUND: In 2005, the European Commission recommended that all member states should establish or strengthen surveillance systems for monitoring the use of antimicrobial agents. There is no evidence in the literature of any surveillance studies having been specifically conducted in nursing homes (NHs) in Northern Ireland (NI).
OBJECTIVE: The aim of this study was to determine the prevalence of antimicrobial prescribing and its relationship with certain factors (e.g. indwelling urinary catheterization, urinary incontinence, disorientation, etc.) in NH residents in NI.
METHODS: This project was carried out in NI as part of a wider European study under the protocols of the European Surveillance of Antimicrobial Consumption group. Two point-prevalence surveys (PPSs) were conducted in 30 NHs in April and November 2009. Data were obtained from nursing notes, medication administration records and staff in relation to antimicrobial prescribing, facility and resident characteristics and were analysed descriptively.
RESULTS: The point prevalence of antimicrobial prescribing was 13.2% in April 2009 and 10.7% in November 2009, with a 10-fold difference existing between the NHs with the highest and lowest antimicrobial prescribing prevalence during both PPSs. The same NH had the highest rate of antimicrobial prescribing during both April (30.6%) and November (26.0%). The group of antimicrobials most commonly prescribed was the penicillins (April 28.6%, November 27.5%) whilst the most prevalent individual antimicrobial prescribed was trimethoprim (April 21.3%, November 24.3%). The majority of antimicrobials were prescribed for the purpose of preventing urinary tract infections (UTIs) in both April (37.8%) and in November (46.7%), with 5% of all participating residents being prescribed an antimicrobial for this reason. Some (20%) antimicrobials were prescribed at inappropriate doses, particularly those which were used for the purpose of preventing UTIs. Indwelling urinary catheterization and wounds were significant risk factors for antimicrobial use in April [odds ratio {OR} (95% CI) 2.0 (1.1, 3.5) and 1.8 (1.1, 3.0), respectively] but not in November 2009 [OR (95% CI) 1.6 (0.8, 3.2) and 1.2 (0.7, 2.2), respectively]. Other resident factors, e.g. disorientation, immobility and incontinence, were not associated with antimicrobial use. Furthermore, none of the NH characteristics investigated (e.g. number of beds, hospitalization episodes, number of general practitioners, etc.) were found to be associated with antimicrobial use in either April or November 2009.
CONCLUSIONS: This study has identified a high overall rate of antimicrobial use in NHs in NI, with variability evident both within and between homes. More research is needed to understand which factors influence antimicrobial use and to determine the appropriateness of antimicrobial prescribing in this population in general and more specifically in the management of recurrent UTIs.