Comparative study for fatigue prevalence in subjects with diseases: a systematic review and meta-analysis.

Fatigue is one of the common symptoms in individuals with diseases or disorders, significantly affecting quality of life (QoL) and the prognosis of diseases. This study aimed to comprehensively compare the features of fatigue across a wide range of diseases. We systematically searched the PubMed and Cochrane Library databases from inception to March 31st, 2021, and conducted a meta-analysis to generate precise estimates. The analyses were stratified by classification of diseases, gender, and severity of fatigue (moderate and severe), and study quality was assessed using the Newcastle-Ottawa Scale (NOS). In total, 214 articles (233 prevalence data) met our eligibility criteria, covering 102,024 participants (mean 438 ± 1,421) across 88 diseases. Among these, seventy-eight data sets (52,082 participants) and thirty-nine data sets (10,389 participants) reported gender- and severity-related fatigue prevalence. The overall prevalence among subjects with 88 diseases was 49.4% [95% CI 46.9-52.1]. According to the International Classification of Diseases-10 (ICD-10) classification, the highest prevalence of fatigue (65.9% [95% CI 54.9-79.6]) was observed in patients with mental/behavioral diseases, whereas the lowest prevalence (34.7% [95% CI 24.5-49.2]) was found among those with circulatory system diseases. A slight female dominance (43.5% vs. 49.8%) was observed in the total data, with the most notable female predominance (1.8-fold) seen in patients with low back pain. The top disease groups with a moderate to severe level of fatigue included gastroparesis (92.3%), pulmonary hypertension (90.0%), chronic obstructive pulmonary disease (COPD, 83.2%), and multiple sclerosis (80.0%). These results are the first to comprehensively show the comparative features of fatigue prevalence among subjects across 88 diseases. Our findings provide valuable reference data for future research on fatigue and for the management of patients with fatigue.Prospero registration number: CRD42021270494.

Effectiveness of meditation for fatigue management: Insight from a comprehensive systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis revealed the effectiveness of meditation in addressing fatigue, given its widespread use as a remedy for sleep disturbances and fatigue. METHOD: We analyzed 29 randomized controlled trials from MEDLINE and the Cochrane Library, spanning from December 31, 2022. We conducted two metaanalyses using mean difference (MD) with normalized data and standardized mean difference (SMD) with original data. RESULTS: These trials included various populations, with baseline fatigue severity observed at 52.2 ± 16.0 points among 4104 participants. After an average meditation duration of 9.6 ± 4.7 weeks, fatigue scores decreased significantly by 6.4 points of MD [95% CI, 4.3-8.5] compared to controls. The most significant reduction occurred in the sub-healthy group (MD 8.2 [95% CI, 2.7 to 13.8]), followed by the general group (MD 6.9 [95% CI, 0.4 to 13.4]), and the disease group (MD 5.7 [95% CI, 3.4 to 8.0]). Notably, meditation-based anti-fatigue effects were particularly pronounced for mental fatigue (MD 10.0 [95% CI, 4.3 to 15.6]), especially with expert guidance and supplementary homework. CONCLUSION: These findings align with meta-analysis results using standardized mean difference (SMD), providing evidence for meditation as an effective nonpharmacological intervention for fatigue management, while also informing effective meditation approaches. REGISTRATION NUMBER: CRD42023395551 in PROSPERO.

