meta-analysis – Page 5 – American ME and CFS Society

Elevated Perceived Exertion in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Meta-analysis

Abstract:

Purpose: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) are two debilitating illnesses primarily characterized by chronic symptoms of fatigue and musculoskeletal pain, respectively. Some investigators have observed an elevated sense of effort in these patient groups, however, this effect has not been substantiated via quantitative review. As such, we conducted a meta-analysis of perceived exertion (RPE) responses to aerobic exercise in ME/CFS and FM compared to healthy adults.

Methods: Case-control studies involving adults with ME/CFS or FM that measured RPE and heart rate responses to acute aerobic exercise were included. Data sources included: PubMed, Scopus/Embase, CINAHL, CENTRAL, and Google Scholar. Risk of bias was assessed by evaluating each study’s description of participant characteristics, matching procedures, and administration of RPE scales. Hedges’ d effect sizes for RPE were calculated and aggregated using random effects models and potential moderators were explored with meta-regression analysis.

Results: Forty-one effects were extracted from 37 studies involving 1016 patients and 686 healthy controls. We observed a large (Hedges’ d=0.85; 95% CI: 0.62, 1.08) effect indicating higher RPE in patients than controls. The mean effect size was significantly moderated (p<0.001; R=0.38) by whether RPE data were analyzed at a peak or submaximal intensity (b=0.60, z=4.6, p<0.001) and the type of patient group that was studied (b = 0.25, z = 2.08, p=0.04).

Conclusions: People with ME/CFS and FM perceive aerobic exercise as more effortful than healthy adults, but the exact causes are unclear. The large magnitude of this effect merits further exploration of underlying mechanisms which could provide insight into the pathophysiology of ME/CFS and FM or the broader debate about the nature of central and/or peripheral signals that influence RPE.

Source: Barhorst EE, Andrae WE, Rayne TJ, Falvo MJ, Cook DB, Lindheimer JB. Elevated Perceived Exertion in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Meta-analysis [published online ahead of print, 2020 Jun 15]. Med Sci Sports Exerc. 2020;10.1249/MSS.0000000000002421. doi:10.1249/MSS.0000000000002421 https://pubmed.ncbi.nlm.nih.gov/32555018/

Inflammatory proteins are altered in chronic fatigue syndrome-A systematic review and meta-analysis

Abstract:

Immune dysfunction has been posited as a key element in the aetiology of chronic fatigue syndrome (CFS) since the illness was first conceived. However, systematic reviews have yet to quantitatively synthesise inflammatory biomarkers across the literature. We undertook a systematic review and meta-analysis to quantify available data on circulating inflammatory proteins, examining studies recruiting patients with a CFS diagnosis and a non-affected control group. Results were meta-analysed from 42 studies.

Patients with CFS had significantly elevated tumour necrosis factor (ES = 0.274, p < 0.001), interleukin-2 (ES = 0.203, p = 0.006), interleukin-4 (ES = 0.373, p = 0.004), transforming growth factor-β (ES = 0.967, p < 0.001) and c-reactive protein (ES = 0.622, p = 0.019). 12 proteins did not differ between groups.

These data provide some support for an inflammatory component in CFS, although inconsistency of results indicates that inflammation is unlikely to be a primary feature in all those suffering from this disorder. It is hoped that further work will elucidate whether there are subgroups of patients with clinically-relevant inflammatory dysfunction, and whether inflammatory cytokines may provide a prognostic biomarker or moderate treatment effects.

Source: Strawbridge R, Sartor ML, Scott F, Cleare AJ. Inflammatory proteins are altered in chronic fatigue syndrome-A systematic review and meta-analysis. Neurosci Biobehav Rev. 2019 Aug 26;107:69-83. doi: 10.1016/j.neubiorev.2019.08.011. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31465778

Meta-analysis investigating post-exertional malaise between patients and controls

Abstract:

Post-exertional malaise is either required or included in many previously proposed case definitions of myalgic encephalomyelitis/chronic fatigue syndrome. A meta-analysis of odds ratios (ORs; association between patient status and post-exertional malaise status) and a number of potential moderators (i.e. study-level characteristics) of effect size were conducted.

