Tag: meta-analysis

Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis

Abstract:

Background: Post-acute COVID-19 Syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity.

Objectives: To estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods.

Data sources: Searches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed.

Study eligibility criteria: Articles in English that reported the prevalence of persistent symptoms among individuals with confirmed SARS-CoV-2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness.

Methods: Random-effect meta-analysis was performed to produce pooled prevalence for each symptom at 4 different follow-up time intervals. Between-studies heterogeneity was evaluated using the I2 statistic and was explored via meta-regression, considering several a priori study level variables. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively.

Results: After screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257,348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder and concentration difficulty (32%, 25%, 24%, and 22% respectively at 3-<6 months follow-up), effort intolerance, fatigue, sleep disorder and dyspnea (45%, 36%, 29% and 25% respectively at 6-<9 months follow-up), fatigue (37%) and dyspnea (21%) at 9-<12 months and fatigue, dyspnea, sleep disorder, myalgia (41%, 31%, 30%, and 22% respectively at >12 months follow-up). There was substantial between-studies heterogeneity for all reported symptoms prevalence. Meta-regressions identified statistically significant effect modifiers: world region, male gender, diabetes mellitus, disease severity and overall study quality score. Five of six studies including a comparator group consisting of COVID-19 negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms.

Conclusions: This systematic review found that a large proportion of patients experience PACS 3 to 12 months after recovery from the acute phase of COVD-19. However, available studies of PACS are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptoms definitions and measurements and longer follow-up.

Source: Alkodaymi MS, Omrani OA, Fawzy NA, Shaar BA, Almamlouk R, Riaz M, Obeidat M, Obeidat Y, Gerberi D, Taha RM, Kashour Z, Kashour T, Berbari EF, Alkattan K, Tleyjeh IM. Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis. Clin Microbiol Infect. 2022 Feb 3:S1198-743X(22)00038-6. doi: 10.1016/j.cmi.2022.01.014. Epub ahead of print. PMID: 35124265; PMCID: PMC8812092. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812092/ (Full text)

Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis

Abstract

Importance: Neurological and neuropsychiatric symptoms that persist or develop three months after the onset of COVID-19 pose a significant threat to the global healthcare system. These symptoms are yet to be synthesized and quantified via meta-analysis.

Objective: To determine the prevalence of neurological and neuropsychiatric symptoms reported 12 weeks (3 months) or more after acute COVID-19 onset in adults.

Data sources: A systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1st, 2020 and August 1st, 2021. The systematic review was guided by Preferred Reporting Items for Systematic Review and Meta-Analyses.

Study selection: Studies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence (NICE) definition of post-COVID-19 syndrome (symptoms that develop or persist ≥3 months after the onset of COVID-19). Additional criteria included the reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19.

Data extraction and synthesis: Two authors independently extracted data on patient characteristics, hospital and/or ICU admission, acute-phase COVID-19 symptoms, length of follow-up, and neurological and neuropsychiatric symptoms.

Main outcome(s) and measure(s): The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported ≥3 months post onset of COVID-19. We also compared post-COVID-19 syndrome in hospitalised vs. non-hospitalised patients, with vs. without ICU admission during the acute phase of infection, and with mid-term (3 to 6 months) and long-term (>6 months) follow-up.

Results: Of 1458 articles, 19 studies, encompassing a total of 11,324 patients, were analysed. Overall prevalence for neurological post-COVID-19 symptoms were: fatigue (37%, 95% CI: 24%-50%), brain fog (32%, 9%-55%), memory issues (27%, 18%-36%), attention disorder (22%, 10%-34%), myalgia (18%, 4%-32%), anosmia (12%, 7%-17%), dysgeusia (11%, 4%-17%) and headache (10%, 1%-21%). Neuropsychiatric conditions included sleep disturbances (31%, 18%-43%), anxiety (23%, 13%-33%) and depression (12%, 7%-21%). Neuropsychiatric symptoms substantially increased in prevalence between mid- and long-term follow-up. Compared to non-hospitalised patients, patients hospitalised for acute COVID-19 had reduced frequency of anosmia, anxiety, depression, dysgeusia, fatigue, headache, myalgia, and sleep disturbance at three (or more) months post-infection. Conversely, hospital admission was associated with higher frequency of memory issues (OR: 1.9, 95% CI: 1.4-2.3). Cohorts with >20% of patients admitted to the ICU during acute COVID-19 experienced higher prevalence of fatigue, anxiety, depression, and sleep disturbances than cohorts with <20% of ICU admission.

