• Title/Summary/Keyword: therapeutic window

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Nonparmetric Method for Identifying Effective and Safe Doses using Placement (유효하고 안전한 용량 결정에 위치를 이용한 비모수적 방법)

  • Kim, Sunhye;Kim, Dongjae
    • The Korean Journal of Applied Statistics
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    • v.27 no.7
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    • pp.1197-1205
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    • 2014
  • Typical clinical dose development studies consist of the comparison of several doses of a drug with a placebo. The primary interest is to find therapeutic window that satisfying both efficacy and safety. In this paper, we propose nonparametric method for identifying effective and safe doses in linear placement using score function. The Monte Carlo simulation is adapted to estimate the power and the family-wise error rate(FWE) of proposed procedure are compared with previous methods.

Early Biologic Treatment in Pediatric Crohn's Disease: Catching the Therapeutic Window of Opportunity in Early Disease by Treat-to-Target

  • Kang, Ben;Choe, Yon Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.21 no.1
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    • pp.1-11
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    • 2018
  • The emergence of mucosal healing as a treatment goal that could modify the natural course of Crohn's disease and the accumulating evidence showing that biologics are most effective in achieving mucosal healing, along with the success of early treatment regimens for rheumatoid arthritis, have led to the identification of early Crohn's disease and development of the concept of catching the therapeutic window during the early disease course. Thus, an increasing number of pediatric gastroenterologists are adopting an early biologic treatment strategy with or without an immunomodulator. Although early biologic treatment is effective, cost and overtreatment are issues that limit its early use. Currently, there are insufficient data on who will benefit most from early biologics, as well as on who will not need early or even any biologics. For now, top-down biologics should be considered for patients with currently known high-risk factors of poor outcomes. For other patients, close, objective monitoring and accelerating the step-up process by means of a treat-to-target approach seems the best way to catch the therapeutic window in early pediatric Crohn's disease. The individual benefits of immunomodulator addition during early biologic treatment should be weighed against its risks and decision on early combination treatment should be made after comprehensive discussion with each patient and guardian.

One-Stage Repair of an Interrupted Aortic Arch with an Aortopulmonary Window in a Premature Neonate

  • Bobos, Dimitrios;Kanakis, Meletios A.;Koulouri, Sofia;Giannopoulos, Nicholas M.
    • Journal of Chest Surgery
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    • v.48 no.6
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    • pp.411-414
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    • 2015
  • Interrupted aortic arch with an aortopulmonary window is a rare congenital entity that is associated with high morbidity and mortality, especially in premature low-birth-weight infants, and the proper timing of surgical correction remains a matter of debate. We present the case of a premature infant weighing 1.6 kg who successfully underwent one stage surgical repair to treat interrupted aortic arch with an aortopulmonary window. The therapeutic management of this patient is described below, and a review of the literature is presented.

Effects of collimator on imaging performance of Yttrium-90 Bremsstrahlung photons: Monte Carlo simulation

  • Kim, Minho;Bae, Jae Keon;Hong, Bong Hwan;Kim, Kyeong Min;Lee, Wonho
    • Nuclear Engineering and Technology
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    • v.51 no.2
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    • pp.539-545
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    • 2019
  • Yttrium-90 is a useful therapeutic radioisotope for tumor treatment because of its high-energy-emitting beta rays. However, it has been difficult to select appropriate collimators and main energy windows for Y-90 Bremsstrahlung imaging using gamma cameras because of the broad energy spectra of Y-90. We used a Monte Carlo simulation to investigate the effects of collimator selection and energy windows on Y-90 Bremsstrahlung imaging. We considered both MELP and HE collimators. Various phantoms were employed in the simulation to determine the main energy window using primary-to-scatter ratios (PSRs). Imaging performance was evaluated using spatial resolution indices, imaging counts, scatter fractions, and contrast-to-noise ratios. Collimator choice slightly affected energy spectrum shapes and improved PSRs. The HE collimator performed better than the MELP collimator on all imaging performance indices (except for imaging count). We observed minor differences in SR and SF values for the HE collimator among the five simulated energy windows. The combination of an HE collimator and improved-PSR energy window produced the best CNR value. In conclusion, appropriate collimator selection is an important component of Bremsstrahlung Y-90 photon imaging and main energy window determination. We found HE collimators to be more appropriate for improving the imaging performance of Bremsstrahlung Y-90 photons.

