Development of the Korean Medicine Core Outcome Set for Facial Palsy: herbal medicine treatment of patients with facial palsy in primary clinics.

Introduction: Facial palsy (FP) significantly affects the quality of life of patients and poses a treatment challenge in primary healthcare settings. This study aimed to develop a Korean medicine (KM) core outcome set (COS) for FP, with a focus on evaluating the effectiveness of herbal medicine (HM) treatments in KM primary clinics. Methods: Outcomes and effect modifiers related to FP treatments were initially identified through related review articles. Subsequently, experts in the field took part in three rounds of modified Delphi consensus exercises to refine and prioritize these outcomes and effect modifiers. Additionally, primary KM clinicians were involved in a Delphi consensus round to assess the suitability and feasibility of the proposed COS in real-world clinical settings. Results: The initial review of related literature identified 44 relevant studies, resulting in an initial selection of 23 outcomes and 10 effect modifiers. The expert consensus process refined these to 8 key outcomes and 6 effect modifiers, which established the foundation of the COS-FP-KM. Subsequently, primary KM clinicians confirmed the practicality and applicability of the COS, endorsing its suitability for use in KM primary clinics. Conclusion: The COS-FP-KM establishes a standardized approach for assessing HM treatment effectiveness in FP patients in KM primary clinics. The COS-FP-KM encourages consistent outcome reporting and enhances patient care quality. Future work should aim to integrate broader stakeholder perspectives to refine and validate the COS further.

Adverse events of herbal decoction: a systematic review and meta-analysis over past 10 years.

BACKGROUND: Herbal decoctions (HDs) are the oldest and most common herbal medicine formulations. Different HDs exist, and some consumers are concerned that they may become contaminated during manufacturing. Therefore, the need for a safety assessment of HDs has been raised. This study aimed to investigate the adverse events (AEs) associated with HDs by comprehensively analyzing randomized controlled trials (RCTs) using systematic reviews and meta-analyses. METHODS: A systematic search was conducted on PubMed, Embase, and the Cochrane Library for articles published up to November 2022. The included RCTs compared HDs with other treatments published between 2013 and 2022, and the risk of bias was assessed using RevMan 5.4. Meta-analyses of the number of AEs associated with HDs reported in the included RCTs were also performed. RESULTS: The systematic review included 26 RCTs, and the meta-analysis included 17 RCTs that reported AEs. The meta-analysis comparing HDs with active controls showed that both the number of AEs (14 studies; risk ratio (RR)=0.50 cases, 95% confidence interval (CI) [0.29, 0.88]; I2=42%) and the number of patients who complained of AEs (seven studies; RR=0.51 patients, 95% CI [0.28, 0.94]; I2=9%) were fewer in the HDs group than in the active control groups. CONCLUSION: This study showed that HDs are safer than other conventional medications based on the results of qualitative and quantitative syntheses of RCTs.

Bee venom acupuncture and herbal medicine for hand eczema: Two case reports and an in vivo study.

INTRODUCTION: Eczema and contact dermatitis are relatively common, non-life-threatening disease, but can reduce the patient's quality-of-life when it becomes chronic. This study describes two cases of bee venom acupuncture (BVA) and herbal medicine (San Wu Huangqin decoction; SWH) co-treatment for hand eczema and contact dermatitis, then confirms the effect of the combination therapy in an in vivo model of eczema. CASE PRESENTATION: A 56-year-old female (case 1) and a 33-year-old male (case 2) presented to the clinic with symptoms of itching and erythema (case 1), and scaliness (case 2) on both hands. Both were diagnosed with hand eczema and contact dermatitis based on examination of the erythema and scaliness. They were treated with BVA and SWH for three months. The lesions were healed and had not recurred after 1 and 3 years of follow-up. A mouse study was conducted by repeated application of 2,4-dinitrochlorobenzene (DNCB) to induce eczema-like contact dermatitis in Balb/c mice. In a DNCB-induced eczema-like contact dermatitis model, BVA and SWH co-administration synergistically improved clinical symptoms seen in eczema. Also, they improved histological changes of the skin, suppressed immune cell infiltration, and decreased inflammatory cytokines and immunoglobulin E in the serum. CONCLUSION: This study suggests BVA and SWH could be an alternative treatment for eczema and contact dermatitis.

