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DESIGN AND ANALYSIS OF RANDOMIZED CLINICAL TRIALS REQUIRING PROLONGED OBSERVATION OF EACH PATIENT I. INTRODUCTION AND DESIGN

  • Peto R.;Pike M.C.;Armitage P.;Breslow N.E.;Cox D.R.;Howard S.V.;Mantel N.;Mcpherson K.;Peto J.;Smith P.G.
    • 대한예방의학회:학술대회논문집
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    • 1994.02b
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    • pp.206-233
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    • 1994
  • The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part!, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and would be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials, however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.

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Blood Pressure and the Risk of Death From Non-cardiovascular Diseases: A Population-based Cohort Study of Korean Adults

  • Choi, Jeoungbin;Jang, Jieun;An, Yoonsuk;Park, Sue K.
    • Journal of Preventive Medicine and Public Health
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    • v.51 no.6
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    • pp.298-309
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    • 2018
  • Objectives: The objective of this study was to assess the relationship between systolic and diastolic blood pressure (SBP, DBP) and the risk of death from specific causes other than cardiovascular diseases. Methods: We calculated the risk of specific death by SBP and DBP categories for 506 508 health examinees in 2002-2003 using hazard ratios (HRs) and 95% confidence intervals (CIs) in a Cox proportional hazards model. Results: Compared to normal levels (SBP <120 or DBP <90 mmHg), stage I systolic and diastolic hypertension (SBP 140-159, DBP 85-89 mmHg, respectively) were associated with an increased risk of death from diabetes mellitus, alcoholic liver disease, and renal failure (HR, 1.83; 95% CI, 1.51 to 2.22; HR, 1.24; 95% CI, 1.06 to 1.46; HR, 2.30; 95% CI, 1.64 to 3.21; HR, 1.67; 95% CI, 1.27 to 2.20; HR, 1.99; 95% CI, 1.41 to 2.81; HR, 1.31; 95% CI, 0.99 to 1.73, respectively), but a decreased risk of death from intestinal pneumonia (HR, 0.64; 95% CI, 0.42 to 0.98; HR, 0.59; 95% CI, 0.39 to 0.91). Only stage II systolic hypertension (SBP ${\geq}160mmHg$) was associated with an increased risk of death from pneumonia, liver cirrhosis, and intestinal ischemia (HR, 1.54; 95% CI, 1.19 to 1.98; HR, 1.46; 95% CI, 1.00 to 2.15; HR, 3.77; 95% CI, 1.24 to 11.40, respectively), and stage I and II diastolic hypertension (SBP 140-159 and ${\geq}160mmHg$) were associated with an increased risk of death from intestinal ischemia (HR, 3.07; 95% CI, 1.27 to 7.38; HR, 4.39; 95% CI, 1.62 to 11.88, respectively). Conclusions: An increase in blood pressure levels may alter the risk of death from certain causes other than cardiovascular diseases, a well-known outcome of hypertension, although the mechanism of these associations is not well documented.

Genetic Diversity of Hard Ticks (Acari: Ixodidae) in the South and East Regions of Kazakhstan and Northwestern China

  • Yang, Yicheng;Tong, Jin;Ruan, Hongyin;Yang, Meihua;Sang, Chunli;Liu, Gang;Hazihan, Wurelihazi;Xu, Bin;Hornok, Sandor;Rizabek, Kadyken;Gulzhan, Kulmanova;Liu, Zhiqiang;Wang, Yuanzhi
    • Parasites, Hosts and Diseases
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    • v.59 no.1
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    • pp.103-108
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    • 2021
  • To date, there is no report on the genetic diversity of ticks in these regions. A total of 370 representative ticks from the south and east regions of Kazakhstan (SERK) and Xinjiang Uygur Autonomous Region (XUAR) were selected for molecular comparison. A fragment of the mitochondrial cytochrome c oxidase subunit I (cox1) gene, ranging from 631 bp to 889 bp, was used to analyze genetic diversity among these ticks. Phylogenetic analyses indicated 7 tick species including Hyalomma asiaticum, Hyalomma detritum, Hyalomma anatolicum, Dermacentor marginatus, Rhipicephalus sanguineus, Rhipicephalus turanicus and Haemaphysalis erinacei from the SERK clustered together with conspecific ticks from the XUAR. The network diagram of haplotypes showed that i) Hy. asiaticum from Almaty and Kyzylorda Oblasts together with that from Yuli County of XUAR constituted haplogroup H-2, and the lineage from Chimkent City of South Kazakhstan was newly evolved; and ii) the R. turanicus ticks sampled in Israel, Almaty, South Kazakhstan, Usu City, Ulugqat and Baicheng Counties of XUAR were derivated from an old lineage in Alataw City of XUAR. These findings indicate that: i) Hy. asiaticum, R. turanicus and Ha. erinacei shared genetic similarities between the SERK and XUAR; and ii) Hy. marginatum and D. reticulatus show differences in their evolution.

