Efficacy and safety of acupuncture treatment as an adjunctive therapy after knee replacement: Single-center, pragmatic, randomized, assessor blinded, pilot study.

INTRODUCTION: Total knee replacement (TKR) is a surgical procedure that is being increasingly performed as a result of population aging and the increased average human life expectancy in South Korea. Consistent with the growing number of TKR procedures, the number of patients seeking acupuncture for relief from adverse effects, effective pain management, and the enhancement of rehabilitative therapy effects and bodily function after TKR has also been increasing. Thus, an objective examination of the evidence regarding the safety and efficacy of acupuncture treatments is essential. The aim of this study is to verify the hypothesis that the concurrent use of acupuncture treatment and usual care after TKR is more effective, safe, and cost-effective for the relief of TKR symptoms than usual care therapy alone. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded randomized controlled trial that includes 50 patients with TKR. After screening the patients and receiving informed consent, the patients are divided into two groups (usual care + acupuncture group and usual care group); the patients will then undergo TKR surgery and will be hospitalized for 2 weeks. The patients will receive a total of 8 acupuncture treatments over 2 weeks after surgery and will be followed up at 3, 4, and 12 weeks after the end of the intervention. The primary outcome is assessed using the Korean version of the Western Ontario and McMaster Universities Arthritis Index (K-WOMAC), and the secondary outcome is measured using the Numerical Rating Scale (NRS), Risk of Fall, and Range of Motion (ROM). Moreover, the cost per quality-adjusted life years (QALYs) is adopted as a primary economic outcome for economic evaluation, and the cost per NRS is adopted as a secondary economic outcome. ETHICS AND DISSEMINATION: This trial has received complete ethical approval from the Ethics Committee of Catholic Kwandong University International St. Mary's Hospital (IS17ENSS0063). We intend to submit the results to a peer-reviewed journal and/or conferences. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03633097.

The efficacy and safety of Sipjeondaebo-tang in Korean patients with cold hypersensitivity in the hands and feet: a protocol for a pilot, randomized, double-blind, placebo-controlled, parallel-group clinical trial.

BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) is frequent in Asian countries including Korea. The quality of life can be degraded by the symptoms of CHHF. In particular, gynecological disorders such as menstrual pain, infertility, leucorrhea, and irregular bleeding may be related to CHHF. Sipjeondaebo-tang (SDT) is widely used in the treatment of various diseases including CHHF by balancing Yin and Yang, restoring the deterioration of physiological function, and improving immunity. However, the efficacy of SDT in the treatment of CHHF has not been assessed in clinical trials. Therefore, we aimed to investigate the feasibility of a full randomized clinical trial of SDT for the treatment of CHHF in Korean women through this trial. METHODS: This study will be a pilot, randomized, double-blind, two-arm, placebo-controlled, parallel-group, multicenter clinical trial. Women aged 19-59 years who present with CHHF will be recruited from five university hospitals. A total of 60 subjects will be randomly assigned to a treatment group (SDT) or a placebo group at a 1:1 ratio. The subjects will receive 3 g of either SDT or placebo three times daily for 8 weeks. The primary outcome measures will be the Visual Analogue Scale scores of CHHF. The secondary outcome measures will be changes in body temperature in both the hands and the feet as measured using a thermometer and the Korean version of the World Health Organization Quality of Life Scale Abbreviated Version. DISCUSSION: This will be the first trial to investigate the efficacy and safety of SDT in the treatment of CHHF. This study will provide basic clinical information regarding Korean herbal medicine treatment of CHHF and a clinical basis for designing a full randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03374345 . Registered on 15 February 2018.

Efficacy and safety of Ojeok-san in Korean female patients with cold hypersensitivity in the hands and feet: study protocol for a randomized, double-blinded, placebo-controlled, multicenter pilot study.

BACKGROUND: This study aims to evaluate the safety, efficacy, and feasibility of a full randomized clinical trial of Ojeok-san in Korean female patients with cold hypersensitivity in the hands and feet. METHODS: This study is a multicenter, double-blinded, randomized, placebo-controlled, two-arm, parallel-group pilot clinical trial. A total of 60 participants will be enrolled and randomly assigned to the Ojeok-san treatment group or the placebo control group, in a 1:1 ratio using an Internet-based randomization system. Each group will be administered Ojeok-san or placebo three times per day for 8 weeks. The primary outcome will be the mean change in the Visual Analog Scale scores of cold hypersensitivity in the hands from baseline to week 8. Secondary outcomes will include the mean changes in the skin temperature of the extremities, recovery rate of the skin temperature of hands after cold stress test, and the score of Korean version of the WHO Quality of Life Scale abbreviated version. DISCUSSION: The findings of this study should provide meaningful information for a further large-scale, randomized controlled trial to confirm the safety and efficacy of Ojeok-san on cold hypersensitivity in the hands and feet in female patients. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03083522 . Registered on 20 March 2017.