Systematic review of fatigue severity in ME/CFS patients: insights from randomized controlled trials.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness medically unexplained, affecting approximately 1% of the global population. Due to the subjective complaint, assessing the exact severity of fatigue is a clinical challenge, thus, this study aimed to produce comprehensive features of fatigue severity in ME/CFS patients. METHODS: We systematically extracted the data for fatigue levels of participants in randomized controlled trials (RCTs) targeting ME/CFS from PubMed, Cochrane Library, Web of Science, and CINAHL throughout January 31, 2024. We normalized each different measurement to a maximum 100-point scale and performed a meta-analysis to assess fatigue severity by subgroups of age, fatigue domain, intervention, case definition, and assessment tool, respectively. RESULTS: Among the total of 497 relevant studies, 60 RCTs finally met our eligibility criteria, which included a total of 7088 ME/CFS patients (males 1815, females 4532, and no information 741). The fatigue severity of the whole 7,088 patients was 77.9 (95% CI 74.7-81.0), showing 77.7 (95% CI 74.3-81.0) from 54 RCTs in 6,706 adults and 79.6 (95% CI 69.8-89.3) from 6 RCTs in 382 adolescents. Regarding the domain of fatigue, 'cognitive' (74.2, 95% CI 65.4-83.0) and 'physical' fatigue (74.3, 95% CI 68.3-80.3) were a little higher than 'mental' fatigue (70.1, 95% CI 64.4-75.8). The ME/CFS participants for non-pharmacological intervention (79.1, 95% CI 75.2-83.0) showed a higher fatigue level than those for pharmacological intervention (75.5, 95% CI 70.0-81.0). The fatigue levels of ME/CFS patients varied according to diagnostic criteria and assessment tools adapted in RCTs, likely from 54.2 by ICC (International Consensus Criteria) to 83.6 by Canadian criteria and 54.2 by MFS (Mental Fatigue Scale) to 88.6 by CIS (Checklist Individual Strength), respectively. CONCLUSIONS: This systematic review firstly produced comprehensive features of fatigue severity in patients with ME/CFS. Our data will provide insights for clinicians in diagnosis, therapeutic assessment, and patient management, as well as for researchers in fatigue-related investigations.

Efficacy of Moxibustion for Cancer-Related Fatigue in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Breast cancer is the most commonly diagnosed cancer worldwide, and most patients experience fatigue. However, there are no effective treatments for cancer-related fatigue (CRF). Several randomized controlled trials (RCTs) have suggested that moxibustion improves CRF. We conducted a systematic review and meta-analysis to compare the differences in fatigue scale scores, quality of life, and clinical efficacy in patients with breast cancer who developed CRF and did versus did not receive moxibustion. METHODS: RCTs were searched in 7 databases using a standardized search method from database inception to March 2023, and RCTs that met the inclusion criteria were selected. RESULTS: Among 1337 initially identified RCTs, 10 RCTs involving 744 participants were selected for this study. The meta-analysis involved assessment of the revised Piper Fatigue Scale scores, Cancer Fatigue Scale scores, Karnofsky Performance Scale scores, Athens Insomnia Scale scores, clinical efficacy, and Qi deficiency syndrome scale scores. Compared with the control, moxibustion was associated with significantly better Piper Fatigue Scale scores (P < 0.0001), quality of life [Karnofsky Performance Scale scores (P < 0.0001)], clinical efficacy (P = 0.0007), and Qi deficiency syndrome scale scores (P = 0.02). CONCLUSIONS: Moxibustion improves CRF in patients with breast cancer. The efficacy of moxibustion should be further examined by high-quality studies in various countries with patients subdivided by their breast cancer treatment status. REGISTRATION: PROSPERO ID: CRD42023451292.

The Clinical Diagnosis-Based Nationwide Epidemiology of Metabolic Dysfunction-Associated Liver Disease in Korea.