The effect and therapeutic compliance of adjuvant therapy in patients with cholangiocarcinoma after R0 resection: a retrospective study

  • Han Taek Jeong;Joonkee Lee;Hyeong Ho Jo;Ho Gak Kim;Jimin Han
    • Journal of Yeungnam Medical Science
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    • v.40 no.1
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    • pp.65-77
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    • 2023
  • Background: This study aimed to compare clinical outcomes between surveillance and adjuvant therapy (AT) groups after R0 resection for cholangiocarcinoma (CCA). Methods: A total of 154 patients who underwent R0 resection for CCA at the Daegu Catholic University Medical Center between January 2010 and December 2019 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed. Results: The median follow-up duration was 899 days. There were 109 patients in the AT group and 45 patients in the surveillance group. The patients in the AT group were younger (67 years vs. 74 years, p<0.001) and included more males (64.2% vs. 46.7%, p=0.044). The proportion of patients with stage III CCA was larger in the AT group than in the surveillance group (13.8% vs. 2.2%, p=0.005). In addition, AT did not improve OS (5-year OS rate, 69.3% in the AT group vs. 64.2% in the surveillance group, p=0.806) or PFS (5-year PFS rate, 42.6% in the AT group vs. 48.9% in the surveillance group, p=0.113). In multivariate analysis using the Cox proportional hazards model, stage III CCA (hazard ratio [HR], 10.81; 95% confidence interval [CI], 2.92-40.00; p<0.001) was a significant predictor of OS. American Society of Anesthesiologists classification II (HR, 0.50; 95% CI, 0.31-0.81; p=0.005), and American Joint Committee on Cancer stages II (HR, 3.14; 95% CI, 1.25-7.89; p=0.015) and III (HR, 8.08; 95% CI, 2.80-23.32; p<0.001) were independent predictors of PFS. Conclusion: AT after R0 resection for CCA did not improve OS or PFS.

Clinical Significance of Detecting Lymphatic and Blood Vessel Invasion in Stage II Colon Cancer Using Markers D2-40 and CD34 in Combination

  • Lai, Jin-Huo;Zhou, Yong-Jian;Bin, Du;Qiangchen, Qiangchen;Wang, Shao-Yuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1363-1367
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    • 2014
  • This research was conducted to compare differences in colon cancer lymphatic vessel invasion (LVI) with D2-40 antibody labeling and regular HE staining, blood vessel invasion (BVI) with CD34 antibody labeling and HE staining and to assess the possibility of using D2-40-LVI/CD34-BVI in combination for predicting stage II colon cancer prognosis and guiding adjuvant chemotherapy.Anti-D2-40 and anti-CD34 antibodies were applied to tissue samples of 220 cases of stage II colon cancer to label lymphatic vessels and small blood vessels, respectively. LVI and BVI were assessed and multivariate COX regression analysis was performed for associations with colon cancer prognosis. Regular HE staining proved unable to differentiate lymphatic vessels from blood vessels, while D2-40 selectively labeled lymphatic endothelial cell cytosol and CD34 was widely expressed in large and small blood vessels of tumors as well as normal tissues. Compared to regular HE staining, D2-40-labeling for LVI and CD34-labeling for BVI significantly increased positive rate (22.3% vs 10.0% for LVI, and 19.1% vs 9.1% for BVI). Multivariate analysis indicated that TNM stage, pathology tissue type, post-surgery adjuvant chemotherapy, D2-40-LVI, and CD34-BVI were independent factors affecting whole group colon cancer prognosis, while HE staining-BVI, HE staining-LVI were not significantly related. When CD34-BVI/D2-40-LVI were used in combination for detection, the risk of death for patients with two or one positive results was 5.003 times that in the LVI(-)&BVI(-) group (95% CI 2.365 - 9.679). D2-40 antibody LVI labeling and CD34 antibody BVI labeling have higher specificity and accuracy than regular HE staining and can be used as molecular biological indicators for prognosis prediction and guidance of adjuvant chemotherapy for stage II colon cancer.

