Tag: editorial

Where are the long COVID trials?

The news in early July, 2023, that STOP-PASC, a clinical trial at Stanford University, CA, USA, testing nirmatrelvir-ritonavir in patients with long COVID, is closing enrolment before the full study size has been reached, is disheartening. STOP-PASC is one of the few clinical trials studying a pharmacological intervention for long COVID and although the reason for termination hasn’t been confirmed yet, it adds to the dismal state of clinical research relative to the substantial burden of the condition.
ClinicalTrials.gov currently lists 386 trials under the search term Long COVID. However, only 94 of those studies are classed as interventional and are currently recruiting, and even more disturbing, only 12 trials are testing pharmacological interventions. The rest comprise follow-up of trials in acute infection, rehabilitation, food supplements, telehealth, psychological support, physiotherapy, acupuncture, light therapy, Chinese herbal medicine etc. While the list ranges from “nice to have additional support” to questionable alternative cures or even potentially harmful treatments, we are clearly lacking tested pharmacological interventions that treat the underlying pathophysiology.
There is a desperate need for long COVID treatments. Although estimates vary quite widely between populations and studies and depending on the definitions and methods used, 1 in 10 people experiences long COVID after infection. Lasting symptoms range from mild to disabling, with people unable to work or even bed-bound and unable to take care of basic personal needs. These individual tragedies have wide-ranging repercussions, leading to lost earnings, a shrinking workforce, and increased healthcare and social care costs. Again, estimates vary widely, but the impact is in the range of billions to trillions US dollars globally. Why do we only have 12 pharmacological interventional trials then?
Read the rest of this article HERE.
Source: Where are the long COVID trials? EDITORIAL, The Lancet Infectious Diseases, VOLUME 23, ISSUE 8, P879, AUGUST  Published:August, 2023. DOI: https://doi.org/10.1016/S1473-3099(23)00440-1 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00440-1/fulltext (Full text)

Special Issue “Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment”