Multitarget effects of Korean Red Ginseng in animal model of Parkinson's disease: antiapoptosis, antioxidant, antiinflammation, and maintenance of blood-brain barrier integrity

  • Choi, Jong Hee;Jang, Minhee;Nah, Seung-Yeol;Oh, Seikwan;Cho, Ik-Hyun
    • Journal of Ginseng Research
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    • v.42 no.3
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    • pp.379-388
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    • 2018
  • Background: Ginsenosides are the main ingredients of Korean Red Ginseng. They have extensively been studied for their beneficial value in neurodegenerative diseases such as Parkinson's disease (PD). However, the multitarget effects of Korean Red Ginseng extract (KRGE) with various components are unclear. Methods: We investigated the multitarget activities of KRGE on neurological dysfunction and neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. KRGE (37.5 mg/ kg/day, 75 mg/kg/day, or 150 mg/kg/day, per os (p.o.)) was given daily before or after MPTP intoxication. Results: Pretreatment with 150 mg/kg/day KRGE produced the greatest positive effect on motor dysfunction as assessed using rotarod, pole, and nesting tests, and on the survival rate. KRGE displayed a wide therapeutic time window. These effects were related to reductions in the loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons, apoptosis, microglial activation, and activation of inflammatory factors in the substantia nigra pars compacta and/or striatum after MPTP intoxication. In addition, pretreatment with KRGE activated the nuclear factor erythroid 2-related factor 2 pathways and inhibited phosphorylation of the mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways, as well as blocked the alteration of blood-brain barrier integrity. Conclusion: These results suggest that KRGE may effectively reduce MPTP-induced neurotoxicity with a wide therapeutic time window through multitarget effects including antiapoptosis, antiinflammation, antioxidant, and maintenance of blood-brain barrier integrity. KRGE has potential as a multitarget drug or functional food for safe preventive and therapeutic strategies for PD.

Evaluated Absorbed Dose According to Prescribed Dose and Therapeutic Technique in Radiation Therapy (방사선치료 시 처방선량과 치료기법에 따른 흡수선량 평가)

  • Lee, Deuk-hee;Park, Eun-tae;Kim, Jung-hoon;Im, In-chul
    • Journal of the Korean Society of Radiology
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    • v.10 no.6
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    • pp.469-476
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    • 2016
  • In this study, evaluated absorbed dose of moving target using PLD according to prescribed dose and therapeutic technique. First, result of MCNPX when target was deviated from exposure field was reduced dose in proportion to distance. According to prescribed dose, absorbed dose of 3D CRT was better than IMRT in low dose and IMRT was more better in high dose. Absorbed dose of 3D CRT was highest according to therapeutic technique. Therefore, 3D CRT was technique of irradiated highest dose to moving target. But, considered protective effect of normal tissue and patient condition that therapeutic technique was selected to maximized treatment efficiency.

Effects of the Brain waves according to participation in Therapeutic recreation programs on the Depression, Sleep Disturbance and Quality of Life in the Elderly with Dementia (치료레크리에이션 프로그램에 따른 치매노인의 뇌파 변화가 우울감 및 수면장애와 삶의 질에 미치는 영향)

