Individualized Diagnosis and Prescription in Traditional Medicine: Decision-Making Process Analysis and Machine Learning-Based Analysis Tool Development.

While pattern identification (PI) is an essential process in traditional medicine (TM), it is difficult to objectify since it relies heavily on implicit knowledge. Therefore, this study aimed to propose a machine learning (ML)-based analysis tool to evaluate the clinical decision-making process of PI in terms of explicit and implicit knowledge, and to observe the actual process by which this knowledge affects the choice of diagnosis and treatment in individual TM doctors. Clinical data for the development of the analysis tool were collected using a questionnaire administered to allergic rhinitis (AR) patients and the diagnosis and prescription results of TM doctors based on the completed AR questionnaires. Explicit knowledge and implicit knowledge were defined based on the doctors' explicit scoring and feature evaluations of ML models, respectively. There were many differences between the explicit and implicit importance scores in this study. Implicit importance is more closely related to explicit importance in prescription than in diagnosis. The analysis results for eight doctors showed that our tool could successfully identify explicit and implicit knowledge in the PI process. This is the first study to evaluate the actual process by which explicit and implicit knowledge affect the choice of individual TM doctors and to identify assessment tools for the definition of the decision-making process in diagnosing PI and prescribing herbal treatments by TM clinicians. The assessment tool suggested in this study could be broadly used for the standardization of precision medicine, including TM therapeutics.

Autonomic Nervous Function in Patients with Sudden Sensorineural Hearing Loss and Its Association with Prognosis and Disease Severity.

INTRODUCTION: Vascular disorder is considered one of the main mechanisms of sudden sensorineural hearing loss (SSNHL) due to the anatomy of the inner ear. One factor that can contribute to vascular disorder is impairment in the autonomic nervous system. This study aims to investigate autonomic function in patients with SSNHL and its association with prognosis and disease severity from January 2018 to October 2019. METHODS: We conducted a cross-sectional study involving 40 healthy controls and 55 subjects with SSNHL. We compared the autonomic function of controls and patients using heart rate variability (HRV). SSNHL patients were divided into improvement and no-improvement groups and into mild and severe groups according to pure-tone audiometry results. RESULTS: The SSNHL group had significantly decreased total power (TP), low frequency (LF), and high frequency (HF) compared to the control group. However, there were no significant differences between the mild and severe groups. In the no-improvement group, LF was significantly higher and normalized HF was significantly lower than in the improvement group. According to a multiple logistic regression analysis, age and LF were significantly correlated with improvement. CONCLUSION: This is the first study to evaluate the significance of HRV in patients with SSNHL, according to prognosis and disease severity. Further studies about the relationship between autonomic nervous system and SSNHL with larger sample size and prospective design are needed.

Safety and efficacy of an herbal formula, Gwakhyangjeonggi-san on atopic dermatitis with gastrointestinal symptoms: Protocol for a randomized controlled trial.

INTRODUCTION: Gwakhyangjeonggi-san (GJS) is an herbal formula with anti-inflammatory and anti-allergic properties that is broadly used to treat a wide range of diseases including gastrointestinal disorders and allergic diseases. There have been several clinical studies conducted on its effects on atopic dermatitis (AD). So far, no randomized controlled trials have been conducted. Here, we describe the protocol for a randomized controlled study designed to investigate the efficacy and safety of GJS for treating patients with AD that have gastrointestinal symptoms. METHODS AND ANALYSIS: A randomized, double-blind, placebo-controlled, parallel-group, clinical trial has been designed to investigate the clinical efficacy and safety of GJS on patients with AD that have gastrointestinal symptoms. A total of 58 participants with AD will be recruited and randomly allocated to the GJS or placebo group in a 1:1 ratio. The participants will be administered GJS or placebo granules 3 times a day for 8 weeks. Data will be collected from the participants at baseline and after 4 and 8 weeks. The primary outcome measure will be the mean change in the SCORing of Atopic Dermatitis (SCORAD) index from baseline to 8 weeks. The secondary outcomes will include the eczema area and severity index (EASI), dermatology life quality index (DLQI), EuroQoL 5 dimensions 5 levels (EQ-5D-5L), and immunological factors. The Korean Gastrointestinal Symptom Rating Scale (KGSRS), Nepean Dyspepsia Index will also be obtained for assessing the gastrointestinal status. DISCUSSION: The findings of this study are expected to provide evidence on the safety and effectiveness of GJS and for treating patients with AD that have gastrointestinal symptoms. Additionally, the study will explore the mechanism of GJS action via gut microbiome. This study will provide new perspectives on approaching treatment for AD. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of Kyung Hee University Korean Medicine Hospital at Gangdong (KHNMCOH2019-06-002-001). TRIAL REGISTRATION NUMBER: This study has been registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0004299).