Introduction:
Chronic fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), is a debilitating disease with unknown causes that is more common in women and tends to develop between patients’ mid-20s and mid-40s. From the perspectives on the etiology and pathophysiology, CFS/ME has been labeled differently, which has influenced changes in case definitions and terminologies. CFS/ME is characterized by persistent asthenia with associated musculoskeletal pain, cognitive disturbance (including attention, memory, and concentration), psychological troubles (depression, anxiety), sleep disorders, and a variety of neurovegetative symptoms. The best appropriate therapeutic is an integrative approach, based on a personalized medical plane that includes distinct groups of procedures: educational, cognitive-behavioral, pharmacological and non-pharmacological such as occupational therapy and rehabilitation. CFS/ME has some common clinical features with fibromyalgia, and a differential diagnosis is difficult for General Practitioners (GPs) [1,2].
The recent opinion is that CFS/ME pathogenesis is dependent on several factors or causes. Different studies have shown evidence for an alteration in immunity system in patients with CFS/ME. A modification in cytokine subsets, a diminished activity of natural killer (NK) lymphocytes, the detection of autoantibodies and a decreased response of T cells to mitogens and specific antigens have been observed. An increased level of pro-inflammatory cytokines may explain some of the clinical features, such as fatigue and flulike symptoms, with an effect on NK activity. Anomalous activation of the T lymphocyte profile and a reduction in antibody-dependent cell-mediated cytotoxicity have been reported. An increased number of CD8+ cytotoxic T lymphocytes and CD38 and HLA-DR activation markers have been demonstrated, and a reduced CD11b expression associated with an increased expression of CD28+ T subsets has been described [3]. An interest towards CFS/ME is increased with the recent pandemic by SARS-CoV-2 because, after the acute phase of disease, some patients have clinical features similar to CFS/ME called Long-COVID, characterized by tiredness, brain fog and headache. There is debate on common aspect between these pathologies but in especially a possible effect of COVID-19 on CFS/ME and the consequences [4].
This Special Issue on CFS/ME collects 18 papers with an interdisciplinary view on the current demographic and epidemiological data and immunological characteristics of CFS/ME and examines the different pathogenic hypotheses, as well as giving information about the latest knowledge on diagnostic investigations, pharmacological, integrative, physical, cognitive-behavioral and psychological curative approaches.
It is known that CFS/ME affects young adults, but there are little studies in pediatric and adolescent age. Australian colleagues Elisha K. Josev and colleagues have carried out a case-controlled follow-up study on the health, wellbeing and prognosis of Australian adolescents with CFS/ME on the comprehension of the important relation between physical and psychological health factors to adolescent’ long-term outcome for approaching future prevention, management and treatment [5]. Concerning epidemiological data, there is little information for Asian countries such Korea and Japan. Eun-Jn Lim and Chang-Gue Son evaluate and match the prevalence of CFS/ME in Korea and Japan, performing a meta-analysis analyzing the main characteristics of these nations [6].
The emerging data of the involvement of immune system confirmed the hypothesis that CFS/ME is an autoimmune disease; recent studies have shown the role of autoantibodies towards the vegetative nervous system. Freitag H. and colleagues reported the reactivity of autoantibodies to vasoregulative G-Protein-Coupled Receptor correlates with autonomic dysfunction, clinical gravity and disability in CFS/ME patients [7]. Another paper, by Kujawski S. and collaborators, studies the differences in CFS patients applying post-exertional malaise (PEM) as indicators of aortic stiffness, autonomic nervous system function and severity of fatigue [8]. Always on the role of the autonomic nervous system dysfunction, Jessica Van Oosterwijck et al. published a paper showing decreased parasympathetic reactivation from physical exercise that could be correlated with a bad prognosis or high risk for adverse cardiac event [8]. Varesi A. and colleagues investigated the emerging role of the modified composition of gut microbiota in relationship with genetic, infection, immunological and other influences that have seen in CFS/ME individuals [9]. The authors discuss the change and the potential therapeutic application of treating the gut in CFS/ME patients [10].
A collection of papers investigates the importance of the diagnostic tools in clinical practice. We start with Baklund H. I. et al., who evaluated the blood test in relationship with clinical features and diagnostic classification, suggesting muscle damage and metabolic abnormalities [11].
A potential blood diagnostic tool, by Castro-Marrero J. and his Spanish collaborators, could be the complement C1 examining in CFS/ME three-symptom clusters, identified as severe, moderate and mild, presenting important differences in five blood parameters [12]. Another objective measurement for PEM, which is a hallmark of CFS/ME, is the application of the two-days cardiopulmonary exercise test (CPET) to assess functional impairment: Eun-Jin Lim and Korean collaborators, in their paper, published the results of a meta-analysis on this diagnostic tool [13]. Moreover, Do-Young Kim and his Korean colleagues examined a systematic review to provide an overview of the adoption of the main measurements in RCTs for CFS/ME. Around 40% of RCTs utilized multiple primary measurements. This information could be helpful in clinical practice in the design of medical studies for CFS/ME-linked therapeutic development [14].
The therapy of CFS/ME is problematic due to lack of knowledge on the etiopathogenesis of this disease, with application of the unconventional and conventional treatments: Tirelli and colleagues compared the application of oxygen–ozone autohemotherapy (O2-O3-AHT) in male vs. female patients, evaluating the differences in their responses to this approach [15]. The effects of exercise from a structured activity program have been disputed; Kujawski S. et al., with a multidisciplinary study, examined the impact of a personalized program of activities associated with cardiovascular, mitochondrial and fatigue parameters, showing a reduction in fatigue and an improving functional performance [16]. An important conventional therapeutic approach is the effect of s.c. IgG self-treatment in ME/CFS patients with IgG/IgG subgroup deficiency. The aim of Scheibenbogen C. and her German collaborators was to study the IgG administration for its immunomodulatory effects. [17].
There are few studies relationship CFS/ME patients and COVID-19 patients [18]. Araja D. and Latvian collaborators researched undiagnosed CFS/ME patients, hypothesizing the expansion of post-viral CFS as an effect of COVID-19 and its social impact. The Latvian research results show that patients with CFS/ME are not a risk group for COVID-19; however, COVID-19 causes symptoms similar to CFS/ME. They concluded that CFS/ME creates a significant social consequence, considering the direct medical costs of undiagnosed patients. At the same time, COVID-19 is responsible for long-lasting complications and a chronic course, such as post-viral CFS [19].
Deumer U-S et al. discuss the role of the gut microbiota on disease progression, highlighting a potential biomarker in non-coding RNA (ncRNA) as a probable diagnostic tool and suggesting the possibility that SARS-CoV-2 infection may result in symptoms similar to CFS [20].
CFS/ME has an overlap with Fibromyalgia, and differential diagnosis is difficult for some clinicians because the diagnosis of fibromyalgia is based only on clinical features that are characterized by widespread pain, fatigue, stiffness and troubles in cognitive functions, such as attention, executive function and verbal memory deficits [21]. It is important to add more tests beyond the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) test in fibromyalgia patients to assess the relationship between physical and cognitive performance, as reported by Murillo-Garcia A. and colleagues [22]. Another potential diagnostic tool is studied by Martin-Brufau R. and collaborators using electroencephalography for patients with fibromyalgia that present lower levels of brain activity with reduced connectivity than controls. The Spanish group identified a possible neurophysiological pattern that could adapt to the clinical features of the disease [23]. The therapeutic approach to this disease is a difficult choice. Rodriguez-Mansilla J. and Spanish collaborators studied the effects of non-pharmacological treatment in terms of the effectiveness of an exercise program compared to wellness activities by improving pain, flexibility, static balance, perceived effort and quality of life in patients with fibromyalgia. Participants in the active exercise program performed better than exercise for well-being [24]. This proposal in fibromyalgia is associated with other conventional treatments based on a multidisciplinary approach.
In conclusion, the papers published within this research topic, with the major contribution of the members of the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE), give us the recent highlight perspective and opportunities for the discovery and development of possible specific biomarkers, diagnostic and therapeutic approaches for these immunological disorders.
Source: Lorusso L, Ricevuti G. Special Issue “Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment”. J Clin Med. 2022 Aug 4;11(15):4563. doi: 10.3390/jcm11154563. PMID: 35956178. https://www.mdpi.com/2077-0383/11/15/4563/htm (Full text)