The Clinical Efficacy and Safety of Gumiganghwal-Tang in Knee Osteoarthritis: A Phase II Randomized Double Blind Placebo Controlled Study.

BACKGROUND: Gumiganghwal-tang (GMGHT) is a traditional herbal medicine consisting of nine different herbs. GMGHT inhibits the mRNA expression and production of inflammatory cytokines tumor necrosis factor-α (TNF- α), interleukin-6 (IL-6), and TNF- ß on lipopolysaccharide- (LPS-) stimulated peritoneal macrophages in a dose-dependent manner. It is empirically used for the treatment of inflammatory disease, but there are few reports of clinical trials that investigate its efficacy and safety. The current study aimed to investigate the clinical efficacy and safety of GMGHT in patients with knee osteoarthritis (OA). METHODS: This was a multicenter, two-armed, double-blinded, randomized, placebo controlled study of GMGHT over 6 weeks. Eligible patients who fulfilled the American College of Rheumatology criteria for OA were randomized to receive either GMGHT or the placebo. Clinical assessments included measurement of knee pain and function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. RESULTS: A total of 128 patients were enrolled (91.4% female; mean age, 58.7 ± 8.1 years). At baseline, pain visual analogue score (VAS) was 67.2 ± 1.4, resp. 71.3 ± 1.6 (treatment, resp. placebo group, p=0.84), and total WOMAC score was 55.2 ± 1.6, resp. 55.6 ± 1.5 (p = 0.84). After 6 weeks, the pain VAS was 43.0 ± 2.5, resp. 61.6 ± 2.5 (p < 0.01) and the total WOMAC score was 34.1 ± 2.4, resp. 46.9 ± 1.8 (p < 0.01). No patients withdrew because of treatment emergent adverse events. Expected adverse events including dyspepsia, liver function abnormality, and lower extremity edema were comparable between both groups. CONCLUSIONS: Treatment with GMGHT resulted in significant improvement in pain, function, and global assessment, and it was generally safe and well tolerated in patients with OA.

Medical service use and usual care of common shoulder disorders in Korea: a cross-sectional study using the Health Insurance Review and Assessment Service National Patient Sample.

OBJECTIVES: This study examined National Health Insurance claims data to investigate the epidemiology of shoulder disorders in Korea. Detailed information on medical services and related costs was assessed by major shoulder disorder category. DESIGN AND SETTING: The 2014 National Patient Sample dataset provided by the Health Insurance Review and Assessment Service was analysed. Among shoulder-related diagnosis codes, adhesive capsulitis of the shoulder (ACS), rotator cuff syndrome (RCS) and shoulder impingement syndrome (SIS) categories were of highest prevalence. Sociodemographic characteristics and medical service use, frequency and medical costs regarding common shoulder disorders were evaluated. RESULTS: The majority of patients with shoulder disorder received ambulatory care (97%). Total and per-patient expenses were highest in patients with RCS. The number of inpatients with RCS was more than twice that of the other two groups, and patients with RCS were more likely to receive surgical management compared with patients with ACS and SIS. Prevalence of shoulder disorders was highest among subjects in their 50s for all three groups. Primary care physicians treated 75.80% of patients with ACS, 56.99% of patients with RCS and 48.06% of patients with SIS, respectively, outlining the difference in medical institution usage patterns. In all three groups, the highest proportion of patients visited orthopaedic surgeons out of medical departments. In the ACS and SIS groups, cost of visits (consultations) took up the largest part of total expenses at 32.30% and 18.88%, respectively, while cost of procedure/surgery constituted the largest portion in patients with RCS (37.77%). The usage proportion of subcutaneous or intramuscular and intra-articular injections ranged between 20% and 30% for outpatients in all three groups. CONCLUSIONS: Medical service use, frequency and cost distributions relating to major shoulder disorders in Korea were assessed using nationwide claims data. These findings are expected to aid policy-makers as well as researchers and practitioners as basic healthcare data.

The efficacy and safety of Danggui-Sayuk-Ga-Osuyu-Saenggang-tang on Korean patients with cold hypersensitivity in the hands: study protocol for a pilot, double-blind, randomized, placebo-controlled, parallel-group clinical trial.

