• Communications for Statistical Applications and Methods
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• v.25 no.4
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• pp.341-354
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• 2018

The one of the principles described in ICH E9 is that only results obtained from pre-specified statistical methods in a protocol are regarded as confirmatory evidence. However, in multi-regional clinical trials, even when results obtained from pre-specified statistical methods in protocol are significant, it does not guarantee that the test treatment is approved by regional regulatory agencies. In other words, there is no so-called global approval, and each regional regulatory agency makes its own decision in the face of the same set of data from a multi-regional clinical trial. Under this situation, there are two natural methods a regional regulatory agency can use to estimate the treatment effect in a particular region. The first method is to use the overall treatment estimate, which is to extrapolate the overall result to the region of interest. The second method is to use regional treatment estimate. If the treatment effect is completely identical across all regions, it is obvious that the overall treatment estimator is more efficient than the regional treatment estimator. However, it is not possible to confirm statistically that the treatment effect is completely identical in all regions. Furthermore, some magnitude of regional differences within the range of clinical relevance may naturally exist for various reasons due to, for instance, intrinsic and extrinsic factors. Nevertheless, if the magnitude of regional differences is relatively small, a conventional method to estimate the treatment effect in the region of interest is to extrapolate the overall result to that region. The purpose of this paper is to investigate the effects produced by this type of extrapolation via estimations, followed by hypothesis testing of the treatment effect in the region of interest. This paper is written from the viewpoint of regional regulatory agencies.

• Korean Journal of Oriental Medicine
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• v.13 no.2 s.20
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• pp.127-133
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• 2007

Objectives : This study were aimed to estimate the needs for clinical research educational program development focused on oriental medicine. Methods : Department Medical Research of Korea Institute of Oriental Medicine surveyed 204 certified subjects in total by using web-based questionnaires through e-mail from Jan. 17th to Jan. 31th, 2007. Reply from 62 on-line correspondents were collected and statistically analyzed. Results : The number of clinical trial involving oriental medicine continues to increase. According to the survey, many Issues were raised as problems such as difficulty of recruitment, lack of fund and lack of stepped program. Emphasized issues were clinical research methodologies, development of protocols and case report form (CRF), and Regulations including Institutional Review Boards (IRBs) in these three consecutive education training program. Conclusion : The results of this study may contribute to the development of an educational program for oriental medicine, a program that should be taken into consideration for developing practical items, such as, problem-based learnings which reflects participants' actual needs in their works. Also this report be used for future strategy plans and execution of training program for oriental medical clinical trial.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.5
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• pp.672-682
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• 2017

Objective: This study was conducted to investigate the effects of probiotic, prebiotic and synbiotic with and without feed restriction on broilers performance, blood parameters, carcass characteristics, and feed cost of production from 1 to 56 days of age. Methods: Two hundred and forty unsexed one day-old chicks of Arbor Acres breed were used. Two trials, I and II, were conducted, with 120 birds in both. Each trial was divided into 4 equal groups. The birds in trial I were fed ad libitum throughout the experiment, while the chicks in trial II were fed ad libitum during the first week of age, then subjected to 5 hours/d of feed restriction from the beginning of the second week up to the end of the experiment. In both trials, the birds in group 1 were fed on a control diet while the other groups were given the same control diet supplemented either with a probiotic in group 2, prebiotic in group 3, or synbiotic in group 4. Results: It was found that chicks fed diets supplemented with probiotic, prebiotic and synbiotic (with and without feed restriction) exhibited higher body weight and feed efficiency than chicks fed the control diets. The feed additives in both trials did not affect hemoglobin, serum total protein, albumin, globulin, glucose, and total cholesterol, except the packed cell volume which was increased in the additive treatments with restriction at the end of the experiment. Moreover, the dietary treatments did not influence the carcass yield. However, the relative weights of liver, gizzard and proventriculus, small intestine and bursa of fabricius were found to be increased. The additives decreased the visible fat in the carcass, with more decreasing effect in the additive groups with restriction. The lowest feed cost per kg of weight gain was observed in the birds fed diets supplemented with synbiotic, probiotic and prebiotic. Feed restriction improved the feed conversion ratio, economic return, but decreased the feed intake, serum total cholesterol and visible fat in comparison with non-restricted groups. Conclusion: The biological feed additives could be routinely added to broiler diets, especially when a feed restriction program is followed. Finally, it can be recommended to restrict feed, and add probiotic or synbiotic to increase weight, improve feed conversion rate and reduce feed cost of production.

• Restorative Dentistry and Endodontics
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• v.47 no.4
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• pp.40.1-40.18
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• 2022

Objectives: This study aimed to investigate the influence of different obturation techniques compared to cold lateral compaction on the success rate of primary non-surgical endodontic treatments. Materials and Methods: Systematic searches were performed for studies published up to May 17^th, 2022 in MEDLINE/PubMed, Cochrane Library, Web of Science, Scopus, EMBASE, and Grey Literature Reports. Randomized clinical trials and nonrandomized (nonrandomized clinical trials, prospective or retrospective) studies that evaluated the success rate of primary non-surgical endodontic treatments obturated with the cold lateral compaction (control) and other obturation techniques were included. The revised Cochrane risk of bias tools for randomized trials (RoB 2) and nonrandomized studies of interventions (ROBINS-I) were used to evaluate the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to evaluate the certainty of evidence. Results: Eleven studies (4 randomized clinical trials (RCTs), 4 prospective, and 3 retrospectives) were included. Two RCTs were classified as having some concerns risk of bias and 2 as a low risk of bias. Two nonrandomized studies were classified as having a critical risk of bias and 5 as having a moderate risk of bias. The GRADE analysis demonstrated a very low to moderate certainty of evidence. Conclusions: This systematic review generally evidenced no differences in the success rate of primary non-surgical endodontic treatments when the cold lateral compaction technique and other obturation techniques are performed. Further well-designed studies are still necessary.