Chronic fatigue syndrome: an old public health issue highlighted by the COVID-19 pandemic

In some cases, C O VID-19 has been shown to cause both acute as well as prolonged neuropsychiatric manifestations, possibly due to CNS immune cell activation.13,14 Between 13 and 23% of hospitalized COVID-19 patients suffer from fatigue and PEM-like symptoms more than 6 months after the infection.15 These numbers, although alarming, are hardly surprising. Looking back at the 2002/03 SARS pandemic, a similar proportion of hospitalized patients with a severe course also developed CFS/ME (27% of survivors 4 years after hospitalisation).16Other common pathogens that can lead to CFS/ME include viruses like Epstein-Barr virus (EBV), cytomegalovirus (CMV) and enteroviruses, bacteria such as mycoplasma, Borrelia burgdorferi (Lyme disease), and Coxiella burnetii (Q fever).17 In fact, in 3 out of 4 cases of CFS/ME, the disease develops following an infectious episode.18 Interestingly, the innate immune response to infections is generally higher among women than men, which could perhaps also explain the higher prevalence of CFS/ME among women given the role that immunity plays in it. With an estimated prevalence of 0.1-0.7%, CFS/ME is far above the threshold value set by the European Union for classification as a rare disease (<5:10,000).

Read the rest of this article HERE. 

Source: Bonk JS, Khedkar PH. Chronic fatigue syndrome: an old public health issue highlighted by the COVID-19 pandemic. Acta Physiol (Oxf). 2022 Jul 30:e13863. doi: 10.1111/apha.13863. Epub ahead of print. PMID: 35906837. https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.13863 (Full text)

Editorial: Current Insights Into Complex Post-infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond

Introduction:

