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Chronic Fatigue Syndrome prevalence is grossly overestimated using Oxford criteria compared to Centers for Disease Control (Fukuda) criteria in a U.S. population study
Abstract
Background:
Results from treatment studies using the low threshold Oxford criteria for recruitment may have been overgeneralized to patients diagnosed by more stringent CFS criteria.
Purpose:
To compare the selectivity of Oxford and Fukuda criteria in a U.S. population.
Methods:
Fukuda (Center for Disease Control (CDC)) criteria, as operationalized with the CFS Severity Questionnaire (CFSQ), were included in the nationwide rc2004 HealthStyles survey mailed to 6,175 participants who were representative of the US 2003 Census population. The 9 questionnaire items (CFS symptoms) were crafted into proxies for Oxford criteria (mild fatigue, minimal exclusions) and Fukuda criteria (fatigue plus ≥4 of 8 ancillary criteria at moderate or severe levels with exclusions). The comparative prevalence estimates of CFS were then determined. Severity scores for fatigue were plotted against the sum of severities for the 8 ancillary criteria. The 4 quadrants of scatter diagrams assessed putative healthy controls, CFS, chronic idiopathic fatigue, and CFS-like with insufficient fatigue subjects.
Results:
The Oxford criteria designated CFS in 25.5% of 2,004 males and 19.9% of 1,954 females. Based on quadrant analysis, 85% of Oxford-defined cases were inappropriately classified as CFS. Fukuda criteria identified CFS in 2.3% of males and 1.8% of females.
Discussion:
CFS prevalence using Fukuda criteria and quadrant analysis were near the upper limits of previous epidemiology studies. The CFSQ may have utility for on-line and outpatient screening. The Oxford criteria were untenable because they inappropriately selected healthy subjects with mild fatigue and chronic idiopathic fatigue and mislabeled them as CFS.
... This makes a meaningful comparison and synthesis of findings reported by various authors using different operational criteria challenging. For example, in a recent study involving an analysis of 6,175 participants, it was reported that only 15% of individuals satisfying the requirements of the widest known definition of CFS, sometimes described as the Oxford criteria, which only mandates the presence of fatigue (5), would qualify for a ME/CFS diagnosis according to internationally recognised criteria (6). Moreover, the use of the Oxford criteria identified healthy individuals with mild fatigue who were inappropriately recognised as having CFS (6). ...
... For example, in a recent study involving an analysis of 6,175 participants, it was reported that only 15% of individuals satisfying the requirements of the widest known definition of CFS, sometimes described as the Oxford criteria, which only mandates the presence of fatigue (5), would qualify for a ME/CFS diagnosis according to internationally recognised criteria (6). Moreover, the use of the Oxford criteria identified healthy individuals with mild fatigue who were inappropriately recognised as having CFS (6). ...
Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a common and disabling condition with a paucity of effective and evidence-based therapies reflecting a major unmet need. Cognitive behavioural therapy and graded exercise are of modest benefit for only some ME/CFS patients, and many sufferers report aggravation of symptoms of fatigue with exercise. The presence of a multiplicity of pathophysiological abnormalities, in at least the subgroup of people with ME/CFS diagnosed with the current international consensus “Fukuda” criteria, points to numerous potential therapeutic targets. Such abnormalities include extensive data showing that at least a subgroup has a pro-inflammatory state, increased oxidative and nitrosative stress, disruption of gut mucosal barriers and mitochondrial dysfunction together with dysregulated bioenergetics. In this paper, these pathways are summarised, and data regarding promising therapeutic options that target these pathways are highlighted; they include coenzyme Q10, melatonin, curcumin, molecular hydrogen and N-acetylcysteine. These data are promising yet preliminary, suggesting hopeful avenues to address this major unmet burden of illness.
... Fatigue may cause depression, aging, Parkinsonian syndrome, multiple sclerosis, cancer, and other diseases [3]. In the United States, the male population suffering from persistent fatigue has reached 2.3%, while the figure for women is 1.9% [4]. A survey investigating the student population in Suzhou found that nearly 1% suffered from long-term fatigue symptoms [5]. ...
Background:
Asiaticoside is one of the main components of triterpenoid saponins extracted from Centella asiatica. Asiaticoside has shown the effects of wound healing, osteoclastogenesis, anti-inflammatory, anti-cancer, and improving cognition in multiple human disease models. However, studies on the antifatigue effects of asiaticoside have not been explored. Therefore, the aim of this study was to investigate the potential antifatigue effect and underlying mechanism of asiaticoside administration on exhaustive exercise performance.
Methods:
Male Kunming mice were divided into four groups randomly (n = 20/group). Saline (10 mL/kg) was administered to the model control group and the other three experimental groups were fed with low (10 mg/kg), medium (20 mg/kg) and high (40 mg/kg) asiaticoside once/daily for 14 days. The antifatigue effect of asiaticoside on mice was estimated by analyzing changes in body weight, weight-loaded swimming time, rotating time, lactic acid, urea nitrogen, liver/muscle glycogen, serumal superoxide dismutase, superoxide dismutase and the liver tissues of hematoxylin and eosin (H&E) staining.
Results:
The results indicated that no significant differences were observed in the body weight of each group (p > 0.05). Compared with the model control group, supplementation of asiaticoside significantly prolonged the weight-loaded swimming time and rotating time; Decreased the blood lactic acid (LA), blood urea nitrogen (BUN), and serumal malonaldehyde (MDA); And increased the content of liver/muscle glycogen and serumal superoxide dismutase levels (SOD) (p < 0.05). Furthermore, the pathological results of the liver were improved greatly. The maximal effect was observed in the medium group of 20 mg/kg.
Conclusions:
Asiaticoside is capable of reducing the fatigue effect by regulating energy consumption, energy metabolism and improving antioxidant activity after exercise. While there are still some shortcomings in this study, our findings provide a scientific basis for developing an asiaticoside-based antifatigue supplement.
... Chronic fatigue states can cause immune deficiency, endocrine disorders, and cognitive impairment, which eventually develop into chronic fatigue syndrome (CFS) [2]. At present, in the United States, 2.3% of men suffer from CFS [3]. In a study, Shi J observed that 12% of secondary school students in China suffered from chronic fatigue [4]. ...
The aim of this study was to clarify the anti-fatigue effect of peanut oligopeptides (POPs) in mice and to investigate its possible underlying mechanism. A total of 150 male ICR mice were randomly assigned into five groups: control, whey protein (0.50 g/kg·bw), and three peanut peptide groups (0.25, 0.50, and 1.00 g/kg·bw). All the mice were treated with intra-gastric administration for 30 days. Following the intervention, a weight-loaded swimming test, blood lactate concentration, glycogen content, the activities of antioxidant factors and energy metabolism enzymes, and the function of mitochondria in the skeletal muscle were examined. The results show that POP intervention significantly prolonged the exhaustive swimming time, decreased blood lactate concentration levels, regulated the process of energy metabolism, and increased the level of antioxidant enzymes, muscle glycogen, and expressions of mtTFA and NRF-1 in the mitochondria of the gastrocnemius muscle. The results suggest that POPs produce an anti-fatigue effect in the animals, and they may exert this effect through the mechanism of improving the animals' antioxidant capacity to reduce oxidative damage levels and regulating the process of energy metabolism.
... Weder die Anzahl der Proband:innen wäre ausreichend, um eine Aussage über die Effektivität der Behandlung zu treffen, noch ist das Messinstrument ausreichend reliabel. Die Studie wurde 9 Jahren später anhand der Oxford-Diagnosekriterien (die aktuell selbst in der Kritik stehen, zu überdiagnostizieren [7]) wiederholt. Dabei wurde dieselbe 3-Punkte-Skala für körperliche Symptome, dieselbe Mischung aus essenziellen Fettsäuren in derselben Dosierung verwendet, aber die Ergebnisse konnten nicht repliziert werden [73]. ...
Zusammenfassung
In den vergangenen 5 Jahren hat sowohl das mediale als auch das wissenschaftliche Interesse an der Erkrankung myalgische Enzephalomyelitis/„chronic fatigue syndrome“ (ME/CFS) signifikant zugenommen; nicht zuletzt auch durch die klinisch ähnliche Manifestation im Rahmen von Long- oder Post-COVID. In dieser Übersichtsarbeit diskutieren wir die klinische Diagnosestellung und therapeutische Studien zu ME/CFS sowie die Gemeinsamkeiten oder Unterschiede zu Long‑/Post-COVID. Bisher liegen weder pathophysiologisch eindeutig kausale noch therapeutisch evidenzbasierte Ergebnisse in der langjährigen wissenschaftlichen Forschung zu ME/CFS vor. Nicht zuletzt aufgrund der relevanten psychiatrischen Komorbiditätsrate beim ME/CFS ist nach der aktuellen Datenlage eine psychosomatische Ätiologie der Erkrankung zu diskutieren. Des Weiteren könnte sich eine genauere und sichere Diagnosestellung anhand strikterer Diagnosekriterien auf die weitere Forschung und vor allem hinsichtlich Therapien positiv auswirken.
... Many clinicians typically explain to patients that "nothing is wrong" because… they can find nothing wrong. One difficulty has been the wide variety of diagnostic criteria so that CFS prevalence is grossly overestimated using the Oxford criteria compared to those of the Centers for Disease Control [82,83,84]. The Oxford criteria specify 'unexplained physical and mental fatigue for at least 6 months, myalgia and sleep and mood disturbances; exclusion of other diseases'. ...
The psychosomatic approach to medically unexplained symptoms, myalgic encephalomyelitis and chronic fatigue syndrome (MUS/ME/CFS) is critically reviewed using scientific criteria. Based on the 'Biopsychosocial Model', the psychosomatic theory proposes that patients' dysfunctional beliefs, deconditioning and attentional biases cause or make illness worse, disrupt therapies, and lead to preventable deaths. The evidence reviewed suggests that none of these psychosomatic hypotheses is empirically supported. The lack of robust supportive evidence together with the use of fal-lacious causal assumptions, inappropriate and harmful therapies, broken scientific principles, repeated methodological flaws and an unwillingness to share data all give the appearance of cargo cult science. The psychosomatic approach needs to be replaced by a scientific, biologically grounded approach to MUS/ME/CFS that can be expected to provide patients with appropriate care and treatments. Patients with MUS/ME/CFS and their families have not been treated with the dignity, respect and care that is their human right. Patients with MUS/ME/CFS and their families could consider a class action legal case against the injuring parties.
