Real-world data analysis on effectiveness of integrative therapies: A practical guide to study design and data analysis using healthcare databases.

Real world data (RWD) is increasingly used to investigate health outcomes and treatment efficacy in the field of integrative medicine. Due to the fact that the majority of RWDs are not intended for research, their secondary use in research necessitates complex study designs to account for bias and confounding. To conduct a robust analysis of RWD in integrative medicine, a comprehensive study design process that reflects the characteristics of integrative therapies is necessary. In this paper, we present a guide for designing comparative effectiveness RWE research in integrative medicine. We discuss key factors to consider when selecting RWDs for research on integrative medicine. We provide practical steps for developing a research question, formulating the PICOT objectives (population, intervention, comparator, outcome, and time horizon), and selecting and defining covariates with a summary table. Specific study designs are depicted with corresponding diagrams. Finally, data analysis procedures are introduced. We hope this article clarifies the importance of RWE research design and related processes in order to improve the rigor of RWD studies in the field of integrative medicine research.

ACURATE: a Guide for Reporting Sham Controls in Trials Using Acupuncture.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT), which is to be used with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when real and sham acupuncture needles are used in a study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist in the reporting of sham acupuncture procedures and related components.

Healthcare utilization for atopic dermatitis: An analysis of the 2010-2018 health insurance review and assessment service national patient sample data.

This cross-sectional, retrospective, observational study aimed to analyze the distribution and healthcare usage patterns of patients with atopic dermatitis using the 2010-2018 Health Insurance Review and Assessment Service data. Patients diagnosed with atopic dermatitis in Korea between January 2010 and December 2018 and registered in the Health Insurance Review and Assessment national database were identified, and 270,008 patients who used healthcare services at least once during this period were evaluated to ascertain the healthcare usage patterns and treatment methods for atopic dermatitis. The number of patients with atopic dermatitis plateaued during the study period, while the number of claims and total expenses increased by a small margin. Atopic dermatitis prevalence was the highest among patients aged <5 years (31.4%), followed by those aged 5-14 years (23.53%) and 15-24 years (15.33%). However, the prevalence in these age groups showed a decreasing trend over time. The most used Western medicine treatments were injections and oral medications involving topical corticosteroids, antihistamine agents, and oral steroids, while it was acupuncture therapy in Korean medicine. The frequency of the most frequently prescribed medication, topical corticosteroid, showed a decreasing trend over time. The findings in this study will inform healthcare policy makers and clinicians across different countries on the usage trends of Western medicine and Korean medicine treatment.

ACURATE: A guide for reporting sham controls in trials using acupuncture.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT) and to be used along with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when both real and sham acupuncture needles are used in the study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist reporting of sham acupuncture procedures and the related components.

ACURATE: A guide for reporting sham controls in trials using acupuncture.

OBJECTIVE: To promote better reporting quality regarding sham acupuncture in clinical trials for a precise appraisal of the adequacy of the sham acupuncture procedure. METHODS: A three-stage online Delphi survey was conducted to a group of experts. Items with higher than 80% consensus from the initial checklist were selected as the final candidates. Further discussion among the working group was convened to preclude potential redundancy among the items. RESULTS: A total of 23 experts out of 35 (66%) responded to the Delphi process. The final checklist consists of 23 items in six categories: type of sham acupuncture, details of sham acupuncture manipulation, location of sham acupuncture, treatment regimen, practitioner, and protocol and settings. CONCLUSION: This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT) and to be used along with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when sham acupuncture needles are used in the study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist reporting sham acupuncture procedures and the related components.

Treatment of nausea and vomiting associated with cerebellar infarction using the traditional herbal medicines banhabaekchulcheonma-tang and oryeong-san: Two case reports (CARE-complaint).