Black plague epidemics in Medieval Europe, the Spanish Flu pandemic during the first world war, and the pandemic of COVID-19 disease are just three devastating examples of the fragile co-existence between human beings and the microbial world. Remarkably, the human immune system with its innate and adaptive arms recognizes and clears the invading pathogens in most cases. However, like a scar after an injury, some people who had suffered from acute infections remain ill long after the clearance of the pathogen itself. These individuals develop complex fatigue-related syndromes whose pathological mechanisms remain poorly understood. A prime example of such syndromes is the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) characterized by persistent fatigue and post-exertional malaise among other symptoms (1). Unfortunately, its diagnosis remains challenging due to the inexistence of objective biomarkers that could identify cases. However, researchers are gathering around multidisciplinary networks, such as the US ME/CFS Clinician Coalition and the European Network on ME/CFS, with the aim of fostering collaboration, standardizing research and clinical practices, while accelerating biomarker discovery (2–5). Less-known fatigue-related syndromes have been recently reported after the outbreaks of Ebola virus, Dengue virus, and Chikungunya virus in the Tropics (6–8). However, it is still unclear whether these syndromes constitute clinical entities beyond ME/CFS itself.

Read the rest of this article HERE.

Source: Westermeier F, Lacerda EM, Scheibenbogen C and Sepúlveda N (2022) Editorial: Current Insights Into Complex Post-infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond. Front. Med. 9:862953. doi: 10.3389/fmed.2022.862953  https://www.frontiersin.org/articles/10.3389/fmed.2022.862953/full (Full text)

Post-COVID syndrome: the aftershock of SARS-CoV-2

Introduction:

Significant time has passed since the coronavirus disease of 2019 (COVID-19) pandemic outbreak, which led to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in hundreds of millions of individuals all around the globe. Accumulation evidence along the pandemic raised an association between the SARS-CoV-2 and autoimmunity (1). SARS-CoV-2 infected patients have a high presence of various autoantibodies (1). Moreover, numerous cases of new-onset of autoimmune-related disorders had been documented following the infection, including both organ-specific and systemic autoimmune diseases (1).

Recent studies focused on analyzing recovered COVID-19 patients demonstrate a broad spectrum of persistent and systemic symptoms, which had got the novel terms of “post-COVID syndrome”, “long COVID” and “chronic COVID-19” (2). This new disorder had led to the understanding that the absence of SARS-CoV-2 following COVID-19 does not necessarily mean full recovery (2).

Studies conducted follow-ups on COVID-19 patients indicate that 50-80% of symptomatic COVID-19 patients who recovered report non-specific symptoms, most commonly fatigue, headache, dyspnea, anosmia, and memory complaint (3–5). An Italian study that examined patients after a mean of 60 days from the first COVID-19 symptom on-set had found only 12.6% of the patients completely recovered; 55% had three or more symptoms, and worsened quality of life was observed among 44% of patients (3). Intriguingly, a systematic review and meta-analysis reported more than 50 possible long-term effects of the SAR-CoV-2 infection (6). The chronic phase of COVID-19 is also presented in objective findings; for example, a study conducted in Germany had found that 78% of recently recovered symptomatic COVID-19 patients had at least one chronic symptom; the most common abnormality was myocardial inflammation (60%) (4).

In this issue of the journal, Bertin D et al. documented a case of post-COVID syndrome with a one-year follow-up. This case describes persistent anti-cardiolipin IgG autoantibodies and eosinopenia with ongoing neurologic symptoms, demonstrating the long-term disease course of COVID-19 in many patients. Anti-cardiolipin autoantibodies and eosinopenia were defined as independent factors associated with COVID-19 severity, indicating their active involvement in the progression of the disease (7,8). Additional studies that included follow-up on recovered COVID-19 patients describe similar findings: patients report respiratory, neurologic, and non-specific symptoms, accompanied by the presents of autoantibodies (6). Interestingly, in a one-year prospective cohort study, neurocognitive symptoms frequency were found significantly higher in patients with ANA titer of ≥1:160 in comparison to <1:160 at 12 months post–COVID-19 symptom onset (9). It should be emphasized that the development of autoantibodies, which appears to be common following symptomatic SARS-CoV-2 infection, could act as the preclinical stage of many autoimmune diseases. Thus, the long-term autoimmune implications of SARS-CoV-2 could be severe.

