Application of One-phase End-point Change System in Two-phase Titration to Amine Drug Analysis

1981 ◽  
Vol 70 (11) ◽  
pp. 1286-1288 ◽  
Author(s):  
Masahiro Tsubouchi ◽  
Hiromi Mitsushio ◽  
Nakamichi Yamasaki ◽  
Kiyoshi Matsuoka
Keyword(s):  
Drug Analysis ◽  
Two Phase ◽  
Point Change ◽  
End Point ◽  
Amine Drug ◽  
Change System

scholarly journals Sampling Strategies to Evaluate the Prognostic Value of a New Biomarker on a Time-to-Event End-Point

2020 ◽  
Author(s):  
Francesca Graziano ◽  
Maria Grazia Valsecchi ◽  
Paola Rebora
Keyword(s):  
Survival Data ◽  
Prognostic Value ◽  
Cox Model ◽  
Lymphoblastic Leukemia ◽  
Case Control ◽  
Time To Event ◽  
Two Phase ◽  
End Point ◽  
Number Of Patients ◽  
Nested Case Control

Abstract Background: The availability of large epidemiological or clinical data storing biological samples allow to study the prognostic value of novel biomarkers, but efficient designs are needed to select a subsample on which to measure them for parsimony and economical reasons. Two-phase stratified sampling is a flexible approach to perform such sub-sampling, but literature on stratification variables to be used in the sampling and power evaluation is lacking especially for survival data.Methods: We compared the performance of different sampling designs to assess the prognostic value of a new biomarker on a time-to-event end-point, applying a two-phase Cox model weighted by the inverse of the empirical inclusion probability. Results: Our simulation results suggest that case-control stratified (or post stratified) by a surrogate variable of the marker can yield higher performances than simple random, probability proportional to size and case-control sampling. In the presence of high censoring rate, results showed an advantage of nested case-control and counter-matching designs in term of design effect, but their constrain in using a fixed ratio between cases and controls might be disadvantageous. On real data on childhood acute lymphoblastic leukemia, we also found that optimal sampling using pilot data is greatly efficient.Conclusions: Our study suggests that, in our sample, case-control stratified by surrogate and nested case-control yield estimates and power comparable to estimates obtained in the full cohort while strongly decreasing the number of patients required. We recommend to plan the sample size and using sampling designs for exploration of novel biomarker in clinical cohort data.

scholarly journals Imatinib Mesylate in Advanced Dermatofibrosarcoma Protuberans: Pooled Analysis of Two Phase II Clinical Trials

2010 ◽  
Vol 28 (10) ◽  
pp. 1772-1779 ◽  
Author(s):  
Piotr Rutkowski ◽  
Martine Van Glabbeke ◽  
Cathryn J. Rankin ◽  
Wlodzimierz Ruka ◽  
Brian P. Rubin ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Dermatofibrosarcoma Protuberans ◽  
Phase Ii Trials ◽  
Two Phase ◽  
End Point ◽  
Best Response

Purpose Dermatofibrosarcoma protuberans (DFSP) is a dermal sarcoma typically carrying a translocation between chromosomes 17 and 22 that generates functional platelet-derived growth factor B (PDGFB). Patients and Methods Two distinct phase II trials of imatinib (400 to 800 mg daily) in patients with locally advanced or metastatic DFSP were conducted and closed prematurely, one in Europe (European Organisation for Research and Treatment of Cancer [EORTC]) with 14-week progression-free rate as the primary end point and the other in North America (Southwest Oncology Group [SWOG]) with confirmed objective response rate as the primary end point. In the EORTC trial, confirmation of PDGFB rearrangement was required, and surgery was undertaken after 14 weeks if feasible. The SWOG study confirmed t(17;22) after enrollment. Results Sixteen and eight patients were enrolled onto the EORTC and SWOG trials, respectively. Tumor size ranged from 1.2 to 49 cm. DFSP was located on head/neck, trunk, and limb in seven, 11, and six patients, respectively, and was classic, pigmented, and fibrosarcomatous DFSP in 13, one, and nine patients, respectively. Metastases were present in seven patients (lung involvement was present six patients). Eleven patients (4%) had partial response as best response, and four patients had progressive disease as best response. Median time to progression (TTP) was 1.7 years. Imatinib was stopped in 11 patients because of progression, one patient because of toxicity, and two patients after complete resection of disease. Median overall survival (OS) time has not been reached; 1-year OS rate was 87.5%. Conclusion Imatinib is active in DFSP harboring t(17;22) including fibrosarcomatous DFSP, with objective response rate approaching 50%. Response rates and TTP did not differ between patients taking 400 mg daily versus 400 mg twice a day.

scholarly journals Olanzapine for the treatment of borderline personality disorder: variable dose 12-week randomised double-blind placebo-controlled study

