1,114 research outputs found
E-2. Dietary and hormonal effects on growth performance and on plasma hormone and metabolite levels of broilers(Abstracts of the International Symposium on Recent Advances in Animal Science(IS-RAAS),Joint meeting of 2^<nd> IS-AS and 3^<rd> IS-IFS)
Assessment of the consistency and robustness of results from a multicenter trial of remission maintenance therapy for acute myeloid leukemia
<p>Abstract</p> <p>Background</p> <p>Data from a randomized multinational phase 3 trial of 320 adults with acute myeloid leukemia (AML) demonstrated that maintenance therapy with 3-week cycles of histamine dihydrochloride plus low-dose interleukin-2 (HDC/IL-2) for up to 18 months significantly improved leukemia-free survival (LFS) but lacked power to detect an overall survival (OS) difference.</p> <p>Purpose</p> <p>To assess the consistency of treatment benefit across patient subsets and the robustness of data with respect to trial centers and endpoints.</p> <p>Methods</p> <p>Forest plots were constructed with hazard ratios (HRs) of HDC/IL-2 treatment effects versus no treatment (control) for prospectively defined patient subsets. Inconsistency coefficients (I<sup>2</sup>) and interaction tests (X<sup>2</sup>) were used to detect any differences in benefit among subsets. Robustness of results to the elimination of individual study centers was performed using "leave-one-center-out" analyses. Associations between treatment effects on the endpoints were evaluated using weighted linear regression between HRs for LFS and OS estimated within countries.</p> <p>Results</p> <p>The benefit of HDC/IL-2 over controls was statistically consistent across all subsets defined by baseline prognostic variables. I<sup>2 </sup>and <it>P</it>-values of X<sup>2 </sup>ranged from 0.00 to 0.51 and 0.14 to 0.91, respectively. Treatment effects were statistically significant in 14 of 28 subsets analyzed. The "leave-one-center-out" analysis confirmed that no single center dominated (<it>P</it>-values ranged from 0.004 to 0.020 [mean 0.009]). The HRs representing the HDC/IL-2 effects on LFS and OS were strongly correlated at the country level (R<sup>2 </sup>= 0.84).</p> <p>Limitations</p> <p>Small sample sizes in some of the subsets analyzed.</p> <p>Conclusions</p> <p>These analyses confirm the consistency and robustness of the HDC/IL-2 effect as compared with no treatment. LFS may be an acceptable surrogate for OS in future AML trials. Analyses of consistency and robustness may aid interpretation of data from multicenter trials, especially in populations with rare diseases, when the size of randomized clinical trials is limited.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00003991">NCT00003991</a></p
Meta-analyses of randomized controlled trials show suboptimal validity of surrogate outcomes for overall survival in advanced colorectal cancer
Comparative StudyMeta-AnalysisReviewValidation StudiesThis is the final version of the article. Available from Elsevier via the DOI in this record.OBJECTIVES: To quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). STUDY DESIGN AND SETTING: We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form. Univariate and multivariate random-effects meta-analyses were used to estimate pooled summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and difference in medians were used to quantify the degree of difference in treatment effects on the surrogate end points and OS. Spearman Ï, surrogate threshold effect (STE), and R(2) were also estimated across predefined trial-level covariates. RESULTS: We included 101 RCTs. In univariate and multivariate meta-analyses, we found larger treatment effects for the surrogates than for OS. Compared with OS, treatment effects were on average 13% higher when HRs were measured and 3% to 45% higher when ORs were considered; differences in median PFS/TTP were higher than on OS by an average of 0.5 month. Spearman Ï ranged from 0.39 to 0.80, mean R(2) from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64 for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability across all strata. CONCLUSION: None of the end points in this study were found to achieve the level of evidence (ie, mean R(2)trial > 0.60) that has been set to select high or excellent correlation levels by common surrogate evaluation tools. Previous surrogacy relationships observed between PFS and TTP vs. OS in selected settings may not apply across other classes or lines of therapy