BACKGROUND: Although most epidemiological studies have been conducted using a relatively small population or subjects who had medical screenings, the present study aimed to investigate the incidence and prevalence of MASLD (formerly NAFLD) in Korea using nationwide registry data provided by the Health Insurance Review and Assessment Service (HIRA). METHODS: Using nationwide medical records provided by HIRA, we analyzed the entire dataset of patients with MASL (KCD10-K76.0) and MASH (KCD10-K75.8) from 2010 to 2021 and calculated the incidence and prevalence by year, age, and gender. The prevalence and incidence rates were calculated by analyzing the HIRA data covering almost the entire population of Korea for 12 years, from 2010 to 2021, with an average population of 50,856,244 during this period. Statistical analyses included calculating confidence intervals using Ulm's formula and conducting sex- and age-specific analyses with a Cochran-Armitage test for trends. RESULTS: The annual incidence of MASL/MASH increased significantly from 9.71/0.37 in 2010 to 13.95/5.52 per 1000 persons in 2021 (p < 0.01). The annual prevalence of MASL increased from 15.69 in 2010 to 34.23 per 1000 persons in 2021, while the annual prevalence of MASH increased from 0.49 to 9.79 per 1000 persons between 2010 and 2021 (p < 0.01). Regarding the sex-dimorphic feature of MASLD, there was a male predominance in those < 50 years old but a female predominance in those ≥ 50 years old for the incidence and prevalence of MASL and the incidence of MASH. CONCLUSION: The incidence of MASL increased by 3% to 4% every year, while the incidence of MASH increased 14.91-fold from 2010 to 2021. The increasing trend is noteworthy compared with previous reports.

Prevalence of cancer-related fatigue based on severity: a systematic review and meta-analysis.

Cancer-related fatigue (CRF) affects therapeutic compliance and clinical outcomes including recurrence and mortality. This study aimed to comprehensively and comparatively assess the severity-based prevalence of CRF. From two public databases (PubMed and Cochrane Library), we extracted data containing information on both prevalence and severity of fatigue in cancer patients through December 2021. We conducted a meta-analysis to produce point estimates using random effects models. Subgroup analyses were used to assess the prevalence and severity by the organ/system tumor development, treatment phase, therapeutic type, sex and assessment method. A total of 151 data (57 studies, 34,310 participants, 11,805 males and 22,505 females) were selected, which indicated 43.0% (95% CI 39.2-47.2) of fatigue prevalence. The total CRF prevalence including 'mild' level of fatigue was 70.7% (95% CI 60.6-83.3 from 37 data). The prevalence of 'severe' fatigue significantly varied by organ/system types of cancer origin (highest in brain tumors 39.7% vs. lowest in gynecologic tumors 3.9%) and treatment phase likely 15.9% (95% CI 8.1-31.3) before treatment, 33.8% (95% CI 27.7-41.2) ongoing treatment, and 24.1% (95% CI 18.6-31.2) after treatment. Chemotherapy (33.1%) induced approximately 1.5-fold higher prevalence for 'severe' CRF than surgery (22.0%) and radiotherapy (24.2%). The self-reported data for 'severe' CRF was 20-fold higher than those assessed by physicians (23.6% vs. 1.6%). Female patients exhibited a 1.4-fold higher prevalence of 'severe' fatigue compared to males. The present data showed quantitative feature of the prevalence and severity of CRF based on the cancer- or treatment-related factors, sex, and perspective of patient versus physician. In the context of the medical impact of CRF, our results provide a comparative reference to oncologists or health care providers making patient-specific decision.

The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis.

