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Chronic Fatigue Syndrome: HELP
Articles by Donald P. Lewis
Based on 11 articles published since 2010
(Why 11 articles?)
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Between 2010 and 2020, D. Lewis wrote the following 11 articles about Fatigue Syndrome, Chronic.
 
+ Citations + Abstracts
1 Review Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review. 2017

Wallis, Amy / Ball, Michelle / McKechnie, Sandra / Butt, Henry / Lewis, Donald P / Bruck, Dorothy. ·Psychology Department, College of Health and Biomedicine, Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia. amy.wallis@vu.edu.au. · Psychology Department, College of Health and Biomedicine, Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia. · College of Engineering & Science, Victoria University, Melbourne, VIC, Australia. · Bioscreen Yarraville (Aust) Pty Ltd, Melbourne, VIC, Australia. · CFS Discovery Clinic, Melbourne, VIC, Australia. ·J Transl Med · Pubmed #28592308.

ABSTRACT: BACKGROUND: The pursuit for clarity in diagnostic and treatment pathways for the complex, chronic condition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continues. This systematic review raises a novel question to explore possible overlapping aetiology in two distinct conditions. Similar neurocognitive symptoms and evidence of D-lactate producing bacteria in ME/CFS raise questions about shared mechanisms with the acute condition of D-lactic acidosis (D-la). METHODS: D-la case reports published between 1965 and March 2016 were reviewed for episodes describing both neurological symptoms and high D-lactate levels. Fifty-nine D-la episodes were included in the qualitative synthesis comparing D-la symptoms with ME/CFS diagnostic criteria. A narrative review of D-la mechanisms and relevance for ME/CFS was provided. RESULTS: The majority of neurological disturbances reported in D-la episodes overlapped with ME/CFS symptoms. Of these, the most frequently reported D-la symptoms were motor disturbances that appear more prominent during severe presentations of ME/CFS. Both patient groups shared a history of gastrointestinal abnormalities and evidence of bacterial dysbiosis, although only preliminary evidence supported the role of lactate-producing bacteria in ME/CFS. LIMITATIONS: Interpretation of results are constrained by both the breadth of symptoms included in ME/CFS diagnostic criteria and the conservative methodology used for D-la symptom classification. Several pathophysiological mechanisms in ME/CFS were not examined. CONCLUSIONS: Shared symptomatology and underlying microbiota-gut-brain interactions raise the possibility of a continuum of acute (D-la) versus chronic (ME/CFS) presentations related to D-lactate absorption. Measurement of D-lactate in ME/CFS is needed to effectively evaluate whether subclinical D-lactate levels affect neurological symptoms in this clinical population.

2 Review Support for the microgenderome invites enquiry into sex differences. 2017

Wallis, Amy / Butt, Henry / Ball, Michelle / Lewis, Donald P / Bruck, Dorothy. ·a Psychology Department , Victoria University , Victoria , Australia. · b Bioscreen (Aust) Pty Ltd , Victoria , Australia. · c CFS Discovery Clinic , Donvale , Victoria , Australia. ·Gut Microbes · Pubmed #27808584.

ABSTRACT: The microgenderome defines the interaction between microbiota, sex hormones and the immune system. Our recent research inferred support for the microgenderome by showing sex differences in microbiota-symptom associations in a clinical sample of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). This addendum expands upon the sex-specific pattern of associations that were observed. Interpretations are hypothesized in relation to genera versus species-level analyses and D-lactate theory. Evidence of sex-differences invites future research to consider sex comparisons in microbial function even when microbial abundance is statistically similar. Pairing assessment of clinical symptoms with microbial culture, DNA sequencing and metabolomics methods will help advance our current understandings of the role of the microbiome in health and disease.

3 Review Myalgic encephalomyelitis: International Consensus Criteria. 2011

Carruthers, B M / van de Sande, M I / De Meirleir, K L / Klimas, N G / Broderick, G / Mitchell, T / Staines, D / Powles, A C P / Speight, N / Vallings, R / Bateman, L / Baumgarten-Austrheim, B / Bell, D S / Carlo-Stella, N / Chia, J / Darragh, A / Jo, D / Lewis, D / Light, A R / Marshall-Gradisnik, S / Mena, I / Mikovits, J A / Miwa, K / Murovska, M / Pall, M L / Stevens, S. ·Department of Physiology and Medicine, Vrije University of Brussels, Himmunitas Foundation, Brussels, Belgium. bcarruth@telus.net ·J Intern Med · Pubmed #21777306.