Conclusions and relevance: Fatigue, cognitive dysfunction (brain fog, memory issues, attention disorder) and sleep disturbances appear to be key features of post-COVID-19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) are common and increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.

Source: Premraj L, Kannapadi NV, Briggs J, Seal SM, Battaglini D, Fanning J, Suen J, Robba C, Fraser J, Cho SM. Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. J Neurol Sci. 2022 Jan 29;434:120162. doi: 10.1016/j.jns.2022.120162. Epub ahead of print. PMID: 35121209; PMCID: PMC8798975. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798975/ (Full text)

Prevalence of Chronic Fatigue Syndrome (CFS) in Korea and Japan: A Meta-Analysis

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness accompanied by fatigue unsolved by rest. However, ME/CFS is a poorly understood illness that lacks a universally accepted pathophysiology and treatment. A lack of CFS-related studies have been conducted in Asian countries. This study aimed to estimate and compare the prevalence of ME/CFS in Korea and Japan and conducted a meta-analysis.

Methods: We searched PubMed, EMBASE, Cochrane, and KMBASE for population-based prevalence studies of the two countries and synthesized the data according to the Fukuda case definition.

Results: Of the eight studies (five in Korea, three in Japan) included, the total prevalence rate of Korean studies was 0.77% (95% CI 0.34-1.76), and 0.76% (95% CI 0.46-1.25) for the Japanese studies. The prevalence rate in females was approximately two-fold higher than males in Korean studies (1.31% female vs. 0.60% male), while the gender difference was less obvious in Japanese studies (0.76% female vs. 0.65% male).

Conclusions: Further epidemiology studies on the female ME/CFS prevalence rate between countries may be required.

Source: Lim EJ, Son CG. Prevalence of Chronic Fatigue Syndrome (CFS) in Korea and Japan: A Meta-Analysis. J Clin Med. 2021 Jul 21;10(15):3204. doi: 10.3390/jcm10153204. PMID: 34361987. https://pubmed.ncbi.nlm.nih.gov/34361987/

Effect of acupoint catgut embedding in chronic fatigue syndrome patients: A protocol for systematic review and meta-analysis

Abstract:

Background: Chronic fatigue syndrome (CFS) is a relatively complex and disabling illness with a substantial economic burden and functional impairment. Until now, many CFS patients lack appropriate healthcare. Acupoint catgut embedding is an effective and emerging alternative therapy for CFE. With this research, we endeavor to investigate the effect and safety of ACE for CFS.

Methods: Eight databases will be searched from inception to December 2020: PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chong-Qing VIP database, and Wan-fang database. We regard studies as eligible for inclusion if they were RCTs done in CFS patients, compare acupoint catgut embedding to another treatment strategy, and report fatigue changes at the end of the intervention period. Two independent reviewers complete the study selection, data extraction, and the risk of bias assessment. We assess pooled data using a random-effects model through Revman software (v.5.3) and Stata (version 15.0).

Ethics and dissemination: Ethics approval is not required because the individual patient data will not be involved, with no privacy concerns. This systematic review and meta-analysis will provide a reference for CFS patients and clinicians on the non-drug interventions. We will publish and disseminate the results of this review in a peer-reviewed journal or relevant conference.