Development of the Blood Stasis Questionnaire for Gynecological Diseases: An Analytical Cross-Sectional Study.

OBJECTIVES: Blood stasis is the slowing or stagnation of blood and can cause metabolic, musculoskeletal, and gynecological diseases. This study developed the Blood Stasis Questionnaire for gynecological disease (BSQ-GD) by extracting clinical indicators related to gynecological diseases using the Blood Stasis Questionnaires I and II (BSQ-I and II, respectively) and analyzed the clinical data of a cross-sectional study. PATIENTS AND METHODS: In total, 103 women aged between 25 and 65 years who met gynecological disease criteria were enrolled in this study. Blood stasis scores (BSS) were evaluated using the BSQ-II and categorized into BSS and non-BSS groups. To assess the reliability of BSQ-GD, the internal consistency coefficient was employed using Cronbach's α. Furthermore, correlation analyses were conducted for the clinical symptoms related to gynecological diseases, and the discriminant validity was confirmed by comparing the two groups. The prediction accuracy was determined using logistic regression and the cut-off value of the BSQ-GD was established via the sensitivity and specificity calculations. RESULTS: The BSQ-GD showed satisfactory internal consistency (Cronbach's α coefficient = 0.71) and validity, with significant differences in mean scores between blood stasis (22.30 ± 3.34) and non-blood stasis (14.93 ± 3.49) groups. The cut-off value of the BSQ-GD score was 19 points when the Youden index (73.45) and the concordance probability (0.75) were at their maximum. The area under the receiver operating characteristic curve was approximately 96%, and the sensitivity and specificity of the diagnostic accuracy according to the cut-off value are 80.95% and 92.50%, respectively. CONCLUSION: The BSQ-GD can be an appropriate instrument to estimate blood stasis in patients with gynecological diseases; its diagnostic sensitivity according to the cut-off value is high.

Safety of herbal decoctions: A scoping review of clinical studies in South Korea focusing on liver and kidney functions.

ETHNOPHARMACOLOGICAL RELEVANCE: Approximately 27% of individuals seeking Korean medicine (KM) services in South Korea are prescribed herbal decoctions. The South Korean government has considered the validity of providing National Health Insurance coverage for herbal decoctions. Therefore, it is important to investigate their safety. AIM OF THE STUDY: To investigate the safety of herbal decoctions commonly prescribed by KM doctors and to assess their effects on liver and kidney function by comprehensively analyzing Korean clinical studies in a scoping review. MATERIALS AND METHODS: The Arksey and O'Malley framework and modified methods were applied in this scoping review. A comprehensive search of seven electronic health databases was conducted, and relevant clinical studies published between 2000 and 2022 were identified. Subsequently, only clinical studies reporting the results of liver and/or renal function tests in patient prescribed herbal decoctions by KM doctors were included. The characteristics of the included clinical studies and the reported proportion of each liver and/or renal function indicator were analyzed. Meta-analyses of the effects of herbal decoction on liver and/or renal function reported in prospective cohort studies were also performed. RESULTS: Fifty-nine clinical studies were included in this review. The proportion of prospective cohort studies markedly decreased in the 2010s compared to the 2000s, while there was no noticeable change in the number of relevant clinical studies. Herbal decoctions were prescribed for less than one month in most included studies. Abnormal changes in liver or renal function indicators were identified in a small number of studies (3.70% and 7.69%, respectively). In a meta-analysis of 15 prospective cohort studies, no statistically significant changes in four liver function indices and two renal function indices were observed before and after the prescription of herbal decoctions. CONCLUSIONS: Qualitative and quantitative analyses demonstrated favorable safety profiles for herbal decoctions. This scoping review includes the gaps noted between clinical application and research regarding the safety profiles of herbal decoctions. These findings could be used as evidence to support the inclusion of herbal decoction prescriptions in the National Health Insurance coverage in South Korea.

