• Title/Summary/Keyword: Endpoints

Search Result 247, Processing Time 0.027 seconds

Meta-analysis of Six Randomized Control Trials of Chemotherapy Plus Anti-HER Monoclonal Antibody for Advanced Gastric and Gastroesophageal Cancer

  • Luo, Huai-Qing;Han, Li;Jiang, Yan
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.13
    • /
    • pp.5343-5348
    • /
    • 2014
  • Background: A meta-analysis was performed to examine the benefit/risk ratio for the addition of anti- HER MoAbs to chemotherapy in patients with advanced gastric and gastroesophageal cancer from six randomized phase II/III trials. Materials and Methods: We searched relative trials from Pubmed, EMBASE, Cochrane library databases, China National Knowledge Infrastructure databases, Google Scholar and the NIH ClinicalTrials. Primary outcomes were overall response rate (ORR), progression-free survival (PFS), overall survival (OS). Secondary outcomes were toxicities. All analyses were performed using STATA 12.0. Results: This meta-analysis included six randomized controlled trials (RCTs) with 2, 297 patients and we demonstrated that the anti-HER MoAbs arm did have a positive effect on ORR in the anti-HER MoAbs arm (OR 1.28, 95% CI 1.00-1.64, p=0.01). There was an increasing benefit regarding OS (HR 0.74, 95% CI 0.60-0.88, p<0.05) and PFS (HR 0.72, 95% CI 0.60-0.84, p<0.05) in the anti-HER2 subgroup, but a reduction of OS (HR 1.11, 95% CI 0.87-1.36, p<0.05) and PFS (HR 1.13, 95% CI 0.98 -1.28, P<0.05) in anti-EGFR subgroup. Some grade 3-4 toxicity had a significantly higher incidence in the anti-HER MoAbs arm. There was no significant publication bias for all endpoints. Conclusions: The addition of trstuzumab MoAb to chemotherapy for gastric and gastroesophageal cancer significantly improved outcome of OS and PFS endpoints, while other MoAbs led to no improvement in results. Some adverse events were increased in anti-HER MoAbs arm compared with the control.

KRAS Mutation as a Biomarker for Survival in Patients with Non-Small Cell Lung Cancer, A Meta-Analysis of 12 Randomized Trials

  • Ying, Min;Zhu, Xiao-Xia;Zhao, Yang;Li, Dian-He;Chen, Long-Hua
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.10
    • /
    • pp.4439-4445
    • /
    • 2015
  • Background: Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion. Materials and Methods: A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors. Results: Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643). Conclusions: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab.

Development of a Data Reduction Algorithm for Optical Wide Field Patrol (OWL) II: Improving Measurement of Lengths of Detected Streaks

  • Park, Sun-Youp;Choi, Jin;Roh, Dong-Goo;Park, Maru;Jo, Jung Hyun;Yim, Hong-Suh;Park, Young-Sik;Bae, Young-Ho;Park, Jang-Hyun;Moon, Hong-Kyu;Choi, Young-Jun;Cho, Sungki;Choi, Eun-Jung
    • Journal of Astronomy and Space Sciences
    • /
    • v.33 no.3
    • /
    • pp.221-227
    • /
    • 2016
  • As described in the previous paper (Park et al. 2013), the detector subsystem of optical wide-field patrol (OWL) provides many observational data points of a single artificial satellite or space debris in the form of small streaks, using a chopper system and a time tagger. The position and the corresponding time data are matched assuming that the length of a streak on the CCD frame is proportional to the time duration of the exposure during which the chopper blades do not obscure the CCD window. In the previous study, however, the length was measured using the diagonal of the rectangle of the image area containing the streak; the results were quite ambiguous and inaccurate, allowing possible matching error of positions and time data. Furthermore, because only one (position, time) data point is created from one streak, the efficiency of the observation decreases. To define the length of a streak correctly, it is important to locate the endpoints of a streak. In this paper, a method using a differential convolution mask pattern is tested. This method can be used to obtain the positions where the pixel values are changed sharply. These endpoints can be regarded as directly detected positional data, and the number of data points is doubled by this result.