  • Lee, Moon-Sook;Cho, Byung-Jun
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.8
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    • pp.5096-5110
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    • 2015
  • The purpose of this study was to identify the effects of brain wave change through therapeutic recreation programs on depression, sleep disturbance and quality of life among elderly with dementia. The subjects of this quasi-experimental study consisted of two groups, one experimental group (N=14) and one control group (N=18), after excluding 8 participants from a total of 40 participants. The subjects of experimental group were randomly selected from the elderly (order than 65 years old) of senior care center in Daejoen and participated in 3-month therapeutic recreation program. On the other hand, the subjects of control group did not participated in any therapeutic recreation program. Each group's pre-post brain wave change, depression, sleep disturbance and quality of life were estimated. Through ANCOVA and Analysis of Structural Equation Modeling with SPSS window 17.0 and AMOS 7.0, this study found followings. Frist, the therapeutic recreation program group indicated significant improvement of brain waves, sleep disturbance and quality of Life. In addition, depression was significantly reduced in the therapeutic recreation program group. Second, significant causal relationships was found among brain waves, depression, sleep disturbance, and Quality of Life.

Dosimetric Evaluation of Static and Dynamic Intensity Modulated Radiation Treatment Planning and Delivery (세기조절방사선치료에서 조사방법이 빔 파라미터 및 선량에 미치는 영향에 대한 연구)

  • Kim Sung-Kyu;Kim Myung-Se;Yun Sang-Mo
    • Progress in Medical Physics
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    • v.17 no.2
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    • pp.114-122
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    • 2006
  • The two commonly used methods in delivering intensity modulated radiation therapy (IMRT) plan are the dynamic (sliding window) and static (stop and shoot) mode. In this study, the two IMRI delivery techniques are compared by measuring point dose and dose distributions. Using treatment planning system, clinical target volume (CTV) was created as a sphere with various diameter (3 cm, 7 cm, 12 cm). Two IMRT plans were peformed to deliver 200 cGy to the CTV in dynamic and static mode. The two plans were delivered on a phantom and central point dose and dose distributions were measured. The central point dose differences between static and dynamic IMRT delivery were 0.2%, 0.2% and 0.4% when the diameter of CTV was 3 cm, 7 cm, and 12 cm, respectively. The differences In volume receiving 90% of the proscribed dose were 2.7%, 2.2%, and 2.9% for the diameter of CTV was 3 cm, 7 cm, and 12 cm, respectively. For lung cancer patients, the differences in central point dose were 0.2%, 0.2%, and 0.4% when the volume of CTV was 35.5 cc, 296.8 cc, and 903.5 cc, respectively. The differences in volume receiving 90% of the prescribed dose were 2.7%, 4.8%, and 9.1% when the volume of CTV was 35.5 cc, 296.8 cc, and 903.5 cc, respectively. In conclusion, it was possible to deliver IMRT plans using dynamic mode of MLC operation although the loaves are In motion during radiation delivery.

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Future Cancer Therapy with Molecularly Targeted Therapeutics: Challenges and Strategies

  • Kim, Mi-Sook
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.371-389
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    • 2011
  • A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.

Latent Autoimmune Diabetes in Adults: A Review on Clinical Implications and Management

  • Pieralice, Silvia;Pozzilli, Paolo
    • Diabetes and Metabolism Journal
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    • v.42 no.6
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    • pp.451-464
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    • 2018
  • Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by a less intensive autoimmune process and a broad clinical phenotype compared to classical type 1 diabetes mellitus (T1DM), sharing features with both type 2 diabetes mellitus (T2DM) and T1DM. Since patients affected by LADA are initially insulin independent and recognizable only by testing for islet-cell autoantibodies, it could be difficult to identify LADA in clinical setting and a high misdiagnosis rate still remains among patients with T2DM. Ideally, islet-cell autoantibodies screening should be performed in subjects with newly diagnosed T2DM, ensuring a closer monitoring of those resulted positive and avoiding treatment of hyperglycaemia which might increase the rate of ${\beta}-cells$ loss. Thus, since the autoimmune process in LADA seems to be slower than in classical T1DM, there is a wider window for new therapeutic interventions that may slow down ${\beta}-cell$ failure. This review summarizes the current understanding of LADA, by evaluating data from most recent studies, the actual gaps in diagnosis and management. Finally, we critically highlight and discuss novel findings and future perspectives on the therapeutic approach in LADA.