... Internasjonalt finnes det minst 20 forskjellige diagnoseveiledere med kriterier som må oppfylles for at behandlende lege skal fastsette ME/CFS-diagnose, og flere studier har demonstrert at den påviste forekomsten av sykdommen varierer basert på hvilke diagnosekriterier som brukes for å definere ME/CFS-populasjonen (Baraniuk, 2017;Lim et al., 2020). Det er allikevel påvist i flere litteraturgjennomganger at det er Fukuda (Fukuda et al., 1994)-og Canadakriteriene (Carruthers et al., 2003) som har blitt hyppigst anvendt (Haney et al, 2015;Brurberg et al., 2013;Jason et al., 2015). ...
Kronisk utmattelsessyndrom/myalgisk encefalopati (CFS/ME) er en kompleks og kronisk sykdom som er assosiert med en betydelig reduksjon i livskvalitet for de rammede. I denne studien estimerer vi insidensraten for ME i den norske befolkningen mellom 2016 og 2018. Data om pasienter er innsamlet fra Norsk pasientregister (NPR). Populasjonen er definert av alle pasienter behandlet i spesialisthelsetjenesten som har blitt diagnostisert med CFS/ME mellom 2016-2018. Vi finner at 5 556 nye pasienter ble diagnostisert med CFS/ME i perioden 2016-2018. Insidensraten var på 36.1 per 100 000 person-år. Av disse var 4 347 kvinner, som betyr at insidensraten for kvinner relativt til menn var 3.7. Vi finner at forekomsten av CFS/ME varierer med alder, og vi finner to alderstopper i gruppene 15-19 og 35-39 år. Vi finner høyere insidens for den samlede populasjonen, sammenlignet med tidligere norsk forskning.
... A report commissioned by the American National Institute of Health came to a similar conclusion in 2014 [78,79]. Moreover, a large study by Baraniuk (n = 6175) [80] concluded that "the Oxford criteria were untenable because they inappropriately selected healthy subjects with mild fatigue and CIF [chronic idiopathic fatigue] and mislabeled them as CFS". ...
The British National Institute for Health and Care Excellence (NICE) recently published its updated guidelines for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). NICE concluded, after an extensive review of the literature, that graded exercise therapy (GET) is harmful and should not be used, and that cognitive behavioural therapy (CBT) is only an adjunctive and not a curative treatment. Leading proponents of the cognitive behavioural model (CBmodel) find it difficult to accept this paradigm shift. In, for example, an article in The Lancet, they try to argue that the new NICE guideline is based on ideology instead of science. In this article we reviewed the evidence they used to support their claims. Our analysis shows that the trials they used in support suffered from serious flaws which included badly designed control groups, relying on subjective primary outcomes in non-blinded studies, including patients in their trials who didn’t have the disease under investigation or had a self-limiting disease, selective reporting, outcome switching and making extensive endpoint changes, which created an overlap in entry and recovery criteria, using a post-hoc definition of recovery which included the severely ill, not publishing results that contradict their own conclusion, ignoring their own (objective) null effect, etc. The flaws in these trials all created a bias in favour of the interventions. Despite all these flaws, treatments that are said to lead to recovery in reality do not lead to objective improvement. Therefore, these studies do not support the claim that CBT and GET are effective treatments. Moreover, the arguments that are used to claim that NICE was wrong, in reality, highlight the absence of evidence for the safety and efficacy of CBT and GET and strengthen the decision by NICE to drop CBT and GET as curative treatments for ME/CFS.
... This is especially apparent with older criteria that rely solely on fatigue as a symptom. They allow the inclusion of chronic idiopathic fatigue and atypical depression in clinical trials and, in contrast to modern criteria, do not explicitly require PEM, interoceptive, nociceptive, autonomic, and functional findings [22]. The imperfect vocabulary describing fatigue and exhaustion is another limit of subjective evaluations. ...
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS and Gulf War Illness (GWI) share features of post-exertional malaise (PEM), exertional exhaustion, or postexertional symptom exacerbation. In a two-day model of PEM, submaximal exercise induced significant changes in activation of the dorsal midbrain during a high cognitive load working memory task (Washington 2020) (Baraniuk this issue). Controls had no net change. However, ME/CFS had increased activity after exercise, while GWI had significantly reduced activity indicating differential responses to exercise and pathological mechanisms. These data plus findings of the midbrain and brainstem atrophy in GWI inspired a review of the anatomy and physiology of the dorsal midbrain and isthmus nuclei in order to infer dysfunctional mechanisms that may contribute to disease pathogenesis and postexertional malaise. The nuclei of the ascending arousal network were addressed. Midbrain and isthmus nuclei participate in threat assessment, awareness, attention, mood, cognition, pain, tenderness, sleep, thermoregulation, light and sound sensitivity, orthostatic symptoms, and autonomic dysfunction and are likely to contribute to the symptoms of postexertional malaise in ME/CFS and GWI.
... 2 One study reported that the Oxford definition was so broad that it identified over 20% of the US population as having CFS (compared to two percent as defined by CDC criteria) but the study had misapplied the criteria. 24,25 A systematic review of studies reported a median prevalence of 1.5% for Oxford defined CFS in the population or in primary care. 2 In the context of the PACE trial, a sensitivity analysis found that the trial participants improved irrespective of the criteria. The London diagnostic criteria for ME require the patient to have post-exertional malaise. ...
Chronic fatigue syndrome (CFS), sometimes referred to as myalgic encephalomyelitis (ME) and often as CFS/ME, is an illness characterized by disabling fatigue and other symptoms, typically worsened by activity. The main evidence-based treatments are rehabilitative in nature and include specific types of cognitive behavior therapy (CBT) and graded exercise therapy (GET). In this article, we briefly review the evidence for their safety and effectiveness and propose that much of the controversy about them arises from misunderstandings about their nature and delivery. In particular, we emphasize that successful rehabilitation from CFS/ME does not indicate that the illness is not real. We recommend that rehabilitative treatment always be preceded by a thorough clinical assessment and delivered by appropriately trained therapists working in close collaboration with the patient. We conclude that properly applied rehabilitative treatments offer the best hope of safely improving fatigue and function for patients with CFS/ME. However, we also recognize the need for more research into the treatment of this neglected condition, especially for those most severely disabled by it.
... Moreover, the younger population would be at more risk for post-infection CFS/EM (Magnus et al. 2015). Our study demonstrated that the measured CFS prevalence following COVID-19 is 2.5% (3 out of 120); on the other hand, the estimated prevalence of chronic fatigue syndrome in a general population using the Fukuda criteria is around 2% (Baraniuk 2017). Therefore, there is well within this ballpark of population prevalence. ...
As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0–44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.
... e prevalence of self-reported CFS has been reported to be 3.28% [7]. e prevalence of diagnosed CFS ranges from 0.083% to 2.3% in males and from 0.37% to 1.8% in females [8,9]. In Korea, the prevalence of chronic fatigue that is physically or psychologically explained is 8.4%, whereas the prevalence of medically unexplained chronic fatigue, including CFS and idiopathic chronic fatigue, is 0.6% [10]. ...
Background. Sipjeondaebo-tang (SDT), also known as Shi-Quan-Da-Bu-Tang, is a treatment for both qi and blood deficiency syndromes in traditional Korean medicine. It is also used to treat chronic fatigue syndrome (CFS) in Korea. Herein, we present the protocol for a study to assess the efficacy and safety of SDT for treating CFS. Methods. This will be a multicenter, randomized, double-blind, controlled trial with two parallel-treatment arms: an SDT group and a placebo group. Ninety-six patients with CFS aged between 19 and 65 years will be recruited from two hospitals in Korea. Participants will be randomly allocated at a ratio of 1 : 1 between the two groups. Participants will receive 3 g doses of SDT or placebo thrice daily for 8 weeks. Follow-up evaluations will be performed for 4–6 weeks after the drug administration period. The primary outcome will be the rating of participants’ fatigue symptoms using the Checklist Individual Strength questionnaire. Outcomes will be assessed at baseline, week 4, and week 8, as well as during follow-up. An efficacy evaluation and safety assessment will be performed. This study will be based on the Consolidated Standards of Reporting Trials (CONSORT) guidelines and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement. This protocol and informed consent guidelines were reviewed and approved by the institutional review board of Kyung Hee University Korean Medicine Hospital at Gangdong in the Republic of Korea (KHNMCOH 2017-06-004-001). The protocol was registered with the Clinical Research Information Service. Written informed consent will be obtained from all study participants prior to enrollment in the study. Results will be published in a peer-reviewed journal and presented at a scientific conference. Discussion. This study is expected to provide novel, accurate information regarding the 38 efficacy and safety of SDT for CFS in adults. Trial Registration. This trial is registered with https://cris.nih.go.kr; CRIS identifier (KCT0002684) registered on February 9, 2018.
1. Introduction
Chronic fatigue syndrome (CFS), which is synonymous with myalgic encephalomyelitis, is a condition characterized by pervasive fatigue (particularly after minimal exertion), chronic pain, and impaired concentration and memory [1]. It is assumed that CFS involves false fatigue alarms generated by predisposing and precipitating factors, which subsequently perpetuate stress responses [2]. There are no established biomarkers for CFS; therefore, the diagnosis must be based on a patient’s description of the symptoms [3]. The most widely used diagnostic criteria are those published by the Centers for Disease Control and Prevention (CDC) in 1994. The diagnosis is made on the basis of prolonged (>6 months), unexplained, and incapacitating fatigue and fulfilling at least four of eight accompanying criteria [4]. The overall incidence rate of diagnosed CFS has been shown to range from 14.8 to 25.8 per 100,000 person-years, peaking in teenagers and adults in their thirties [5, 6]. The prevalence of self-reported CFS has been reported to be 3.28% [7]. The prevalence of diagnosed CFS ranges from 0.083% to 2.3% in males and from 0.37% to 1.8% in females [8, 9]. In Korea, the prevalence of chronic fatigue that is physically or psychologically explained is 8.4%, whereas the prevalence of medically unexplained chronic fatigue, including CFS and idiopathic chronic fatigue, is 0.6% [10].