ABSTRACT: The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization's International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.

4 Clinical Trial Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons. 2018

Wallis, Amy / Ball, Michelle / Butt, Henry / Lewis, Donald P / McKechnie, Sandra / Paull, Phillip / Jaa-Kwee, Amber / Bruck, Dorothy. ·Psychology Department, College of Health and Biomedicine, Victoria University, Melbourne, Australia. Amy.Wallis@vu.edu.au. · Psychology Department, College of Health and Biomedicine, Victoria University, Melbourne, Australia. · Bioscreen (Aust) Pty Ltd., Melbourne, Australia. · CFS Discovery Clinic, Donvale, Melbourne, Australia. · College of Engineering and Science, Victoria University, Melbourne, Australia. ·J Transl Med · Pubmed #29409505.

ABSTRACT: BACKGROUND: Preliminary evidence suggests that the enteric microbiota may play a role in the expression of neurological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms with the acute presentation of D-lactic acidosis has prompted the use of antibiotic treatment to target the overgrowth of species within the Streptococcus genus found in commensal enteric microbiota as a possible treatment for neurological symptoms in ME/CFS. METHODS: An open-label, repeated measures design was used to examine treatment efficacy and enable sex comparisons. Participants included 44 adult ME/CFS patients (27 females) from one specialist medical clinic with Streptococcus viable counts above 3.00 × 10 RESULTS: Large treatment effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency). Mood, fatigue and urine D:L lactate ratio remained similar across time. Ancillary results infer that shifts in microbiota were associated with more of the variance in clinical changes for males compared with females. CONCLUSIONS: Results support the notion that specific microorganisms interact with some ME/CFS symptoms and offer promise for the therapeutic potential of targeting gut dysbiosis in this population. Streptococcus spp. are not the primary or sole producers of D-lactate. Further investigation of lactate concentrations are needed to elucidate any role of D-lactate in this population. Concurrent microbial shifts that may be associated with clinical improvement (i.e., increased Bacteroides and Bifidobacterium or decreased Clostridium in males) invite enquiry into alternative strategies for individualised treatment. Trial Registration Australian and New Zealand Clinical Trial Registry (ACTRN12614001077651) 9th October 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366933&isReview=true.

5 Article An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients. 2020

Missailidis, Daniel / Annesley, Sarah J / Allan, Claire Y / Sanislav, Oana / Lidbury, Brett A / Lewis, Donald P / Fisher, Paul R. ·Department of Physiology, Anatomy, and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia. · National Centre for Epidemiology and Population Health, Research School of Population Health, Australian National University, Canberra, ACT 2601, Australia. ·Int J Mol Sci · Pubmed #32041178.

ABSTRACT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an enigmatic condition characterized by exacerbation of symptoms after exertion (post-exertional malaise or "PEM"), and by fatigue whose severity and associated requirement for rest are excessive and disproportionate to the fatigue-inducing activity. There is no definitive molecular marker or known underlying pathological mechanism for the condition. Increasing evidence for aberrant energy metabolism suggests a role for mitochondrial dysfunction in ME/CFS. Our objective was therefore to measure mitochondrial function and cellular stress sensing in actively metabolizing patient blood cells. We immortalized lymphoblasts isolated from 51 ME/CFS patients diagnosed according to the Canadian Consensus Criteria and an age- and gender-matched control group. Parameters of mitochondrial function and energy stress sensing were assessed by Seahorse extracellular flux analysis, proteomics, and an array of additional biochemical assays. As a proportion of the basal oxygen consumption rate (OCR), the rate of ATP synthesis by Complex V was significantly reduced in ME/CFS lymphoblasts, while significant elevations were observed in Complex I OCR, maximum OCR, spare respiratory capacity, nonmitochondrial OCR and "proton leak" as a proportion of the basal OCR. This was accompanied by a reduction of mitochondrial membrane potential, chronically hyperactivated TOR Complex I stress signaling and upregulated expression of mitochondrial respiratory complexes, fatty acid transporters, and enzymes of the β-oxidation and TCA cycles. By contrast, mitochondrial mass and genome copy number, as well as glycolytic rates and steady state ATP levels were unchanged. Our results suggest a model in which ME/CFS lymphoblasts have a Complex V defect accompanied by compensatory upregulation of their respiratory capacity that includes the mitochondrial respiratory complexes, membrane transporters and enzymes involved in fatty acid β-oxidation. This homeostatically returns ATP synthesis and steady state levels to "normal" in the resting cells, but may leave them unable to adequately respond to acute increases in energy demand as the relevant homeostatic pathways are already activated.