Source: Zhang ML, Fu HJ, Tang Y, Luo ZG, Li JY, Li R. Effect of acupoint catgut embedding in chronic fatigue syndrome patients: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021 Feb 5;100(5):e23946. doi: 10.1097/MD.0000000000023946. PMID: 33592847; PMCID: PMC7870242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870242/ (Full text)

The Prospects of the Two-Day Cardiopulmonary Exercise Test (CPET) in ME/CFS Patients: A Meta-Analysis

Abstract:

Background: The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is problematic due to the lack of established objective measurements. Postexertional malaise (PEM) is a hallmark of ME/CFS, and the two-day cardiopulmonary exercise test (CPET) has been tested as a tool to assess functional impairment in ME/CFS patients. This study aimed to estimate the potential of the CPET.

Methods: We reviewed studies of the two-day CPET and meta-analyzed the differences between ME/CFS patients and controls regarding four parameters: volume of oxygen consumption and level of workload at peak (VO2peak, Workloadpeak) and at ventilatory threshold (VO2@VT, Workload@VT).

Results: The overall mean values of all parameters were lower on the 2nd day of the CPET than the 1st in ME/CFS patients, while it increased in the controls. From the meta-analysis, the difference between patients and controls was highly significant at Workload@VT (overall mean: -10.8 at Test 1 vs. -33.0 at Test 2, p < 0.05), which may reflect present the functional impairment associated with PEM.

Conclusions: Our results show the potential of the two-day CPET to serve as an objective assessment of PEM in ME/CFS patients. Further clinical trials are required to validate this tool compared to other fatigue-inducing disorders, including depression, using well-designed large-scale studies.

Source: Lim EJ, Kang EB, Jang ES, Son CG. The Prospects of the Two-Day Cardiopulmonary Exercise Test (CPET) in ME/CFS Patients: A Meta-Analysis. J Clin Med. 2020 Dec 14;9(12):E4040. doi: 10.3390/jcm9124040. PMID: 33327624. https://pubmed.ncbi.nlm.nih.gov/33327624/

Reduced Heart Rate Variability in Patients with Medically Unexplained Physical Symptoms: A Meta-Analysis of HF-HRV and RMSSD

Abstract:

Objectives: Medically unexplained physical symptoms (MUPS) and related syndromes are common and place a substantial burden on both patients and society. Chronic psychological distress and dysregulation of the autonomic nervous system may be common factors associated with MUPS, although previous studies have reported mixed results. The aim of this meta-analysis is to provide an updated synthesis of studies investigating heart rate variability (HRV) indices associated with autonomic nervous system functioning in three common MUPS-syndromes and to explain inconsistencies in previous study findings.

Method: Literature search yielded 58 studies comparing HRV indices of reduced parasympathetic activity of healthy individuals to patients with chronic fatigue syndrome (Npatients = 271), irritable bowel syndrome (Npatients = 1005), and fibromyalgia (Npatients = 534). Separate random-effects meta-analyses were conducted on studies measuring root mean square of successive differences (RMSSD) and high frequency HRV (HF-HRV).

Results: Regardless of syndrome type, patients had significantly lower RMSSD (k = 22, Hedges’ g = – 0.37 [-0.53; -0.21], p < .001) and HF-HRV (k = 52, Hedges’ g = -0.69 [-1.03; -0.36], p < .001) than healthy individuals. Sample age and publication year explained substantial variation in RMSSD, whereas controlling for confounders in statistical analyses explained variation in HF-HRV.

Conclusions: Lower RMSSD and HF-HRV in patients with MUPS versus healthy controls indicates that autonomic nervous system dysregulation, particularly lower parasympathetic activity, may play a role in patients with these conditions. This conclusion may have important implications for the underlying mechanisms and treatment of MUPS and related syndromes.

Source: Vreijling SR, Troudart Y, Brosschot JF. Reduced Heart Rate Variability in Patients with Medically Unexplained Physical Symptoms: A Meta-Analysis of HF-HRV and RMSSD. Psychosom Med. 2020 Oct 14. doi: 10.1097/PSY.0000000000000874. Epub ahead of print. PMID: 33065584. https://pubmed.ncbi.nlm.nih.gov/33065584/

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.

Copyright © 2019. Published by Elsevier Ltd.

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