Currently, there is no cure or approved treatment for CFS. However, patients may find some symptom relief through nutritional supplements, exercise, rehabilitation programs, and cognitive behavioral therapy [11–14]. Intravenous injection of rituximab has been used to treat CFS in the past decade; however, a recent study showed that rituximab had no effect on CFS [15]. Research on herbal medications in East Asia has been conducted to find a curative treatment for CFS because some medications from the region are thought to be effective for fatigue and weariness. In previous studies, traditional Chinese medicine (TCM) has been proven effective for chronic fatigue [16–24]. However, according to a recent systematic review, previous studies evaluating the efficacy of TCM on CFS have not provided enough evidence or lacked methodological rigorousness to draw firm conclusions [25, 26]. In traditional Korean medicine (TKM), there have been some randomized controlled trials (RCTs) evaluating the efficacy of some herbal medications on CFS [27–29]. However, no study up to now has focused on the efficacy of traditional herbal formulas used clinically for patients with chronic fatigue. Therefore, well-designed RCTs evaluating the efficacy of herbal TCM and TKM medications for CFS are needed.
Sipjeondaebo-tang (SDT), also called Shi-Quan-Da-Bu-Tang in China and Juzen-taiho-to in Japan [30], is one of the most popular TKM formulas for the treatment of chronic fatigue. It is approved by the Ministry of Food and Drug Safety to treat weakness after illness, anorexia, abnormal sweating, peripheral coldness, and anemia [31]. Previous clinical trials have shown that it alleviates hematotoxicity, activates an anti-inflammatory effect, and promotes hematopoiesis [32–36]. In TKM, the main contributors to CFS are considered to be qi and blood deficiencies; if the flow of blood or qi is not smooth, fatigue may occur. SDT is used to treat chronic illnesses, including CFS, caused by both qi and blood deficiencies by balancing yin and yang. This is known to restore the deterioration of physiological function and activate immune function [37]. Although SDT is generally used to treat CFS clinically, no RCT has examined the efficacy of SDT for CFS. Therefore, in this study, we aim to assess the efficacy and safety of SDT for the treatment of CFS.
2. Materials and Methods
2.1. Study Design and Setting
This clinical trial will be conducted as a randomized, double-blind, placebo-controlled, parallel-group, multicenter study within 12–14 weeks at the Kyung Hee University Korean Medicine Hospital at Gangdong and the Woosuk University Korean Medicine Medical Center, both of which are clinical centers in the Republic of Korea. The study was designed in accordance with the Declaration of Helsinki and the Guidelines for Good Clinical Practice.
The principal investigator or researcher will obtain written informed consent from all participants after they have received a sufficient explanation of the study and made a thoughtful, voluntary decision. Each subject will be screened up to 7 days prior to randomization to avoid changes in subjects’ health conditions. Once participants pass the eligibility assessment and receive a trial subject identifier, they will be randomly assigned to either the treatment group or the control group in a 1 : 1 ratio. The treatment group will be prescribed SDT, and the control group will be prescribed a placebo for 8 weeks after attending an educational session regarding the clinical trial. Participants will visit the study site every 4 weeks during the treatment period to allow researchers to evaluate their compliance and the efficacy and safety of the treatment. A follow-up will be completed by phone 4–6 weeks after the completion of the drug administration to evaluate safety. Any medication not consumed by the participants will be returned at visits 2 and 3 to allow us to calculate drug compliance. The evaluation of participants and analysis of the results will be performed by professionals blinded to the group allocation. Figure 1 shows a schematic flow diagram of the study. The schedule of enrollment, intervention, and assessment is presented in Table 1.
... Ook de evidentie over schadelijke neveneffecten is onduidelijk. Vermeldenswaard is dat alle studies de patiënten selecteerden op basis van de CDC/Fukuda-criteria of de nog oudere Oxfordcriteria; de Cochrane-auteurs benadrukken dat patiënten, gediagnosticeerd op basis van andere, meer recente criteria, andere effecten zouden kunnen ervaren (zie ook Baraniuk, 2017). ...
... In 1991, a UK panel of medical experts met in Oxford to discuss CFS: from a panel of 27 invited experts, community doctors, scientists and others, 7 were psychiatrists, representing the largest professional block [56]. From this meeting, the 'Oxford Criteria' for CFS emerged -a diagnostic criteria that has been criticised for being too broad and lacking specificity: "…studies based on Oxford criteria for participant inclusion may be seriously flawed because they can potentially select a cross-section of the healthy general population, rather than a rigorously defined CFS group" p229-230 [57]. Psychiatry, like other fields of medicine, has a record of getting things wrong, multiple sclerosis being hysterical paralysis for example, or homosexuality being deemed a mental disorder. ...
Background
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling condition that greatly impacts the lives of sufferers. Many sufferers report problems getting a confirmatory diagnosis and difficulties getting doctors to believe them and offer support. Objective: This paper explores this issue by examining a biopsychosocial (BPS) model of ME/CFS promoted within psychiatry and its potential influence on how doctors might view and manage the illness. Method: A narrative literature review is undertaken to identify salient theory and discourse for consideration. Findings: Psychiatrists proffer a hypothetical model of ME/CFS aetiology and continuance, that instructs doctors to view the illness as a syndrome perpetuated by psycho-social factors that sustain unexplained symptoms such as fatigue, pain and post-exertional malaise, rather than symptoms being related to biological disease processes. The psychiatric model theorises that patients’ symptoms are maintained by their maladaptive beliefs and behaviours, requiring psychotherapy. Conclusion: The psychiatric BPS model of ME/CFS may negatively bias how physicians approach the illness, with doctors directed to view patients’ complaints as manifestations of psychological distress, rather than physical symptoms that require medical investigation or intervention. This finding may help explain why many ME/CFS patients feel disbelieved and unsupported after seeking medical care. Psychiatric theory fails to acknowledge or incorporate a substantial body of evidence showing biological deficits associated with ME/CFS. Medical trainees and physicians need more training and clinical exposure to ME/CFS patients, armed with better awareness of misleading and unproven claims associated with the BPS model.
... In a study by Friedberg et al. [21], 15% of people labelled by the Fukuda criteria as having ME/CFS, were in fact healthy people. Baraniuk [22] found that the Oxford criteria inappropriately select healthy subjects with mild or chronic idiopathic fatigue and mislabel them as ME/CFS. A report commissioned by the American National Institute of Health (NIH), concluded in 2014 that the Oxford criteria are flawed and lead to the inclusion of people with other conditions, confounding the ability to interpret the science [23]. ...
Background:
Cochrane recently amended its exercise review for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in response to an official complaint.
Objective:
To determine if the amended review has addressed the concerns raised about the previous review and if exercise is an effective treatment that restores the ability to work in ME/CFS.
Method:
The authors reviewed the amended Cochrane exercise review and the eight trials in it by paying particular interest to the objective outcomes. We also summarised the recently published review of work rehabilitation and medical retirement for ME/CFS.
Results:
The Cochrane review concluded that graded exercise therapy (GET) improves fatigue at the end of treatment compared to no-treatment. However, the review did not consider the unreliability of subjective outcomes in non-blinded trials, the objective outcomes which showed that GET is not effective, or the serious flaws of the studies included in the review. These flaws included badly matched control groups, relying on an unreliable fatigue instrument as primary outcome, outcome switching, p-hacking, ignoring evidence of harms, etc. The review did also not take into account that GET does not restore the ability to work.
Conclusion:
GET not only fails to objectively improve function significantly or to restore the ability to work, but it's also detrimental to the health of≥50% of patients, according to a multitude of patient surveys. Consequently, it should not be recommended.
... The main characteristic of ME/CFS, postexertional malaise [1], however is not required for diagnosis. Consequently, 85% of Oxford-defined cases are healthy subjects with mild fatigue or chronic idiopathic fatigue who are misclassified as ME/CFS according to a large study by Baraniuk [14]. Both the American National Institute of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ) concluded that the Oxford criteria are flawed and that using the Oxford case definition results in a high risk of including patients who may have an alternate fatiguing illness or whose illness resolves spontaneously with time. ...
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome leads to severe functional impairment and work disability in a considerable number of patients. The majority of patients who manage to continue or return to work, work part-time instead of full time in a physically less demanding job. The prognosis in terms of returning to work is poor if patients have been on long-term sick leave for more than two to three years. Being older and more ill when falling ill are associated with a worse employment outcome. Cognitive behavioural therapy and graded exercise therapy do not restore the ability to work. Consequently, many patients will eventually be medically retired depending on the requirements of the retirement policy, the progress that has been made since they have fallen ill in combination with the severity of their impairments compared to the sort of work they do or are offered to do. However, there is one thing that occupational health physicians and other doctors can do to try and prevent chronic and severe incapacity in the absence of effective treatments. Patients who are given a period of enforced rest from the onset, have the best prognosis. Moreover, those who work or go back to work should not be forced to do more than they can to try and prevent relapses, long-term sick leave and medical retirement.
... It was created as an alternative, less strict, operational definition which is essentially chronic fatigue in the absence of neurological signs with psychiatric symptoms as common associated features (David, 1991). The Oxford criteria are untenable because they inappropriately select healthy subjects with mild fatigue and chronic idiopathic fatigue and mislabel them as CFS (Baraniuk, 2017). The American National Institute of Health (NIH) concluded in 2014 that the Oxford criteria are flawed and include people with other conditions, confounding the ability to interpret the science (Green et al., 2014a). ...
Analysis of the 2008 Cochrane review of cognitive behavioural therapy for chronic fatigue syndrome shows that seven patients with mild chronic fatigue syndrome need to be treated for one to report a small, short-lived subjective improvement of fatigue. This is not matched by an objective improvement of physical fitness or employment and illness benefit status. Most studies in the Cochrane review failed to report on safety or adverse reactions. Patient evidence suggests adverse outcomes in 20 per cent of cases. If a trial of a drug or surgical procedure uncovered a similar high rate, it would be unlikely to be accepted as safe. It is time to downgrade cognitive behavioural therapy to an adjunct support-level therapy, rather than a treatment for chronic fatigue syndrome.
... The diagnosis of chronic fatigue syndrome can be scrutinized using the scoring sheet in Table 1 that is based on the 1994 Centers for Disease Control criteria. 24,29 The fatigue must have been moderate or severe for at least 6 months, with other symptoms starting after the fatigue. PEM is a key indicator of CFS (Figures 1 and 4). ...
Purpose:
Chronic fatigue syndrome (CFS) is a debilitating disease characterized by fatigue, postexertional malaise, cognitive dysfunction, sleep disturbances, and widespread pain. A pilot, online survey was used to determine the common presentations of CFS patients in the emergency department (ED) and attitudes about their encounters.
Methods:
The anonymous survey was created to score the severity of core CFS symptoms, reasons for going to the ED, and Likert scales to grade attitudes and impressions of care. Open text fields were qualitatively categorized to determine common themes about encounters.