Analysis of Risk Factors for Conversion from Off-Pump to On-Pump Coronary Artery Bypass Graft

  • Lim, Junghyeon;Lee, Won Yong;Ra, Yong Joon;Jeong, Jae Han;Ko, Ho Hyun
    • Journal of Chest Surgery
    • /
    • v.50 no.1
    • /
    • pp.14-21
    • /
    • 2017
  • Background: Off-pump coronary artery bypass (OPCAB) is performed worldwide, but significant risks are associated with conversion to on-pump surgery. Therefore, we evaluated the composite outcomes between an OPCAB group and a conversion group. Methods: From January 2008 to December 2012, 100 consecutive patients underwent OPCAB at Hallym University Sacred Heart Hospital, of whom 84 underwent OPCAB without adverse events (OPCAB group), and 16 were converted to on-pump surgery (conversion group). Early morbidity, early and long-term mortality, and major adverse cardiac and cerebrovascular events (MACCEs) were the primary and long-term composite endpoints. Results: The mean follow-up period was $55{\pm}26months$, with 93% of the patients completing follow-up. The composite outcomes in the OPCAB and conversion groups were as follows: early morbidity, 2.3% versus 12.5%; early mortality, 4.7% versus 0%; long-term mortality, 14.3% versus 25.0%; and MACCEs, 14.3% versus 18.8%, respectively. No composite endpoints showed statistically significant differences. Preoperative acute myocardial infarction (AMI) was identified as an independent risk factor for conversion (p=0.025). Conclusion: The conversion group showed no statistically significant differences in early mortality and morbidity, MACCEs, or long-term mortality compared with the OPCAB group. The preoperative diagnosis of AMI was associated with an increased number of conversions to on-pump surgery.

MODULATION OF TOXICITY AND CARCINOGENESIS BY CALORIC RESTRICTION

  • Allaben, William T.;Chou, Ming W.;Pegram, Rex A.;Leakey, Julian;Feuers, Ritchie J.;Duffy, Peter H.;Turturro, Angelo;Hart, Ronald W.
    • Toxicological Research
    • /
    • v.6 no.2
    • /
    • pp.167-182
    • /
    • 1990
  • Dietary restriction (caloric restriction) is the only intervention which has been reliably shown to extend the maximum life span of warm-blooded animals and delay the many phenomena associated with aging. It is also one of the most effective modulators of toxicity, especially cancer endpoints. In spite of the known modulator effects of caloric restriction, the biological mechanisms responsible for these effects had not been in vestigated until recently. The National Center for Toxicological Research (NCTR), in a collaborative effort with the National Institute of Aging (NIA), initiated a project whereby nine (9) combinations of rodent species/strains and diets were fed both restricted and ad libitum. The NIA's initiative was to identify biomarkers of aging whereas NCTR's initiative was to identify the biological effects associated with the profound effects caloric restriction has in protecting against both spontaneous (age-related) and chemically-induced toxic endpoints. Independent of sex or species, caloric restriction has similar effects on body temperature, oxygen consumption and $CO_2$production. Caloric restriction also decreased lipid glycolysis and metabolism in rats and mice, which suggest decreased production of metabolites which could lead to fatty acid epoxide formation. The age-associated loss of ciradian regulation of intermediate enzymes is also significantly reduced. Moreover, caloric restriction reduced the age-associated feminization of sexually dimorphic liver isozymes, increased several glucocorticoid responsive isozymes, elevated glucagon/insulin ratios, produced less microsomal superoxide and enhanced the capacity for utilzing detoxicating metabolic pathways. Calorically restricted rats have less than half the number of aflatoxin ($AFB_1$)-DNA adducts than ad libitum animals and urinary excretion of $AFB_1$ was increased significantly. Finally, DNA repair mechanisms are enhanced and oncogene expression is decreased in calorically restricted animals.

  • PDF

Biomarkers and Surrogate Endpoints for Development of New Drug on Pulmonary Disease (폐질환 치료제의 효율적인 신약개발을 위한 생체표지자 및 대리결과 변수)

  • Seo, Jeong-Won;Lee, Byung-Yo;Chae, Jung-Woo;Son, Chu-Young;Kang, Won-Ku;Chae, Han-Jung;Kwon, Kwang-Il
    • YAKHAK HOEJI
    • /
    • v.54 no.2
    • /
    • pp.75-90
    • /
    • 2010
  • Biomarkers are likely to be important in the study of various pulmonary diseases for many reasons. Research efforts in developing biomarkers and surrogate endpoints of lung diseases have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in new drug development and advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Though the area of pulmonology has received much attention in the past decades, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review critically summarized several biomarker researches such as Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study with objectives of identifying the parameters that predict disease progression of COPD, as well as biomarkers that may serve as surrogate end-points.