A multicenter study on the efficacy and safety of So-Cheong-Ryong-Tang for perennial allergic rhinitis.

BACKGROUND: So-Cheong-Ryong-Tang (SCRT), also known as Xiao-Qing-Long-Tang or Sho-seiryo-to, is a mixed herbal formula that is used to treat allergic rhinitis, bronchitis, allergic asthma, and common cold in traditional Korean medicine. OBJECTIVE: To assess the efficacy and safety of the SCRT for the treatment of allergic rhinitis. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group, multicenter study of Korean adults with perennial allergic rhinitis. The trial consisted of a 4-week oral administration of SCRT or placebo, with two visits at 2-week intervals, and an 8-week follow-up period, with two visits at 4-week intervals. The primary outcome was a change in the total nasal symptoms score. The secondary outcomes included changes in the Rhinoconjunctivitis Quality of Life Questionnaire score, total serum immunoglobulin E (IgE), cytokines levels, and nasal endoscopy index. RESULTS: SCRT improved nasal symptoms and quality of life in patients with PAR after 4 weeks medication, and these effects did not last 8 weeks after the end of medication. The level of serum IgE, eosinophil counts, and cytokines did not alter after medication. Nasal endoscopy index did not show significant difference. No serious AEs and safety assessment changes were observed in this trial. CONCLUSION: SCRT is an effective and safe medication for patients with chronic, perennial, and moderate to severe AR. A clinical study with a >4-week period of medication use, and more participants for immune material test is needed to investigate the long-term efficacy of SCRT in relieving the symptoms of nasal obstruction and identifying the underlying mechanisms of action and indications for traditional Korean medicine.

Clinical efficacy of herbal extract cream on the skin hydration, elasticity, thickness, and dermis density for aged skin: A randomized controlled double-blind study.

BACKGROUND: Traditional medicine herbal prescriptions used for the treatment of skin disease have been developed into cosmetics. Sang-Hyul-Yun-Boo-Em (SHYBE) is a mixed herbal formula prescribed for patients with yin or blood deficiency patterns of skin disease. A previous study reported that SHYBE exercises anti-allergic and anti-inflammatory effects. To date, no study has reported the efficacy of cosmetics containing the SHYBE extract. AIMS: To observe the efficacy of SHYBE extract cream on hydration, elasticity, thickness, and dermis density in aged skin. METHODS: This was a double-blind randomized placebo-controlled parallel-group trial. The trial consisted of an 8-week topical application of the test or placebo products with two visits at 4-week intervals. A total of 46 healthy Korean females, aged 40-59, were enrolled in this study. Objective skin assessments for hydration, elasticity, thickness and dermis density, self-assessment, and safety assessment were conducted. RESULTS: Sang-Hyul-Yun-Boo-Em extract cream improved skin hydration, elasticity, and dermal density in Asian middle-aged females compared with placebo cream, which excluded SHYBE extract and contained other cosmetic materials. CONCLUSIONS: Sang-Hyul-Yun-Boo-Em extract cream showed anti-aging properties in middle-aged women. It could be recommended for aging skin with dryness, and loss of elasticity and density.

Delayed recovery of pediatric sudden sensorineural hearing loss treated with acupuncture: A case report.

