• The Korean Journal of Applied Statistics
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• v.15 no.2
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• pp.323-336
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• 2002

In this paper we consider the modified continual reassessment method in which a cohort consists of three patients. Simulation has been a main research tool in the investigation of CRM. In this paper we propose complete enumeration as an alternative of simulation. Using new method we show that the expected toxicity rate at the MTD converges to the target toxicity rate well as the sample size increases.

• Journal of Gastric Cancer
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• v.21 no.4
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• pp.418-425
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• 2021

Purpose: We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients. Materials and Methods: Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m²/day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m² on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m², and the dose escalation was set in units of 20 mg/m² up to 80 mg/m². Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia. Results: Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m². Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination. Conclusions: The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m², when combined with a systemic SOX regimen.

• BMB Reports
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• v.36 no.1
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• pp.110-119
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• 2003

The acetylation state of histone is reversibly regulated by histone acetyltransferase (HAT) and deacetylase (HDAC). An imbalance of this reaction leads to an aberrant behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, these key enzymes in the gene expression were cloned. They revealed a broad use of this modification, not only in histone, but also other proteins that involved transcription, nuclear transport, and cytoskeleton. These results suggest that HAT/HDAC takes charge of multiple-functions in the cell, not just the gene expression. HDAC is especially known to play an important role in carcinogenesis. The enzyme has been considered a target molecule for cancer therapy. The inhibition of HDAC activity by a specific inhibitor induces growth arrest, differentiation, and apoptosis of transformed or several cancer cells. Some of these inhibitors are in a clinical trial at phase I or phase II. The discovery and development of specific HDAC inhibitors are helpful for cancer therapy, and decipher the molecular mode of action for HDAC.

• Journal of Dental Rehabilitation and Applied Science
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• v.28 no.1
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• pp.15-25
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• 2012

The relationship between occlusion and periodontal health has been extensively studied. However, reports on the effects of passive eruption using occlusal reduction has not been sufficient. The purpose of the present randomized clinical trial was to assess the influence of passive eruption using occlusal reduction on the clinical periodontal parameters consisting of attachment level, pocket depth, tooth mobility, width of keratinized gingiva and osseous defect. The study was performed on 40 teeth of 16 subjects who have been treated for the moderate periodontitis at the Department of Periodontology, Pusan National University Hospital. At the baseline examination, after hygienic-phase and after 6 month from passive eruption using occlusal reduction, clinical parameters were monitored and radiographs were taken. The 20 teeth in the test group received passive eruption using occlusal reduction while the 20 control teeth did not receive any occlusal reduction. The results were as follows; 1) Degree of inflammation of periodontium was improved by initial therapy 2) Teeth received passive eruption using occlusal reduction demonstrated significantly greater reduction in pocket depth, tooth mobility and amount of bone loss, and increase in the width of keratinized gingiva, but no significant changes in the attachment level compared to the control teeth 3) There was significantly greater reduction in pocket depth, mobility, amount of bone loss and attachment level in the test teeth after initial hygienic phase when compared with baseline data. Taken together, these results suggest that the passive eruption using occlusal reduction would be helpful to improve periodontal health.

• Sleep Medicine and Psychophysiology
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• v.6 no.1
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• pp.46-51
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• 1999

Objectives: Patients with premenstrual dysphoric disorder(or PMDD) have impairments of the social, occupational or academic function due to psychological or somatic symptoms, which have the characteristic pattern of symptom exacerbation in the week before menses begin and remission shortly after the onset of menses. In the chronobiological view, many researchers have assumed that the etiology of PMDD is the advanced circadian rhythm. It has been suggested that light has a therapeutic effect on PMDD, because evening light results in phase delay of circadian rhythm through the biochemical changes including melatonin. Methods: The authors investigated the therapeutic effect of light therapy on four patients with prospectively diagnosed PMDD by DSM-IV criteria using clinical psychiatric interview, Premenstrual Assessment Form(PAF) and Daily Rating Form(or DRF). In the evening(6:30pm-8:00pm), the 2,500 lux light administered for seven consecutive days during the symptomatic late luteal phase of menstrual cycle. Beck Depression Inventory(or BDI), Hamilton Rating Scale for Depression(or HAM-D), Spielberg State Anxiety Inventory(or SA), and DRF were evaluated before and after seven days of light therapy. Results: Premenstrual symptoms of PMDD could be effectively treated with the evening bright light therapy, especially in PMDD patients with atypical symptoms. In addition, the light therapy seemed to more effective on the psychologic symptoms than the somatic symptoms of PMDD. There was no significant side-effect of light therapy, except the transient and mild eye-strain in one case. Conclusions: In spite of the results of limited data from our clinical trial, the authors suggest that the potential use of light therapy as an alternative to the pharmacological management of patients with PMDD.