Results:
Fifty-nine percent of respondents with physician-diagnosed CFS (total n=282) had gone to an ED. One-third of ED presentations were consistent with orthostatic intolerance; 42% of participants were dismissed as having psychosomatic complaints. ED staff were not knowledgeable about CFS. Encounters were unfavorable (3.6 on 10-point scale). The remaining 41% of subjects did not go to ED, stating nothing could be done or they would not be taken seriously. CFS subjects can be identified by a CFS questionnaire and the prolonged presence (>6 months) of unremitting fatigue, cognitive, sleep, and postexertional malaise problems.
Conclusion:
This is the first investigation of the presentation of CFS in the ED and indicates the importance of orthostatic intolerance as the most frequent acute cause for a visit. The self-report CFS questionnaire may be useful as a screening instrument in the ED. Education of ED staff about modern concepts of CFS is necessary to improve patient and staff satisfaction. Guidance is provided for the diagnosis and treatment of CFS in these challenging encounters.
... Recovery research has not been based on objective criteria (Twisk, 2014); There are no proven, effective treatments or management that effects recovery or cure (Lloyd, 2018); Recovery is rare, and 1 in 5 patients worsen over time (Baraniuk, 2017, p. 53); RACP Guidelines assert "complete recovery was uncommon (6%)": ( (Mathers, 1999: 201) Does ME/CFS meet the NDIS Disability Critiera? (Cont'd) ...
CFS/ME International Conference 2018
National Centre for Neuroimmunology and Emerging Diseases Crowne Plaza, Surfers Paradise, Qld
26-27 November 2018
Abstract Title: ME/CFS: NDIS and the Disability Hurdle
Authors: Geoffrey Hallmann
Background: B.Bus.(Hons), LLB (Hons). DipLegPrac, DipFinPlan; Chair of ME/CFS (Australia), PhD Candidate (Southern Cross University); Masters of Public Health Student (Griffith University)
Question: What is the position of the National Disability Insurance Scheme (‘NDIS’) with respect to claimants MyalgicEncephalomyelitis/Chronic Fatigue Syndrome (‘ME/CFS’)?
Methods: A literature review was conducted with respect to the background and purposes of the NDIS, with a specific emphasis upon ME/CFS. Direct feedback from the National Disability Insurance Agency (‘NDIA’) with respect to its policy and the foundation for it was obtained. Publicly available grey literature was accessed to identify current issues affecting NDIS claimants with ME/CFS.
Results: The NDIA is currently assessing claims on the basis that ME/CFS is not a permanent condition. The primary reason for the NDIA’s position is a misinterpretation of piece of 2006 research known colloquially as the Dubbo study and reliance upon long outdated guidelines.
Conclusions: The NDIA is does not presently have an established policy for claimants with ME/CFS, and the current view of permanency is flawed, hence people with ME/CFS are being turned away from the scheme.
Abstract Submission:
Established by the National Disability Insurance Scheme Act 2013, the NDIS was formally rolled out on a national basis on 1 July 2016. The NDIS has not been without controversy, A recent report by Flinders University identified that NDIS recipients were received around half of the assistance that they had received prior to the introduction of the scheme (Mavromaras, et al., 2018). The scheme currently operates on a staffing cap, hence is heavily understaffed (Productivity Commission, 2017).
The NDIS spends approximately $ 10 million a year defending matters involving claimants contesting the decisions of the NDIA. Approximately 40% of appeals yield an improved outcome (Productivity Commission, 2017). A review of the AAT caselaw reveals no cases have been decided with respect to ME/CFS presently. There are a number of cases pending (ME/CFS Legal Resources, 2017).
The current anecdotal evidence identifies that ME/CFS applicants are not succeeding in their claims (Reilly & Buchanan, 2018; Emerge, 2018; Hutchinson, 2018; Ludlam, 2018). ME/CFS is a debilitating condition. For the majority, it is permanent (ME/CFS Legal Resources, 2017).
The NDIA deny the condition is permanent and are relying upon the 2006 Dubbo Infection Outcomes study (Hickie, et al., 2006) to assert that “many individuals recover without intervention over weeks or months, but approximately 10% will meet the criteria of ME/chronic fatigue syndrome at six months”. The NDIA claim that “[o]f these, a small subset may go on to suffer from both severely disabling and prolonged (greater than 5 years) ME/chronic fatigue syndrome” (Faulkner, 2018). The NDIA rely upon the 2002 Australian CFS guidelines (Loblay, et al., 2002) and the UK’s NICE guidelines (Turnbull, et al., 2007). Cognitive Behavioural Therapy (CBT) and Graded Exercise therapy (GET) are considered the evidence based management of the condition – despite significant evidence to the contrary.
Both guidelines are under review, with a particular focus upon the appropriateness of CBT and GET, both of which are of questionable value (Vink & Vink-Niese, 2018; Various Authors, 2017).
ME/CFS is not currently a “List B” condition, hence not presumed to be a disability. The current stance is therefore making it near impossible for people with ME/CFS to succeed. The NDIS require more contemporary insight into the condition to assist them to a more realistic view of ME/CFS claimants.
References:
Emerge. (2018, October). National Disability Insurance Scheme (NDIS). Retrieved October 12, 2018, from Emerge: emerge.org.au/support-services/financial-services/ndis
Faulkner, C. (2018, August 17). Personal Communication from NDIA.
Hickie, I., Davenport, T., Wakefield, D., Vollmer-Conna, U., Cameron, B., Vernon, S. D., . . . Lloyd, A. (2006). Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. British Medical Journal, 333(7568), 575. doi:http://doi.org/10.1136/bmj.38933.585764.AE
Hutchinson, S. (2018, April 10). OPINION: NDIS must recognise chronic fatigue syndrome or suicide will follow. Retrieved October 12, 2018, from The Feed: https://www.sbs.com.au/news/the-feed/opinion-ndis-must-recognise-chronic-fatigue-syndrome-or-suicide-will-follow
Loblay, R., Stewart, G., Bertouch, J., Cistulli, P., Darvenzia, P., Ellis, C., . . . Toulkidis, V. (2002). Chronic Fatigue Syndrome - Clinical Practice Guidelines. Medical Journal of Australia, 176(6 May), S17-S46.
Ludlam, S. (2018, May 12). To the #MillionsMissing With ME/CFS Something Remarkable is Happening. Retrieved October 12, 2018, from The Guardian: https://www.theguardian.com/commentisfree/2018/may/12/to-the-millionsmissing-with-mecfs-something-remarkable-is-happening
Mavromaras, K., Moskos, M., Isherwood, L., Goode, A., Walton, H., Smith, L., . . . Flavel, J. (2018). Evaluation of the NDIS. Finliders University, National Institute of Labour Studies. Adelaide: Department of Social Services. Retrieved October 12, 2018, from https://www.dss.gov.au/disability-and-carers/programs-services/for-people-with-disability/national-disability-insurance-scheme/ndis-evaluation-consolidated-report
ME/CFS Legal Resources. (2017, November 13). Submission to the Joint Parliamentary Committee on the National Disability Insurance Scheme. Retrieved October 12, 2018, from Parliament of Australian: https://www.google.com.au/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=2ahUKEwjxjKXX-f7dAhUCIIgKHTR9Cr8QFjAAegQIAhAC&url=https%3A%2F%2Fwww.aph.gov.au%2FDocumentStore.ashx%3Fid%3D09902d19-3475-4f08-b222-62e15ed32dfe%26subId%3D561511&usg=AOvV
Morton, R. (2018, May 17). NDIS legal bill hitting $10m a year. The Australian. Retrieved October 12, 2018, from https://www.theaustralian.com.au/national-affairs/health/ndis-legal-bill-hitting-10m-a-year/news-story/c048d6028a8363597a30115d3cdb921f
Productivity Commission. (2017). National Disability Insurance Scheme (NDIS) Costs. Australian Government, Productivity Commission. Canberra: Commonwealth of Australia. Retrieved October 12, 2018, from https://www.pc.gov.au/inquiries/completed/ndis-costs/report/ndis-costs.pdf
Reilly, A., & Buchanan, R. (2018, August 24). ME/CFS National Disability Agreement Review Submissio. Retrieved October 12, 2018, from Productivity Commission: https://www.pc.gov.au/__data/assets/pdf_file/0004/230953/sub023-disability-agreement.pdf
Turnbull, N., Shaw, E. J., Dundson, S., Costin, N., Britton, G., Kuntze, S., & Norman, R. (2007). Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management of Chronic Fatigue Syndrome/Myagic Encephalomyelitis (or Encepaholpathy) in Adults and Children. London: Royal College of General Physicians.
Various Authors. (2017). Special Issue: The PACE Trial. Journal of Health Psychology, 22(9), 1103-1216. Retrieved from http://journals.sagepub.com/toc/hpqa/22/9
Vink, M., & Vink-Niese, A. (2018). Graded Exercise Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is Not Effective and Unsafe. Re-Analysis of a Cochrane Review. Health Psychology Open, July-December, 1-12. doi:https://doi.org/10.1177/2055102918805187
... The Oxford criteria are untenable because they inappropriately select healthy subjects with mild fatigue and chronic idiopathic fatigue and mislabel them as CFS (Baraniuk, 2017). The American National Institutes of Health (NIH) concluded in 2014 that the Oxford criteria are flawed and include people with other conditions, confounding the ability to interpret the science (Green et al., 2014a). ...
The analysis of the 2017 Cochrane review reveals flaws, which means that contrary to its findings, there is no evidence that graded exercise therapy is effective. Because of the failure to report harms adequately in the trials covered by the review, it cannot be said that graded exercise therapy is safe. The analysis of the objective outcomes in the trials provides sufficient evidence to conclude that graded exercise therapy is an ineffective treatment for myalgic encephalomyelitis/chronic fatigue syndrome.
Fatigue is a common age-related symptom among community-dwelling adults aged 65 years and older. Yet, a systematic approach has rarely been applied to review definitions, measures, related factors, and consequences of fatigue in this population. A scoping review was conducted in December 2020 to fill the gap, and 36 articles met the inclusion criteria. Definitions, albeit diverse, included at least one of the following attributes: an early indicator of disablement, subjective, a lack of energy, multidimensional, impaired daily activities, and temporal. A summary of fatigue measures used in this population was provided, including a brief overview, number of items, reliability, and validity. In general, different measures were used with considerable variability in the content. Additionally, most measures had limited information on test-retest reliability and validity. Fatigue-related factors mapped into biological, psychological, social, and behavioral factors. Fatigue consequences were primarily declines in physical and cognitive functions. (100-150 words)
Fatigue is an important health dimension. What are the characteristics of fatigue? What are the mechanisms? Etiology? What are health effects? What is the approach towards fatigue?