Background: Fatigue is one of the most common subjective symptoms that impairs daily life and predict health-related events. This study aimed to estimate the prevalence of fatigue in the global population. Methods: PubMed and the Cochrane Library were used to search for relevant articles from inception to December 31, 2021. Studies with prevalence data of fatigue in the general population were selected and reviewed by three authors independently and cross-checked. Regarding subgroups, adults (≥18 years), minors (<18 years), and specific occupation population (participants in each study being limited to a specific occupational group), and fatigue types and severity, meta-analysis was conducted to produce point estimates and 95% confidence intervals (95% CI). Results: From the initial 3,432 studies, 91 studies accounting for 115 prevalence data points (623,624 participants) were finally selected. The prevalence of general fatigue (fatigue lasting < 6 months, or fatigue of unspecified duration) was 20.4% (95% CI, 16.7-25.0) in adults, 11.7% (95% CI, 5.2-26.6) in minors, and 42.3% (95% CI, 33.0-54.2) in specific occupations. Chronic fatigue (fatigue lasting more than 6 months) affected 10.1% (95% CI, 8.2-12.5) of adults, 1.5% (95% CI, 0.5-4.7) of minors, and 5.5% (95% CI, 1.4-21.6) of subjects in specific occupations. There was an overall female-predominant prevalence for all subgroup analyses, with a total odds ratio of 1.4 (95% CI, 1.3-1.6). Regarding the severity and presence of medical causes, the total prevalence of moderate fatigue [14.6% (95% CI, 9.8-21.8)] was 2.4-fold that of severe fatigue [6.1% (95% CI, 3.4-11.0)], while unexplained fatigue (fatigue experienced by individuals without any underlying medical condition that can explain the fatigue) was ~2.7-fold that of explained fatigue (fatigue experienced by individuals with a medical condition that can explain the fatigue); as proportion of 40.0% of physical, 8.6% of mental, and 28.4% of mixed cause. Conclusions: This study has produced the first comprehensive picture of global fatigue prevalence in the general population, which will provide vital reference data contributing to fatigue-related research, including the prevention of diseases. Systematic review registration: Identifier: CRD42021270498.

Ginseng Sprouts Attenuate Mortality and Systemic Inflammation by Modulating TLR4/NF-κB Signaling in an LPS-Induced Mouse Model of Sepsis.

Sepsis leads to multi-organ failure due to aggressive systemic inflammation, which is one of the main causes of death clinically. This study aimed to evaluate whether ginseng sprout extracts (GSE) can rescue sepsis and explore its underlying mechanisms. C57BL/6J male mice (n = 15/group) were pre-administered with GSE (25, 50, and 100 mg/kg, p.o) for 5 days, and a single injection of lipopolysaccharide (LPS, 30 mg/kg, i.p) was administered to construct a sepsis model. Additionally, RAW264.7 cells were treated with LPS with/without GSE/its main components (Rd and Re) to explain the mechanisms corresponding to the animal-derived effects. LPS injection led to the death of all mice within 38 h, while GSE pretreatment delayed the time to death. GSE pretreatment also notably ameliorated LPS-induced systemic inflammation such as histological destruction in both the lung and liver, along with reductions in inflammatory cytokines, such as TNF-α, IL-6, and IL-1ß, in both tissues and serum. Additionally, GSE markedly diminished the drastic secretion of nitric oxide (NO) by suppressing the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) in both tissues. Similar changes in TNF-α, IL-1ß, NO, iNOS, and COX2 were observed in LPS-stimulated RAW264.7 cells, and protein expression data and nuclear translocation assays suggested GSE could modulate LPS-binding protein (LBP), Toll-like receptor 4 (TLR4), and NF-κB. Ginsenoside Rd could be a major active component in GSE that produces the anti-sepsis effects. Our data support that ginseng sprouts could be used as an herbal resource to reduce the risk of sepsis. The corresponding mechanisms may involve TLR4/NF-κB signaling and a potentially active component.

Nationwide epidemiological characteristics of chronic fatigue syndrome in South Korea.

BACKGROUND: Chronic fatigue syndrome (CFS) is a long-term disabling illness accompanied by medically unexplained fatigue. This study aimed to explore the epidemiological characteristics of CFS in South Korea. METHODS: Using the nationwide medical records provided by the Korean Health Insurance Review & Assessment Service (HIRA), we analyzed the entire dataset for CFS patients diagnosed by physicians in South Korea from January 2010 to December 2020. RESULTS: The annual mean incidence of CFS was estimated to be 44.71 ± 6.10 cases per 100,000 individuals [95% CI: 40.57, 48.76], and the prevalence rate was 57.70 ± 12.20 cases per 100,000 individuals [95% CI: 49.40, 65.79]. These two rates increased by 1.53- and 1.94-fold from 2010 to 2020, respectively, and showed an increasing trend with aging and an approximately 1.5-fold female predominance. CONCLUSIONS: This study is the first to report the nationwide epidemiological features of CFS, which reflects the clinical reality of CFS diagnosis and care in South Korea. This study will be a valuable reference for studies of CFS in the future.