RATIONALE: Metoclopramide is commonly used to treat nausea and vomiting. However, long-term administration of metoclopramide is associated with various adverse effects, and its therapeutic effects are short-lasting. Hence, traditional East Asian medicine has received increasing attention as a short-term strategy for treating these symptoms. PATIENT CONCERNS: The present report discusses the cases of a 71-year-old man and an 80-year-old woman diagnosed with cerebellar infarction. Both patients reported nausea and vomiting, which appeared during hospitalization following cerebellar infarction. DIAGNOSES: One patient was diagnosed with a left cerebellar infarction and hemorrhagic transformation, while the other was diagnosed with a bilateral cerebellar infarction. INTERVENTIONS: Both patients took Banhabaekchulcheonma-tang (BT) and Oryeong-san (OS) extracts. OUTCOMES: The patient in Case 1 experienced a rapid decrease in nausea from day 5 of BT and OS administration, and metoclopramide was discontinued on day 7. The patient in Case 2 experienced a clear decrease in the number of vomiting episodes from day 6 of BT and OS administration and did not take metoclopramide thereafter. LESSONS: Other than drugs used to mitigate symptoms, there are no suitable treatments available for nausea and vomiting caused by cerebellar infarction. In the present cases, nausea and vomiting remained unresolved even after 3 weeks of treatment with conventional therapies; however, these symptoms significantly improved after administration of the traditional East Asian herbal medicines BT and OS, and there were no recurrences. These cases demonstrate that traditional herbal medicine can reduce the side effects associated with long-term administration of metoclopramide and help patients resume their daily lifestyle. In addition, BT and OS treatment can facilitate administration of other drugs, highlighting its potential to aid in the treatment of stroke. Further research including relevant clinical trials is required to obtain more conclusive evidence.

Symptom Management and Quality of Life of Breast Cancer Patients Using Acupuncture-Related Therapies and Herbal Medicine: A Scoping Review.

The side effects associated with breast cancer treatments often reduce the patients' quality of life. The effectiveness of acupuncture-related therapies and herbal medicine in managing the side effect is not fully understood. The study included clinical studies published in the 10 years since 2011 and analyzed the effectiveness of the therapies for managing side effects of anticancer treatment. The databases of MEDLINE via PubMed, CENTRAL, EMBASE, OASIS, and NSDL were searched. Thirty studies, including 13 (43.3%) randomized controlled trials (RCTs), 12 (40.0%) before-and-after studies, three (10.0%) case series, one (3.3%) case report, and one (3.3%) non-RCT, were included in this review. The main symptoms identified were aromatase inhibitors-induced arthralgia (AIA), lymphedema, and chemotherapy-induced peripheral neuropathy (CIPN). The types of acupuncture-related therapies applied included manual acupuncture, electro-acupuncture, moxibustion, and electro-moxibustion. In ten studies, eight herbal medications were administered. The Brief Pain Inventory-Short Form (BPI-SF) and Functional Assessment of Cancer Therapy-General (FACT-G) and -Breast (FACT-B) were frequently used to evaluate pain and QoL, respectively. Most studies suggested beneficial effects of acupuncture and herbal medicine on managing pain, daily function, and quality of life in patients going through AIA, CIPN, and/or lymphedema, with mild side effects. The scoping review implies the potential of CAM therapies as promising interventions for managing symptoms which otherwise lack alternative management options, and for improving the quality of life of breast cancer patients.

Acupuncture Regulates Symptoms of Parkinson's Disease via Brain Neural Activity and Functional Connectivity in Mice.

Parkinson's disease (PD) is a multilayered progressive brain disease characterized by motor dysfunction and a variety of other symptoms. Although acupuncture has been used to ameliorate various symptoms of neurodegenerative disorders, including PD, the underlying mechanisms are unclear. Here, we investigated the mechanism of acupuncture by revealing the effects of acupuncture treatment on brain neural responses and its functional connectivity in an animal model of PD. We observed that destruction of neuronal network between many brain regions in PD mice were reversed by acupuncture. Using machine learning analysis, we found that the key region associated with the improvement of abnormal behaviors might be related to the neural activity of M1, suggesting that the changes of c-Fos in M1 could predict the improvement of motor function induced by acupuncture treatment. In addition, acupuncture treatment was shown to significantly normalize the brain neural activity not only in M1 but also in other brain regions related to motor behavior (striatum, substantia nigra pars compacta, and globus pallidus) and non-motor symptoms (hippocampus, lateral hypothalamus, and solitary tract) of PD. Taken together, our results demonstrate that acupuncture treatment might improve the PD symptoms by normalizing the brain functional connectivity in PD mice model and provide new insights that enhance our current understanding of acupuncture mechanisms for non-motor symptoms.

Reporting quality of sham needles used as controls in acupuncture trials: a methodological evaluation.