2008 ◽  
Vol 193 (6) ◽  
pp. 485-492 ◽  
Author(s):  
S. Charles Schulz ◽  
Mary C. Zanarini ◽  
Anthony Bateman ◽  
Martin Bohus ◽  
Holland C. Detke ◽  
...  
Keyword(s):  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Rating Scale ◽  
Borderline Personality ◽  
Controlled Study ◽  
Double Blind ◽  
Point Change ◽  
End Point ◽  
Primary Efficacy Measure ◽  
Efficacy Measure

BackgroundDespite the prevalence and clinical significance of borderline personality disorder, its treatment remains understudied.AimsTo evaluate treatment with variably dosed olanzapine in individuals with borderline personality disorder.MethodIn this 12-week randomised, double-blind trial, individuals received olanzapine (2.5–20 mg/day; n=155) or placebo (n=159) (trial registry: NCT00091650). The primary efficacy measure was baseline to end-point change on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN–BPD) using last-observation-carried-forward methodology.ResultsBoth olanzapine and placebo groups showed significant improvements but did not differ in magnitude at end-point (76.56 v. 76.25, P=0.661). Response rates (50% reduction in ZAN–BPD) were 64.7% with olanzapine and 53.5% with placebo (P=0.062); however, time to response was significantly shorter for olanzapine (P=0.022). Weight gain was significantly greater (2.86 v. 70.35 kg, P50.001), with higher incidence of treatment-emergent abnormal high levels of prolactin for the olanzapine group.ConclusionsIndividuals treated with olanzapine and placebo showed significant but not statistically different improvements on overall symptoms of borderline personality disorder. The types of adverse events observed with olanzapine treatment appeared similar to those observed previously in adult populations.

scholarly journals Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study

2014 ◽  
Vol 74 (6) ◽  
pp. 979-984 ◽  
Author(s):  
P Emery ◽  
J E Gottenberg ◽  
A Rubbert-Roth ◽  
P Sarzi-Puttini ◽  
D Choquette ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Real Life ◽  
Clinical Effectiveness ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Point Change ◽  
Life Study ◽  
End Point ◽  
Comparative Effectiveness Study ◽  
The Difference

ObjectivesTo compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi.MethodsSWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)–erythrocyte sedimentation rate (ESR) over 6 months.Results604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3–ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3–ESR at 6 months was significantly greater in rituximab than TNFi patients: −1.5 (0.2) vs −1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (−1.7 vs −1.3; p=0.017) but not intolerance (−0.7 vs −0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3–ESR with rituximab than with TNFi (−1.6 (0.3) vs −1.2 (0.3); p=0.011), particularly those switching because of inefficacy (−1.9 (0.3) vs −1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups.ConclusionsThese real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy.

Effect of Shock Loading on the Microstructure of Uniloy 326

1974 ◽  
Vol 32 ◽  
pp. 504-505
Author(s):  
K. P. Staudhammer ◽  
L. E. Murr
Keyword(s):  
Grain Size ◽  
Shock Loading ◽  
Current Investigation ◽  
Two Phase ◽  
05 C ◽  
Shock Deformation ◽  
Heat Treated

The effect of shock loading on a variety of steels has been reviewed recently by Leslie. It is generally observed that significant changes in microstructure and microhardness are produced by explosive shock deformation. While the effect of shock loading on austenitic, ferritic, martensitic, and pearlitic structures has been investigated, there have been no systematic studies of the shock-loading of microduplex structures.In the current investigation, the shock-loading response of millrolled and heat-treated Uniloy 326 (thickness 60 mil) having a residual grain size of 1 to 2μ before shock loading was studied. Uniloy 326 is a two phase (microduplex) alloy consisting of 30% austenite (γ) in a ferrite (α) matrix; with the composition.3% Ti, 1% Mn, .6% Si,.05% C, 6% Ni, 26% Cr, balance Fe.

Exsolution and inversion in pigeonite from the Whin Sill, Northern England

1978 ◽  
Vol 36 (1) ◽  
pp. 474-475
Author(s):  
P.P.K. Smith
Keyword(s):  
High Temperature ◽  
Low Temperature ◽  
Homogeneous Nucleation ◽  
Silicate Mineral ◽  
Antiphase Boundaries ◽  
Two Phase ◽  
Primitive Form ◽  
The Core ◽  
Nucleation Mechanisms ◽  
And Inversion

Grains of pigeonite, a calcium-poor silicate mineral of the pyroxene group, from the Whin Sill dolerite have been ion-thinned and examined by TEM. The pigeonite is strongly zoned chemically from the composition Wo8En64FS28 in the core to Wo13En34FS53 at the rim. Two phase transformations have occurred during the cooling of this pigeonite:- exsolution of augite, a more calcic pyroxene, and inversion of the pigeonite from the high- temperature C face-centred form to the low-temperature primitive form, with the formation of antiphase boundaries (APB's). Different sequences of these exsolution and inversion reactions, together with different nucleation mechanisms of the augite, have created three distinct microstructures depending on the position in the grain.In the core of the grains small platelets of augite about 0.02μm thick have farmed parallel to the (001) plane (Fig. 1). These are thought to have exsolved by homogeneous nucleation. Subsequently the inversion of the pigeonite has led to the creation of APB's.

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