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Immune Checkpoint Inhibitors in 10 Years: Contribution of Basic Research and Clinical Application in Cancer Immunotherapy

  • Jii Bum Lee;Hye Ryun Kim;Sang-Jun Ha
    • 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.

The anatomy of temporal muscle in botulinum toxin injection (측두근 보툴리눔 독소 주사 시 고려해야 할 해부학)

  • Lee, Won-Kang;Choi, Young-Chan;Hong, Jung-Hun;Kim, Seong-Teak
    • Journal of Dental Rehabilitation and Applied Science
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    • v.30 no.3
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    • pp.231-237
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    • 2014
  • Botulinum toxin has been used for treating chronic migraine under US Food and Drug Administration approval since 2010. However there is no definitive guideline for injection point. The aim of this study is to propose an effective and safe injection guideline by reviewing the previous studies.

The Domestic Trends of Korean Medical Treatments for Neck Pain Caused by Whiplash Injury (편타성 손상으로 인해 발생된 경부통의 한의학적 치료에 대한 국내 연구 동향)

  • Jeong, Seong-Hyun;Lee, Hyun-Ho;Lee, Gi-Eon;Choi, Ji-Hoon;Kim, Donghoo;Lee, Jong-Ha
    • Journal of Korean Medicine Rehabilitation
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    • v.27 no.4
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    • pp.11-19
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    • 2017
  • Objectives We attempted to investigate the trends of Korean Medical treatments for neck pain caused by whiplash injury by analyzing domestic clinical studies. Methods We searched for studies listed on Korean electronic databases (KTKP, OASIS, RISS, KMbase, NDSL, KCI, and National Assembly Library). Clinical studies were chosen according to the inclusion criteria. Subsequently, we compared and analyzed the data. Results The search yielded 35 studies, of which there were 12 randomized controlled trials (RCTs), 15 non-randomized controlled trials (NRCTs), 6 case reports, and 2 before-after studies. Among these, 54.7% of participants were in the acute stage of the damage period. Pharmacopuncture was used the most in main treatment methods. Only 14.3% of studies mentioned approval by an institutional review board (IRB) and only 8.6% of studies considered side effects. Conclusions There is some evidence that Korean Medical treatment is effective for neck pain caused by whiplash injury. Since all studies, however, were exposed to the risk of bias. Therefore, future studies of a higher quality are required.

A Review on Clinical Studies of Acupuncture and Moxibustion Therapy for Acute Herpes Zoster (급성기 대상포진의 침구치료에 대한 임상 연구 문헌 고찰)

  • Choi, Yoo Min;Kim, Seok Hee;Kim, Ju Yong;Park, Sang Hun;Yook, Tae Han;Kim, Jong Uk
    • Journal of Acupuncture Research
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    • v.32 no.3
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    • pp.147-161
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    • 2015
  • Objectives : The purpose of this study was to review the effectiveness of acupuncture and moxibustion therapy for the treatment of acute herpes zoster. Methods : Data was collected by two researchers. Clinical trials on PubMed were retrieved using MeSH terms including "herpes zoster" combined with "acupuncture therapy", "moxibustion", "bloodletting", "electroacupuncture", and related keywords. We excluded irrelevant studies and included randomized and non-randomized controlled trials, case series and case reports. Finally, we selected a total of thirteen studies and conducted a literature analysis and an object quality assessment. Results : Twelve of thirteen studies were about acupuncture and moxibustion combined therapy. Only one study suggested that a single acupuncture therapy is expected to be equally as effective as a common western medicine therapy. There was some evidence related to the effectiveness of moxibustion, venesection and electroacupuncture, but it dealt with combining therapy and was insufficient, and with an inclusion of potential risk factors. Only one study was conducted under approval from an institutional review board. No severe treatment-related adverse events were observed. A quality assessment suggested that there was some weakness in the areas of blinding and concealment. Conclusions : There is some evidence that suggests the effectiveness and safety of acupuncture and moxibustion combined therapy as a treatment for acute herpes zoster.