OBJECTIVE: The description of controls is important in acupuncture clinical trials to interpret its effectiveness without fallacy. This paper aims to evaluate the reporting quality of acupuncture studies on the characteristics of sham needles. STUDY DESIGN AND SETTING: Using a checklist developed from previously published reporting guidelines, the distribution of reported items and changes of reporting rates over time were investigated. Two-way ANOVA and linear regression were conducted. RESULTS: Original articles of RCTs of any design involving sham needles as controls were eligible for assessment. 117 trials from three 2-year time periods between 2009 and 2018 were included. Seven items out of 25 were reported in more than 50% of the studies. While significant differences of reporting scores among categories were observed, there were no significant differences among time periods; no significant improvement was observed over time. CONCLUSIONS: Low reporting qualities of sham needles used in acupuncture studies may influence how researchers understand the effectiveness of acupuncture. This study evaluated previous publications from 2009 to 2018 and found that reporting qualities on sham needles did not improve over time. Further studies are required to validate the items used in this study to endorse better reporting of controls in acupuncture trials.

Healthcare Utilization for Lateral Epicondylitis: A 9-Year Analysis of the 2010-2018 Health Insurance Review and Assessment Service National Patient Sample Data.

This retrospective cross-sectional study examined healthcare utilization among 213,025 patients with lateral epicondylitis over a nine-year period using the 2010-2018 Health Insurance Review and Assessment Service (HIRA) data (ICD code M771). Healthcare utilization, types of treatment, and the route of the visit were analyzed with frequency analysis for Western medicine (WM) and Korean medicine (KM). The findings revealed that the number of patients visiting WM and KM facilities for lateral epicondylitis rose every year from 2010 to 2018. Over this period, the age distribution of patients was 45-54 years (39.93%), 55-64 (23.12%), and 35-44 years (21.07%), and there were slightly more female patients (53.66%) than male patients (46.34%). The number of claims for lateral epicondylitis tended to increase with decreasing average monthly temperature; an increased proportion of middle-aged patients (45-64 years) was the most evident. The most frequently performed interventions in WM were subcutaneous or intramuscular injection (injection), deep heat therapy (physical therapy), and spinal peripheral nerve block-axillary nerve block (treatment/operation); the most frequently performed intervention in KM was acupuncture (injection). For pharmacological treatment, analgesics and anti-inflammatory medications were most frequently prescribed. The findings can be useful for health policymakers and as foundational data for clinicians and researchers.

Successful treatment of restless leg syndrome with the traditional herbal medicines Dangguijakyak-san and Shihogyeji-tang: A case report (CARE-compliant).

RATIONALE: Dopamine replacement is currently the standard treatment for restless leg syndrome (RLS); however, various adverse effects are associated with long-term therapy, and the benefits disappear upon discontinuation. To overcome these limitations, interest in traditional East Asian medicine has increased. PATIENT CONCERNS: A 72-year-old Asian woman originally admitted for an intracerebral hemorrhage presented with complaints of an unpleasant sensation throughout the body that appeared at night. DIAGNOSES: The patient was diagnosed with chronic persistent RLS based on the 2012 Revised International Restless Leg Syndrome Study Group Diagnostic Criteria. INTERVENTIONS: The patient was treated with extracts of the traditional herbal medicines Dangguijakyak-san (DS) and Shihogyeji-tang (ST). After 47 days of therapy, all herbal medicines were discontinued, and symptoms had not returned by the last follow-up 244 days after the initial treatment. OUTCOMES: One week after initiating herbal treatment with DS and ST, the RLS symptoms began to improve, and the total hours of sleep had increased from 2 to 9 hours by day 21, with a Korean version of the international restless legs scale score of 11 points. On day 36, ST was discontinued, given the continued improvement of symptoms. On day 47, symptoms had disappeared (Korean version of the international restless legs scale score: 0), and sleep disturbances caused by RLS had completely resolved. After day 47, DS was also discontinued. There were no adverse effects associated with the administration of DS and ST, and the symptoms had not recurred by the last follow-up on day 244. LESSONS: In this case, RLS related symptoms, which had been present for approximately 60 years, were improved using only the traditional herbal medicines DS and ST (without dopamine replacement), and no symptoms recurred for 244 days. This case suggests that if replacement therapy is difficult or not desired, herbal medicinal therapies may be an effective alternative. This also suggests that the effect of herbal medicine on RLS might be semi-permanent. Further investigations, including clinical trials, are needed to confirm these effects.

Traditional East Asian herbal medicines for the treatment of poststroke constipation: A protocol for systematic review and meta analysis.