RATIONALE: The rate of spontaneous recovery of sudden sensorineural hearing loss (SSNHL) has been reported to be as high as 32% to 65%. Although the majority of spontaneous recoveries occur within 2 weeks, treatment of refractory SSNHL failing conventional therapy is difficult. In particular, it is more difficult to treat children-who have a worse prognosis than adults-with SSNHL refractory to conventional therapy. No studies reported delayed recovery of pediatric SSNHL later than 3 months after onset, or delayed recovery treated with acupuncture. PATIENT CONCERNS: A 15-year-old girl experienced hearing loss after acquiring a cold. DIAGNOSIS: She did not undergo audiometry and only took medicine for a common cold after diagnosis by an internal medicine doctor. Ninety-three days after onset, she visited an otorhinolaryngology clinic and was diagnosed with SSNHL. Seven rounds of intratympanic steroid (ITS) treatment were performed 93 to 135 days after onset; audiogram at 149 days did not demonstrate improvement. INTERVENTIONS: Two-hundred sixty-six days after onset, she visited to TKM hospital and was admitted for 21 days and received outpatient treatment for 1 month after discharge. She was treated acupuncture, transcutaneous electrical nerve stimulation, and moxibustion. OUTCOMES: She experienced improvement in experienced improvement in pure tone average, speech recognition threshold, and word recognition scores after acupuncture treatment. Delayed ITS treatment at 93 to 135 days after onset did not improve the patient's hearing loss. However, slight recovery was achieved at the conclusion of treatment. LESSONS: Acupuncture may be a therapeutic option for individuals who do not experience improvement after the use of steroids or miss early treatment.

Exploring the efficacy and safety of topical Jaungo application in patients with atopic dermatitis: A pilot randomized, double-blind, placebo-controlled study.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease with an increasing prevalence. In Korea, Jaungo is a traditional medicinal ointment, which is commonly used for treating skin wounds. OBJECTIVE: Thus, we aim to explore the basic clinical efficacy and safety data for Jaungo in patients with AD. METHODS: This study was a pilot randomized, double-blind, placebo-controlled, single-center trial with three groups. The participants in treatment group 1 applied Jaungo to the lesion twice a day for 3 weeks. Those in treatment group 2 applied Jaungo and placebo ointments to the lesion once a day for 3 weeks. Those in the placebo group applied placebo ointments to the lesion twice a day for 3 weeks. The Eczema Area and Severity Index and SCORing Atopic Dermatitis scores, transepidermal water loss value, and Dermatology Life Quality Index score were assessed. The outcomes used to evaluate safety were the Draize score, blood test results, and expert opinion. RESULTS: In total, 28 patients (82.4%) completed the study. During the study, significant decline of EASI scores in treatment group 2 and placebo group was observed (p < 0.05). And there was significant decline of SCORAD scores in treatment group1 and placebo group (p < 0.05). Patients in all groups showed decreased TEWL and DLQI scores with no significant difference. There was significant decline of IL-17 in all groups (p < 0.05). No serious adverse event was observed. CONCLUSION: This is the first study that has explored the potential therapeutic effect of Jaungo as a complementary therapy for AD. However, further large study with adjusting placebo ingredients is needed to confirm the effectiveness of Jaungo in patients with chronic-phase AD.

Efficacy and safety of So-Cheong-Ryong-Tang in treatment of perennial allergic rhinitis: study protocol for a double-blind, randomised, parallel-group, multicentre trial.