Involvement of the autonomic nervous system dysfunction in post-COVID syndrome

Many viruses are well known to contribute to autoimmunity in genetically pre dispositioned individuals, such as those with human leukocyte antigen B27 (10). SARS-CoV-2 had been associated with numerous autoantibodies (1); some are believed to be the basis of the severe forms of COVID-19 (11). Furthermore, these autoantibodies, along with others, could lead to the multi-organ involvement of post-COVID syndrome, which manifests as broad and unspecific symptoms (6). Autoantibodies against the autonomic nervous system compounds are believed to be an incremental part of the post-COVID syndrome etiology. A study that included post-COVID syndrome patients had unidentified in all the subjects between 2 and 7 different functionally active autoantibodies that acted as receptor agonists, such as β2-adrenoceptor, α1-adrenoceptor, and angiotensin II receptor type 1 receptor (12). Functionally active autoantibodies such as those were present in several neurological and cardiac disorders, which might clarify the onset of neurological and cardiovascular symptoms of the post-COVID syndrome (12).

Post-COVID patients commonly have a clinical presentation similar to the encephalomyelitis/chronic fatigue syndrome (ME/CFS): severe fatigue, sleep disorders, cognition impairments, and different manifestations of autonomic dysfunction exacerbated in physical exercise (6,13–15). ME/CFS has an autoimmune etiology, which can be demonstrated by high titers of autoantibodies against autonomic receptors, such as beta-adrenergic and muscarinic receptors (16,17). These autoantibodies, similar to those found in patients with post-COVID symptoms, lead to unspecific symptoms due to autonomic nervous system dysregulation. In addition to ME/CFS, many features of the post-COVID syndrome are shared with fibromyalgia patients. It had been shown that 189/616 (30.7%) of COVID-19 recovered patients satisfied the American College of Rheumatology criteria for fibromyalgia, 43.4% of which were men (18).

Therapeutic options and vaccination

ME/CFS and fibromyalgia have solid evidence of dysregulated immune involvement (16,17,19). Moreover, current studies suggest that immunosuppression, such as monoclonal anti-CD20 antibody and cyclophosphamide, may benefit patients suffering from ME/CFS (20,21). Such immunosuppressive therapeutic options can assist in the depletion of B cells, thus reducing the functionally active autoantibodies linked to autonomic dysfunction. Beneficial effects had also been demonstrated by the use of anti-ß2 adrenergic receptor-binding immunoadsorption (22). It should be emphasized that such treatment can diminish other pathogenic antibodies that the medical community had not yet recognized. Due to the possible involvement of autoantibodies against the autonomic nervous system in the post-COVID syndrome, similar immunosuppressive options in these patients may be effective, thereby should be investigated.

Most individuals infected by SARS-CoV-2 are asymptomatic or experience mild symptoms (23,24). While the frequency of post-COVID syndrome in such individuals is still uncertain, it seems to be much lower than in symptomatic patients (9). Thus, avoiding COVID-19 with SARS-CoV-2 vaccination could prominently assist in preventing long-term symptoms of COVID-19, lower the prevalence of post-COVID syndrome and help overcome the pandemic. Nonetheless, even with the ongoing heist mass vaccination programs, the COVID-19 pandemic will leave its mark.

Conclusion

Due to the accumulating evidence of persistent post-infectious symptoms reported by numerous recovered patients, the focus of the medical and research communities might need to start shifting focus from the acute phase of COVID-19 to the chronic manifestations of the SARS-CoV-2 infection, referred to as by “post-COVID syndrome”. Post-COVID syndrome presents as non-specific symptoms, most commonly fatigue, headache, dyspnea, anosmia, and memory complaint, which is suspiciously similar to the infection-induced myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (15,18). As current studies suggest an involvement of immune-related dysfunction in the development of post-COVID syndrome, immunosuppressive therapeutic options could be beneficial in parallel to heist SARS-CoV-2 vaccination of the population (15,20,21).