Beneficial Potential of Banha-Sasim-Tang for Stress-Sensitive Functional Dyspepsia via Modulation of Ghrelin: A Randomized Controlled Trial.

Background: Functional dyspepsia (FD) is a highly complex pathophysiologic disease, which shows low recovery and high relapse rates. Therefore, a growing number of clinicians and patients are looking for alternative herbal medicine. Banha-Sasim-Tang (BST) is an herbal prescription for treating a wide range of dyspepsia in traditional Korean medicine (TKM). Aim of the study: This study aimed to evaluate the efficacy of BST on FD in patients with psychological stress-related symptoms and to investigate the involvement of ghrelin. This study is registered at https://cris.nih.go.kr/with the identification number KCT 0002811. Materials and methods: A total of 31 participants with FD who met the Rome IV criteria and the psychological stress-related pattern were enrolled in a double-blind, randomized, and controlled study. Participants were randomly assigned to the BST group (10 g twice daily for 4 weeks) or placebo group. The primary endpoint was a change in the Nepean Dyspepsia Index-Korean (NDI-K) score. The secondary endpoints were changes in the Visual Analog Scale (VAS) scores and plasma ghrelin level. Results: All participants completed the study (n = 15 for BST, n = 16 for placebo). BST decreased NDI-K scores compared with placebo, but the difference was not statistically significant (37.40 ± 27.40 vs 22.50 ± 23.85, p = 0.12). VAS scores and plasma total ghrelin levels were significantly improved in patients who were treated with BST (3.19 ± 1.60 vs 1.38 ± 2.85, p = 0.03 for VAS and 105.69 ± 287.89 vs -142.31 ± 314.32, p = 0.03 for total ghrelin). No BST-related adverse effects were observed during the trial. Conclusion: Our results indicate the clinical potential of BST for FD patients and are the first study to show the modulation of plasma ghrelin as one of its corresponding mechanisms. Clinical Trial Registration: https://cris.nih.go.kr/, identifier KCT 0002811.

Risk levels of herb-induced liver injury in Korea: from a meta-analysis.

BACKGROUND: As the use of herbal medicines increased worldwide, there has been concern about the risk of herb-induced liver injury (HILI). Many clinical studies have assessed the risk of HILI in Korea. METHODS: Therefore, we conducted a meta-analysis of the incidence of HILI in Korea, by analyzing nine clinical studies. These involved 8625 participants (3274 males; 5351 females), including 436 outpatients (three studies) and 8189 inpatients (six studies). RESULTS: As a result, the overall incidence of HILI in Korea was 0.49% (95% CI 0.33-0.74%), and it was 0.57% in males and 0.30% in females. We found a similar incidence of HILI in prospective (0.51%) and retrospective (0.50%) studies. The incidence of HILI was higher in inpatients (0.62%) than outpatients (0.03%). CONCLUSION: Although there are limitations regarding study quality and the number of participants, we systematically estimated the risk of HILI in Korea. We anticipate this study would be a helpful information for prescribing herbal medicines and researching the safety of herbs.

Systematic review on the prevalence of nonalcoholic fatty liver disease in South Korea.