INTRODUCTION: So-Cheong-Ryong-Tang (SCRT) is a herbal medicine widely used in traditional medicine for treating allergic rhinitis (AR). In animal studies, SCRT has suppressed the progression of AR. The main purpose of this study is to assess the efficacy and safety of the SCRT for the treatment of perennial allergic rhinitis (PAR) and discover the underlying mechanisms resulting in anti-inflammatory effects in humans. METHODS AND ANALYSIS: We will conduct a double-blind, randomised, placebo-controlled, parallel-group, multicentre trial of Korean adults with PAR. For the study, 156 subjects with PAR will be recruited. The trial will consist of a 4-week oral administration of SCRT or placebo with two visits at 2-week intervals and an 8-week follow-up period with two visits at 4-week intervals. The primary outcome is a change in the total nasal symptoms score. The secondary outcomes include changes in the Rhinoconjunctivitis Quality of Life Questionnaire score, total serum IgE and cytokines levels. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board at each research centre (name of each centres and approval numbers): Kyung Hee University Hospital at Gangdong (KHNMC-OH-IRB 2015-04-009), Kyung Hee University Medical Centre (KOMCIRB-160321-HRBR-011), Pusan National University Hospital (2016-004), Dongguk University Medical Centre (2016-03) and Semyung University hospital (2016-01). This result will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03009136; Pre-results.

Effectiveness and safety of combination treatment of herbal medicines and oral antihistamines for atopic dermatitis: a retrospective chart review.

BACKGROUND: Patients with atopic dermatitis (AD) exhibit various symptoms, especially itching. Recently, herbal medicines (HMs) are being used in combination with antihistamines for the treatment of AD in Korea. While oral antihistamines can alleviate itching, HMs appear to exert anti-inflammatory effects with minimal side effects. However, there is little evidence regarding the effectiveness and safety of using HMs in combination with antihistamines for AD. METHODS: To observe the effectiveness and safety of combination treatment with HMs and antihistamines, we performed a retrospective chart review of inpatients with AD who received this combination treatment for at least 7 days in a hospital. RESULTS: Of 163 inpatients, 40 met the inclusion criteria. All patients received HMs three times, and one or two antihistamines, a day after HM intake. A large proportion of patients received first-generation antihistamines. HMs comprised a mixture of an average of 20.69 different herbs in decoction. The mean total, objective, and subjective SCORing Atopic Dermatitis scores showed a significant decrease after combination treatment. Changes in the mean levels of aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine were not statistically significant among treatments. There were no adverse events of pseudoaldosteronism or interstitial pneumonia. CONCLUSION: We observed that the short-term use of HMs in combination with oral antihistamines was safe and effective, with a low risk of adverse reactions. This study was limited by its retrospective design, and prospective studies with long-term follow-up periods are warranted to further elucidate the safety of this combination treatment for AD.

Exploring syndrome differentiation using non-negative matrix factorization and cluster analysis in patients with atopic dermatitis.

Syndrome differentiation (SD) results in a diagnostic conclusion based on a cluster of concurrent symptoms and signs, including pulse form and tongue color. In Korea, there is a strong interest in the standardization of Traditional Medicine (TM). In order to standardize TM treatment, standardization of SD should be given priority. The aim of this study was to explore the SD, or symptom clusters, of patients with atopic dermatitis (AD) using non-negative factorization methods and k-means clustering analysis. We screened 80 patients and enrolled 73 eligible patients. One TM dermatologist evaluated the symptoms/signs using an existing clinical dataset from patients with AD. This dataset was designed to collect 15 dermatologic and 18 systemic symptoms/signs associated with AD. Non-negative matrix factorization was used to decompose the original data into a matrix with three features and a weight matrix. The point of intersection of the three coordinates from each patient was placed in three-dimensional space. With five clusters, the silhouette score reached 0.484, and this was the best silhouette score obtained from two to nine clusters. Patients were clustered according to the varying severity of concurrent symptoms/signs. Through the distribution of the null hypothesis generated by 10,000 permutation tests, we found significant cluster-specific symptoms/signs from the confidence intervals in the upper and lower 2.5% of the distribution. Patients in each cluster showed differences in symptoms/signs and severity. In a clinical situation, SD and treatment are based on the practitioners' observations and clinical experience. SD, identified through informatics, can contribute to development of standardized, objective, and consistent SD for each disease.