The Effects of Acupuncture on Crohn's Disease: a systematic review and meta-analysis.

Objectives: Crohn's disease is a chronic gastrointestinal disease that belongs to inflammatory bowel disease. This systematic review aims to assess the level of evidence in randomized controlled trials (RCTs) on the effects of acupuncture for Crohn's disease. Methods: We searched 12 databases from the date of the establishment of each database up to May, 2023 for relevant RCTs. The risk of bias of each study was assessed independently by three reviewers. The level of evidence of meta-analysis was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Results: A total of 12 studies were included. The effective rate (odds ratio [OR] 3.23, 95% confidence interval [CI] 1.43, 7.30) for mild to moderate Crohn's disease patients showed a significant difference between the acupuncture with moxibustion group and the sham-acupuncture with sham-moxibustion group. CDAI change (mean difference [MD] -74.15, 95% CI -93.28, -55.01) for mild to moderate Crohn's disease showed a significant difference between the acupuncture with moxibustion group and the sham-acupuncture with sham-moxibustion group. Conclusion: Although acupuncture with moxibustion showed significant effects compared to sham-acupuncture with sham-moxibustion, the effect of acupuncture alone is inconclusive. Moreover, only the effect of acupuncture treatment on mild to moderate Crohn's disease patients was derived as a remarkable result. To confirm the effectiveness of acupuncture treatment for Crohn's disease, studies using only acupuncture for intervention or more RCTs targeting various Crohn's disease patients according to the CDAI are required.

Cost-effectiveness analysis of herbal medicines in children with idiopathic short stature.

BACKGROUND: Herbal medicines have been used for a long time to treat idiopathic short stature (ISS) in children in East Asian countries. The aim of this study was to analyze the cost-effectiveness of 5 herbal medicines frequently used in clinical settings for children with ISS based on medical records. METHODS: Patients with ISS who had been prescribed a 60-day supply of herbal medicines in 1 Korean medicine hospital were included in this analysis. Their height and height percentile were measured before and after treatment within 6-months. The average cost-effectiveness ratios (ACERs) of 5 herbal medicines for height (cm) and height percentile were calculated for boys and girls, respectively. RESULTS: The ACERs per 1 cm height growth were USD 56.2 (Naesohwajung-Tang), USD 74.8 (Ogapi-Growth decoction), USD 86.6 (Gamcho-Growth decoction), USD 94.6 (Gwakhyangjeonggi-San plus Yukmijihwang-Tang), and USD 113.8 (Boyang-Growth decoction). The ACERs per 1 percentile height growth were USD 205 (Naesohwajung-Tang), USD 293 (Ogapi-Growth decoction), USD 470 (Gamcho-Growth decoction), USD 949 (Boyang-Growth decoction), and USD 1051 (Gwakhyangjeonggi-San plus Yukmijihwang-Tang). CONCLUSION: Herbal medicine might be a potential economical alternative treatment for ISS.

Bee Venom Acupuncture for Neck Pain: A Review of the Korean Literature.

Bee venom is a natural toxin that is effective in treating various types of pain. The purpose of this paper was to review all the features of clinical studies conducted on bee venom acupuncture (BVA) for the treatment of neck pain in Korean publications. Six Korean databases and 16 Korean journals were searched in August 2022 for clinical studies on BVA for neck pain. We identified 24 trials that met our inclusion criteria, of which 316 patients with neck pain were treated with BVA. The most common diagnosis in the patients with neck pain was herniated intervertebral discs (HIVDs) of the cervical spine (C-spine) (29.2%), and the concentration and dosage per session were 0.05-0.5 mg/mL and 0.1-1.5 mL, respectively. The visual analog scale was most often measured for neck pain severity (62.5%), and all clinical research reported improvements in 16 outcome measures. This study shows that BVA could be recommended for the treatment of neck pain, especially HIVD of the C-spine; however, the adverse effects of BVA must be examined in future studies.

Modified Sipjeondaebo-tang (JAROTANG) for Henoch-Schonlein purpura nephritis (HSPN): Two case reports.