AIMS: We aimed to conduct a systematic review and a meta-analysis to estimate NAFLD prevalence and its change in Korea. METHODS: We searched the literature involving NAFLD prevalence in Korea in PubMed, RISS, and KMBASE from inception to June 2017. Studies with subjects with certain disorders, population limitations, or subjects who consume alcohol were excluded. Analysis was stratified by publication year, age, gender, severity, body mass index (BMI), and diagnostic technique. Random-effects models were used to provide point estimates (95% confidence interval) of prevalence with subgroup analysis to account for heterogeneity. RESULTS: A total of 61 studies (837,897 participants) were included. The overall NAFLD prevalence in Korea was 30.3% (men: 41.1%, women: 20.3%), with a slight increase from 29.0% to 31.0% over an approximately 10-year period. BMI significantly affected NAFLD prevalence (≤ or > 25 kg/m2, 12.3% vs. 41.7%, p < 0.001), while women were significantly affected by aging (< or ≥ 50 years, 17.0% vs. 25.8%, p < 0.01). The prevalence of steatosis by severity was 22.6% for mild, 9.8% for moderate to severe and 2.2% for nonalcoholic steatohepatitis (NASH), with different patterns by gender. CONCLUSION: The current study is the first systematic analysis on NAFLD prevalence in Korea and found a change in NAFLD prevalence during the recent decade.

Incidence Rate of Hypersensitivity Reactions to Bee-Venom Acupuncture.

INTRODUCTION: Bee-venom acupuncture (BVA) has been widely applied to various disorders including pain-related diseases; however, patients are often warned of adverse reactions such as anaphylaxis. This study aimed to estimate the risk of hypersensitivity reactions to BVA and to determine their clinical features. METHODS: We retrospectively surveyed the medical records of patients treated by BVA between January 2010 and April 2019 in Dunsan Hospital of Daejeon University, and all cases of allergic reactions and their clinical symptoms were analyzed. RESULTS: A total of 8,580 patients (males 4,081 and females 4,499) were treated with BVA which amounts to a total of 60,654 treatments (average 7.1 ± 14.8 times). A total of fifteen patients (7 males and 8 females) reported an allergic reaction (0.175%, 95% CI, 0.086-0.263) of type 1 hypersensitivity, indicating a rate of allergic reaction in 0.025% (95% CI, 0.012-0.037) of the total BVA treatments. The average number of BVA treatments in those patients was 6.9 ± 6.5 (males: 4.1 ± 3.4 and females: 9.3 ± 7.9). Among the cases of hypersensitivity reactions, 4 involved anaphylactic shock; therefore, the incidence rate of anaphylaxis was 0.047% (95% CI, 0.001-0.092) for the 8,580 subjects and 0.007% (95% CI, 0.000-0.013) for the 60,654 treatments. All grade 1 cases were recovered within 1 day, whereas others took up to 30 days for complete recovery. CONCLUSION: Our results may emphasize paying attention to unforeseeable risks of anaphylaxis after bee-venom acupuncture. This study could be essential reference data for the guidelines of appropriate use of bee-venom acupuncture and bee-venom-derived interventions in clinical applications.

Reliability and Validity of the Modified Korean Version of the Chalder Fatigue Scale (mKCFQ11).

Fatigue can accompany various diseases; however, fatigue itself is a key symptom for patients with chronic fatigue syndrome (CFS). Due to the absence of biological parameters for the diagnosis and severity of CFS, the assessment tool for the degree of fatigue is very important. This study aims to verify the reliability and validity of the modified Korean version of the Chalder Fatigue Scale (mKCFQ11). This study was performed using data from 97 participants (Male: 37, Female: 60) enrolled in a clinical trial for an intervention of CFS. The analyses of the coefficient between the mKCFQ11 score and the Fatigue Severity Scale (FSS), the Visual Analogue Scale (VAS) or the 36-item Short-Form Health Survey (SF-36) at two time points (baseline and 12 weeks) as well as their changed values were conducted. The mKCFQ11 showed strong reliability, as evidenced by the Cronbach's alpha coefficient of 0.967 for the whole item and two subclasses (0.963 for physical and 0.958 for mental fatigue) along with the suitable validity of the mKCFQ11 structure shown by the principal component analysis. The mKCFQ11 scores also strongly correlated (higher than 0.7) with the VAS, FSS and SF-36 on all data from baseline and 12 weeks and changed values. This study demonstrated the clinical usefulness of the mKCFQ11 instrument, particularly in assessing the severity of fatigue and the evaluation of treatments for patients suffering from CFS.