Post-exertional malaise was found to be 10.4 times more likely to be associated with a myalgic encephalomyelitis/chronic fatigue syndrome diagnosis than with control status. Significant moderators of effect size included patient recruitment strategy and control selection. These findings suggest that post-exertional malaise should be considered a cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome.

Source: Brown A, Jason LA. Meta-analysis investigating post-exertional malaise between patients and controls. J Health Psychol. 2018 Jul 1:1359105318784161. doi: 10.1177/1359105318784161. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29974812

Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis

Abstract:

PURPOSE: A prominent symptom of myalgic encephalomyelitis, chronic fatigue syndrome, or systemic exertion intolerance disease (ME/CFS/SEID) is persistent fatigue that is worsened by physical exertion. Here the population effect of a single bout of exercise on fatigue symptoms in people with ME/CFS/SEID was estimated and effect moderators were identified.

METHODS: Google Scholar was systematically searched for peer-reviewed articles published between February 1991 and May 2015. Studies were included where people diagnosed with ME/CFS/SEID and matched control participants completed a single bout of exercise and fatigue self-reports were obtained before and after exercise. Fatigue means, standard deviations, and sample sizes were extracted to calculate effect sizes and the 95% confidence interval. Effects were pooled using a random-effects model and corrected for small sample bias to generate mean Δ. Multilevel regression modeling adjusted for nesting of effects within studies. Moderators identified a priori were diagnostic criteria, fibromyalgia comorbidity, exercise factors (intensity, duration, and type), and measurement factors.

RESULTS: Seven studies examining 159 people with ME/CFS/SEID met inclusion criteria, and 47 fatigue effects were derived. The mean fatigue effect was Δ = 0.73 (95% confidence interval = 0.24-1.23). Fatigue increases were larger for people with ME/CFS/SEID when fatigue was measured 4 h or more after exercise ended rather than during or immediately after exercise ceased.

CONCLUSIONS: This preliminary evidence indicates that acute exercise increases fatigue in people with ME/CFS/SEID more than that in control groups, but effects were heterogeneous between studies. Future studies with no-exercise control groups of people with ME/CFS/SEID are needed to obtain a more precise estimate of the effect of exercise on fatigue in this population.

Source: Loy BD, O’Connor PJ, Dishman RK. Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis. Med Sci Sports Exerc. 2016 Oct;48(10):2003-12. doi: 10.1249/MSS.0000000000000990. https://www.ncbi.nlm.nih.gov/pubmed/27187093

Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: a systematic review and subset meta-analysis

Abstract:

The hypothalamic-pituitary-adrenal (HPA) axis is a psychoneuroendocrine regulator of the stress response and immune system, and dysfunctions have been associated with outcomes in several physical health conditions. Its end product, cortisol, is relevant to fatigue due to its role in energy metabolism.

The systematic review examined the relationship between different markers of unstimulated salivary cortisol activity in everyday life in chronic fatigue syndrome (CFS) and fatigue assessed in other clinical and general populations. Search terms for the review related to salivary cortisol assessments, everyday life contexts, and fatigue. All eligible studies (n=19) were reviewed narratively in terms of associations between fatigue and assessed cortisol markers, including the cortisol awakening response (CAR), circadian profile (CP) output, and diurnal cortisol slope (DCS).

Subset meta-analyses were conducted of case-control CFS studies examining group differences in three cortisol outcomes: CAR output; CAR increase; and CP output. Meta-analyses revealed an attenuation of the CAR increase within CFS compared to controls (d=-.34) but no statistically significant differences between groups for other markers. In the narrative review, total cortisol output (CAR or CP) was rarely associated with fatigue in any population; CAR increase and DCS were most relevant.

Outcomes reflecting within-day change in cortisol levels (CAR increase; DCS) may be the most relevant to fatigue experience, and future research in this area should report at least one such marker. Results should be considered with caution due to heterogeneity in one meta-analysis and the small number of studies.

Source: Powell DJ, Liossi C, Moss-Morris R, Schlotz W. Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: a systematic review and subset meta-analysis. Psychoneuroendocrinology. 2013 Nov;38(11):2405-22. doi: 10.1016/j.psyneuen.2013.07.004. Epub 2013 Aug 2. http://www.psyneuen-journal.com/article/S0306-4530(13)00254-0/fulltext (Full article)

The prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis: a meta-analysis

Abstract:

PURPOSE: To perform a meta-analysis to examine variability among prevalence estimates for CFS/ME, according to the method of assessment used.