Biblical verses describing fatigue were studied from a contemporary viewpoint.
Background
Chronic fatigue syndrome (CFS) represents a unique clinical challenge for patients and health care providers due to unclear etiology and lack of specific treatment. Characteristic patterns of behavior and cognitions might be related to how CFS patients respond to management strategies. Methods
This study investigates control beliefs in a population-based sample of 113 CFS patients, 264 individuals with insufficient symptoms or fatigue for CFS diagnosis (ISF), and 124 well individuals. ResultsControlling for personality and coping, individuals with low confidence in their problem-solving capacity were almost 8 times more likely to be classified as ISF and 5 times more likely to be classified as CFS compared to being classified as well. However there was a wide distribution within groups and individuals with “low confidence” scores were found in 31.7% of Well individuals. Individuals with low levels of anxiety and who were more outgoing were less likely to be classified as ISF or CFS. Conclusions
These findings suggest that fostering control beliefs could be an important focus for developing behavioral management strategies in CFS and other chronic conditions.
Background:
No epidemiological investigations have previously been conducted in Australia according to the current clinical definitions of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The aim of this study was to describe sociodemographic and illness characteristics of Australian patients with CFS/ME.
Methods:
A cross-sectional survey on the medical history of patients enrolled in an Australian CFS/ME research database between April 2013 and April 2015. Participants were classified according to Fukuda criteria and International Consensus Criteria.
Results:
A total of 535 patients diagnosed with CFS/ME by a primary care physician were identified. The mean age of all patients was 46.4 years (standard deviation 12.0); the majority were female (78.61%), Caucasian, and highly educated. Of these, 30.28% met Fukuda criteria. A further 31.96% met both Fukuda criteria and International Consensus Criteria. There were 14.58% reporting chronic fatigue but did not meet criteria for CFS/ME and 23.18% were considered noncases due to exclusionary conditions. Within those meeting CFS/ME criteria, the most common events prior to illness included cold or flu, gastrointestinal illness, and periods of undue stress. Of the 60 symptoms surveyed, fatigue, cognitive, and short-term memory symptoms, headaches, muscle and joint pain, unrefreshed sleep, sensory disturbances, muscle weakness, and intolerance to extremes of temperature were the most commonly occurring symptoms (reported by more than two-thirds of patients). Significant differences in symptom occurrence between Fukuda- and International Consensus Criteria-defined cases were also identified.
Conclusion:
This is the first study to summarize sociodemographic and illness characteristics of a cohort of Australian CFS/ME patients. This is vital for identifying potential risk factors and predictors associated with CFS/ME and for guiding decisions regarding health care provision, diagnosis, and management.
Chronic fatigue syndrome (CFS) is a chronic, debilitating illness that has posed considerable challenges for both patients and health care providers. Individuals with CFS often deal with considerable stigma and difficulties accessing appropriate care. Many medical professionals are increasingly recognizing the devastating nature of this illness, but at this time, few health care workers are knowledgeable and experienced enough to provide adequate patient care. There is a need for further efforts to educate health care workers on CFS diagnostic, assessment, and treatment issues. The present article reviews controversies regarding CFS case definitions, diagnostic criteria, the name of the illness, and epidemiological and treatment studies. We conclude that an imprecise case definition underlies many of the problems with diagnostic and treatment issues..
Recent years have brought growing recognition of the need for clinical criteria for myalgic encephalomyelitis (ME), which is also called chronic fatigue syndrome (CFS). An Expert Subcommittee of Health Canada established the Terms of Reference, and selected an Expert Medical Consensus Panel representing treating physicians, teaching faculty and researchers. A Consensus Workshop was held on March 30 to April 1,2001 to culminate the review process and establish consensus for a clinical working case definition, diagnostic protocols and treatment protocols. We present a systematic clinical working case definition that encourages a diagnosis based on characteristic patterns of symptom clusters, which reflect specific areas of pathogenesis. Diagnostic and treatment protocols, and a short overview of research are given to facilitate a comprehensive and integrated approach to this illness. Throughout this paper, “myalgic encephalomyelitis” and “chronic fatigue syndrome” are used interchangeably and this illness is referred to as “ME/CFS.”
To identify case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and explore how the validity of case definitions can be evaluated in the absence of a reference standard.
Systematic review.
International.
A literature search, updated as of November 2013, led to the identification of 20 case definitions and inclusion of 38 validation studies.
Validation studies were assessed for risk of bias and categorised according to three validation models: (1) independent application of several case definitions on the same population, (2) sequential application of different case definitions on patients diagnosed with CFS/ME with one set of diagnostic criteria or (3) comparison of prevalence estimates from different case definitions applied on different populations.
A total of 38 studies contributed data of sufficient quality and consistency for evaluation of validity, with CDC-1994/Fukuda as the most frequently applied case definition. No study rigorously assessed the reproducibility or feasibility of case definitions. Validation studies were small with methodological weaknesses and inconsistent results. No empirical data indicated that any case definition specifically identified patients with a neuroimmunological condition.
Classification of patients according to severity and symptom patterns, aiming to predict prognosis or effectiveness of therapy, seems useful. Development of further case definitions of CFS/ME should be given a low priority. Consistency in research can be achieved by applying diagnostic criteria that have been subjected to systematic evaluation.
• The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, system atic, and integrated approach to the evaluation, classi fication, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.
The Centers for Disease Control and Prevention (CDC) recently developed an empirical case definition that specifies
criteria and instruments to diagnose chronic fatigue syndrome (CFS) in order to bring more methodological rigor to the
current CFS case definition. The present study investigated this new definition with 27 participants with a diagnosis of CFS
and 37 participants with a diagnosis of a Major Depressive Disorder. Participants completed questionnaires measuring
disability, fatigue, and symptoms. Findings indicated that 38% of those with a diagnosis of a Major Depressive Disorder
were misclassified as having CFS using the new CDC definition. Given the CDC’s stature and respect in the scientific
world, this new definition might be widely used by investigators and clinicians. This might result in the erroneous inclusion
of people with primary psychiatric conditions in CFS samples, with detrimental consequences for the interpretation of
epidemiologic, etiologic, and treatment efficacy findings for people with CFS.
Chronic Fatigue Syndrome case designation criteria are scored as physicians' subjective, nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes), cognitive dysfunction, sleep and exertional exhaustion.
Subjects self-reported symptoms using an anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of 3 or 4 distinguished "Fatigued" from "Not Fatigued" subjects. The sum of the 8(Sum8) ancillary criteria was tested as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure categorization as healthy or CFS subjects.
Fatigued subjects were divided into CFS with ≥4 symptoms or Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a threshold of 14 (specificity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls (HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS-Like With Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R(2)=0.977; Cronbach's alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4 clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from cerebrospinal fluid.
Plotting Fatigue severity versus Sum8 produced an internally consistent classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their pathophysiological mechanisms.
This article presents a health lifestyle audience segmentation analysis based primarily on social cognitive theory. Two linked mail surveys were conducted among a representative group of US adults (N = 2967). Segmentation variables included data on five health behaviors (smoking, alcohol consumption, physical activity, nutrition and weight control), internal personal and social/ environmental variables associated with each of the health behaviors, as well as health value, sensation- seeking, life satisfaction and age. K-means classification analysis was employed; seven health lifestyles were identified. The majority of the health lifestyles are reliable, and as a whole, all demonstrate both discriminative, construct and predictive validity. The health-lifestyle audience segments are briefly profiled, and an argument is made that health- lifestyle segmentation, more than demographic or behavioral segmentation alone, can advance the goals of public health communication.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or chronic fatigue syndrome (CFS) has been used to name a range of chronic conditions characterized by extreme fatigue and other disabling symptoms. Attempts to estimate the burden of disease have been limited by selection bias, and by lack of diagnostic biomarkers and of agreed reproducible case definitions. We estimated the prevalence and incidence of ME/CFS in three regions in England, and discussed the implications of frequency statistics and the use of different case definitions for health and social care planning and for research.
We compared the clinical presentation, prevalence and incidence of ME/CFS based on a sample of 143,000 individuals aged 18 to 64 years, covered by primary care services in three regions of England. Case ascertainment involved: 1) electronic search for chronic fatigue cases; 2) direct questioning of general practitioners (GPs) on cases not previously identified by the search; and 3) clinical review of identified cases according to CDC-1994, Canadian and Epidemiological Case (ECD) Definitions. This enabled the identification of cases with high validity.
The estimated minimum prevalence rate of ME/CFS was 0.2% for cases meeting any of the study case definitions, 0.19% for the CDC-1994 definition, 0.11% for the Canadian definition and 0.03% for the ECD. The overall estimated minimal yearly incidence was 0.015%. The highest rates were found in London and the lowest in East Yorkshire. All but one of the cases conforming to the Canadian criteria also met the CDC-1994 criteria, however presented higher prevalence and severity of symptoms.
ME/CFS is not uncommon in England and represents a significant burden to patients and society. The number of people with chronic fatigue who do not meet specific criteria for ME/CFS is higher still. Both groups have high levels of need for service provision, including health and social care. We suggest combining the use of both the CDC-1994 and Canadian criteria for ascertainment of ME/CFS cases, alongside careful clinical phenotyping of study participants. This combination if used systematically will enable international comparisons, minimization of bias, and the identification and investigation of distinct sub-groups of patients with possibly distinct aetiologies and pathophysiologies, standing a better chance of translation into effective specific treatments.
Trial findings show cognitive behaviour therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome, but patients' organisations have reported that these treatments can be harmful and favour pacing and specialist health care. We aimed to assess effectiveness and safety of all four treatments.
In our parallel-group randomised trial, patients meeting Oxford criteria for chronic fatigue syndrome were recruited from six secondary-care clinics in the UK and randomly allocated by computer-generated sequence to receive specialist medical care (SMC) alone or with adaptive pacing therapy (APT), CBT, or GET. Primary outcomes were fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks after randomisation, and safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes. We used longitudinal regression models to compare SMC alone with other treatments, APT with CBT, and APT with GET. The final analysis included all participants for whom we had data for primary outcomes. This trial is registered at http://isrctn.org, number ISRCTN54285094.