6 Article Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity. 2019

Lidbury, Brett A / Kita, Badia / Richardson, Alice M / Lewis, Donald P / Privitera, Edwina / Hayward, Susan / de Kretser, David / Hedger, Mark. ·National Centre for Epidemiology and Population Health, RSPH, College of Health and Medicine, The Australian National University, Canberra, ACT 2601, Australia. brett.lidbury@anu.edu.au. · Paranta Biosciences Limited, Suite 549, 1 Queens Rd, Melbourne, VIC 3004, Australia. · National Centre for Epidemiology and Population Health, RSPH, College of Health and Medicine, The Australian National University, Canberra, ACT 2601, Australia. · CFS Discovery, Donvale Specialist Medical Centre, Donvale, VIC 3111, Australia. · Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia. · Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia. ·Diagnostics (Basel) · Pubmed #31331036.

ABSTRACT: Biomarker discovery applied to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disabling disease of inconclusive aetiology, has identified several cytokines to potentially fulfil a role as a quantitative blood/serum marker for laboratory diagnosis, with activin B a recent addition. We explored further the potential of serum activin B as a ME/CFS biomarker, alone and in combination with a range of routine test results obtained from pathology laboratories. Previous pilot study results showed that activin B was significantly elevated for the ME/CFS participants compared to healthy (control) participants. All the participants were recruited via CFS Discovery and assessed via the Canadian/International Consensus Criteria. A significant difference for serum activin B was also detected for ME/CFS and control cohorts recruited for this study, but median levels were significantly lower for the ME/CFS cohort. Random Forest (RF) modelling identified five routine pathology blood test markers that collectively predicted ME/CFS at ≥62% when compared via weighted standing time (WST) severity classes. A closer analysis revealed that the inclusion of activin B to the panel of pathology markers improved the prediction of mild to moderate ME/CFS cases. Applying correct WST class prediction from RFA modelling, new reference intervals were calculated for activin B and associated pathology markers, where 24-h urinary creatinine clearance, serum urea and serum activin B showed the best potential as diagnostic markers. While the serum activin B results remained statistically significant for the new participant cohorts, activin B was found to also have utility in enhancing the prediction of symptom severity, as represented by WST class.

7 Article Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection. 2018

Richardson, Alice M / Lewis, Don P / Kita, Badia / Ludlow, Helen / Groome, Nigel P / Hedger, Mark P / de Kretser, David M / Lidbury, Brett A. ·National Centre for Epidemiology and Public Health, Research School of Population Health, ANU, Acton, ACT, 2601, Australia. alice.richardson@anu.edu.au. · CFS Discovery, Donvale Medical Specialist Centre, Donvale, VIC, 3111, Australia. · Paranta Biosciences Limited, Melbourne, VIC, 3004, Australia. · School of Life Sciences, Oxford Brookes University, Headington, Oxford, OX3 0BP, UK. · The Hudson Medical Research Institute, Monash University, Clayton, VIC, 3168, Australia. · Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, 3168, Australia. · National Centre for Epidemiology and Public Health, Research School of Population Health, ANU, Acton, ACT, 2601, Australia. ·J Transl Med · Pubmed #29650052.