METHODS: Databases were systematically searched for studies on CFS/ME prevalence in adults that applied the 1994 Centers for Disease Control (CDC) case definition.1 Estimates were categorized into two methods of assessment: self-reporting of symptoms versus clinical assessment of symptoms. Meta-analysis was performed to pool prevalences by assessment using random effects modeling. This was stratified by sample setting (community or primary care) and heterogeneity was examined using the I (2) statistic.

RESULTS: Of 216 records found, 14 studies were considered suitable for inclusion. The pooled prevalence for self-reporting assessment was 3.28% (95% CI: 2.24-4.33) and 0.76% (95% CI: 0.23-1.29) for clinical assessment. High variability was observed among self-reported estimates, while clinically assessed estimates showed greater consistency.

CONCLUSION: The observed heterogeneity in CFS/ME prevalence may be due to differences in method of assessment. Stakeholders should be cautious of prevalence determined by the self-reporting of symptoms alone. The 1994 CDC case definition appeared to be the most reliable clinical assessment tool available at the time of these studies. Improving clinical case definitions and their adoption internationally will enable better comparisons of findings and inform health systems about the true burden of CFS/ME.

Source: Johnston S, Brenu EW, Staines D, Marshall-Gradisnik S. The prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis: a meta-analysis. Clin Epidemiol. 2013;5:105-10. doi: 10.2147/CLEP.S39876. Epub 2013 Mar 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616604/ (Full article)

Daily physical activity of patients with the chronic fatigue syndrome: a systematic review

Abstract:

OBJECTIVE: To give an overview of the physical activity level of patients with chronic fatigue syndrome in comparison with asymptomatic controls.

DATA SOURCES: MEDLINE, Web of Science, EMBASE, PsycINFO, Picarta, the Cochrane Controlled Trial Register that is included in the Cochrane Library and reference tracking.

REVIEW METHODS: A systematic literature search was conducted focusing on studies concerning physical activity levels of patients with chronic fatigue syndrome compared to controls. A meta-analysis was performed to pool data of the studies.

RESULTS: Seventeen studies were included with 22 different comparisons between patients with chronic fatigue syndrome and controls. Fourteen studies, including 18 comparisons, showed lower physical activity levels in patients with chronic fatigue syndrome as compared to controls. Four studies, including four comparisons, showed no differences between both groups. The meta-analysis included seven studies and showed a daily physical activity level in patients with chronic fatigue syndrome of only 68% of the physical activity level observed in control subjects. The pooled mean coefficient of variation in patients with chronic fatigue syndrome was higher as compared to control subjects (34.3% versus 31.5%), but this difference did not reach significance.

CONCLUSION: Patients with chronic fatigue syndrome appear to be less physically active compared with asymptomatic controls. There is no difference in variation of physical activity levels between patients with chronic fatigue syndrome and healthy control subjects, but the validity and reliability of some methods of measuring physical activity is questionable or unknown.

Source: Evering RM, van Weering MG, Groothuis-Oudshoorn KC, Vollenbroek-Hutten MM. Daily physical activity of patients with the chronic fatigue syndrome: a systematic review. Clin Rehabil. 2011 Feb;25(2):112-33. doi: 10.1177/0269215510380831. Epub 2010 Oct 13. https://www.ncbi.nlm.nih.gov/pubmed/20943713

A meta analysis on randomized controlled trials of acupuncture treatment of chronic fatigue syndrome

Abstract:

OBJECTIVE: To assess the effectiveness of acupuncture treatment of chronic fatigue syndrome (CFS).

METHODS: According to the requirement of evidence-based medicine, CFS, fatigue syndrome, acupuncture and moxibustion, acupuncture, electroacupuncture, auricular acupuncture, auricular pellet pressure, plum-blossom needle, intradermal needle, moxibustion, three edged needle, cupping, cup-moving, acupoint injection, etc. were selected as the subject words for retrieving the related papers form domestic and foreign medical databases. The RCT was used as the enrolled criteria, and the clinical cure rate, markedly effective rate, total effective rate, and the scores of the Fatigue Assessment Instrument Questionnaire (FAI) and fatigue scale (FS) were used as the assessment indexes. The statistical package (RevMan 4.2) was used to review management and analysis of 13 papers.