An Observational Multi-Center Study Protocol for Distribution of Pattern Identification and Clinical Index in Parkinson's Disease (파킨슨병 변증 유형 및 지표 분포에 대한 전향적 다기관 관찰연구 프로토콜)

  • HuiYan Zhao;Ojin Kwon;Bok-Nam Seo;Seong-Uk Park;Horyong Yoo;Jung-Hee Jang
    • The Journal of Internal Korean Medicine
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    • v.45 no.1
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    • pp.1-10
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    • 2024
  • Objectives: This study investigated the pattern identification (PI) and clinical index of Parkinson's disease (PD) for personalized diagnosis and treatment. Methods: This prospective observational multi-center study recruited 100 patients diagnosed with PD from two Korean medicine hospitals. To cluster new subtypes of PD, items on a PI questionnaire (heat and cold, deficiency and excess, visceral PI) were evaluated along with pulse and tongue analysis. Gait analysis was performed and blood and feces molecular signature changes were assessed to explore biomarkers for new subtypes. In addition, unified PD rating scale II and III scores and the European quality of life 5-dimension questionnaire were assessed. Results: The clinical index obtained in this study analyzed the frequency statistics and hierarchical clustering analysis to classify new subtypes based on PI. Moreover, the biomarkers and current status of herbal medicine treatment were analyzed using the new subtypes. The results provide comprehensive data to investigate new subtypes and subtype-based biomarkers for the personalized diagnosis and treatment of PD patients. Ethical approval was obtained from the medical ethics committees of the two Korean medicine hospitals. All amendments to the research protocol were submitted and approved. Conclusions: An objective and standardized diagnostic tool is needed for the personalized treatment of PD by traditional Korean medicine. Therefore, we developed a clinical index as the basis for the PI clinical evaluation of PD. Trial Registration: This trial is registered with the Clinical Research Information Service (CRIS) (KCT0008677)

Development Protocol of Korean Medicine Clinical Practice Guideline for Myofascial Pain Syndrome (근막통증증후군의 한의표준임상진료지침 개발 프로토콜)

  • Byeonghyeon Jeon;Hyeonjun Woo;Won-Bae Ha;Cheoung Su Kim;Jung-Han Lee
    • Journal of Korean Medicine Rehabilitation
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    • v.33 no.4
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    • pp.203-213
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    • 2023
  • Objectives This study aimed to develop a Korean medicine (KM) clinical practice guideline for myofascial pain syndrome (MPS) via the collaboration of clinical and methodological experts. Methods The study will include an initial survey to establish a common understanding of MPS. To develop the clinical guideline, a multidisciplinary development group was formed. The group will finalize the clinical questions based on a preliminary draft. The GRADE methodology is going to be applied to determine the level of evidence and grading of the recommendations. Finally, approval from the relevant medical societies will be obtained. Results A protocol for developing a KM clinical guideline for MPS was presented. Before finalizing the clinical key questions, a literature search was conducted according to the protocol, and a draft of 19 clinical key questions was established. Conclusions An evidence-based KM clinical guideline for MPS is expected to contribute to the management of MPS. This may also serve as a reference for the development of other KM clinical practice guidelines in the future.

Pathophysiology of Potassium-competitive Acid Blocker-refractory Gastroesophageal Reflux and the Potential of Potassium-competitive Acid Blocker Test

  • Masaoka, Tatsuhiro;Kameyama, Hisako;Yamane, Tsuyoshi;Yamamoto, Yuta;Takeuchi, Hiroya;Suzuki, Hidekazu;Kitagawa, Yuko;Kanai, Takanori
    • Journal of Neurogastroenterology and Motility
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    • v.24 no.4
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    • pp.577-583
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    • 2018
  • Background/Aims Potassium-competitive acid blockers are expected to be the next generation of drugs for the treatment of diseases caused by gastric acid. In 2015, vonoprazan fumarate, a novel potassium-competitive acid blocker, was approved by the Japanese health insurance system. Since its approval, patients refractory to vonoprazan can be encountered in clinical settings. We designed this study to clarify the pathophysiology of gastroesophageal reflux disease refractory to vonoprazan. Methods In this retrospective study, we involved patients who had refractory symptoms after administration of standard-dose proton pump inhibitors or vonoprazan and underwent diagnostic testing with esophageal high-resolution manometry and 24-hour multichannel intraluminal impedance and pH monitoring while using proton pump inhibitors or vonoprazan. Patients were diagnosed based on the Rome IV criteria for functional gastrointestinal disorders and diagnostic test results. Results Twenty-seven patients were analyzed during this study. Gastric pH ${\geq}4$ was sustained for a longer period of time, and the esophageal acid exposure time and number of acid reflux events were shorter in the vonoprazan group than in the proton pump inhibitor group. The percentage of patients diagnosed with acidic gastroesophageal reflux disease in the vonoprazan group was lower than that in the proton pump inhibitor group. Conclusions Intra-gastric pH and acid reflux were strongly suppressed by 20-mg vonoprazan. When patients with gastroesophageal reflux disease present symptoms after administration of 20-mg vonoprazan, the possibility of pathophysiologies other than acid reflux should be considered.

