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Landmark Analysis (landmark + analysis)
Selected AbstractsA Landmark Analysis-Based Approach to Age and Sex Classification of the Skull of the Mediterranean Monk Seal (Monachus monachus) (Hermann, 1779)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2009C. Brombin Summary This work aimed at applying geometric morphometric analysis techniques to the skull of the Mediterranean monk seal (Monachus monachus, Hermann, 1779). Inferential analyses were performed using a non-parameteric permutation framework based on a series of skulls of different age classes belonging to individuals of both sexes. Our goal was to establish whether a statistical approach based on osteometric measurements and surface analysis of photographs of the left lateral plane of the skull may lead to a different and scientifically sound method of age and sex classification in this critically endangered marine mammal. Our data indicate that non-parametric combination methodology enables the researcher to give local assessment using a combination with domains. Developing geometric morphometric techniques in a non-parametric permutation framework could be useful in solving high dimensional and small sample size problems as well as classification problems, including zoological classification of specimens within a specific population. The Mediterranean monk seal is believed to be the world's rarest pinniped and one of the most endangered mammals of the world, with fewer than 600 individuals currently surviving. The use of shape analysis would allow new insights into the biological characteristics of the monk seal by simply extracting potentially new information on age and size from museal specimens. [source] Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: The randomized, double-blind, phase ii/iii systemic lupus erythematosus evaluation of rituximab trial,ARTHRITIS & RHEUMATISM, Issue 1 2010Joan T. Merrill Objective B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus (SLE), and rituximab induces depletion of B cells. The Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE. Methods Patients entered with ,1 British Isles Lupus Assessment Group (BILAG) A score or ,2 BILAG B scores despite background immunosuppressant therapy, which was continued during the trial. Prednisone was added and subsequently tapered. Patients were randomized at a ratio of 2:1 to receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. Results In the intent-to-treat analysis of 257 patients, background treatment was evenly distributed among azathioprine, mycophenolate mofetil, and methotrexate. Fifty-three percent of the patients had ,1 BILAG A score at entry, and 57% of the patients were categorized as being steroid dependent. No differences were observed between placebo and rituximab in the primary and secondary efficacy end points, including the BILAG-defined response, in terms of both area under the curve and landmark analyses. A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups. Safety and tolerability were similar in patients receiving placebo and those receiving rituximab. Conclusion The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse. No differences were noted between placebo and rituximab in the primary and secondary end points. Further evaluation of patient subsets, biomarkers, and exploratory outcome models may improve the design of future SLE clinical trials. [source] Competing Risks and Time-Dependent CovariatesBIOMETRICAL JOURNAL, Issue 1 2010Giuliana Cortese Abstract Time-dependent covariates are frequently encountered in regression analysis for event history data and competing risks. They are often essential predictors, which cannot be substituted by time-fixed covariates. This study briefly recalls the different types of time-dependent covariates, as classified by Kalbfleisch and Prentice [The Statistical Analysis of Failure Time Data, Wiley, New York, 2002] with the intent of clarifying their role and emphasizing the limitations in standard survival models and in the competing risks setting. If random (internal) time-dependent covariates are to be included in the modeling process, then it is still possible to estimate cause-specific hazards but prediction of the cumulative incidences and survival probabilities based on these is no longer feasible. This article aims at providing some possible strategies for dealing with these prediction problems. In a multi-state framework, a first approach uses internal covariates to define additional (intermediate) transient states in the competing risks model. Another approach is to apply the landmark analysis as described by van Houwelingen [Scandinavian Journal of Statistics 2007, 34, 70,85] in order to study cumulative incidences at different subintervals of the entire study period. The final strategy is to extend the competing risks model by considering all the possible combinations between internal covariate levels and cause-specific events as final states. In all of those proposals, it is possible to estimate the changes/differences of the cumulative risks associated with simple internal covariates. An illustrative example based on bone marrow transplant data is presented in order to compare the different methods. [source] Residual serum monoclonal protein predicts progression-free survival in patients with previously untreated multiple myelomaCANCER, Issue 3 2010Eric W. Schaefer MS Abstract BACKGROUND: Currently used treatment response criteria in multiple myeloma (MM) are based in part on serum monoclonal protein (M-protein) measurements. A drawback of these criteria is that response is determined solely by the best level of M-protein reduction, without considering the serial trend. The authors hypothesized that metrics incorporating the serial trend of M-protein would be better predictors of progression-free survival (PFS). METHODS: Fifty-five patients with measurable disease at baseline (M-protein ,1 g/dL) who received ,4 cycles of treatment from 2 clinical trials in previously untreated MM were included. Three metrics based on the percentage of M-protein remaining relative to baseline (residual M-protein) were considered: metrics based on the number of times residual M-protein fell within prespecified thresholds, metrics based on area under the residual M-protein curve, and metrics based on the average residual M-protein reduction between Cycles 1 and 4. The predictive value of these metrics was assessed in Cox models using landmark analysis. RESULTS: The average residual M-protein reduction was found to be significantly predictive of PFS (P = .02; hazard ratio, 0.37), in which a patient with a 10% lower average residual M-protein reduction from Cycle 1 to 4 was estimated to be at least 2.7× more likely to develop disease progression or die early. None of the other metrics was predictive of PFS. The concordance index for the average residual M-protein reduction was 0.63, compared with 0.56 for best response. CONCLUSIONS: The average residual M-protein reduction metric is promising and needs further validation. This exploratory analysis is the first step in the search for treatment-based trend metrics predictive of outcomes in MM. Cancer 2010. © 2009 American Cancer Society. [source] Reduced intensity conditioning prior to allogeneic stem cell transplantation for patients with acute myeloblastic leukemia as a first-line treatmentCANCER, Issue 9 2005Didier P. Blaise M.D. Abstract BACKGROUND Thirty-three patients (median age 52; range 26,60) with acute myeloblastic leukemia (AML) were included in a pilot study of allogeneic stem cell transplantation (Allo-SCT) following a reduced-intensity conditioning (RIC). METHODS Patients achieving first complete remission (CR1) were selected for their high-risk clinical and/or leukemic features. All patients received two courses of consolidation chemotherapy including one high-dose cytarabine course. Among them, 13 patients in addition received a high-dose melphalan course followed by autologous SCT. Then, all patients received an RIC Allo-SCT combining fludarabine, busulfan, and antithymocyte globulin. RESULTS All patients engrafted had cumulative incidences of Gluksberg System Grade 2 acute and chronic graft-versus-host-disease (GVHD) of 24 (9,39%) and 64 (48,80%), respectively. Three patients died from nonrelapse causes (NRD) (cumulative incidence: 9%, 95% confidence interval (CI): 0-19) and 6 relapsed (cumulative incidence: 18%, 95% CI: 5,31). With a median follow-up of 18 months (range 7,52) after Allo-SCT, 26 patients are alive, of whom 24 remained in CR1 for a 2-year overall survival and leukemia-free survival (LFS) probabilities of 79 (range 61,90%) and 76 (range 59,87%), respectively. In a ,landmark' analysis starting on Day 100, the occurrence of chronic GVHD was associated with a lower relapse rate (0% vs. 44%: P = 0.007) and improved outcome (LFS; 95% vs. 53%, P = 0.007; overall survival, 95% vs. 61%, P = 0.05). CONCLUSIONS We conclude that the sequential combination of intensive chemotherapy and allogeneic immunotherapy might offer relatively low NRD and leukemia relapse rates even in high-risk patients. Cancer 2005. © 2005 American Cancer Society. [source] | ||||||||||