Niveaux hormonaux plasmatiques de poules albinos (sal-c) et non albinos (S)
Des poules albinos (mutation s al-c) et non-albinos (colorĂ©es) de mĂȘme origine ont Ă©tĂ© comparĂ©es pour des niveaux plasmatiques hormonaux, triiodothyronine (T3), thyroxine (T4), hormone de croissance (GH) et corticostĂ©rone, avant lâentrĂ©e en ponte puis aprĂšs 3 Ă 4 mois de ponte. Le rapport T3/T4 Ă©tait plus Ă©levĂ© chez les poules albinos que chez les non-albinos aux 2 Ăąges; cette diffĂ©rence sâapproche de la signification aprĂšs lâentrĂ©e en ponte. La variance intra-gĂ©notype de ce rapport est plus Ă©levĂ©e pour les poules s al-c que pour les non-albinos (P < 0,01). Dâautre part, le taux de lâhormone de croissance ne diffĂšre pas entre gĂ©notypes avant lâentrĂ©e en ponte, mais en pĂ©riode de ponte il est significativement plus Ă©levĂ© chez les poules s al. Il existe donc certaines diffĂ©rences dans lâĂ©quilibre hormonal des 2 gĂ©notypes. On peut espĂ©rer que ceci aide Ă lâinterprĂ©tation des effets trouvĂ©s associĂ©s au gĂšne albinos sur la production dâoeufs.Albino (s al-c) and non-albino (colored) hens from the same origin were compared for several plasmatic hormonal levels (triiodothyronine (T3), thyroxine (T4), growth hormone (GH), and corticosterone) before the onset of laying and after 3-4 months of production. The T3/T4 ratio was higher among albino than among non-albino females at the 2 ages; this difference approached significance after sexuaL maturity. The within-genotype variance of this ratio was higher for s al-c hens than for non-albino ones (P<0.01). On the other hand, the GH level did not differ between the 2 genotypes before the onset of laying, but during laying it was significantly higher for the s al-c females. There are therefore some differences in the general hormonal balance of the 2 genotypes. It is hoped that this may help in an interpretation of the effects on egg production associated with the albino gene
Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma
The RIZ (PRDM2) locus commonly undergoes loss of heterozygosity (LOH) and maps within the minimal deleted region on 1p36 in hepatocellular carcinoma (HCC). Although peptide-altering mutations of RIZ are rare in HCC, the RIZ1 product is commonly lost in HCC and has tumour suppressive activities. Here, we analysed RIZ gene mutations and LOH in HCC, breast cancer, familial melanoma, colon cancer, and stomach cancer. We found 7 polymorphisms but no mutations. By analysing the Pro704-deletion polymorphism, we detected LOH of RIZ in 31 of 79 (39%) informative HCC cases, 11 of 47 (23%) colon cancer cases, 8 of 43 (19%) breast cancer cases, 8 of 66 (12%) stomach cancer cases. Importantly, loss of the Pro704+allele was found in 74% of the 31 LOH positive HCC cases (P< 0.01), indicating a preferential loss and hence a stronger tumour suppressor role for this allele compared to the P704âallele. In addition, the Pro704+allele was found to be more common in Asians (0.61) than Caucasians (0.42) (P = 0.0000), suggesting an interesting link between gene polymorphisms and potential differences in tumour incidence between racial groups. © 2001 Cancer Research Campaign http://www.bjcancer.co
A literature review of the predictive validity of European dental school selection methods
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Non peer reviewedPostprin
An investigation of minimisation criteria
Minimisation can be used within treatment trials to ensure that prognostic factors are evenly distributed between treatment groups. The technique is relatively straightforward to apply but does require running tallies of patient recruitments to be made and some simple calculations to be performed prior to each allocation. As computing facilities have become more widely available, minimisation has become a more feasible option for many. Although the technique has increased in popularity, the mode of application is often poorly reported and the choice of input parameters not justified in any logical way
Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5
Background The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients and Methods Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m2) followed by 4 cycles of docetaxel (100 mg/m2). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria for a CE were met. Results A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. Conclusion The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations
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