BACKGROUND: Post-stroke constipation is a major complication of stroke and increases the incidence of poor neurological outcomes and infectious complications and, therefore, warrants active and prompt treatment. In East Asian countries, several types of herbal medicines have been used for the treatment of post-stroke constipation because they are considered safer than existing pharmacotherapies. However, no systematic review has investigated the efficacy and safety of traditional East Asian herbal medicine in the treatment of post-stroke constipation. With this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of traditional East Asian herbal medicines for the treatment of post-stroke constipation. METHODS AND ANALYSIS: Eight electronic databases will be searched for relevant studies published from inception to April 2021. Only randomized controlled trials (RCTs) that assess the efficacy and safety of traditional East Asian herbal medicines for the treatment of post-stroke constipation will be included in this study. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool. After screening the studies, a meta-analysis of the RCTs will be performed, if possible. RESULTS: This study is expected to generate high-quality evidence of the efficacy and safety of herbal medicines to treat post-stroke constipation. CONCLUSION: Our systematic review will provide evidence to determine whether herbal medicines can be effective interventions for patients with post-stroke constipation. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study was based on a review of published research. This review will be published in a peer-reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION NUMBER: Research registry reviewregistry1117.

Standardized herbal extract PM014 alleviates fine dust-induced lung inflammation in mice.

BACKGROUND: Fine dust penetrates deep into the human alveoli, and the fine dust accumulated in the bronchus and lungs can directly trigger various respiratory diseases. PM014 (HL301) is the herbal extract derived from the herbal medicine Chung-Sang-Bo-Ha-Tang which is used for the treatment of lung diseases. METHODS: To evaluate the effect of PM014 on the lung inflammation induced by fine dust, this study investigated inflammatory responses in the lung upon pm10 exposure by examining the infiltration of inflammatory cell profiles from bronchial alveolar lavage fluid (BALF), lung histology, and production of pro-inflammatory cytokines measured by RT-PCR and ELISA. RESULTS: PM014-treated mice exhibited reduced lung tissue damage and inflammatory cell infiltration. Bronchoalveolar lavage fluid (BALF) analysis showed significant decrease in the population of total cells, macrophages, eosinophils, and neutrophils in PM014-treated mice. PM014 treatment downregulated the pro-inflammatory cytokine expressions including IL-1b, IL-8, IL-6, TNF-alpha, IL-21 and IL-17. ELISA analysis also showed reduced production of IL-1b, IL-6 and IL-17 in PM014-treated mice. CONCLUSION: PM014 suppressed the pm10-induced inflammatory response in mice. This study shows that PM014 is a possible therapeutic agent for lung inflammation induced by fine dust.

Commonality and Specificity of Acupuncture Point Selections.

OBJECTIVE: Because individual acupoints have a wide variety of indications, it is difficult to accurately identify the associations between acupoints and specific diseases. Thus, the present study aimed at revealing the commonality and specificity of acupoint selections using virtual medical diagnoses based on several cases. METHODS: Eighty currently practicing Korean Medicine doctors were asked to prescribe acupoints for virtual acupuncture treatment after being presented with medical information extracted from 10 case reports. The acupoints prescribed for each case were quantified; the data were normalised and compared among the 10 cases using z-scores. A hierarchical cluster analysis was conducted to categorise diseases treated based on the acupoint prescription patterns. Additionally, network analyses were performed on the acupoint prescriptions, at the individual case and cluster level. RESULTS: Acupoints ST36, LI4, and LR3 were most commonly prescribed across all diseases. Regarding the specific acupoints prescribed in each cluster, acupoints around the disease site (knee and lower back) were frequently used in cluster A (musculoskeletal symptoms), acupoints LI4, LR3, PC6, and KI3 were frequently used in cluster B (psychiatric symptoms), and acupoints ST36, LI4, LR3, PC6, CV12, and SP6 were frequently used in cluster C (several symptoms of diseases of internal medicine). CONCLUSIONS: The present study identified the commonality and specificity of acupoint selections based on virtual acupuncture treatments prescribed by practicing clinicians. Acupoint selection patterns, which were defined using a top-down approach in previous studies and classical medical texts, may be further elucidated using a bottom-up approach based on patient medical records.

Treatment of ankle sprain or instability in Korean medicine clinics: A protocol for a prospective multicenter observational study.

BACKGROUND: Korean medicine (KM), including acupuncture, has been used to treat many patients with ankle sprains in Korea. The purpose of this prospective observational study is to determine how ankle sprains are treated using KM practice and to assess the outcomes of these treatments. METHODS: We will perform a prospective observational study to include around 200 participants from KM clinics with a chief complaint of ankle sprain or ankle instability. All participants will receive individualized KM treatments which may include acupuncture, pharmacopuncture, moxibustion, cupping therapy, and herbal medicine. The participants will be assessed on the information related to both ankle discomfort using a visual analogue scale and on the participant's overall condition including quality of life. DISCUSSION: Through this study, we would be able to collect specific and detailed data for various treatments from actual practice, such as the characteristics of the KM treatment system for treating ankle sprains or the method of acupuncture point selection. We also expect that the results of this study based on daily clinical practice will allow other researchers to create research questions that are beneficial from a clinical, societal, and patient's perspective. CLINICAL RESEARCH REGISTRATION: This study has been registered at the Clinical Research Information Service (CRiS) of Korea: KCT0004016.

