• Title/Summary/Keyword: clinical response

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Prediction of the human in vivo antiplatelet effect of S- and R-indobufen using population pharmacodynamic modeling and simulation based on in vitro platelet aggregation test

  • Noh, Yook-Hwan;Han, Sungpil;Choe, Sangmin;Jung, Jin-Ah;Jung, Jin-Ah;Hwang, Ae-Kyung;Lim, Hyeong-Seok
    • Translational and Clinical Pharmacology
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    • v.26 no.4
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    • pp.160-165
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    • 2018
  • Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.

A study of detector size effect using Monte Carlo simulation

  • Park, Kwang-Yl;Yi, Byong-Yong;Vahc, Young W.
    • Proceedings of the Korean Society of Medical Physics Conference
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    • 2004.11a
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    • pp.36-38
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    • 2004
  • The detector size effect due to the spatial response of defectors is one critical source of inaccuracy in clinical dosimetry and has been a subject of numerous studies. Conventionally, the detector response kernel contains all of the influence that the detector size has on the measured beam profile. Various analytic models for this kernel have been proposed and studied in theoretical and experimental works. Here, we use a method to determine detector response kernel simply by using Monte Carlo simulation and convolution theory. Based on this numerical method and DOSIMETER, an EGS4 Monte Carlo code, the detector response for a Farmer type ion chamber embedded in water phantom is obtained. There exists characteristic difference in the simulated chamber readings between one with carbon graphite wall and the other with Acrylic wail. Using the obtained response and the convolution theory, we are planning to derive the detector response kernel numerically and remove detector size effect from measurements for 6MV, 10${\times}$l0cm2 and 0.5${\times}$10 cm2 photon beam.

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Effect of Juglandis Semen BL13·BL17 Aqua-acupuncture and Acupuncture on the Allergic Response (폐유(肺兪)·격유(膈兪)의 호도약침(胡桃藥鍼) 자극이 알레르기 반응에 미치는 영향)

  • Baek, Seung-il;Lee, Yong-tae;Jang, Kyung-jeon
    • Journal of Acupuncture Research
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    • v.20 no.4
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    • pp.180-191
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    • 2003
  • Objective & Methods : Experimental studies were done to research the clinical effects of Juglandis Semen aqua-acupuncture and acupuncture($BL_{13}{\cdot}BL_{17}$) on the anti-allergic response. anaphylaxis provoked by the compound48/80, delayed type hypersensitivity response to picryl chloride and SRBC and inflammation response to egg albumin. Results : The following results have been obtained; 1. Juglandis Semen aqua-acupuncture and acupuncture($BL_{13}{\cdot}BL_{17}$) group were increased the survival rate in compound 48/80 induced systemic anaphylactic reaction. 2. Picryl chloride induced contact dermatitis and delayed type hypersensitivity in SRBC challenged mouse were significantly decreased in Juglandis Semen aqua-acupuncture and acupuncture($BL_{13}{\cdot}BL_{17}$) group. 3. Inflammation response-WBC, CRP and Nitric Oxide in egg albumin induced allergic rat were significantly decreased in Juglandis Semen aqua-acupuncture and acupuncture($BL_{13}{\cdot}BL_{17}$) group. Conclusions : According to the above results, Semen aqua-acupuncture and acupuncture($BL_{13}{\cdot}BL_{17}$) both depress the allergy reaction.

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A Study on the Nurse's Response for the Clinical Application of Nursing Diagnosis (간호진단 임상적용을 위한 교육프로그램의 효과 및 간호사의 반응조사 연구)