Atractylenoide II Isolated from Atractylodes macrocephala Inhibited Inflammatory Responses in Lipopolysaccharide-induced RAW264.7 Macrophages and BV2 Microglial Cells (백출에서 분리된 Atractylenolide II의 RAW264.7 대식세포와 BV2 미세아교세포에서의 항염증 효과)

  • Jin, Hong-Guang;Kim, Kwan-Woo;Li, Jing;Im, Hyeri;Lee, Dae Young;Yoon, Dahye;Jeong, Jin Tae;Kim, Geum-Soog;Oh, Hyuncheol;An, Ren-Bo;Kim, Youn-Chul
    • Korean Journal of Pharmacognosy
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    • v.51 no.4
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    • pp.244-254
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    • 2020
  • Atractylodes macrocephala is a perennial herb and is a member of the Compositae family. This plant is known to contain various bioactive constituents indicating anti-inflammatory, neuroprotective, anti-oxidant, immunological enhancement, and gastroprotective effects. In this investigation, we isolated four compounds with similar chemical structures from A. macrocephala, and evaluated their anti-inflammatory effects. Among the four compounds, compound 2(atractylenolide II) showed the second-best inhibitory effect on the lipopolysaccharide(LPS)-induced production of nitric oxide in RAW264.7 macrophages and BV2 microglial cells. Compound 2 also inhibited the LPS-induced the production of prostaglandin E2(PGE2), and the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 proteins in both cells. In addition, compound 2 suppressed the production of pro-inflammatory cytokines including interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. These inhibitory effects were contributed by inactivation of nuclear factor kappa B(NF-κB) and mitogen-activated protein kinases(MAPKs) pathways by treatment with compound 2. This compound did not induce the expression of heme oxygenase(HO)-1 protein indicating that the anti-inflammatory effect of compound 2 was independent with HO-1 protein. Taken together, these results suggested that atractylenolide II can be a candidate material to treat inflammatory diseases.

Inhibitory Effect of Kamisopunghwalhyeol-tang (Jiaweishufenghuoxie-tang) on Inflammatory Cytokine Production and $NF-{\kappa}B$ and AP-1 Activation in Cultured Humau Fibroblast-like Synoviocytes (가미속풍활형탕이 human fibroblast-like synoviocytes 내 염증 유발 cytokine과 전사인자에 미치는 영향)

  • 양동원;오민석;김동희
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.84-95
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    • 2003
  • Objective : This study was carried out to investigate the effects of Kamisopunghwalhyeol-tang (Jiaweishujenghuoxie-tang; Kami-SPHHT) on the immunity responses of the Synoviocytes isolated from the patients on rheumatoid arthritis. Methods : Cells were stimulated by $Interleukin-1{\beta}$ and Tumor Necrosis $Factor-{\alpha}$ in the presence or absence of Kami-SPHHT, and then induced cytokine mRNA levels were determined by RT-PCR and real-time quantitative RT-PCR. Results : Levels of $IL-1{\beta},{\;}IL-6,{\;}TNF-{\alpha}$, COX-2, and NOS II mRNA expressions significantly decreased in Kami-SPHHT treated cells compared to non-treated control cells. Also, DNA-binding activity of $NF-{\kappa}B$ and AP-l decreased in Kami- SPHHT treated hFLSs. Conclusion : These results suggest that Kami-SPHHT may be involved in anti-inflammatory reactions by inducing cytokine gene expression in synoviocytes, and further in vivo examination on its efficacy can provide potential application for the treatment of rheumatoid arthritis.