Association Between the Frailty Index and Clinical Outcomes after Coronary Artery Bypass Grafting

  • Kim, Chan Hyeong;Kang, Yoonjin;Kim, Ji Seong;Sohn, Suk Ho;Hwang, Ho Young
    • Journal of Chest Surgery
    • /
    • v.55 no.3
    • /
    • pp.189-196
    • /
    • 2022
  • Background: This study investigated the predictive value of the frailty index calculated using laboratory data and vital signs (FI-L) in patients who underwent coronary artery bypass grafting (CABG). Methods: This study included 508 patients (age 67.3±9.7 years, male 78.0%) who underwent CABG between 2018 and 2021. The FI-L, which estimates patients' frailty based on laboratory data and vital signs, was calculated as the ratio of variables outside the normal range for 32 preoperative parameters. The primary endpoints were operative and medium-term all-cause mortality. The secondary endpoints were early postoperative complications and major adverse cardiac and cerebrovascular events (MACCEs). Results: The mean FI-L was 20.9%±10.9%. The early mortality rate was 1.6% (n=8). Postoperative complications were atrial fibrillation (n=148, 29.1%), respiratory complications (n=38, 7.5%), and acute kidney injury (n=15, 3.0%). The 1- and 3-year survival rates were 96.0% and 88.7%, and the 1- and 3-year cumulative incidence rates of MACCEs were 4.87% and 8.98%. In multivariable analyses, the FI-L showed statistically significant associations with medium-term all-cause mortality (hazard ratio [HR], 1.042; 95% confidence interval [CI], 1.010-1.076), MACCEs (subdistribution HR, 1.054; 95% CI, 1.030-1.078), atrial fibrillation (odds ratio [OR], 1.02; 95% CI, 1.002-1.039), acute kidney injury (OR, 1.06; 95% CI, 1.014-1.108), and re-operation for bleeding (OR, 1.09; 95% CI, 1.032-1.152). The minimal p-value approach showed that 32% was the best cutoff for the FI-L as a predictor of all-cause mortality post-CABG. Conclusion: The FI-L was a significant prognostic factor related to all-cause mortality and postoperative complications in patients who underwent CABG.

MEAN-VALUE PROPERTY AND CHARACTERIZATIONS OF SOME ELEMENTARY FUNCTIONS

  • Matkowski, Janusz
    • Bulletin of the Korean Mathematical Society
    • /
    • v.50 no.1
    • /
    • pp.263-273
    • /
    • 2013
  • A mean-value result, saying that the difference quotient of a differentiable function in a real interval is a mean value of its derivatives at the endpoints of the interval, leads to the functional equation $$\frac{f(x)-F(y)}{x-y}=M(g(x),\;G(y)),\;x{\neq}y$$, where M is a given mean and $f$, F, $g$, G are the unknown functions. Solving this equation for the arithmetic, geometric and harmonic means, we obtain, respectively, characterizations of square polynomials, homographic and square-root functions. A new criterion of the monotonicity of a real function is presented.

Understanding of Clinical Trials and Application to the Real Practice (임상시험의 단계별 이해 및 실제)

  • Choi, SungKu
    • Korean Journal of Biological Psychiatry
    • /
    • v.19 no.4
    • /
    • pp.153-158
    • /
    • 2012
  • Understanding of a clinical trial is essential in developing clinical guideline and adopting evidence based practice. In designing and executing clinical trials, following ethical requirements should be considered : social value, scientific validity, fair subject selection, informed consent, favorable risk-benefit ratio, institutional review board, and respect for human subjects. According to the stage of drug development, purpose of trials, accumulated scientific data, clinical trials for drug development are classified as phase 1, 2, 3, and 4. Phases of clinical trials can be overlapped and the judgment of entering into the next phase should be considered highly strategically. In reading, evaluating and interpreting clinical trial reports, various skills and challenges exist. Patient sample composition, trial duration, selection of endpoints, responders and non-responders, placebo effect, patient recruitment, and extrapolation to the real world are the examples of those challenges. Treatment success will come from the well balanced approach of evidence based decision making and consideration of specific single case.

Development of multiple channel EPD controller (다중 채널 EPD제어기의 개발)

  • 최순혁;차상엽;이종민;우광방
    • 제어로봇시스템학회:학술대회논문집
    • /
    • 1997.10a
    • /
    • pp.1500-1503
    • /
    • 1997
  • In this paper a multiple channel EPD controller is developed which enables us to detect endpoints simultaneously in the plasma etching process operated in multiple etching chambers and its performance characteristic are investigated. for the accurate detectiion of endpoint the developed EDP controller was able to implement endpoint detectiions by integrating the existing EPD controllers with the techiques of artificial intellignet, to enhance its performance. The performance of the developed EPD controller was carried out by repeated experiments of endpoint detection in the acrual production line of semiconductor manufacturing. It's utility for endpoint detectiion was accurately evaluated in various etching process. The control capability of multiple etching chambers enhances its application compared with the existing one, and also increases the user utility os that the efficiency of operation was improved.

  • PDF