  • Chun, C.Y.;Lim, Y.S.;Kim, Y.S.;Park, J.W.;Cho, K.S.
    • The Korean Nurse
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    • v.29 no.1
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    • pp.59-71
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    • 1990
  • Although the usefulness and importance of clinical application of nursing diagnosis are well recognized by the academic circle, it is not yet generally practiced. In order to provide data for establishing a policy for clinical nursing diagnosis; a study was made at a seminar, sponsored by the Department of nursing, Severance Hospital, with participation of 190 nurses from 33 hospitals. The objective of the study was to find out; 1) if the nurses agree with the academic community in recognizing the benefits and problems of clinical application of nursing diagnosis; 2) how the nurses evaluate their ability to carry out nursing diagnosis; and 3) if educational programs would help enhance ability of nursing diagnosis among nurses. The summary of findings by the study is as follows; 1. While all nurses responded positively on the question of benefits improving science and quality of nursing, thus elevating credibility and position of nurses, some expressed concern on the practicality of the system in setting up nursing objectiveness, confirming the nursing problems and utilizing patient information. For the 20 questions and the scale of 1~5, the lowest average score was 3.223 and the highest 4.066. 2. The study attempted to find out the opinion of the nurses on the problems that 'would make difficult to adopt the nursing diagnosis in clinics. The result of the study indicates the nurses believe the major problems are the fact that the subject of nursing diagnosis are not well defined and that the form sheets do not match with the ones that are currently being used. However, comparing it with the result of the previous study on the same question (inadequate manpower and insufficienf time allocated for the job were two major problems pointed out then.), it can be said that the opinion of the nurses studied this time was much more positive and it suggests that they believe the system can be adopted without increasing manpower and only by giving additional training and by adjusting the format of nursing record sheets. It suggests that the future for adopting a clinical nursing diagnosis is very bright. 3. As the most urgent problem to be solved for adopting clinical nursing diagnosis, 38. 5% responded that it was "education of nurses, "and 34.2% responded that it was "staffing adequate number of nurses". 4. For the 10 questions asked for self-evaluation of ability to adopt the system, with the scale of 1~5, average score was lower than 3. This indicate that they evaluate their ability to adopt the system is low. 5. The results of study taken before and after the educational programs for clinical nursing diagnosis were compared with overall score in order to determine if such program would cause changes in the response to the effect of clinical application of nursing diagnosis, and it was found that there was statistically significant changes suggesting that the education contributed to positive change in the response. 6. The results of study taken before and after the educational programs for clinical nursing diagnosis were compared with overall score in order to determine how the proble~ ms for adopting nursing system would be effected by such educational programs, and it was found that those problems be not soived with a short course of training. 7. The results of study taken before and after the educational programs for clinical nursing diagnosis were compared with overall score in order to determine if such programs would bring changes in the self-evaluation of nurses on the ability of nursing diagno sis, and it was found that program improve score of self-evaluation their ability of the nursing diagnosis. As seen in the above reports, it was found that the nu'rses are very positive about the clinical nursing diagnosis, that educational program for the clinical nursing diagnosis helps nurses for positively changing their attitude for ,the nursing diagnosis, for their self-confidence on their ability to perform nursing diagnosis. With improved know-how and self"confictence of nurses gained through educational and .training programs, the future of clinical application of nursing diagnosis is very bright.diagnosis is very bright.

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Efficacy and Toxicity of Anti-VEGF Agents in Patients with Castration-Resistant Prostate Cancer: a Meta-analysis of Prospective Clinical Studies

  • Qi, Wei-Xiang;Fu, Shen;Zhang, Qing;Guo, Xiao-Mao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8177-8182
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    • 2014
  • Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ${\geq}50%$) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.

Predictive Value of IHC4 Score for Pathological Response to Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer

  • Elsamany, Shereef;Elmorsy, Soha;Alzahrani, Abdullah;Rasmy, Ayman;Abozeed, Waleed N;Mohammed, Amrallah A;Sherisher, Mohamed A;Abbas, Mohammed M;Mashhour, Miral
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7975-7979
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    • 2015
  • Purpose: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). Materials and Methods: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. Results: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI=1.28-13.16, p=0.018) and a lower pathological stage (OR=3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI=1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. Conclusions: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.

Clinical Application and Limitations of Myeloma Response Assessment and Diagnosis System (MY-RADS) (골수종 반응평가와 진단체계의 임상적용 및 제한점)

  • Dong Kyun Kim;Sung-Soo Park; Joon-Yong Jung
    • Journal of the Korean Society of Radiology
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    • v.84 no.1
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    • pp.51-74
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    • 2023
  • Multiple myeloma, which is a proliferative disease of plasma cells that originate from a single clone, is the second most common hematologic malignancy following non-Hodgkin lymphoma. In the past, its diagnosis was made based on clinical findings (so-called "CRAB") and a skeletal survey using radiographs. However, since the implementation of the International Myeloma Working Group's revised guideline regarding the radiologic diagnosis of multiple myeloma, whole-body (WB) MRI has emerged to play a central role in the early diagnosis of multiple myeloma. Diffusion-weighted imaging and fat quantification using Dixon methods enable treatment response assessment by MRI. In keeping with the trend, a multi-institutional and multidisciplinary consensus for standardized image acquisition and reporting known as the Myeloma Response Assessment and Diagnostic System (MY-RADS) has recently been proposed. This review aims to describe the clinical application of WB-MRI based on MY-RADS in multiple myeloma, discuss its limitations, and suggest future directions for improvement.