References

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    Wallukat G, Hohberger B, Wenzel K, Fürst J, Schulze-Rothe S, Wallukat A, et al. Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms. J Transl Autoimmun. 2021 Jan 1;4:100100.
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Article Info

Publication History

Accepted: November 9, 2021
Received: November 9, 2021

Publication stage

In Press Journal Pre-Proof

Identification

DOI: https://doi.org/10.1016/j.ijid.2021.11.020

Copyright

© 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Editorial: Advances in ME/CFS Research and Clinical Care

Editorial:

Advances in ME/CFS Research and Clinical Care spotlights Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a maligned, stigmatized, under-researched disease, which lacks a definitive, objective clinical test for its diagnosis, and definitive palliative and curative treatments. A few brave physicians attempt to alleviate the suffering of the afflicted. They rely upon the patients’ symptoms to guide them. Physicians can provide symptomatic relief and improve upon patients’ abnormal physiological and metabolic parameters by intervening to cause the latter to approach normal limits.

Documented to be more severely disabling than HIV-AIDS, ME/CFS receives disturbingly little funding in the United States and around the world. ME/CFS patients constitute an identifiable, underserved population that is in need of the recognition which would raise them from their current, underserved or non-served patient status into the mainstream of healthcare worldwide. ME/CFS is a common disease worldwide, affecting approximately 1 percent of the world’s population.

You can read the rest of this article HERE.

Source: Friedman KJ, Bateman L, Bested A, Nahle Z. Editorial: Advances in ME/CFS Research and Clinical Care. Front Pediatr. 2019 Sep 18;7:370. doi: 10.3389/fped.2019.00370. eCollection 2019. https://www.frontiersin.org/articles/10.3389/fped.2019.00370/full (Full article)

The importance of a research case definition

Abstract:

All scientific activities with diseases rely on the selection of reliable and valid case definitions in order to accurately estimate prevalence rates, to identify biological markers, and to understand the outcomes of treatment trials. The failure to develop a consensus on which research case definition to use for defining Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS) has had negative consequences for the scientific and patient community.

If case definition criteria inappropriately select patients with symptoms due to primary affective disorders, other fatiguing medical conditions, burnout, or over-committed lifestyle issues, the scientific consequences are serious. For example, a case definition that is too broad would include individuals with other illnesses and conditions, complicating the tasks of estimating prevalence rates or identifying effective treatment programs.

A consensus on a research case definition and its operationalization and assessment would enable investigators to select more homogenous samples that could expedite the identification of valid biological markers, and consequently reduce misperceptions regarding the role of psychogenic versus biomedical factors. Our editorial reviews the implications of previous research and clinical case definitions in CFS and ME domains.

Source: Leonard A. Jason, Pamela A. Fox & Kristen D. Gleason. The importance of a research case definition.  Fatigue: Biomedicine, Health & Behavior. Pages 1-7 | Received 01 Aug 2017, Accepted 04 Oct 2017, Published online: 12 Oct 2017.    http://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1389336?journalCode=rftg20 

Managing chronic fatigue syndrome in children

Last month the British press made much of a study purporting to show that chronic fatigue syndrome was the single commonest cause of long term absence from school in Britain.1 The authors claimed to have calculated prevalence figures for both pupils (0.07%) and teachers (0.5%) similar to previously reported figures for the general population.2-4 Dowsett and Colby make much of “clusters” of cases, defined as three or more cases in a school. The press release distributed by one of the authors states that 39% of cases occurred in such clusters, saying that this “suggests that ME results from an infection.” It refers to one cluster extending over several schools in an area where there was “recreational water heavily polluted by sewage.” The published paper contains no reference to pollution by sewage or anything else, but only to several cases in “schools near two new towns in a rural environment alongside recreational water.”

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126833/pdf/9193280.pdf

Comment in:

Graded exercise in chronic fatigue syndrome. Including patients who rated themselves as a little better would have altered results. [BMJ. 1997]

Chronic fatigue syndrome in children. Journal was wrong to critizise study in schoolchildren. [BMJ. 1997]

Chronic fatigue syndrome in children. Patient organisations are denied a voice. [BMJ. 1997]

Comment on:

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

 

Source: Marcovitch H. Managing chronic fatigue syndrome in children. BMJ. 1997 Jun 7;314(7095):1635-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126833/pdf/9193280.pdf (Full article)