We recruited 641 eligible patients, of whom 160 were assigned to the APT group, 161 to the CBT group, 160 to the GET group, and 160 to the SMC-alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3·4 (95% CI 1·8 to 5·0) points lower for CBT (p = 0·0001) and 3·2 (1·7 to 4·8) points lower for GET (p = 0·0003), but did not differ for APT (0·7 [-0·9 to 2·3] points lower; p = 0·38). Compared with SMC alone, mean physical function scores were 7·1 (2·0 to 12·1) points higher for CBT (p = 0·0068) and 9·4 (4·4 to 14·4) points higher for GET (p = 0·0005), but did not differ for APT (3·4 [-1·6 to 8·4] points lower; p=0·18). Compared with APT, CBT and GET were associated with less fatigue (CBT p = 0·0027; GET p = 0·0059) and better physical function (CBT p=0·0002; GET p<0·0001). Subgroup analysis of 427 participants meeting international criteria for chronic fatigue syndrome and 329 participants meeting London criteria for myalgic encephalomyelitis yielded equivalent results. Serious adverse reactions were recorded in two (1%) of 159 participants in the APT group, three (2%) of 161 in the CBT group, two (1%) of 160 in the GET group, and two (1%) of 160 in the SMC-alone group.
CBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition.
UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions.
In England the Department of Health has funded specialist clinical services aimed at diagnosing and managing the symptoms of chronic fatigue syndrome (CFS). These services are not available to those who do not fulfil the diagnostic criteria for CFS. This service evaluation examined the proportion of those referred to a specialist CFS service fulfilling the Fukuda diagnostic criteria for CFS and the alternative fatigue-associated diagnoses. The CFS database was interrogated to include every patient referred to the Newcastle service from November 2008 to December 2009. All medical notes were reviewed and the diagnosis, sex and age recorded. Data were compared to a previous service evaluation (2005-07). In 2008-09, 260 subjects were referred: 19 referrals per month (260/14), compared with 17 referrals per month in 2005-07 (375/24). The proportion of patients diagnosed with CFS increased significantly compared with 2007 (36% [20/56] vs 60% [157/260]; p < 0.0001). Of the 40% of patients subsequently found not to have CFS the most common diagnosis was fatigue associated with a chronic disease (47% of all alternative diagnoses); 20% had primary sleep disorders, 15% psychological/psychiatric illnesses and 4% a cardiovascular disorder. Thirteen per cent remained unexplained (5.2% of the total referrals). This study found a significant increase in the proportion of patients referred to National Health Service (NHS) CFS services diagnosed with CFS. A large proportion of patients presenting with fatigue are not eligible for referral to the Department of Health specialist fatigue services, which represents an unmet need in terms of symptom management in current NHS services.
The diagnosis of chronic fatigue syndrome (CFS) in research studies requires the exclusion of subjects with medical and psychiatric conditions that could confound the analysis and interpretation of results. This study compares illness parameters between individuals with CFS who have and those who do not have exclusionary conditions.
We used a population-based telephone survey of randomly selected individuals, followed by a clinical evaluation in the study metropolitan, urban, and rural counties of Georgia, USA. The medical and psychiatric histories of the subjects were examined and they underwent physical and psychiatric examinations and laboratory screening. We also employed the multidimensional fatigue inventory (MFI), the medical outcomes survey short form-36 (SF-36) and the US Centres for Disease Control and Prevention symptom inventory (SI).
Twenty-nine percent (1,609) of the 5623 subjects who completed the detailed telephone interview reported exclusionary diagnoses and we diagnosed an exclusionary condition in 36% of 781 clinically evaluated subjects. Both medical and psychiatric exclusionary conditions were more common in women, blacks and participants from rural areas. Subjects with and without exclusions had similar levels of fatigue and impairment as measured by the MFI and SF-36; those with CFS-like illness (not meeting the formal CFS definition) were more likely to have an exclusionary diagnosis. After adjusting for demographics, body mass index, fatigue subscales, SF-36 subscales and CFS symptoms, CFS-like illness did not remain significantly associated with having an exclusionary diagnosis.
Medical and psychiatric illnesses associated with fatigue are common among the unwell. Those who fulfill CFS-like criteria need to be evaluated for potentially treatable conditions. Those with exclusionary conditions are equally impaired as those without exclusions.
Chronic fatigue syndrome (CFS) is a debilitating condition of unknown etiology and no definitive pharmacotherapy. Patients are usually prescribed symptomatic treatment or self-medicate. We evaluated prescription and non-prescription drug use among persons with CFS in Georgia and compared it to that in non-fatigued Well controls and also to chronically Unwell individuals not fully meeting criteria for CFS.
A population-based, case-control study. To identify persons with possible CFS-like illness and controls, we conducted a random-digit dialing telephone screening of 19,807 Georgia residents, followed by a detailed telephone interview of 5,630 to identify subjects with CFS-like illness, other chronically Unwell, and Well subjects. All those with CFS-like illness (n = 469), a random sample of chronically Unwell subjects (n = 505), and Well individuals (n = 641) who were age-, sex-, race-, and geographically matched to those with CFS-like illness were invited for a clinical evaluation and 783 participated (48% overall response rate). Clinical evaluation identified 113 persons with CFS, 264 Unwell subjects with insufficient symptoms for CFS (named ISF), and 124 Well controls; the remaining 280 subjects had exclusionary medical or psychiatric conditions, and 2 subjects could not be classified. Subjects were asked to bring all medications taken in the past 2 weeks to the clinic where a research nurse viewed and recorded the name and the dose of each medication.
More than 90% of persons with CFS used at least one drug or supplement within the preceding two weeks. Among users, people with CFS used an average of 5.8 drugs or supplements, compared to 4.1 by ISF and 3.7 by Well controls. Persons with CFS were significantly more likely to use antidepressants, sedatives, muscle relaxants, and anti-acids than either Well controls or the ISF group. In addition, persons with CFS were significantly more likely to use pain-relievers, anti-histamines and cold/sinus medications than were Well controls.
Medical care providers of patients with chronic fatigue syndrome should be aware of polypharmacy as a problem in such patients, and the related potential iatrogenic effects and drug interactions.
Chronic fatigue syndrome (CFS) is a debilitating illness with no known cause or effective therapy. Population-based epidemiologic data on CFS prevalence and incidence are critical to put CFS in a realistic context for public health officials and others responsible for allocating resources and for practicing physicians when examining and caring for patients.
We conducted a random digit-dialing survey and clinical examination to estimate the prevalence of CFS in the general population of Wichita, Kan, and a 1-year follow-up telephone interview and clinical examination to estimate the incidence of CFS. The survey included 33 997 households representing 90 316 residents. This report focuses on 7162 respondents aged 18 to 69 years. Fatigued (n = 3528) and randomly selected nonfatigued (n = 3634) respondents completed telephone questionnaires concerning fatigue, other symptoms, and medical history. The clinical examination included the Diagnostic Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, laboratory testing, and a physical examination.
The overall weighted point prevalence of CFS, adjusted for nonresponse, was 235 per 100,000 persons (95% confidence interval, 142-327 per 100,000 persons). The prevalence of CFS was higher among women, 373 per 100,000 persons (95% confidence interval, 210-536 per 100,000 persons), than among men, 83 per 100,000 persons (95% confidence interval, 15-150 per 100,000 persons). Among subjects nonfatigued and fatigued for less than 6 months, the 1-year incidence of CFS was 180 per 100,000 persons (95% confidence interval, 0-466 per 100,000 persons).
Chronic fatigue syndrome constitutes a major public health problem. Longitudinal follow-up of this cohort will be used to further evaluate the natural history of this illness.
Chronic fatigue syndrome (CFS) is defined by symptoms and disability, has no confirmatory physical signs or characteristic laboratory abnormalities, and the etiology and pathophysiology remain unknown. Difficulties with accurate case ascertainment contribute to this ignorance.
Experienced investigators from around the world who are involved in CFS research met for a series of three day workshops in 2000, 2001 and 2002 intended to identify the problems in application of the current CFS case definition. The investigators were divided into focus groups and each group was charged with a topic. The investigators in each focus group relied on their own clinical and scientific knowledge, brainstorming within each group and with all investigators when focus group summaries were presented. Relevant literature was selected and reviewed independent of the workshops. The relevant literature was circulated via list-serves and resolved as being relevant by group consensus. Focus group reports were analyzed and compiled into the recommendations presented here.
Ambiguities in the current CFS research definition that contribute to inconsistent case identification were identified. Recommendations for use of the definition, standardization of classification instruments and study design issues are presented that are intended to improve the precision of case ascertainment. The International CFS Study Group also identified ambiguities associated with exclusionary and comorbid conditions and reviewed the standardized, internationally applicable instruments used to measure symptoms, fatigue intensity and associated disability.
This paper provides an approach to guide systematic, and hopefully reproducible, application of the current case definition, so that case ascertainment would be more uniform across sites. Ultimately, an operational CFS case definition will need to be based on empirical studies designed to delineate the possibly distinct biological pathways that result in chronic fatigue.
Validated or standardized self-report questionnaires used in research studies and clinical evaluation of chronic fatigue syndrome (CFS) generally focus on the assessment of fatigue. There are relatively few published questionnaires that evaluate case defining and other accompanying symptoms in CFS. This paper introduces the self-report CDC CFS Symptom Inventory and analyzes its psychometric properties.
One hundred sixty-four subjects (with CFS, other fatiguing illnesses and non fatigued controls) identified from the general population of Wichita, Kansas were enrolled. Evaluation included a physical examination, a standardized psychiatric interview, three previously validated self-report questionnaires measuring fatigue and illness impact (Medical Outcomes Survey Short-Form-36 [MOS SF-36], Multidimensional Fatigue Inventory [MFI], Chalder Fatigue Scale), and the CDC CFS Symptom Inventory. Based on theoretical assumptions and statistical analyses, we developed several different Symptom Inventory scores and evaluated them on their ability to differentiate between participants with CFS and non-fatigued controls.
The Symptom Inventory had good internal consistency and excellent convergent validity. A Total score (all symptoms), Case Definition score (CFS case defining symptoms) and Short Form score (6 symptoms with minimal correlation) differentiated CFS cases from controls. Furthermore, both the Case Definition and Short Form scores distinguished people with CFS from fatigued subjects who did not meet criteria for CFS.