INTRODUCTION: Henoch-Schönlein purpura (HSP) is a disease commonly manifesting purpura, joint pain, and gastrointestinal symptoms. It can lead to glomerulonephritis (Henoch-Schönlein purpura nephritis, HSPN), which is directly associated with mortality and progression to chronic kidney disease (CKD). While HSP occurs more commonly in children, deadly outcomes occur at a higher rate in adult patients. Previous studies have not reported effective treatment of HSPN by Western or traditional medicine. Here, we report two cases of adult HSPN patients treated with the herbal medicine Jarotang (JRT, modified Sipjeondaebo-tang, modified SJDBT). CASE SUMMARY: Two female patients (Cases 1 and 2), who were 26 and 27 years old, respectively, came to visit us complaining mainly of cutaneous purpura. Both women were diagnosed with HSP, and the results of urinalysis indicated that the HSP had already progressed to renal involvement (3+ proteinuria with 3+ urine occult blood in case 1; 100-120 RBC/HPF with 2+ urine occult blood in Case 2). Both patients were given modified SJDBT in the name of JRT, with some herbs added to disperse and circulate stagnant qi, relieve indigestion, and clear heat. After treatment, patient 1 showed only a trace level of urine occult blood, with disappearance of purpura and proteinuria. Patient 2 showed complete remission of purpura and hematuria. CONCLUSIONS: Modified SJDBT, namely, JRT was effective in treating 2 cases of adulthood HSP and subsequent nephritis. This may be due to the ability of this therapy to replenish qi and blood and/or its immunological effect on T cells. The medication can serve as an effective cure for HSPN.

Korean medicine treatment for premature ovarian failure: Three case reports.

INTRODUCTION: Premature ovarian failure (POF) is defined as amenorrhea lasting for more than 4 months before 40 years of age, which is accompanied by a serum follicle-stimulating hormone (FSH) concentration above 40 mlU/mL. POF can cause a series of symptoms associated with low estrogen levels, such as hot flushes, excessive sweating, and infertility. This study aimed to report three cases of POF that were treated successfully with Korean medicine. CASE REPRESENTATION: Three patients with POF were selected for inclusion in this study. The treatment regimen consisted of herbal medicines, electroacupuncture, moxibustion, and Hominis placental pharmacopuncture. The basic treatment period was 3 months, and follow-up was performed after menstrual recovery. Following treatment, all three patients resumed menstruation without any adverse events. One patient also conceived successfully. CONCLUSIONS: These case reports suggest that Korean medicine could be effective for treating POF. Further preclinical and clinical studies are needed to investigate the mechanism of action of herbal medicines and acupuncture in improving menstruation and FSH levels.

Development of the Korean Medicine Core Outcome Set for Primary Dysmenorrhea (COS-PD-KM) for Herbal Medicine Treatment of Primary Dysmenorrhea in Primary Clinics.

The aim of this study was to develop a Korean medicine (KM) core outcome set (COS) for primary dysmenorrhea to evaluate the effectiveness of herbal medicine (HM) in treating primary dysmenorrhea in patients visiting KM primary clinics. Previously reported outcomes were identified through a literature review to define outcomes and effect modifiers (EMs) for the questionnaire. Experts were invited to conduct modified Delphi consensus exercises, and primary care clinicians were invited to conduct Delphi consensus exercises to evaluate suitability and feasibility. Finally, an additional round of a modified Delphi exercise was conducted with experts to obtain a final agreement on the COS. Seventeen outcomes and 15 EMs were included from a literature review, and one effect modifier was suggested by the experts (Phase 1). In Phase 2, after the modified Delphi consensus exercises by experts, 10 outcomes and 11 EMs were included in the COS. The clinicians all agreed on the feasibility of COS (Phase 3). Finally, 10 outcomes and 6 EMs were included in the COS-PD-KM after the final modified Delphi consensus exercise (Phase 4). The effectiveness of HM used in primary clinics could be evaluated with this COS in patients with primary dysmenorrhea. Further studies that involve more relevant stakeholder groups, such as patient representatives and gynecological experts, are needed.