BACKGROUND: In recent years, cold hypersensitivity in the hands (CHH) has become a common ailment of women in Korea. It can lead to gynecological problems such as irregular menstruation, miscarriage, and infertility. Traditionally, Korean herbal medicine has been the primary treatment method used to balance thermoregulation in the human body; however, its effectiveness has not been confirmed through systematic study. Thus, in this trial, we will investigate the feasibility of a full randomized clinical trial, Danggui-Sayuk-Ga-Osuyu-Saenggang-tang (DSGOST) in Korean women with CHH. METHODS: This study will be a pilot, multicenter, double-blind, randomized, parallel-group, two-arm, placebo-controlled clinical trial. A total of 66 participants will be randomly divided into two groups, a DSGOST treatment group and a placebo control group, in a 1:1 ratio using a web-based randomization system. Each group will take DSGOST or placebo three times daily for 6 weeks. The primary outcome will be measured using Visual Analogue Scale (VAS) scores of CHH. Secondary outcomes will include changes in skin temperature of the hands, Clinical Global Impressions (CGI) scale scores, recovery rate of skin temperature of the hands after the cold stress test, and the Korean version of the WHO Quality of Life Scale, abbreviated version (WHOQOL-BREF). DISCUSSION: This trial will be the first trial to reflect the newly defined disease range of CHH which was compiled by Korean medicine expert consensus. This study will provide considerable evidence for further large-scale trials and general clinical guidelines for CHH in the Korean medical field. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov, ID: NCT02645916 . Registered on 30 December 2015.

Inhibitory effect of Angelica gigas on cold­induced RhoA activation in vascular cells.

The herbal extract Angelica gigas (AG) has been applied as a vasodilating agent for patients suffering from vascular diseases for many years; however, the underlying mechanism has not been fully elucidated. The present study hypothesized that the anti­vasoconstrictive effect of AG may be effective in the treatment of abnormal cold­mediated vasospasms that occur in Raynaud's phenomenon (RP). The effect of AG on the activity of ras homolog gene family member A (RhoA) was investigated in cold­exposed vascular cells. Vascular cells were pretreated to AG, followed by a warm (37˚C) or cold (25˚C) incubation for 30 min and investigated with western blotting, ELISA and confocal microscopy. Cold treatment induced the activation of RhoA in pericytes and vascular endothelial cells, however this was reduced by treatment with AG. Furthermore, AG treatment reduced the endothelin­1 (ET­1)­mediated RhoA activation in pericytes; however, cold­induced ET­1 production by vascular endothelial cells was not affected by treatment with AG. In addition, AG treatment suppressed the formation of stress fibers and focal adhesion complexes, and the cold­induced phosphorylation of focal adhesion kinase, proto­oncogene tyrosine­protein kinase Src and extracellular signal­related kinase. Therefore, AG treatment demonstrated an ability to reduce cold­induced RhoA activation in pericytes and vascular endothelial cells, and attenuated ET­1­mediated RhoA activation in pericytes. In conclusion, the present study indicated that AG may be useful for the treatment of RP.

Daesiho-Tang Is an Effective Herbal Formulation in Attenuation of Obesity in Mice through Alteration of Gene Expression and Modulation of Intestinal Microbiota.

BACKGROUND: Obesity has become a major global health challenge due to its increasing prevalence, and the associated health risk. It is the main cause of various metabolic diseases including diabetes, hypertension, cardiovascular disease, stroke and certain forms of cancer. METHODS AND RESULTS: In the present study we evaluated the anti-obesity property of Daesiho-tang (DSHT), an herbal medicine, using high fat diet (HFD)-induced obese mice as a model. Our results showed that DSHT ameliorated body weight gain, decreased total body fat, regulated expression of leptin and adiponectin genes of adipose tissue and exerted an anti-diabetic effect by attenuating fasting glucose level and serum insulin level in HFD-fed animals. In addition, DSHT-treatment significantly reduced total cholesterol (TC), triglycerides (TG) and increased high density lipoprotein-cholesterol (HDL), glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) levels in serum and reduced deposition of fat droplets in liver. DSHT treatment resulted in significantly increased relative abundance of bacteria including Bacteroidetes, Bacteroidetes/Firmicutes ratio, Akkermansia Bifidobacterium., Lactobacillus, and decreased the level of Firmicutes. Using RT2 profiler PCR array, 39 (46%) genes were found to be differentially expressed in HFD-fed mice compared to normal control. However, normal gene expressions were restored in 36 (92%) genes of HFD-fed mice, when co-exposed to DSHT. CONCLUSION/MAJOR FINDINGS: The results of this study demonstrated that DSHT is an effective herbal formulation in attenuation of obesity in HFD-fed mice through alteration of gene expressions and modulation of intestinal microbiota.