• Journal of mucopolysaccharidosis and rare diseases
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• v.3 no.2
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• pp.41-43
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• 2017

Prader-Willi syndrome (PWS) is a genetic disorder that is considered, especially on child, to cause poor feeding, hypotonia, failure to thrive, developmental delay and hypogonadism which is known to affect between 1 in 10,000 and 30,000 people. The children with PWS are viewed as affected by growth hormone (GH) insufficiency, although the exact mechanisms of GH deficiency are not fully understood. However, the benefits of GH treatment in children with PWS are well established. Myers, et al. (2006), Grugni, et al. (2016) indicated its positive effects on linear growth, body composition, motor function, respiratory function and psychomotor development. Despite of its effectiveness and advantages had been well known and proven in many other studies, there is only one recombinant GH product that is approved for PWS in Korea, $Genotropin^{(R)}$, till now. A phase III clinical study of GH treatment with $Eutropin^{TM}$, in 34 Korean PWS children is in progress, which is expected to have comparable effects and safety profile with the active control by assessing auxological changes such as height standard deviation score, body composition changes such as lean body mass and percent body fat, motor and cognitive development using Bayley scale, and safety profiles.

• Journal of Gastric Cancer
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• v.17 no.2
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• Women's Health Nursing
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• v.7 no.1
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• pp.67-79
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• 2001

This study was designed to verify the effect of Doula-type-delivery nursing care on plasma $\beta$-endorphin, serum cortisol, related to delivery stress during labor, and postpartum anxiety of primipara by a quasi experiment(nonequivalent control group pretest-posttest design), from December, 1999 to August, 2000. The subjects of this experiment consisted of sixty eight primipara, with single gestation, full term, uncomplicated pregnancies, thirty three for the experimental group and thirty five for the control group. Their mean age was 26.1 years for the experimental group and 25.5 years for the control group. Their mean gestation period was 39.7 weeks for the experimental group and 40.1 weeks for the control group. As treatment, Doula-type-delivery nursing care was given for the experimental group. Data assessed plasma $\beta$-endorphin, serum cortisol during labor, and anxiety during postpartum. Plasma $\beta$-endorphin, serum cortisol were measured in the latent phase before treatment(pre-test) and the transition phase after treatment(posttest). Also, anxiety was measured in the latent phase before treatment(pre-test) and 24 hours postpartum after treatment(posttest). Data was analyzed by t-test, $x^2$-test, Repeated measures ANOVA with SAS Program. The results of this study were as follows; 1. Plasma $\beta$-endorphin was significantly elevated in the experimental group who were cared for with Doula-type-delivery nursing care during labor(P=.0463). 2. No significant group effects were found, but significant time effects were found for serum cortisol. 3. The postpartum anxiety of the experimental group was significantly lower than the control group(P=.0110). In conclusion, these findings indicate that Doula-type-delivery nursing care during labor could be effective in increasing maternal plasma $\beta$-endorphin and decreasing postpartum anxiety. Doula-type-delivery nursing care during labor could be applied as an effective nursing treatment for primipara.

• The Journal of KAIRB
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• v.2 no.1
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• pp.23-31
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• 2020

Purpose: To obtain opinions from Korean Institutional Review Board (IRB) members' self-evaluation on ability to conduct fairness review of clinical trial protocol with presence of conflict of interest and from investigators and IRB members on financial conflict of interest through surveying. Methods: IRB members and researchers in 9 different hospitals were asked to answer survey questions via email. Results: Responders were 115 personnel (IRB Chair/vice 18, medical member 30, non-medical member 28, and researcher 39) from 9 centers. Compared to IRB medical members, IRB chair/vice respondents scored higher with statistically significance on 10 point scale (8.44±1.381 vs. 7.30±1.685, p=0.005) when asked to self-evaluate fairness reviewing a protocol proposed by an investigator from the same department and a protocol from the company that supports the scientific committee of responders. When reviewing a protocol proposed by a hospital director, non-medical members scored statistically significantly higher than medical-members (7.47±1.76 vs. 8.07±2.70, p=0.034). When asked about the limitation of labor fee for principal investigator on phase 3 Human clinical trials of the Investigational new drug, while the responses range was wide, 60% answered that labor cost of principal investigator should be less than 30% of total budget for clinical trials with a budget of 100 million won. 51.3% answered that there is no need to disclose the labor cost of the principal investigator in the consent form. Since every investigator can be influenced unconsciously by conflict of interest, the answer that 'responder agrees that there is need for management' was the most chosen answer (IRB member 61.8%, investigator 64.1%, multiple answers allowed). Conclusion: Considering scores on questions of fairness by IRB members were between 7.23-8.56 on scale of 0 to 10 point when IRB members were asked about reviewing a clinical trial protocol, it cannot be said with absolute certainty that there is no issue regarding fairness in the review process. Therefore, there should be more ways to safeguard fairness for these issues. There is a need that the disclosure amount of honorarium from sponsor should be lower than 100 million Korean won. Considering the results of the survey in which respondents expressed their thoughts, it is likely that more education on the concept of conflict of interest is needed.

• Radiation Oncology Journal
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• v.35 no.1
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• pp.32-38
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• 2017

Purpose: Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. Materials and Methods: Forty-two patients aged ${\geq}65$ years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. Results: The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. Conclusion: In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.