Tag: meta-analysis

Meta-analysis of natural killer cell cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Reduced natural killer (NK) cell cytotoxicity is the most consistent immune finding in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Meta-analysis of the published literature determined the effect size of the decrement in ME/CFS. Databases were screened for papers comparing NK cell cytotoxicity in ME/CFS and healthy controls. A total of 28 papers and 55 effector:target cell ratio (E:T) data points were collected.

Cytotoxicity in ME/CFS was significantly reduced to about half of healthy control levels, with an overall Hedges’ g of 0.96 (0.75-1.18). Heterogeneity was high but was explained by the range of E:T ratios, different methods, and potential outliers. The outcomes confirm reproducible NK cell dysfunction in ME/CFS and will guide studies using the NK cell model system for pathomechanistic investigations.

Source: Baraniuk JN, Eaton-Fitch N, Marshall-Gradisnik S. Meta-analysis of natural killer cell cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome. Front Immunol. 2024 Oct 17;15:1440643. doi: 10.3389/fimmu.2024.1440643. PMID: 39483457; PMCID: PMC11524851. https://pmc.ncbi.nlm.nih.gov/articles/PMC11524851/ (Full text)

The persistence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis

Highlights:

  • SARS-CoV-2 can trigger Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
  • 51% of Long COVID-19 patients have Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
  • Long COVID-19 is a new name for an old disease.

Abstract:

Objectives: Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria.

Methods: Clinical studies published between January 2020 to May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool.

Results: We identified 13 eligible studies that reported a total of 1,973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%-60%) of LC patients satisfied ME/CFS diagnostic criteria with fatigue, sleep disruption, and muscle/joint pain being the most common symptoms. Importantly, LC patients also experienced the ME/CFS hallmark symptom, post-exertional malaise.

Conclusions: Our study not only demonstrates that LC patients exhibit similar symptom clusters to ME/CFS, but that approximately half of LC patients satisfy a diagnosis of ME/CFS. Our findings suggest that current ME/CFS criteria could be adapted to the identification of a subset of LC patients that may facilitate the standardized diagnosis, management and the recruitment for clinical studies in the future.

Source: Ankush Dehlia, Mark A. Guthridge. The persistence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis. Journal of Infection, 2024, 106297, ISSN 0163-4453, https://doi.org/10.1016/j.jinf.2024.106297.
https://www.sciencedirect.com/science/article/pii/S0163445324002317 (Full text)

Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms.

Methods: A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software.

Results: This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31-.67]; Z = 5.29, p < .01) and β1 adrenergic receptor expression (SMD = .79 [.06-1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18-.97]; Z = 2.85, p < .01), β2 AR (SMD = .41 [.02-.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03-.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [-.47 to -.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = -.79 [-1.27 to -.30]; Z = -3.14; p < .01).

Conclusion: This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.

Source: Hendrix J, Fanning L, Wyns A, Ahmed I, Patil MS, Richter E, Van Campenhout J, Ickmans K, Mertens R, Nijs J, Godderis L, Polli A. Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis. Eur J Clin Invest. 2024 Sep 25:e14318. doi: 10.1111/eci.14318. Epub ahead of print. PMID: 39319943. https://pubmed.ncbi.nlm.nih.gov/39319943/

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

Abstract:

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.

Source: Park JW, Park BJ, Lee JS, Lee EJ, Ahn YC, Son CG. Systematic review of fatigue severity in ME/CFS patients: insights from randomized controlled trials. J Transl Med. 2024 Jun 3;22(1):529. doi: 10.1186/s12967-024-05349-7. PMID: 38831460; PMCID: PMC11145935. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145935/ (Full text)

Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis

Abstract:

Objective: This meta-analysis investigated the prevalence of post-COVID symptoms two-years after SARS-CoV-2 infection.

Methods: Electronic literature searches on PubMed, MEDLINE, CINAHL, EMBASE, Web of Science databases, and on medRxiv/bioRxiv preprint servers were conducted up to October 1, 2023. Studies reporting data on post-COVID symptoms at two-years after infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Random-effects models were used for meta-analytical pooled prevalence of each symptom.

Results: From 742 studies identified, twelve met inclusion criteria. The sample included 7912 COVID-19 survivors (50.7% female; age: 59.5, SD: 16.3). Post-COVID symptoms were assessed at a follow-up of 722.9 (SD: 51.5) days after. The overall methodological quality of studies was moderate (mean: 6/10, SD: 1.2 points). The most prevalent post-COVID symptoms two-years after SARS-CoV-2 infection were fatigue (28.0%, 95%CI 12.0-47.0), cognitive impairments (27.6%, 95%CI 12.6-45.8), and pain (8.4%, 95%CI 4.9-12.8). Psychological disturbances such as anxiety (13.4%, 95%CI 6.3-22.5) and depressive (18.0%, 95%CI 4.8-36.7) levels as well as sleep problems (20.9%, 95%CI 5.25-43.25) were also prevalent. Pooled data showed high heterogeneity (I2 ≥ 75%).

Conclusion: This meta-analysis shows the presence of post-COVID symptoms in 30% of patients two-years after COVID-19. Fatigue, cognitive disorders, and pain were the most prevalent post-COVID symptoms. Psychological disturbances as well as sleep problems were still present two-years after COVID-19.