Herbal Medicines for Post-Acute Sequelae (Fatigue or Cognitive Dysfunction) of SARS-CoV-2 Infection: A Phase 2 Pilot Clinical Study Protocol.

Long-term sequelae refer to persistent symptoms or signs for >6 months after SARS-CoV-2 infection. The most common symptoms of sequelae are fatigue and neuropsychiatric symptoms (concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression). However, approved treatments have not been fully established. Herbal medicines are administered for 12 weeks to patients who continuously complain of fatigue or cognitive dysfunction for >4 weeks that only occurred after COVID-19 diagnoses. Based on the Korean Medicine syndrome differentiation diagnosis, patients with fatigue will be administered Bojungikgi-tang or Kyungok-go, whereas those with cognitive dysfunction will be administered Cheonwangbosim-dan. Results could support evidence that herbal medicines may mitigate fatigue and cognitive dysfunction caused by COVID-19. Furthermore, by investigating the effects of herbal medicines on changes in metabolite and immune response due to COVID-19, which may be responsible for sequelae, the potential of herbal medicines as one of the therapeutic interventions for post-acute sequelae of SARS-CoV-2 infection can be evaluated. Therefore, the effects of herbal medicine on fatigue and cognitive dysfunction sequelae due to COVID-19 will be elucidated in this study to provide an insight into the preparation of medical management for the post-acute sequelae of SARS-CoV-2 infection.

Herbal Decoctions for the Levels of Sulfur Dioxide, Benzopyrene, and Mycotoxin from Traditional Korean Medicine Clinics: A Preliminary Study.

In this study, we investigated whether the levels of sulfur dioxide (SO2), benzopyrene, and mycotoxins in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for SO2, benzopyrene, and mycotoxins using 10 samples. SO2 and benzopyrene were not detected in any of the herbal decoctions. With regard to mycotoxins, aflatoxin B1 was not detected, but B2 was detected in 7 cases (0.00~0.04 ppb), G1 in 13 cases (0.03~0.29 ppb), and G2 in 9 cases (0.02~0.93 ppb). None of these values exceeded the restrictions in prior studies. Thus, we confirm that the amounts of SO2, benzopyrene, and mycotoxins in herbal decoctions are at safe levels and provides the basis of establishing safety management criteria for herbal decoctions.

Clinical Practice Pattern of Korean Medicine Doctors in Idiopathic Short Stature Treatment: A Survey Study.

Background: Korean medicine (KM) interventions are attractive for children with idiopathic short stature (ISS). We investigated the real-world clinical practice patterns of KM doctors in ISS treatment. Methods: The survey targeted KM doctors who have treated patients with ISS in KM clinical settings for >3 years. We included questions on the diagnosis and treatment patterns, effects, cost, and opinions of doctors on KM treatment for ISS. A frequency analysis was performed. Results: There were 58 respondents, and "heights of parents" (n = 57, 98.3%), "height, weight, and growth rate of child" (n = 55, 94.8%), and "amount of meals, digestive function" (n = 52, 89.7%) were frequently used as indicators for diagnosis and treatment. The most frequently used KM interventions were "herbal medicine" (n = 58, 100%), "acupuncture" (n = 49, 84.5%), "moxibustion" (n = 38, 65.5%), "dry cupping" (n = 26, 44.8%), and "physiotherapy" (n = 22, 37.9%). Herbal medicines were generally prescribed to tonify the spleen or kidney, and the most frequently used individual herbs were Acanthopanacis cortex, Astragali Radix, and Cervi parvum cornu. The most common acupuncture points were ST36, GB34, SP6, EX-LE5, and LI4. Conclusions: This study showed the use of KM for ISS in real-world clinical settings. In the future, well-designed clinical studies to verify the effect of KM treatment on ISS based on real-world clinical practice patterns should be actively performed.

Clinical Studies of Bee Venom Acupuncture for Lower Back Pain in the Korean Literature.

