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.

Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor ß (TGF-ß) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-ß expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.

The association between coronary artery calcification and mean platelet volume in the general population.

Patients with coronary artery calcification have an increased risk of coronary vascular events and mortality. Coronary artery calcification can be quantified using the coronary calcium score (CCS) from multi-detected row computed tomography (MDCT), and the score is proportionally related to the severity of atherosclerotic disease. Mean platelet volume (MPV) is gaining interest as a new independent cardiovascular risk factor. Accordingly, the aim of our study was to evaluate the relationship between CCS and MPV in the general population. A total of 2116 individuals were enrolled from a health promotion center between July 2007 and June 2010. Among them, 259 subjects were included in the final analysis. MDCT was used to measure CCS and CCS > 1 was defined as the presence of coronary calcification. The MPV value was significantly higher in the coronary artery calcification group than in the control group. Multivariate analyses showed that MPV was positively associated with coronary calcification (OR, 1.61; 95% CI 1.02-2.55). In summary, there was a significant association between coronary artery calcification and MPV in the general population. Therefore, the detection of elevated MPV should alert clinicians to the coexistence of multiple underlying CVD risk factors warranting early evaluation and treatment.

Association between Household Food Insecurity and Asthma in Korean Adults.

Household food insecurity has been associated with noncommunicable diseases. The aim of this study was to investigate the association between household food insecurity and asthma in Korean adults. Household food security statuses were classified into three groups: Food-secure household, food-insecure household without hunger, and food-insecure household with hunger. The odds ratios and 95% confidence intervals for the presence of asthma according to household food security status were calculated using multiple logistic regression analyses after adjusting for confounding factors. A total of 14,770 participants were included in the analysis. The prevalence of asthma was 2.6% in those with a secure food status, 3.2% in those with an insecure food status without hunger, and 7.6% in those with an insecure food status with hunger (p < 0.001). Compared with that in participants with a household food secure status, the odds ratios (95% confidence intervals) for asthma were 1.12 (0.73-1.73) in those with a food-insecure household without hunger status and 2.44 (1.33-4.46) in those with a food-insecure household with hunger status after additionally adjusting for confounding factors. We found that household food insecurity with hunger was significantly associated with asthma prevalence in Korean adults. Implementation of household food security screening and public health intervention could be helpful to prevent and reduce asthma in adults.

Serotonin receptor 3B polymorphisms are associated with type 2 diabetes: The Korean Genome and Epidemiology Study.

AIMS: Serotonin, or 5-hydroxytryptamine (5-HT), and serotonin receptor (HTR) subtypes contribute to controlling energy homeostasis. We investigated the association of polymorphisms of serotonin related genes with type 2 diabetes in Korean adults using a community-based prospective cohort study. METHODS: A total of 8840 participants (4205 Ansung, 4635 Ansan) from the Korean Genome and Epidemiology Study (KoGES)-Ansan and Ansung were included. The mean follow-up duration was 7.6 years, and the Ansan and Ansung cohorts were treated as independent replicates. Individuals with existing and new-onset type 2 diabetes were identified at baseline and follow-up evaluations, respectively. Logistic regression analysis was used to evaluate the association of 3402 single nucleotide polymorphisms (SNPs) in serotonin related genes with type 2 diabetes after adjusting for baseline age, sex, body mass index, drinking status, and smoking status. RESULTS: The baseline case-control comparison revealed significant association of 26 SNPs in HTR3B and HTR2A with type 2 diabetes. Interestingly, HTR3B SNP rs1176744, which is involved in behavioral disorders, was associated with type 2 diabetes (p-value = 0.0002). Furthermore, HTR3B polymorphisms that significantly associated with type 2 diabetes were located in the 3' downstream region. The new-onset type 2 diabetes case-control study revealed significant association of 3 additional SNPs of the HTR4. CONCLUSIONS: We found that rs1176744 in HTR3B was associated with type 2 diabetes. Additionally, our study suggests that polymorphisms in the downstream region of HTR3B may contribute to the development of type 2 diabetes.