Source: Fernandez-de-Las-Peñas C, Notarte KI, Macasaet R, Velasco JV, Catahay JA, Ver AT, Chung W, Valera-Calero JA, Navarro-Santana M. Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis. J Infect. 2023 Dec 13:S0163-4453(23)00590-X. doi: 10.1016/j.jinf.2023.12.004. Epub ahead of print. PMID: 38101521. https://www.journalofinfection.com/article/S0163-4453(23)00590-X/fulltext (Full text)

Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis

Abstract:

Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment.
A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409–0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697–0.794).
Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.
Source: Choi YJ, Seo YB, Seo J-W, Lee J, Nham E, Seong H, Yoon JG, Noh JY, Cheong HJ, Kim WJ, et al. Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2023; 12(23):7375. https://doi.org/10.3390/jcm12237375 https://www.mdpi.com/2077-0383/12/23/7375 (Full text)

Effects of traditional Chinese mind-body exercises for patients with chronic fatigue syndrome: A systematic review and meta-analysis

Abstract:

Background: Chronic fatigue syndrome (CFS) is a global public health concern. We performed this systematic review of randomised controlled trials (RCTs) to evaluate the effects and safety of traditional Chinese mind-body exercises (TCME) for patients with CFS.

Methods: We comprehensively searched MEDLINE, Embase, Web of Science, PsycINFO, Cochrane Library, CNKI, VIP databases, and Wanfang Data from inception to October 2022 for eligible RCTs of TCME for CFS management. We used Cochran’s Q statistic and I2 to assess heterogeneity and conducted subgroup analyses based on different types of TCME, background therapy, and types of fatigue. We also assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.

Results: We included 13 studies (n = 1187) with a maximal follow-up of 12 weeks. TCME included Qigong and Tai Chi. At the end of the treatment, compared with passive control, TCME probably reduces the severity of fatigue (standardised mean differences (SMD) = 0.85; 95% confidence interval (CI) = 0.64, 1.07, moderate certainty), depression (SMD = 0.53; 95% CI = 0.34, 0.72, moderate certainty), anxiety (SMD = 0.29; 95% CI = 0.11, 0.48, moderate certainty), sleep quality (SMD = 0.34; 95% CI = 0.10, 0.57, low certainty) and mental functioning (SMD = 0.90; 95% CI = 0.50, 1.29, low certainty).

Compared with other active control therapies, TCME results in little to no difference in the severity of fatigue (SMD = 0.08; 95% CI = -0.18, 0.34, low certainty). For long-term outcomes, TCME may improve anxiety (SMD = 1.74; 95% CI = 0.44, 3.03, low certainty) compared to passive control. We did not identify TCME-related serious adverse events.

Conclusions: In patients with CFS, TCME probably reduces post-intervention fatigue, depression, and anxiety and may improve sleep quality and mental function compared with passive control, but has limited long-term effects. These findings will help health professionals and patients with better clinical decision-making.

Source: Kong L, Ren J, Fang S, Li Y, Wu Z, Zhou X, Hao Q, Fang M, Zhang YQ. Effects of traditional Chinese mind-body exercises for patients with chronic fatigue syndrome: A systematic review and meta-analysis. J Glob Health. 2023 Nov 24;13:04157. doi: 10.7189/jogh.13.04157. PMID: 37994837; PMCID: PMC10666566. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666566/ (Full text)

Brain-regional characteristics and neuroinflammation in ME/CFS patients from neuroimaging: A systematic review and meta-analysis

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by an elusive etiology and pathophysiology. This study aims to evaluate the pathological role of neuroinflammation in ME/CFS by conducting an exhaustive analysis of 65 observational studies.

Four neuroimaging techniques, including magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), and positron emission tomography (PET), were employed to comparatively assess brain regional structure, metabolite profiles, electrical activity, and glial activity in 1529 ME/CFS patients (277 males, 1252 females) and 1715 controls (469 males, 1246 females). Clinical characteristics, including sex, age, and fatigue severity, were consistent with established epidemiological patterns.

Regional alterations were most frequently identified in the cerebral cortex, with a notable focus on the frontal cortex. However, our meta-analysis data revealed a significant hypoactivity in the insular and thalamic regions, contrary to observed frequencies. These abnormalities, occurring in pivotal network hubs bridging reason and emotion, disrupt connections with the limbic system, contributing to the hallmark symptoms of ME/CFS.

Furthermore, we discuss the regions where neuroinflammatory features are frequently observed and address critical neuroimaging limitations, including issues related to inter-rater reliability. This systematic review serves as a valuable guide for defining regions of interest (ROI) in future neuroimaging investigations of ME/CFS

Source: Lee JS, Sato W, Son CG. Brain-regional characteristics and neuroinflammation in ME/CFS patients from neuroimaging: A systematic review and meta-analysis. Autoimmun Rev. 2023 Nov 26:103484. doi: 10.1016/j.autrev.2023.103484. Epub ahead of print. PMID: 38016575. https://www.sciencedirect.com/science/article/pii/S1568997223002185 (Full text)

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

Abstract:

Background: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.

Methods: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections’ contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).

Results: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a “moderate association” by Cohen’s d test) compared to both healthy and diseased controls.

Conclusion: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

Source: Hwang, JH., Lee, JS., Oh, HM. et al. Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis. J Transl Med 21, 763 (2023). https://doi.org/10.1186/s12967-023-04635-0 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04635-0 (Full text)

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

Abstract:

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.

Source: Yoon JH, Park NH, Kang YE, Ahn YC, Lee EJ, Son CG. The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis. Front Public Health. 2023 Jul 28;11:1192121. doi: 10.3389/fpubh.2023.1192121. PMID: 37575103; PMCID: PMC10416797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10416797/ (Full text)