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Factors Influencing on Pressure Ulcer Incidence among Older Patients with Hip Fracture in a Hospital (고관절 골절로 입원한 노인 환자의 욕창 발생 위험요인)

  • Lee, Sun Jin;Jeong, Jae Shim;Lim, Kyung-Choon;Park, Eun Young;Kim, Hye Youn
    • Journal of Korean Biological Nursing Science
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    • v.21 no.1
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    • pp.54-61
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    • 2019
  • Purpose: This study aimed to identify the incidence and risks for pressure ulcer among older patients with hip fracture. Methods: The subject were 215 older patients suffering from hip fracture who were admitted for surgical operation from January 1, 2012 to April 30, 2016 in a university-affiliated hospital. The incidence of pressure ulcer was collected retrospectively through medical record review and the risk factors were analyzed using Cox's proportional hazard model. Results: Out of the total, 32 patients (14.9%) developed pressure ulcer with the average occurrence period being 4.72 (${\pm}3.81$) days. Stage II pressure ulcer was the most common at 72.0%. Risk factors included ambulation status before injury (p= .039), spinal anesthesia (p= .029), and stay at intensive care unit after operation (p= .009). Conclusion: Despite pressure ulcer prevention efforts, the incidence remained relatively high. Considering the identified risk factors, more efforts is needed for early detection and prevention of pressure ulcers in such patients.

Anti-inflammatory effect of barley leaf ethanol extract in LPS-stimulated RAW264.7 macrophage (LPS로 자극한 RAW264.7 대식세포에서 보리순 에탄올 추출물의 항염증 효과)

  • Kim, Mee-Kyung;Kim, Dae-Yong
    • Food Science and Preservation
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    • v.22 no.5
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    • pp.735-743
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    • 2015
  • This study investigated the anti-inflammatory activity of barley leaf extract in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and hairless mice. Pre-treatment with barley leaf extract significantly inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-II (COX-II) in a dose-dependent manner in LPS-stimulated RAW264.7 cells. Barley leaf extract also significantly inhibited the secretion of inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) were strongly suppressed by barley leaf extract in LPS-stimulated cells. In hairless mice, barley extract significantly decreased the pathological phenotypes of contact dermatitis, such as erythema, edema, and scabs. These results indicate that barley leaf extract has an anti-inflammatory effect and therefore a possible role in the treatment of inflammatory diseases or in functional cosmetics.

The Role of Radiation Therapy in Adenocarcinoma of Endometrium (자궁 체부암의 방사선 치료)

  • Yun Hyong Geun;Ha Sung Whan;kang Soon Beom;Lee Hyo Pyo
    • Radiation Oncology Journal
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    • v.8 no.1
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    • pp.95-102
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    • 1990
  • From May, 1979 to October,1987, 38 patients with endometrial carcinoma were treated with radiotherapy at Seoul National University Hospital. Of these, 32 patients received radiotherapy Postoperatively, one received radiotherapy preoperatively, and five received radiotherapy only. Relative frequencies of obesity, nulliparity, late menopause, diabetes mellitus, and hypertension were all higher than those reported in normal women in Korea, and those of obesity, diabetes mellitus, and nulliparity were significantly high. The overall actuarial five-year survival rate was $75.6\%$. The overall actuarial five year survival rates of stage I (22 cases), stage II (six cases), and stage III (10 cases) were $90.0\%,\;80.0\%,\;and\;44.4\%$, respectively, and were significantly different from each other. Among various factors, stage only proved to be prognostic by multivariate analysis. There were two local failures, three local failures combined with distant metastasis, and three distant metastasis. Stages I and II could be adequately controlled by local modalities without severe complications, stage III endometrial carcinoma might need more aggressive treatment for better survival.

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