• Clinical Endoscopy
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• v.57 no.3
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• pp.283-292
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• 2024

We developed three e-learning systems for endoscopists to acquire the necessary skills to improve the diagnosis of early gastric cancer (EGC) and demonstrated their usefulness using randomized controlled trials. The subjects of the three e-learning systems were "detection", "characterization", and "preoperative assessment". The contents of each e-learning system included "technique", "knowledge", and "obtaining experience". All e-learning systems proved useful for endoscopists to learn how to diagnose EGC. Lecture videos describing "the technique" and "the knowledge" can be beneficial. In addition, repeating 100 self-study cases allows learners to gain "experience" and improve their diagnostic skills further. Web-based e-learning systems have more advantages than other teaching methods because the number of participants is unlimited. Histopathological diagnosis is the gold standard for the diagnosis of gastric cancer. Therefore, we developed a comprehensive diagnostic algorithm to standardize the histopathological diagnosis of gastric cancer. Once we have successfully shown that this algorithm is helpful for the accurate histopathological diagnosis of cancer, we will complete a series of e-learning systems designed to assess EGC accurately.

• Journal of Gastric Cancer
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• v.23 no.1
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• pp.182-193
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• 2023

Presently, surgery is the only treatment approach for gastric cancer and improving the prognosis of locally advanced gastric cancer is one of the key factors in promoting gastric cancer survival benefit. The MAGIC study was the first to demonstrate the efficacy of neoadjuvant chemotherapy (NAC) in European countries. In recent years, several clinical trials have provided evidence for the use of NAC in Asian patients with locally advanced gastric cancer. However, clinical practice guidelines vary between Asian and non-Asian populations. Optimal NAC regimens, proper target populations, and predictors of NAC outcomes in Asian patients are still under investigation. Herein, we summarized the current progress in the administration of NAC in Asian patients with gastric cancer.

• IMMUNE NETWORK
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• v.20 no.6
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• pp.47.1-47.13
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• 2020

Tetracyclines, which have long been used as broad-spectrum antibiotics, also exhibit a variety of nonantibiotic activities including anti-inflammatory and immunomodulatory properties. Tetracyclines bind to the 30S ribosome of the bacteria and inhibit protein synthesis. Unlike antimicrobial activity, the primary molecular target for the nonantibiotic activity of tetracycline remains to be clarified. Nonetheless, the therapeutic efficacies of tetracyclines, particularly minocycline and doxycycline, have been demonstrated in various animal models of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and asthma. In this study, we summarized the anti-inflammatory and immunomodulatory activities of tetracyclines, focusing on the mechanisms underlying these activities. In addition, we highlighted the on-going or completed clinical trials with reported outcomes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2619-2627
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• 2015

There are several studies that relate oxidative damage as possible mechanism for many cancers. Many studies have also shown that anti-oxidants like selenium and vitamin E decrease the risk for prostate cancer. The main objective of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) study was to look for the benefits of selenium and vitamin E supplementation on prostate cancer. The study had a large sample size, stringent experimental conditions, very long duration, standardized laboratories for biochemical analyses and other factors that contribute to high external validity. The SELECT study failed to show any significant risk reduction for prostate cancers ascribable to selenium and vitamin E supplementations. Because of these conflicting results, many researchers argue about the methods used, supplementations administered (selenium and vitamin E) and indicators used for assessing levels of supplementations. We reviewed many epidemiological studies, clinical trials, and pre-clinical studies. With corroborative evidences we justify that SELECT study has a sound methodology and rationale. In lieu of the contrary results of the select study, researchers should focus on the probable mechanisms for these contrary findings and continue their search for newer and effective agents for prevention of prostate cancer.

• Journal of Pharmacopuncture
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• v.27 no.3
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• pp.177-189
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• 2024

Objectives: Cupping therapy is a widely used complementary medicine for the treatment of migraine headaches globally. However, conflicting evidence exists on its effectiveness. To evaluate the safety and efficacy of cupping therapy in treating migraine headache disorder. Methods: Seven databases were systematically searched: PubMed/MEDLINE, Clinicaltrials.gov, Cochrane CENTRAL, ScienceDirect, ProQuest, SinoMed, and the National Science and Technology Library. The primary endpoints are the treatment success and the pain intensity reduction. The secondary endpoints were adverse events (AEs) risk and improvement in quality of life (QoL), which was based on the Migraine Disability Scale (MIDAS). Subgroup analyses were performed based on the cupping techniques (wet and dry cupping) and adjunctive complementary treatments (i.e. acupuncture and/or collateral pricking). Results: Eighteen trials out of 348 records were included, pooling 1,446 participants (n = 797 received cupping therapy). Treatment success was significantly higher among those with cupping therapy (risk ratio [RR] [95% CI] = 1.83 [1.52-2.21]); with significant improvement observed only with wet cupping (RR [95% CI] = 1.88 [1.53-2.30]). The adjunctive complementary therapy did not achieve a greater amplitude of treatment success compared to cupping therapy alone. Furthermore, cupping therapy showed significant pain reduction compared to baseline (standardized mean difference [SMD] [95% CI] = 0.55 [0.39-0.70]) and achieved fewer risks of AEs (RR [95% CI] = 1.88 [1.53-2.30]). However, cupping did not improve the overall QoL (MIDAS SMD [95% CI] = -0.79 [-3.55-1.98]). Conclusion: Cupping therapy was an effective complementary modality to treat migraine headaches. However, it did not demonstrate improvement in QoL (PROSPERO: CRD42024514509).

• IMMUNE NETWORK
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• v.22 no.1
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• pp.2.1-2.22
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• 2022

Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.