The Symptom Inventory appears to be a reliable and valid instrument to assess symptoms that accompany CFS. It is a positive addition to existing instruments measuring fatigue because it allows other dimensions of the illness to be assessed. Further research is needed to confirm and replicate the current findings in a normative population.
The lack of standardized criteria for defining chronic fatigue syndrome (CFS) has constrained research. The objective of this study was to apply the 1994 CFS criteria by standardized reproducible criteria.
This population-based case control study enrolled 227 adults identified from the population of Wichita with: (1) CFS (n = 58); (2) non-fatigued controls matched to CFS on sex, race, age and body mass index (n = 55); (3) persons with medically unexplained fatigue not CFS, which we term ISF (n = 59); (4) CFS accompanied by melancholic depression (n = 27); and (5) ISF plus melancholic depression (n = 28). Participants were admitted to a hospital for two days and underwent medical history and physical examination, the Diagnostic Interview Schedule, and laboratory testing to identify medical and psychiatric conditions exclusionary for CFS. Illness classification at the time of the clinical study utilized two algorithms: (1) the same criteria as in the surveillance study; (2) a standardized clinically empirical algorithm based on quantitative assessment of the major domains of CFS (impairment, fatigue, and accompanying symptoms).
One hundred and sixty-four participants had no exclusionary conditions at the time of this study. Clinically empirical classification identified 43 subjects as CFS, 57 as ISF, and 64 as not ill. There was minimal association between the empirical classification and classification by the surveillance criteria. Subjects empirically classified as CFS had significantly worse impairment (evaluated by the SF-36), more severe fatigue (documented by the multidimensional fatigue inventory), more frequent and severe accompanying symptoms than those with ISF, who in turn had significantly worse scores than the not ill; this was not true for classification by the surveillance algorithm.
The empirical definition includes all aspects of CFS specified in the 1994 case definition and identifies persons with CFS in a precise manner that can be readily reproduced by both investigators and clinicians.
Chronic fatigue syndrome (CFS) is a debilitating illness with no known cause or effective therapy. Population-based epidemiologic data on CFS prevalence are critical to put CFS in a realistic context for public health officials and others responsible for allocating resources.
Based on a random-digit dialing survey we ascertained CFS cases and controls to estimate the prevalence of CFS in metropolitan, urban, and rural populations of Georgia. This report focuses on the 5,623 of 19,381 respondents ages 18 to 59 years old. Fatigued (2,438), randomly selected unwell not fatigued (1,429) and randomly selected well (1,756) respondents completed telephone questionnaires concerning fatigue, other symptoms, and medical history. Subsets of those identified by interview as having CFS-like illness (292), chronic unwellness which was not CFS-like (268 - randomly selected), and well subjects (223, matched to those with CFS-like illness on sex, race, and age) completed a clinical evaluation.
We estimated that 2.54% of persons 18 to 59 years of age suffered from CFS. There were no significant differences in prevalence of CFS between metropolitan, urban or rural populations or between white and black residents of the three regions. However, there were significant differences in female-to-male ratios of prevalence across the strata (metropolitan female: male 11.2 : 1, urban 1.7 : 1, rural 0.8 : 1).
We estimated that 2.54% of the Georgia population suffers from CFS, which is 6- to 10-fold higher than previous population-based estimates in other geographic areas. These differences may reflect broader screening criteria and differences in the application of the case definition. However, we cannot exclude the possibility that CFS prevalence may be higher in Georgia than other areas where it has been measured. Although the study did not identify differences in overall prevalence between metropolitan, urban, and rural Georgia populations, it did suggest the need for additional stratified analyses by geographic strata.
Objectives:
This systematic review summarizes research on methods of diagnosing myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and benefits and harms of multiple medical and nonmedical treatments. It identifies evidence gaps and limitations to inform future research.
Data sources:
Searches of electronic databases included MEDLINE® (1988 to September 2014), PsycINFO® (1988 to September 2014), and the Cochrane Library (through the third quarter of 2014). The searches were supplemented by reviewing reference lists, seeking suggestions from reviewers, and requesting scientific information from drug and device manufacturers.
Review methods:
Two investigators reviewed abstracts and full-text articles for inclusion based on predefined criteria. Discrepancies were resolved through discussion and consensus, with a third investigator making the final decision.
Results:
A total of 6,175 potentially relevant articles were identified, 1,069 were selected for full-text review, and 71 studies in 81 publications were included (36 observational studies on diagnosis and 35 trials of treatments). Eight case definitions have been used to define ME/CFS; those for ME, requiring the presence of postexertional malaise, represent a more symptomatic subset of the broader ME/CFS population. Researchers are unable to determine differences in accuracy between case definitions because there is no universally accepted reference standard for diagnosing ME/CFS. The Oxford criteria are the least restrictive and include patients who would not otherwise meet criteria for ME/CFS. Self-reported symptom scales may differentiate ME/CFS patients from healthy controls but have not been adequately evaluated to determine validity and generalizability in large populations with diagnostic uncertainty. Fourteen studies reported the consequences of diagnosis, including perceived stigma and the burden of misdiagnosis, as well as feelings of legitimacy upon receiving the diagnosis of ME/CFS.
Of the 35 trials of treatment, rintatolimod compared with placebo improved measures of exercise performance; counseling therapies and graded exercise treatment (GET) compared with no treatment, relaxation, or support improved fatigue, function, and quality of life, and counseling therapies also improved employment outcomes. Other treatments either provided no benefit or results were insufficient to draw conclusions. GET was associated with higher numbers of reported adverse events compared with counseling therapies or controls. Harms were generally inadequately reported across trials.
Limitations:
Diagnostic methods were studied only in highly selected patient populations. Treatment trials were limited in number and had small sample sizes and methodological shortcomings.
Conclusions:
None of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. Rintatolimod improves exercise performance in some patients (low strength of evidence), while counseling therapies and GET have broader benefit but have not been adequately tested in more disabled populations (low to moderate strength of evidence). Other treatments and harms have been inadequately studied (insufficient evidence). More definitive studies are needed to fill the many research gaps in diagnosing and treating ME/CFS.
Exercise therapy for chronic fatigue syndrome - Volume 23 Issue 3 - Lillebeth Larun, Kjetil G. Brurberg, Jan Odgaard-Jensen, Jonathan R. Price
Background:
Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004.
Objectives:
The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone).
Search methods:
We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy.
Data collection and analysis:
Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome.
Main results:
We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions.
Authors' conclusions:
Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.
Background:
The PACE trial found that, when added to specialist medical care (SMC), cognitive behavioural therapy (CBT), or graded exercise therapy (GET) were superior to adaptive pacing therapy (APT) or SMC alone in improving fatigue and physical functioning in people with chronic fatigue syndrome 1 year after randomisation. In this pre-specified follow-up study, we aimed to assess additional treatments received after the trial and investigate long-term outcomes (at least 2 years after randomisation) within and between original treatment groups in those originally included in the PACE trial.
Methods:
The PACE trial was a parallel-group randomised controlled trial of patients meeting Oxford criteria for chronic fatigue syndrome who were recruited from six secondary care clinics in the UK between March 18, 2005, and Nov 28, 2008. Participants were randomly allocated to receive SMC alone or plus APT, CBT, or GET. Primary outcomes (were fatigue measured with Chalder fatigue questionnaire score and physical functioning with short form-36 subscale score, assessed 1 year after randomisation. In this long-term follow-up, we sent postal questionnaires to assess treatment received after the trial and outcomes a minimum of 2 years after randomisation. We assessed long-term differences in outcomes within and between originally randomised groups. The PACE trial is registered at http://isrctn.org, number ISRCTN54285094.
Findings:
Between May 8, 2008, and April 26, 2011, 481 (75%) participants from the PACE trial returned questionnaires. Median time from randomisation to return of long-term follow-up assessment was 31 months (IQR 30-32; range 24-53). 210 (44%) participants received additional treatment (mostly CBT or GET) after the trial; with participants originally assigned to SMC alone (73 [63%] of 115) or APT (60 [50%] of 119) more likely to seek treatment than those originally assigned to GET (41 [32%] of 127) or CBT (36 [31%] of 118; p<0·0001). Improvements in fatigue and physical functioning reported by participants originally assigned to CBT and GET were maintained (within-group comparison of fatigue and physical functioning, respectively, at long-term follow-up as compared with 1 year: CBT -2·2 [95% CI -3·7 to -0·6], 3·3 [0·02 to 6·7]; GET -1·3 [-2·7 to 0·1], 0·5 [-2·7 to 3·6]). Participants allocated to APT and to SMC alone in the trial improved over the follow-up period compared with 1 year (fatigue and physical functioning, respectively: APT -3·0 [-4·4 to -1·6], 8·5 [4·5 to 12·5]; SMC -3·9 [-5·3 to -2·6], 7·1 [4·0 to 10·3]). There was little evidence of differences in outcomes between the randomised treatment groups at long-term follow-up.
Interpretation:
The beneficial effects of CBT and GET seen at 1 year were maintained at long-term follow-up a median of 2·5 years after randomisation. Outcomes with SMC alone or APT improved from the 1 year outcome and were similar to CBT and GET at long-term follow-up, but these data should be interpreted in the context of additional therapies having being given according to physician choice and patient preference after the 1 year trial final assessment. Future research should identify predictors of response to CBT and GET and also develop better treatments for those who respond to neither.
Funding:
UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions, National Institute for Health Research (NIHR), NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust, King's College London.
The diagnosis of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is based on clinical criteria, yet there has been no consensus regarding which set of criteria best identifies patients with the condition. The Institute of Medicine has recently proposed a new case definition and diagnostic algorithm.
To review methods to diagnose ME/CFS in adults and identify research gaps and needs for future research.
MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; and reference lists.
English-language studies describing methods of diagnosis of ME/CFS and their accuracy.
Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria, and discrepancies were resolved through consensus.
Forty-four studies met inclusion criteria. Eight case definitions have been used to define ME/CFS; a ninth, recently proposed by the Institute of Medicine, includes principal elements of previous definitions. Patients meeting criteria for ME represent a more symptomatic subset of the broader ME/CFS population. Scales rating self-reported symptoms differentiate patients with ME/CFS from healthy controls under study conditions but have not been evaluated in clinically undiagnosed patients to determine validity and generalizability.
Studies were heterogeneous and were limited by size, number, applicability, and methodological quality. Most methods were tested in highly selected patient populations.
Nine sets of clinical criteria are available to define ME/CFS, yet none of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. More definitive studies in broader populations are needed to address these research gaps.