Anti-hepatofibrotic effects of CGX, a standardized herbal formula: A multicenter randomized clinical trial.

BACKGROUND: Chunggan extract (CGX) is an herbal formula used for the treatment of chronic liver disease in traditional Korean medicine. Many preclinical studies have suggested its therapeutic or preventive effects on liver fibrosis. To evaluate the efficacy and safety of CGX, we conducted a randomized controlled clinical trial of CGX in patients with liver fibrosis diagnosed by Fibroscan. METHODS: We enrolled 67 subjects at two hospitals with chronic liver disorders with a 5.5 ≤ liver stiffness measurement (LSM) score ≤ 16 kPa. Subjects were randomly assigned at a 1:1:1 ratio with stratification (with/without concomitant use of antivirals) and orally administered CGX (1 g or 2 g) or placebo twice daily for 24 weeks. The end point was the change in instantaneous elasticity of the liver assessed by Fibroscan before and after treatment. RESULTS: LSM scores were significantly decreased in both the CGX1 g (2.5 ± 1.7 kPa, p < 0.01) and CGX2 g (1.9 ± 2.0 kPa, p < 0.05) groups compared to the placebo (0.6 ± 1.6 kPa) group. The change was also significant in 35 subjects without concomitant use of antiviral agents in the CGX1 g group (placebo 0.1 ± 1.4 kPa vs. 2.7 ± 1.6 kPa, p < 0.01) but not in those with concomitant antiviral use (p > 0.05). No notable adverse events were present. CONCLUSION: CGX appeared to have a pharmacological effect against liver fibrosis. Further studies to confirm the results are needed in the future using a larger sample size.

Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been emerging as a significant health issue worldwide. This study aimed to systemically assess the prevalence of CFS/ME in various aspects of analyses for precise assessment. METHODS: We systematically searched prevalence of CFS/ME from public databases from 1980 to December 2018. Data were extracted according to 7 categories for analysis: study participants, gender and age of the participants, case definition, diagnostic method, publication year, and country of the study conducted. Prevalence data were collected and counted individually for studies adopted various case definitions. We analyzed and estimated prevalence rates in various angles: average prevalence, pooled prevalence and meta-analysis of all studies. RESULTS: A total of 1291 articles were initially identified, and 45 articles (46 studies, 56 prevalence data) were selected for this study. Total 1085,976 participants were enrolled from community-based survey (540,901) and primary care sites (545,075). The total average prevalence was 1.40 ± 1.57%, pooled prevalence 0.39%, and meta-analysis 0.68% [95% CI 0.48-0.97]. The prevalence rates were varied by enrolled participants (gender, study participants, and population group), case definitions and diagnostic methods. For example, in the meta-analysis; women (1.36% [95% CI 0.48-0.97]) vs. men (0.86% [95% CI 0.48-0.97]), community-based samples (0.76% [95% CI 0.53-1.10]) vs. primary care sites (0.63% [95% CI 0.37-1.10]), adults ≥ 18 years (0.65% [95% CI 0.43-0.99]) vs. children and adolescents < 18 years (0.55% [95% CI 0.22-1.35]), CDC-1994 (0.89% [95% CI 0.60-1.33]) vs. Holmes (0.17% [95% CI 0.06-0.49]), and interviews (1.14% [95% CI 0.76-1.72]) vs. physician diagnosis (0.09% [95% CI 0.05-0.13]), respectively. CONCLUSIONS: This study comprehensively estimated the prevalence of CFS/ME; 0.89% according to the most commonly used case definition CDC-1994, with women approximately 1.5 to 2 folds higher than men in all categories. However, we observed the prevalence rates are widely varied particularly by case definitions and diagnostic methods. An objective diagnostic tool is urgently required for rigorous assessment of the prevalence of CFS/ME.