This study aimed to identify all of the characteristics of bee venom acupuncture (BVA) for the treatment of lower back pain (LBP) that are described in the Korean literature, and to provide English-speaking researchers with bibliometrics. Six Korean electronic databases and sixteen Korean journals on BVA treatment for back pain were searched up to February 2022. This report included and analyzed 64 clinical studies on BVA interventions for back pain and 1297 patients with LBP. The most common disease in patients with back pain was lumbar herniated intervertebral discs (HIVD) of the lumbar spine (L-spine). All studies used bee venom (BV) diluted with distilled water. The concentration of BVA for HIVD of L-spine patients with LBP ranged from 0.01 to 5.0 mg/mL; the dosage per treatment was 0.02-2.0 mL, and for a total session was 0.3-40.0 mL. The most used outcome measure was the visual analogue scale for back pain (n = 45, 70.3%), and most of the papers reported that each outcome measure had a positive effect. Korean clinical studies were typically omitted from the review research, resulting in potential language bias. This study provides clinical cases in Korea for future development and standardization of BVA treatment for back pain.

Utilization of Traditional Korean Medicine Services by the Older Population: A Cross-Sectional Study.

Korean healthcare service is divided into conventional medicine and traditional Korean medicine (TKM). This cross-sectional study compared the older population (65 years and older) with two groups of the general population (19-50 years and 51-64 years) to understand the current patterns in the use of TKM services by the older population. Using data from the 2017 National Survey of TKM Usage, we analyzed the main purpose and diseases or symptoms for TKM use, the reason for choosing TKM over other types of medicine, and the treatments provided. Both age groups sought TKM services to "[treat] a disease". The top five diseases and symptoms in the older adult (65 and older) group were musculoskeletal and are as follows: arthritis and joint diseases (37.8%, n = 166), disc-related diseases (25.5%, n = 112), back pain (8.4%, n = 37), frozen shoulder and shoulder pain (7.7%, n = 34), and sprain (5.9%, n = 26). The most frequently used treatments for these diseases were acupuncture, moxibustion, cupping, and physiotherapy. The present study suggests that older adults primarily used TKM clinics for the treatment of musculoskeletal diseases. Further studies are necessary to assess the clinical effectiveness of conventional medicine versus TKM versus a combination of both in treating musculoskeletal disorders.

Integrative traditional Korean medicine treatment for children with idiopathic short stature: A STROBE-compliant case series.

Integrative traditional Korean medicine (TKM) treatment including herbal medicine and acupuncture has been used frequently by parents in South Korea for the treatment of children with idiopathic short stature (ISS). We aimed to report the TKM treatments currently being used for children with ISS and explore their therapeutic effects. The medical records of children who met the criteria for ISS and who had been treated with TKM for the management of ISS were retrospectively reviewed. In total, 116 patients (mean [standard deviation] age, 8.07 [3.08] years; 52.6% girls) enrolled in the study. Their mean height percentile was 1.45 and body mass index was 16.19 kg/m2. During the study period of 5 years, participants visited the outpatient clinic an average of 2.93 times; the mean number of days to the next visit was 101 days. All patients received herbal medicine treatment, and the formulation was mainly decoction type. Additional treatments including ear acupuncture and moxibustion were also used. After treatment with TKM, the height percentile and standard deviation scores increased in both girls and boys (P < .001 and P < .01, respectively). Additionally, the predicted adult height, estimated based on bone age, increased in girls (P < .05). This study provided preliminary data for future research in TKM use in children with ISS.

Morus alba L. for Blood Sugar Management: A Systematic Review and Meta-Analysis.

Introduction: Morus alba L. is used for blood sugar management in patients with diabetes mellitus. This review aimed to evaluate the effect of Morus alba on blood sugar management. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). We searched PubMed, EMBASE, and four Korean medical databases (RISS, OASIS, NDSL, and KISS) using relevant keywords. Randomized controlled trials with any type of control intervention were included. The selection of studies, data extraction, and quality assessment were performed independently by two researchers. Results: Our results showed that Morus alba can reduce postprandial glucose and insulin levels. However, it is insufficient to conclude that Morus alba is an effective intervention for lowering blood glucose levels. Therefore, more rigorous studies are needed to reveal the effect of MA on blood glucose levels. Conclusion: The conclusion of this review provides evidence that Morus alba can control blood sugar level. This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021255940).