Prediction model for utilization of complementary and alternative medicine for sports injuries among Korean elite collegiate athletes.

BACKGROUND: The purpose of this study was to describe the use of complementary and alternative medicine (CAM) services by Korean elite collegiate athletes and to examine the factors influencing the utilization of CAM, or Korean Medicine (KM). METHODS: Students in Korea National Sport University (KNSU) enrolled and in training during August to December 2017 completed the survey. Data from the survey was analyzed through path analysis. RESULTS: Students who were training in the Department of Physical Education, KNSU (n = 624, 70% males, mean age 21.3 ± 1.2) participated in this study. 15% of the respondents chose KM clinics for sports injuries, a higher rate than that of the general population, and 44% of KM interventions involved acupuncture. In the path analysis, sports injuries were positive predictors for utilization of medical services and the perception of KM, and KM utilization and the perception of KM were positive predictors of the willingness to receive KM treatments. CONCLUSIONS: The use of KM such as acupuncture was relatively high in elite collegiate athletes. The perception of KM and willingness to receive KM treatments were mediated by previous KM experiences. A higher accessibility towards KM treatments are necessary.

Understanding the multi-herbal composition of Buyang Huanwu Decoction: A review for better clinical use.

ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu Decoction (BHD) is a multi-herbal composition commonly prescribed in the treatment of cerebrovascular diseases such as stroke. Although studies have been conducted at the cellular (in vitro), animal and human (in vivo) level, there was no detailed analysis on how the composition and proportion of BHD is modified according to target diseases. AIM OF STUDY: The purpose of this study is to investigate the composition and proportion of each herb in BHD to summarize how the original BHD was modified according to the target disease. MATERIALS AND METHODS: Electronic literature searches were performed in three databases, collecting sixty-eight studies for the final analysis. The studies were divided into three types: cell studies, animal experiments and clinical trial. In the analysis, the decoction formula including the composition and the weight proportion of the herbs in BHD used in the studies and the target diseases were examined. RESULTS: The result showed that in cell studies, the targets were mostly cell differentiation, cell injury and immune activation. In animal studies, cerebrovascular diseases such as cerebral ischemia were the most identified target diseases followed by nervous system and cardiovascular diseases. While the proportions of the herbs in BHD used in these studies were in general similar to the original formula, some studies reduced the amount of Astragali Radix to half of the original amount. Modified BHDs were used in four studies for cerebrovascular and peripheral nerve diseases. However, no significant correlation has been observed between the target diseases and the change of the proportion of the herbs in BHD. CONCLUSIONS: The most commonly used formula was the original composition of BHD, and modified BHDs were reported to be used to treat cerebrovascular and nervous diseases. Further studies about the effects of BHD by composition and proportion of herbs are needed in the future.

Distribution of monetary incentives in health insurance scheme influences acupuncture treatment choices: An experimental study.

BACKGROUND: Understanding how doctors respond to occupational and monetary incentives in health care payment systems is important for determining the effectiveness of such systems. This study examined changes in doctors' behaviors in response to monetary incentives within health care payment systems in a ceteris paribus setting. METHODS: An online experiment was developed to analyze the effect of monetary incentives similar to fee-for-service (FFS) and capitation (CAP) on doctors' prescription patterns. In the first session, no monetary values were presented. In the second session conducted 1 week later, doctors were randomly assigned to one of two monetary incentive groups (FFS group: n = 25, CAP group: n = 25). In all sessions, doctors were presented with 10 cases and asked to determine the type and number of treatments. RESULTS: In the first session with no monetary incentives, there was no significant difference between the FFS and CAP groups in the number of treatments. When monetary incentives were provided, doctors in the CAP group prescribed fewer treatments than the FFS group. The perceived severity of the cases did not change significantly between sessions and between groups. linear mixed-effects regression model indicated the treatment choices were influenced by monetary incentives, but not by the perceived severity of the patient's symptoms. CONCLUSION: The monetary values incentivized the doctors' treatment choices, but not their professional evaluation of patients. Monetary values designed within health care systems influence the doctor's decisions in the form of external rewards, in addition to occupational values, and can thus be adjusted by more effective incentives.