Agency for Healthcare Research and Quality. (PROSPERO: CRD42014009779).
Background:
Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004.
Objectives:
The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone).
Search methods:
We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies
Selection criteria:
Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy.
Data collection and analysis:
Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome.
Main results:
We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions.
Authors' conclusions:
Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.
Objective:
To estimate the prevalence and incidence of chronic fatigue syndrome in Olmsted County, Minnesota, using the 1994 case definition and describe exclusionary and comorbid conditions observed in patients who presented for evaluation of long-standing fatigue.
Patients and methods:
We conducted a retrospective medical record review of potential cases of chronic fatigue syndrome identified from January 1, 1998, through December 31, 2002, using the Rochester Epidemiology Project, a population-based database. Patients were classified as having chronic fatigue syndrome if the medical record review documented fatigue of 6 months' duration, at least 4 of 8 chronic fatigue syndrome-defining symptoms, and symptoms that interfered with daily work or activities. Patients not meeting all of the criteria were classified as having insufficient/idiopathic fatigue.
Results:
We identified 686 potential patients with chronic fatigue, 2 of whom declined consent for medical record review. Of the remaining 684 patients, 151 (22%) met criteria for chronic fatigue syndrome or insufficient/idiopathic fatigue. The overall prevalence and incidence of chronic fatigue syndrome and insufficient/idiopathic fatigue were 71.34 per 100,000 persons and 13.16 per 100,000 person-years vs 73.70 per 100,000 persons and 13.58 per 100,000 person-years, respectively. The potential cases included 482 patients (70%) who had an exclusionary condition, and almost half the patients who met either criterion had at least one nonexclusionary comorbid condition.
Conclusion:
The incidence and prevalence of chronic fatigue syndrome and insufficient/idiopathic fatigue are relatively low in Olmsted County. Careful clinical evaluation to identify whether fatigue could be attributed to exclusionary or comorbid conditions rather than chronic fatigue syndrome itself will ensure appropriate assessment for patients without chronic fatigue syndrome.
Unlabelled:
In 2008, according to the Medical Expenditure Panel Survey (MEPS), about 100 million adults in the United States were affected by chronic pain, including joint pain or arthritis. Pain is costly to the nation because it requires medical treatment and complicates treatment for other ailments. Also, pain lowers worker productivity. Using the 2008 MEPS, we estimated 1) the portion of total U.S. health care costs attributable to pain; and 2) the annual costs of pain associated with lower worker productivity. We found that the total costs ranged from $560 to $635 billion in 2010 dollars. The additional health care costs due to pain ranged from $261 to $300 billion. This represents an increase in annual per person health care costs ranging from $261 to $300 compared to a base of about $4,250 for persons without pain. The value of lost productivity due to pain ranged from $299 to $335 billion. We found that the annual cost of pain was greater than the annual costs of heart disease ($309 billion), cancer ($243 billion), and diabetes ($188 billion). Our estimates are conservative because they do not include costs associated with pain for nursing home residents, children, military personnel, and persons who are incarcerated.
Perspective:
This study estimates that the national cost of pain ranges from $560 to $635 billion, larger than the cost of the nation's priority health conditions. Because of its economic toll on society, the nation should invest in research, education, and training to advocate the successful treatment, management, and prevention of pain.
The American Geriatrics Society, with support from the National Institute on Aging and the John A. Hartford Foundation, held its fifth Bedside-to-Bench research conference, “Idiopathic Fatigue and Aging,” to provide participants with opportunities to learn about cutting-edge research developments, draft recommendations for future research, and network with colleagues and leaders in the field.
Fatigue is a symptom that older persons, especially by those with chronic diseases, frequently experience. Definitions and prevalence of fatigue may vary across studies, across diseases, and even between investigators and patients. The focus of this review is on physical fatigue, recognizing that there are other related domains of fatigue (such as cognitive fatigue).
Many definitions of fatigue involve a sensation of “low” energy, suggesting that fatigue could be a disorder of energy balance. Poor energy utilization efficiency has not been considered in previous studies but is likely to be one of the most important determinants of fatigue in older individuals. Relationships between activity level, capacity for activity, a tolerable rate of activity, and a tolerable fatigue threshold or ceiling underlie a notion of fatiguability. Mechanisms probably contributing to fatigue in older adults include decline in mitochondrial function, alterations in brain neurotransmitters, oxidative stress, and inflammation. The relationships between muscle function and fatigue are complex. A number of diseases (such as cancer) are known to cause fatigue and may serve as models for how underlying impaired physiological processes contribute to fatigue, particularly those in which energy utilization may be an important factor. A further understanding of fatigue will require two key strategies: to develop and refine fatigue definitions and measurement tools and to explore underlying mechanisms using animal and human models.
The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.
We compared three case definitions of chronic fatigue syndrome (CFS) applied to patients followed in CFS clinics at two institutions.
All patients had debilitating fatigue without apparent etiology; patients with medical conditions associated with chronic
fatigue and with major psychiatric disorders were stratified and presented separately. Patients were classified according
to whether they met case definitions developed by a Centers for Disease Control and Prevention (CDC) Working Group, a British
group, or an Australian group. When findings for 805 patients followed at the two clinics were combined, 61% met the CDC criteria,
55% met the British criteria, and 56% met the Australian criteria; these proportions were relatively similar at both sites.
In addition, similar laboratory abnormalities were found for all case groups and for fatigued patients who met none of the
three case definitions. These data suggest that more inclusive case definitions may be superior.
Our goals were to determine the prevalence of unusual, debilitating fatigue and the frequency with which it was associated with the chronic fatigue syndrome (CFS) or other physical or psychological illness in an outpatient clinic population.
We prospectively evaluated a cohort of 1000 consecutive patients in a primary care clinic in an urban, hospital-based general medicine practice. The study protocol included a detailed history, physical examination, and laboratory and psychiatric testing.
Five patients who came because of CFS studies were excluded. Of the remaining 995, 323 reported fatigue, and 271 (27%) complained of at least 6 months of unusual fatigue that interfered with their daily lives. Of the 271, self-report or record review revealed a medical or psychiatric condition that could have explained the fatigue in 186 (69%). Thus, 85 (8.5%) of 995 patients had a debilitating fatigue of at least 6 months' duration, without apparent cause. Of these patients, 48 refused further evaluation, and 11 were unavailable for follow-up; 26 completed the protocol. Three of the 26 were hypothyroid, and one had a major psychiatric disorder. Of the remaining 22 patients, three met Centers for Disease Control and Prevention criteria for CFS, four met British criteria, and 10 met the Australian case definition. The point prevalences of CFS were thus 0.3% (95% confidence interval [CI], 0% to 0.6%), 0.4% (95% CI, 0% to 0.8%), and 1.0% (95% CI, 0.4% to 1.6%) using the Centers for Disease Control and Prevention, British, and Australian case definitions, respectively. These estimates were conservative, because they assumed that none of the patients who refused evaluation or were unavailable for follow-up would meet criteria for CFS.
While chronic, debilitating fatigue is common in medical outpatients, CFS is relatively uncommon. Prevalence depends substantially on the case definition used.
Our objective was to evaluate symptom patterns in patients with chronic fatigue syndrome (CFS) who were ill for 10 or more years.
This cross-sectional self-report study compared patient groups with long-duration (median = 18 years; n = 258) and short-duration (median = 3 years; n = 28) CFS to a group of healthy significant others (n = 79) on symptomatic, neurocognitive, and psychological variables. Data were gathered from a 574-item postal questionnaire.
A principal-components analysis of CFS symptom data yielded a three-factor solution: cognitive problems; flu-like symptoms; and neurologic symptoms. Compared with the short-duration CFS group, the long-duration group had significantly higher CFS symptom severity scores (p < 0.04), largely attributable to increased cognitive difficulties. A subgroup comparison of subjects ill for < 3 years versus those ill 4-7 years suggested that denial coping strategies were more likely in those participants with the shorter illness duration. Significant differences between both CFS groups and healthy controls were found in a number of comorbid disorders. Participants with CFS most often endorsed immune/viral abnormalities and persistent stress as important perceived causes of their illness.
Participants with long-duration CFS reported a large number of specific cognitive difficulties that were greater in severity than those reported by participants with short-duration CFS. The pattern of comorbid disorders in the CFS groups was consistent with hypersensitivity and viral reactivation hypotheses.
A perspective on the various definitions of myalgic encephalomyelitis and the process of discovering its aetiology is presented. The importance of clinical guidelines is emphasised to encourage clinicians to provide clear descriptions of their individual patients required for proper clinical activity; diagnosis, estimation of severity of effect, prognosis, treatment and rehabilitation. This individual knowledge is informed by general and (hopefully) publicly confirmed knowledge resulting from scientific research during the second-person interaction which lies at the core of the clinical encounter. Both types of knowledge are essential.
To examine the prevalence of self-reported epilepsy or seizure disorder and its association with self-reported recent depression and anxiety in a large sample of the U.S. adult population.
We analyzed data from adults aged 18 years or older (n = 4,345) who participated in the 2004 HealthStyles Survey, a large mail panel survey designed to be representative of the U.S. population.
Among U.S. adults aged 18 years or older, we estimated that 2.9% have been told by a doctor that they had epilepsy or seizure disorder, and an estimated 1.6% and 0.9% had active and inactive epilepsy, respectively. After controlling for demographic characteristics, we estimated that adults with self-reported epilepsy were twice as likely to self-report depression or anxiety in the previous year as were adults without epilepsy, and adults with active epilepsy were 3 times as likely to self-report depression and twice as likely to have anxiety in the previous year as were adults without epilepsy.
Our findings highlight the burden of self-reported depression and anxiety among adults with self-reported epilepsy or seizure disorder, and suggest that healthcare providers should attempt to determine whether adult patients with epilepsy have any psychiatric comorbidity potentially to improve health outcomes. Questions about epilepsy and related factors should be routinely included on population-based surveys so that we can better understand the epilepsy distribution in the U.S. population and identify the unmet health and psychosocial needs of people with epilepsy.
- Smith MEB
Pacific Northwest Evidence-based Practice Center Diagnosis and treatment of myalgic encephalomyelitis/chronic fatigue syndrome Evidence Reports/Technology Assessments Agency for Healthcare Research and Quality (US)
- Meb Smith
- Hd Nelson
- E Haney
Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Board on the Health of Select Populations, Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness
Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome,
Board on the Health of Select Populations, Institute of Medicine. Beyond Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness Washington (DC): National
Academies Press (US); 2015 2 10.