Metabolomic analysis of Gyejibongnyeong-Hwan for shoulder pain: A randomized, wait-list controlled pilot trial.

BACKGROUND: In Korea, Gyejibongnyeong-Hwan (GBH), a herbal decoction used to treat blood stasis (BS), is widely used to treat shoulder pain in clinics. Nevertheless, the therapeutic mechanism of GBH in alleviating shoulder pain has not yet been elucidated. PURPOSE: In this study, we applied mass spectrometry-based metabolomics to explore the therapeutic mechanism of GBH in BS-induced shoulder pain. STUDY DESIGN: We conducted a two-center, randomized, wait-list controlled pilot trial to explore the therapeutic effect of GBH on shoulder discomfort related to BS. METHODS: A total of 40 participants with shoulder pain were randomly assigned to either the immediate treatment (GBH-Treat; n = 20) or waiting treatment (Wait-List; n = 20) group. A non-targeted metabolomics approach was then applied to investigate the therapeutic mechanism of GBH. RESULTS: After 8 weeks of treatment, the visual analog scale (VAS) scores for shoulder pain decreased significantly in the GBH-Treat and Wait-List groups compared with baseline VAS scores (p = 0.004 and p = 0.013, respectively). However, the VAS and BS scores were significantly more reduced in the GBH-Treat group than in the Wait-List group. The plasma metabolic pattern between GBH-Treat and Wait-List groups also differed significantly, which was shown by the score plot of a partial least-squared-discriminant analysis (R2 = 0.806 and Q2 = 0.229, p = 0.016). Arginine, bilirubin, carnitine, glutamine, maltol, mystic acid, N,N dimethylarginine, trimethylamine N-oxide, valine, kynurenine, and linoleic acid significantly contributed to the different metabolic patterns between the GBH-Treat and Wait-List groups (all p < 0.05). Pathway analysis revealed that these metabolites were involved in arginine biosynthesis and tryptophan metabolism, which are related to pain generation and transmission. We also confirmed that the ratio of kynurenine to tryptophan, one of the indicators for chronic pain and neuro-inflammation, was significantly lower in the GBH-Treat group than in the Wait-List group (p = 0.02). CONCLUSION: These results demonstrated that GBH may be a potential treatment option for shoulder pain, and it acts by regulating metabolic patterns. In particular, our study provides evidence for the use of GBH treatment for patients with should pain caused by BS, and we believe that our findings can provide evidence for precision medicine based on traditional Chinese medicine (TCM) or traditional Korean medicine (TKM). We also verified that metabolomics studies provide comprehensive understanding of herbal decoctions in TCM or TKM.

Development of the Korean Medicine Core Outcome Set for Stroke Sequelae: Herbal Medicine Treatment of Elderly Patients With Stroke Sequelae in Primary Clinics.

Objectives: We developed a Korean medicine core outcome set for stroke sequelae (COS-SS-KM) to evaluate the effectiveness and safety of herbal medicine (HM) for stroke sequelae, especially for elderly stroke patients in primary clinics. Methods: We identified previously reported outcomes from a literature review and defined the list of outcomes and effect modifiers for the core outcome set (COS) questionnaire. Three rounds of modified Delphi consensus exercises with experts were conducted online for suitability assessment, and one round of a modified Delphi consensus exercise with primary clinicians was conducted for feasibility assessment. Results: The review identified 17 outcomes and 16 effect modifiers; moreover, six outcomes and one effect modifier were suggested by the experts. The final COS comprised 8 outcomes and 12 effect modifiers for history taking, and experts listed 13 major symptoms of stroke sequelae for symptom assessment. The clinicians agreed on the feasibility of the COS. Conclusion: This COS will help primary care researchers assess the effectiveness of pharmacotherapy, including HM, for elderly patients with stroke sequelae. Future studies should focus on reflecting the opinions of all stakeholders.