Placebo Effects and Clinical Trials of Neuropsychiatric Drugs (위약효과와 신경정신약물의 임상시험)

  • Kim, Sung-Wan;Jang, Ji-Eun;Yoon, Jin-Sang
    • Korean Journal of Biological Psychiatry
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    • v.19 no.4
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    • pp.164-171
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    • 2012
  • The placebo effect, a response observed during the placebo arm of a clinical trial, is produced by the psychobiological action of the placebo as well as by other potential contributors to symptom amelioration such as spontaneous improvement, regression to the mean, biases, concurrent treatments, and study design. From a psychological viewpoint, there are many mechanisms that contribute to placebo effects, including expectations, conditioning, learning, and anxiety reduction. Placebo responses are also mediated by opioid and non-opioid mechanisms including dopamine, serotonin, cholecystokinin, and immune mediators. During recent years, a trend towards increased placebo effects in clinical trials of neuropsychiatric drugs has been noted. Indeed, the placebo effects observed in clinical trials constitute an increasing problem and interfere with signal-detection analyses of potential treatments. Several potential factors including protocol/study design and conduct related factors may account for the placebo effect observed in clinical trials. This paper reviews key issues related to this problem and aims to identify potential solutions.

A clinical literature review and research-trends analysis of bee venom pharmacopuncture for cancer patients (암 환자에 대한 봉독 약침요법의 임상문헌 고찰 및 연구동향 분석)

  • Kim, Joo-Hee
    • The Journal of Korean Medicine
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    • v.41 no.3
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    • pp.247-259
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    • 2020
  • Objectives: This review aims to investigate clinical studies related to bee venom pharmacopuncture for cancer patients and to analyze the research trend for further study. Methods: We searched for clinical studies using bee venom pharmacopuncture therapy on patients with cancer through the electronic databases including Pubmed, Cochrane library, OASIS, KISS, NDSL, and KMBASE. There was no restriction on language and publication date, and after selection/exclusion process, the study design, target disease, intervention details including acupoints, treatment frequency and period, outcomes, study results and adverse events were extracted. Results: Thirteen clinical studies were finally selected. There were a randomized controlled trial RCT about the effect of sweet bee venom pharmacopuncture on cancer-related pain, and three case series about chemotherapy-induced peripheral neuropathy. In case reports, there were nine studies about oligodendroglioma, plexiform neurofibroma, breast cancer, prostate cancer, lung cancer, urachal adenocarcinoma, malignant melanoma, and atypical squamous cells of undetermined significance. The bee venom therapy affected the improvement of outcomes such as symptoms, quality of life, tumor response, and lab findings. Conclusions: The present study found that bee venom therapy is applicable to the treatment of cancer patients, and showed some effect on various symptoms. However, due to insufficient number and quality of studies, well designed and high-quality clinical trials are necessary to confirm the effectiveness and safety of bee venom pharmacopuncture therapy in patients with cancer.

Effect of Varying the Energy Density of Protein-adequate Diets on Nutrient Metabolism, Clinical Chemistry, Immune Response and Growth of Muzaffarnagari Lambs

  • Singh, V.K.;Pattanaik, Ashok Kumar;Goswami, T.K.;Sharma, K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.8
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    • pp.1089-1101
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    • 2013
  • Effects of varied dietary energy densities on immune response and performance of Muzzafarnagari lambs were ascertained in a 180-d study. Animals (n = 24), in three groups, were fed diets providing 100% (100E), 80% (80E) or 70% (70E) of their metabolizable energy requirement. Mean nutrient digestibilities varied significantly among treatments. Nitrogen intake was lower (p<0.01) in the 70E. Nitrogen retention, was reduced (p<0.001) in 80E and 70E vs 100E. The average daily gain (p<0.001) was $47.01{\pm}4.23$, $13.54{\pm}1.72$ and $-16.67{\pm}8.24$ g for 100E, 80E and 70E, respectively. Hemoglobin concentration, haematocrit, total and differential leukocyte counts were lower (p<0.001) for 80E and 70E than for 100E with a similar trend (p<0.05) for serum glucose and total protein. Serum cortisol was reduced (p<0.001) with decreased energy availability. Antibody titre to Brucella abortus S19 showed an initial reduction in 80E and 70E vs 100E. Delayed-type hypersensitivity response was lower (p<0.001) in 80E and 70E vs 100E, accompanying a lower (p<0.001) nitric oxide production by the peripheral lymphocytes. It is concluded that the reduced dietary energy density significantly affects the growth performance and immune response of lambs.