The Efficacy and Safety of Myelophil, an Ethanol Extract Mixture of Astragali Radix and Salviae Radix, for Chronic Fatigue Syndrome: A Randomized Clinical Trial.

Background: There is a strong demand for therapeutics to treat chronic fatigue syndrome (CFS), although there are limitations. Myelophil, which is a combination of extracts from Astragali Radix and Salviae Miltiorrhizae Radix, has been clinically used to treat fatigue-related disorders in South Korea. We conducted a randomized controlled clinical trial of Myelophil in patients with CFS and evaluated its efficacy and safety in two hospitals. Methods: We enrolled 98 participants (M: 38, F: 60) with CFS in a phase 2 trial of oral Myelophil (2 g daily) or placebo for 12 weeks. The primary end point was a change in the Chalder fatigue scale, as scored by a numeric rating scale (NRS). The secondary end points included changes in the visual analogue scale, fatigue severity scale (FSS), and 36-item short-form health survey (SF-36). Biomarkers of oxidative stress and cytokines were evaluated by blood tests. Results: Ninety-seven participants (48 in the Myelophil group and 49 in the placebo group) completed the trial. An analysis of all participants showed that Myelophil slightly improved fatigue symptoms compared with those of the placebo, but this effect was not statistically significant (p > 0.05 for the NRS, VAS, FSS, and SF-36). By contrast, an analysis of the subpopulation (53 participants, M: 24, F: 29) with severe symptoms (≥63, median NRS value of total participants) showed a statistically significant improvement in fatigue symptoms in the Myelophil group compared with the placebo (p < 0.05 for NRS, FSS, and SF-36). There were no significant changes in the biomarkers for oxidative stress and cytokines before or after the treatment. No Myelophil-related adverse response was observed during the trial. Conclusion: These results support the hypothesis that Myelophil can be a therapeutic candidate to manage CFS and provide the rationale for its progression to a phase 3 clinical trial. Clinical Trial Registration: www.ClinicalTrials.gov, identifier KCT0002317.

Systematic review of published data on herb induced liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal products have been widely used as a means of ethnomedicine worldwide. Recently, the potential hepatotoxicity of herbs has become a medical issue but comprehensive studies are limited. AIM OF THE STUDY: This study aims to determine the clinical features of herb induced liver injury (HILI) including its constituent ratio among liver injury case cohorts that included both HILI and drug induced liver injury (DILI). MATERIALS AND METHODS: A systematic review was conducted using a literature search for DILI/HILI in seven electric databases including PubMed, Cochrane and Embase. We analyzed the DILI/HILI cases and clinical characteristics in terms of herbs, conventional drugs, concomitant, or others. RESULTS: Thirty-one studies met the necessary criteria and included 9 prospective and 22 retrospective studies. Among total number of overall DILI/HILI cases (7511, male 2819, female 3669 and unknown 1023), 25.0% (1874 cases) were implicated in herbs. HILI was relatively higher in females (69.8% vs. 30.2% male), compared to conventional drugs (57.3% female vs. 42.7% male, p < 0.01), while it was prone to induce hepatocellular injury (hepatocellular 78.8%, cholestatic 8.9%, mixed type 12.3%), contrary to conventional drugs (hepatocellular 56.7% vs. cholestatic 22.1% vs. mixed 21.2%), respectively (p < 0.01). The main herbs causing HILI included Polygonum multiflorum, Psoralea corylifolia, Corydalis yanhusuo, and Rheum officinale. CONCLUSIONS: This review created the comparative and comprehensive feature of hepatotoxicity by herbal products, which provides reference data for the clinical applications and establishing pharmacovigilance system of herbs.

A nationwide study of the incidence rate of herb-induced liver injury in Korea.

Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy's law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12-1.08; women: 0.95%, 95% CI 0.19-1.68] and described its features in hospitalized participants.