ABSTRACT: BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is clinically defined and characterised by persistent disabling tiredness and exertional malaise, leading to functional impairment. METHODS: This study introduces the weighted standing time (WST) as a proxy for ME/CFS severity, and investigates its behaviour in an Australian cohort. WST was calculated from standing time and subjective standing difficulty data, collected via orthostatic intolerance assessments. The distribution of WST for healthy controls and ME/CFS patients was correlated with the clinical criteria, as well as pathology and cytokine markers. Included in the WST cytokine analyses were activins A and B, cytokines causally linked to inflammation, and previously demonstrated to separate ME/CFS from healthy controls. Forty-five ME/CFS patients were recruited from the CFS Discovery Clinic (Victoria) between 2011 and 2013. Seventeen healthy controls were recruited concurrently and identically assessed. RESULTS: WST distribution was significantly different between ME/CFS participants and controls, with six diagnostic criteria, five analytes and one cytokine also significantly different when comparing severity via WST. On direct comparison of ME/CFS to study controls, only serum activin B was significantly elevated, with no significant variation observed for a broad range of serum and urine markers, or other serum cytokines. CONCLUSIONS: The enhanced understanding of standing test behaviour to reflect orthostatic intolerance as a ME/CFS symptom, and the subsequent calculation of WST, will encourage the greater implementation of this simple test as a measure of ME/CFS diagnosis, and symptom severity, to the benefit of improved diagnosis and guidance for potential treatments.

8 Article Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study. 2017

Lidbury, Brett A / Kita, Badia / Lewis, Donald P / Hayward, Susan / Ludlow, Helen / Hedger, Mark P / de Kretser, David M. ·Pattern Recognition and Pathology, Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia. brett.lidbury@anu.edu.au. · The National Centre for Epidemiology and Public Health, The Research School of Population Health, ANU, Canberra, ACT, 2601, Australia. brett.lidbury@anu.edu.au. · Paranta Biosciences Limited, Caulfield North, VIC, 3161, Australia. · CFS Discovery, Donvale Medical Specialist Centre, Donvale, VIC, 3111, Australia. · The Hudson Medical Research Institute, Monash University, Clayton, VIC, 3168, Australia. · Centre for Proteins and Peptides, School of Life Sciences, Oxford Brookes University, Headington, Oxford, OX3 0BP, UK. · Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, 3168, Australia. ·J Transl Med · Pubmed #28302133.

ABSTRACT: BACKGROUND: Investigations of activin family proteins as serum biomarkers for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). CFS/ME is a disease with complex, wide-ranging symptoms, featuring persistent fatigue of 6 months or longer, particularly post exertion. No definitive biomarkers are available. METHODS: A cross-sectional, observational study of CFS/ME patients fulfilling the 2003 Canadian Consensus Criteria, in parallel with healthy non-fatigued controls, was conducted. Comparisons with a previously defined activin reference population were also performed. For the total study cohort the age range was 18-65 years with a female: male participant ratio of greater than 3:1. All participants were assessed via a primary care community clinic. Blood samples were collected for pathology testing after physical examination and orthostatic intolerance assessment. Cytokines, activin A, activin B and follistatin were also measured in sera from these samples. All data were compared between the CFS/ME and control cohorts, with the activins and follistatin also compared with previously defined reference intervals. RESULTS: Serum activin B levels for CFS/ME participants were significantly elevated when compared to the study controls, as well as the established reference interval. Serum activin A and follistatin were within their normal ranges. All routine and special pathology markers were within the normal laboratory reference intervals for the total study cohort, with no significant differences detected between CFS/ME and control groups. Also, no significant differences were detected for IL-2, IL-4, IL-6, IL-10, IL-17A, TNF or IFN-gamma. CONCLUSION: Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients.

9 Article Support for the Microgenderome: Associations in a Human Clinical Population. 2016

Wallis, Amy / Butt, Henry / Ball, Michelle / Lewis, Donald P / Bruck, Dorothy. ·Psychology Department, Victoria University, Victoria, Australia. · Bioscreen (Aust) Pty Ltd, Victoria, Australia. · CFS Discovery Clinic, Donvale, Victoria, Australia. ·Sci Rep · Pubmed #26757840.

ABSTRACT: The 'microgenderome' provides a paradigm shift that highlights the role of sex differences in the host-microbiota interaction relevant for autoimmune and neuro-immune conditions. Analysis of cross-sectional self-report and faecal microbial data from 274 patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) suggests that commensal gut microorganisms may play both protective and deleterious roles in symptom expression. Results revealed significant sex-specific interactions between Firmicutes (Clostridium, Streptococcus, Lactobacillus and Enterococcus) and ME/CFS symptoms (including neurological, immune and mood symptoms), regardless of compositional similarity in microbial levels across the sexes. Extending animal studies, we provide support for the microgenderome in a human clinical population. Applied and mechanistic research needs to consider sex-interactions when examining the composition and function of human microbiota.