RESULTS: A total of 28 papers were enrolled. Logistic regression analysis showed that the total odds ratio (OR) was 4.56, with 95% confidence interval (CI) [2.84, 7.33] for the total effective rate in 10 studies, the total OR was 2.07 with 95% CI [1.49, 2.88] for the markedly effective rate in 8 studies, and the total OR was 2.51 with 95% CI [1.64, 3.85] for the clinical cure rate in 8 studies. The weighted mean difference (WMD) was -29.52 with 95% CI [-36.17, -22.88] for the FAI score in 3 studies, and the WMD -1.22 with 95% CI [-1.77, -0.67] for the FS score in 4 studies. The therapeutic effect in the treatment group of CFS was superior to that in the control group (P<0.01).

CONCLUSION: Acupuncture therapy is effective for CFS, but still needs being confirmed by more high-quality studies.

Source: Wang JJ, Song YJ, Wu ZC, Chu XO, Wang XH, Wang XJ, Wei LN, Wang QM. A meta analysis on randomized controlled trials of acupuncture treatment of chronic fatigue syndrome. Zhen Ci Yan Jiu. 2009 Dec;34(6):421-8. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/20209981

Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis

Abstract:

A meta-analysis of the efficacy of cognitive behavioral therapy (CBT) in treating chronic fatigue included 15 effect sizes for between-group outcome comparisons. Across analyses, which included a total of 1371 participants, there was a significant difference, d=0.48, in post-treatment fatigue between participants receiving CBT and those in control conditions. Results indicate that CBT for chronic fatigue syndrome tends to be moderately efficacious. Dropout rates in CBT varied from 0-42%, with a mean of 16%. In the five studies that reported the number of CBT clients who were no longer in the clinical range with regard to fatigue at the latest follow-up, the percentage varied from 33% to 73% of those assigned to CBT, with a mean of 50%. Moderator results suggest directions for future investigations.

Source: Malouff JM, Thorsteinsson EB, Rooke SE, Bhullar N, Schutte NS. Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis. Clin Psychol Rev. 2008 Jun;28(5):736-45. Epub 2007 Nov 1. https://www.ncbi.nlm.nih.gov/pubmed/18060672

The placebo response in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis

Abstract:

OBJECTIVE: The placebo response is conventionally asserted to be high in chronic fatigue syndrome (CFS) because of the latter’s subjective nature and obscure pathogenesis, but no systematic review of placebo responses has been undertaken. We report such a study. Patient expectation is known to be important in the placebo response. It is also known that CFS patients attending specialist clinics often have strong physical attributions regarding causation and hence skepticism about psychological or psychiatric interventions. If so, the placebo response in CFS may be influenced by the type of intervention according to its perceived rationale. We aimed to estimate the summary placebo response in clinical trials of CFS and to determine whether intervention type influences the placebo response in CFS.

METHODS: We searched Medline, Embase, Cochrane Library, PsychInfo, and the references of the identified articles, and contacted experts for controlled trials (randomized or nonrandomized) of any intervention on CFS patients reporting the placebo response as a clinical improvement in physical or general outcomes. Data were extracted from the articles and validity assessment conducted by one reviewer and checked by a second. Meta-analysis and metaregression were performed.

RESULTS: The pooled placebo response was 19.6% (95% confidence interval, 15.4-23.7), lower than predicted and lower than in some other medical conditions. The meta-regression revealed that intervention type significantly contributed to the heterogeneity of placebo response (p = .03).

CONCLUSION: In contrast with the conventional wisdom, the placebo response in CFS is low. Psychological-psychiatric interventions were shown to have a lower placebo response, perhaps linked to patient expectations.

Source: Cho HJ, Hotopf M, Wessely S. The placebo response in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis. Psychosom Med. 2005 Mar-Apr;67(2):301-13. http://www.ncbi.nlm.nih.gov/pubmed/15784798