A Validation Study of the Sasang Constitution Questionnaire for Japanese(SSCQ-J) (일본인용 사상체질진단지의 타당화 연구)

  • Jo, Hoon-Seuk;Jeon, Soo-Hyung;Jeong, Jong-Hun;Kim, Kyu-Kon;Kim, Jong-Won
    • Journal of Sasang Constitutional Medicine
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    • v.25 no.4
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    • pp.289-296
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    • 2013
  • Objectives This study was aimed to validate Sasang Constitution Questionnaire for Japanese (SSCQ-J). Methods Sasang Constitution Questionnaire for Patients (SSCQ-P) was developed by joint researches between the Society of Sasang Constitutional Medicine and Korea Institute of Oriental Medicine. We translated SSCQ-P into Japanese and modified some items of that for Japanese. By getting approval from the Institutional Review Board(IRB)of School of Medicine, Keio University, we conducted a questionnaire survey of patients who visited Oriental Medicine Center from early January until mid-February 2011. The total of 364 patients filled out that Questionnaire and gave an interview with a Sasang constitution specialist. Using this Questionnaire data, we made Sasang constitutional classification functions and calculated diagnostic accuracy rate of SSCQ-J using discrimination analysis. Results 1. Male group's diagnostic accuracy rate of SSCQ-J was 77.01% and female was 78.10%. 2. Diagnostic accuracy of SSCQ-J was a little higher than SSCQ-P Conclusions 1. SSCQ-J can be considered to have good discriminant power compared with SSCQ-P 2. Further research with SSCQ-J will be helpful in the comparison study on the usual symptoms between Korean and Japanese as well as development of good discriminant function.

A case study on benefit coverage of complementary medicine in public health insurance by the referendum in Switzerland (스위스에서의 국민투표에 의한 보완의학 건강보험 급여화 사례 연구)

  • Kim, Dongsu;Lim, Byungmook;Park, Inhyo;Lee, Yoon Jae
    • Journal of Society of Preventive Korean Medicine
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    • v.21 no.3
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    • pp.29-42
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    • 2017
  • Background : Efforts towards increasing insurance coverage for traditional Korean medicine (TKM) are being continued. However, various difficulties are faced in generating evidence for TKM due to limited financial support and the low quality of research methodology. Objectives : The objectives of this study were to review the Swiss evaluation program for complementary and alternative medicine (CAM) and assess the expansion in public health insurance coverage of complementary medicine as approved by referendum in Switzerland. Methods : The regulations of CAM in the European Union were assessed. Research articles, reports, government publications and websites which deal with the 'Programm Evaluation $Komplement{\ddot{a}}rmedizin$ (PEK)' and the referendum in Switzerland were searched for and analyzed. Results : The PEK was conducted from 1998 to 2005. The PEK evaluated the efficacy, utilization and cost-effectiveness of anthroposophical medicine, homeopathy, neural therapy, phytotherapy and traditional Chinese medicine. However, clear conclusions could not be drawn from the evaluation according to the PEK Report. Later, a referendum was implemented in which 5 therapies would be added to the Switzerland Constitution with the support of the public. The coverage of CAM was approved by Swiss a plebiscite with an approval rate of 67.0%. Conclusions : The reason for the successful referendum is suggested to be public support and the solidarity with CAM experts and politicians. It may be surmised that recognition of the political efforts and scientific aspects required to expand insurance coverage of TKM, and towards obtaining public support, is necessary.

Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmacopuncture in Sprague-Dawley Rats

  • Sun, Seung-Ho;Park, Sunju;Jeong, Jong-Jin;Lee, Kwang-Ho;Yu, Jun-Sang;Seo, Hyung-Sik;Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.18 no.2
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    • pp.42-50
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    • 2015
  • Objectives: The aims of the study were to test the single- dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.