10 Article Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study. 2015

Jackson, Melinda L / Butt, Henry / Ball, Michelle / Lewis, Donald P / Bruck, Dorothy. ·College of Arts, Victoria University, Victoria, Australia. · Bioscreen (Aust) Pty Ltd., Victoria, Australia. · CFS Discovery, Victoria, Australia. ·Sleep Sci · Pubmed #26779319.

ABSTRACT: Chronic Fatigue Syndrome (CFS) is a multisystem illness, which may be associated with imbalances in gut microbiota. This study builds on recent evidence that sleep may be influenced by gut microbiota, by assessing whether changes to microbiota in a clinical population known to have both poor sleep and high rates of colonization with gram-positive faecal Streptococcus, can improve sleep. Twenty-one CFS participants completed a 22- day open label trial. Faecal microbiota analysis was performed at baseline and at the end of the trial. Participants were administered erythromycin 400 mg b.d. for 6 days. Actigraphy and questionnaires were used to monitor sleep, symptoms and mood. Changes in patients who showed a clinically significant change in faecal Streptococcus after treatment (responders; defined as post-therapy distribution<6%) were compared to participants who did not respond to treatment. In the seven responders, there was a significant increase in actigraphic total sleep time (p=0.028) from baseline to follow up, compared with non-responders. Improved vigour scores were associated with a lower Streptococcus count (ρ=-0.90, p=0.037). For both the responders and the whole group, poorer mood was associated with higher Lactobacillus. Short term antibiotic treatment appears to be insufficient to effect sustainable changes in the gut ecosystem in most CFS participants. Some improvement in objective sleep parameters and mood were found in participants with reduced levels of gram-positive gut microbiota after antibiotic treatment, which is encouraging. Further study of possible links between gut microorganisms and sleep and mood disturbances is warranted.

11 Article Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort. 2014

Reynolds, G K / Lewis, D P / Richardson, A M / Lidbury, B A. ·Department of Genome Biology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia. ·J Intern Med · Pubmed #24206536.

ABSTRACT: OBJECTIVE: Patients with chronic fatigue syndrome (CFS) are frequently diagnosed with comorbid postural orthostatic tachycardia syndrome (POTS), suggesting a shared pathogenesis. The aim of this study was to examine the relationship between demographic characteristics, autonomic functioning and fatigue levels amongst CFS patients with and without comorbid POTS. DESIGN AND SETTING: All patients presenting to the CFS Discovery Clinic between 2009 and 2012 completed a 20-min standing task as part of their initial assessment. Heart rate and pulse pressure were recorded at baseline, at 2-min intervals poststanding, at the end of the task and following a recovery period. Average heart rate and pulse pressure variability were calculated from this data. Age, gender, length of illness and self-reported fatigue scores were also recorded. POTS patients were diagnosed by an orthostatic increase in heart rate >30 beats per min, concomitant symptoms of orthostatic intolerance and no orthostatic hypotension. Differences in autonomic functioning between POTS and CFS patients were compared using independent samples t-tests, whilst logistic and linear regressions were performed to examine the contribution of autonomic functioning to task completion and perceived fatigue, respectively. RESULTS: Comorbidity of CFS and POTS (CFS-POTS) was observed in 11% (33/306) of patients. CFS-POTS patients were significantly younger (P < 0.001), had a shorter length of illness (P = 0.034), experienced greater task difficulty (P = 0.002) and were able to stand for significantly shorter periods compared to the CFS-only patients (P < 0.001). CFS-POTS patients experienced significantly lower baseline diastolic blood pressure (P = 0.002), significantly higher heart rate and lower pulse pressures at each standing measurement. Early heart rate changes (P = 0.002) and overall heart rate change (P < 0.001) were significant predictors of completion status, whereas heart rate variability (P < 0.001) and female gender (P < 0.001) were significant predictors of increased perceived task difficulty. CONCLUSIONS: Haemodynamic and demographic differences between CFS-POTS and CFS-only patients suggest that the former group reflects a distinct subgroup of the CFS population. The findings highlight the utility of screening younger patients with fatigue for POTS, and identified heart rate variability as an important marker of fatigue for CFS patients in general.