Topical application of Jaungo in atopic dermatitis patients: study protocol for a randomized, controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with increasing prevalence. It can manifest with many different clinical phenotypes; however, in its chronic stage, hyperpigmentation, excoriation, lichenification, and dryness are the main symptoms. Jaungo comprises two herbs, Lithospermi radix and Angelica gigantis radix, and three carrier oils, and is an approved herbal ointment for xerosis cutis in Korea. In past studies, we demonstrated that Jaungo had anti-inflammatory and antiallergic activity in in vitro and in vivo AD models; however, there are few relevant randomized controlled clinical trials on Jaungo in AD. METHODS/DESIGN: A randomized, double-blind, placebo-controlled, single-center, phase IIa clinical trial was designed to investigate the safety, preliminary efficacy, and dose response of Jaungo in AD. The study protocol was approved by the Institutional Review Boards of the Kyung Hee University Korean Medicine Hospital (No. KOMCIRB-160617-HR-027) and the Korea Food and Drug Administration (No. 30907). The study aims to enroll 34 AD patients to be randomly distributed among three parallel groups: treatment 1, treatment 2, and the placebo group. Treatment group 1 applies Jaungo twice a day, while treatment group 2 applies Jaungo and the placebo ointment once a day, separately, and the placebo group applies the placebo ointment twice a day, for a total of 3 weeks each. Participants will be evaluated for eczema before and after the application of the ointments based on several parameters including the Eczema Area and Severity Index, the SCORing of Atopic Dermatitis Index, the Dermatology Life Quality Index, transepidermal water loss, total IgE level, eosinophil count, and IL-17, IL-22, and IFN-γ levels. DISCUSSION: The trial is currently ongoing and the enrollment of subjects has been initiated. There is an urgent need to develop a drug for the treatment of dry, hyperpigmented, scaly, and thickened skin in chronic-stage AD. This study will determine the efficacy and safety of Jaungo in AD, providing evidence for specific AD symptoms treated by Jaungo. TRIAL REGISTRATION: Clinical Trials.gov, identifier: NCT02900131 . Registered on 2 September 2016. Korea Clinical Research Information Service, identifier: KCT0002060 . Registered on 22 July 2016.

Autonomic function in adults with allergic rhinitis and its association with disease severity and duration.

BACKGROUND: The association between allergic rhinitis (AR) and the autonomic nervous system (ANS) has recently received substantial attention. However, no studies have assessed how the heart rate variability (HRV) parameters are associated with duration and disease severity in AR. OBJECTIVE: To compare the difference in autonomic conditions among individuals with AR of various durations and severities and healthy controls. METHODS: We divided individuals with AR into subgroups based on duration and severity of disease. Next, we measured HRV, and the results were compared among subgroups and healthy controls. RESULTS: High frequency (HF) and normalized high frequency (NHF) were significantly higher in the intermittent group than in the control group, whereas normalized low frequency (NLF) and the ratio of absolute LF to HF power (LF/HF) were significantly lower in the intermittent group than in the control group. Furthermore, NLF was significantly higher in the persistent group than in the intermittent group. HF and NHF were significantly higher in the mild group than in the control group, whereas NLF and LF/HF were significantly lower in the mild group than in the control group. The total nasal symptom and itchy nose scores were negatively correlated with NHF. CONCLUSION: Our results indicate that patients with intermittent and mild AR have hypervagal activity and hyposympathetic activity, and the predominance lessens in patients with more persistent AR and severe symptoms. Further investigation of the mechanisms underlying the association between autonomic function and persistent and severe AR is needed.

Effect of thread embedding acupuncture for facial wrinkles and laxity: a single-arm, prospective, open-label study.

BACKGROUND: There is a growing trend for patients to seek the least invasive treatments with less risk of complications and downtime for facial rejuvenation. Thread embedding acupuncture has become popular as a minimally invasive treatment. However, there is little clinical evidence in the literature regarding its effects. METHODS: This single-arm, prospective, open-label study recruited participants who were women aged 40-59 years, with Glogau photoaging scale III-IV. Fourteen participants received thread embedding acupuncture one time and were measured before and after 1 week from the procedure. The primary outcome was a jowl to subnasale vertical distance. The secondary outcomes were facial wrinkle distances, global esthetic improvement scale, Alexiades-Armenakas laxity scale, and patient-oriented self-assessment scale. RESULTS: Fourteen participants underwent thread embedding acupuncture alone, and 12 participants revisited for follow-up outcome measures. For the primary outcome measure, both jowls were elevated in vertical height by 1.87 mm (left) and 1.43 mm (right). Distances of both melolabial and nasolabial folds showed significant improvement. In the Alexiades-Armenakas laxity scale, each evaluator evaluated for four and nine participants by 0.5 grades improved. In the global aesthetic improvement scale, improvement was graded as 1 and 2 in nine and five cases, respectively. The most common adverse events were mild bruising, swelling, and pain. However, adverse events occurred, although mostly minor and of short duration. CONCLUSION: In this study, thread embedding acupuncture showed clinical potential for facial wrinkles and laxity. However, further large-scale trials with a controlled design and objective measurements are needed.

Hyeonggaeyeongyo-Tang for Treatment of Allergic and Nonallergic Rhinitis: A Prospective, Nonrandomized, Pre-Post Study.

Hyeonggaeyeongyo-tang (HYT) is an ancient formula of oriental medicine traditionally used to treat rhinitis; however, clinical evidence has not yet been established. The aim of this study was to investigate the short-term and long-term efficacy and safety of HYT for chronic rhinitis. Adult subjects with chronic rhinitis symptoms were recruited. The subjects received HYT for 4 weeks and had follow-up period of 8 weeks. Any medicines used to treat nasal symptoms were not permitted during the study. The skin prick test was performed to distinguish the subjects with allergic rhinitis from those with nonallergic rhinitis. After treatment, the total nasal symptoms score and the Rhinoconjunctivitis Quality of Life Questionnaire score significantly improved in the whole subject group, in the allergic rhinitis group, and in the nonallergic rhinitis group, with no adverse events. This improvement lasted during a follow-up period of 8 weeks. Total IgE and eosinophil levels showed no significant difference after treatment in the allergic rhinitis group. HYT improved nasal symptoms and quality of life in patients with allergic rhinitis and nonallergic rhinitis. This is the first clinical study to evaluate the use of HYT to treat patients with rhinitis. This trial has been registered with the ClinicalTrials.gov Identifier NCT02477293.

Three Cases of Cutaneous Warts Treated With Moxibustion.

Moxibustion is a treatment that uses thermal stimulation generated when herbal materials are burned, indirectly or directly, on the affected area or acupoint. Three cases are presented to report the efficacy of direct moxibustion on cutaneous warts. Three patients with chronic cutaneous warts received direct moxibustion made of Artemisia argyi (Dongbang Inc., Chungnam, Korea). Moxa burning was performed using moxa cones. Approximately 80% of a cone was burned, until patients reported feeling a burning sensation, at which time the cone was removed and another one burned. As part of this approach, patients underwent 5-19 moxibustion procedures during and after wart removal. After warts were completely eliminated, moxa burning was performed on each patient until approximately 60% of a cone was burned or the patient felt heat sensitization but no pain. In these cases, moxibustion seemed to have an effect on cutaneous warts. A possible mechanism is that direct moxibustion likely induces tissue damage from burning and, subsequently, a wound healing effect at a different temperature level. Our reports suggest that it would be worthwhile to conduct further studies on the safety and efficacy of moxibustion on warts or to develop a medical device that uses modified moxibustion.

Topical herbal application in the management of atopic dermatitis: a review of animal studies.

Herbs are widely used in the treatment of atopic dermatitis (AD) in Eastern Asian countries, and certain herbs regarded have anti-inflammatory properties that can help with AD. With the goal of developing a topical herbal agent for AD, we conducted a systematic review of in vivo studies of AD-like skin models for screening potential herbs. Searches were conducted from PubMed and EMBASE. After all, 22 studies were included for this review. We judged most of the domains of all studies to be at unclear risk of bias. Among 22 included studies, 21 herbs have been reported to reduce AD-like skin lesions in mouse models by suppressing Th2 cell response. Our findings may offer potential herbs for the topical application treatment of AD.