Tag: review

Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians

Abstract:

This review was written from the viewpoint of the treating clinician to educate health care professionals and the public about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). It includes: the clinical definition of ME/CFS with emphasis on how to diagnose ME/CFS; the etiology, pathophysiology, management approach, long-term prognosis and economic cost of ME/CFS. After reading this review, you will be better able to diagnose and treat your patients with ME/CFS using the tools and information provided.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic medical condition characterized by symptom clusters that include: pathological fatigue and malaise that is worse after exertion, cognitive dysfunction, immune dysfunction, unrefreshing sleep, pain, autonomic dysfunction, neuroendocrine and immune symptoms. ME/CFS is common, often severely disabling and costly. The Institute of Medicine (IOM) reviewed the ME/CFS literature and estimates that between 836,000 and 2.5 million Americans have ME/CFS at a cost of between 17 and 24 billion dollars annually in the US. The IOM suggested a new name for ME/CFS and called it Systemic Exertion Intolerance Disease (SEID). SEID’s diagnostic criteria are less specific and do not exclude psychiatric disorders in the criteria.

The 2010 Canadian Community Health Survey discovered that 29% of patients with ME/CFS had unmet health care needs and 20% had food insecurity–lack of access to sufficient healthy foods. ME/CFS can be severely disabling and cause patients to be bedridden. Yet most patients (80%) struggle to get a diagnosis because doctors have not been taught how to diagnose or treat ME/CFS in medical schools or in their post-graduate educational training. Consequently, the patients with ME/CFS suffer.

They are not diagnosed with ME/CFS and are not treated accordingly. Instead of compassionate care from their doctors, they are often ridiculed by the very people from whom they seek help.

The precise etiology of ME/CFS remains unknown, but recent advances and research discoveries are beginning to shed light on the enigma of this disease including the following contributors: infectious, genetic, immune, cognitive including sleep, metabolic and biochemical abnormalities.

Management of patients with ME/CFS is supportive symptomatic treatment with a patient centered care approach that begins with the symptoms that are most troublesome for the patient. Pacing of activities with strategic rest periods is, in our opinion, the most important coping strategy patients can learn to better manage their illness and stop their post-exertional fatigue and malaise. Pacing allows patients to regain the ability to plan activities and begin to make slow incremental improvements in functionality.

 

Source: Bested AC, Marshall LM. Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians. Rev Environ Health. 2015;30(4):223-49. doi: 10.1515/reveh-2015-0026. https://www.ncbi.nlm.nih.gov/pubmed/26613325

 

A systematic review of the comorbidity between Temporomandibular Disorders and Chronic Fatigue Syndrome

Abstract:

The most common cause of chronic oro-facial pain is a group of disorders collectively termed temporomandibular disorders (TMDs). Chronic painful TMD is thought to be a ‘central sensitivity syndrome’ related to hypersensitivity of the nervous system, but the cause is unknown. A similar understanding is proposed for other unexplained conditions, including chronic fatigue syndrome (CFS). Exploring the comorbidity of the two conditions is a valuable first step in identifying potential common aetiological mechanisms or treatment targets.

METHOD: Systematic literature review. Studies were included if they recruited community or control samples and identified how many reported having both TMD and CFS, or if they recruited a sample of patients with either TMD or CFS and measured the presence of the other condition.

RESULTS: Six papers met inclusion criteria. In studies of patients with CFS (n = 3), 21-32% reported having TMD. In a sample of people with CFS and fibromyalgia, 50% reported having TMD. Studies in people with TMD (n = 3) reported 0-43% having CFS. Studies in samples recruited from oro-facial pain clinics (n = 2) reported a lower comorbidity with CFS (0-10%) than a study that recruited individuals from a TMD self-help organisation (43%).

CONCLUSION: The review highlights the limited standard of evidence addressing the comorbidity between oro-facial pain and CFS. There is a valuable signal that the potential overlap in these two conditions could be high; however, studies employing more rigorous methodology including standardised clinical assessments rather than self-report of prior diagnosis are needed.

© 2015 John Wiley & Sons Ltd.

 

Source: Robinson LJ, Durham J, Newton JL. A systematic review of the comorbidity between Temporomandibular Disorders and Chronic Fatigue Syndrome. J Oral Rehabil. 2016 Apr;43(4):306-16. doi: 10.1111/joor.12367. Epub 2015 Nov 9. https://www.ncbi.nlm.nih.gov/pubmed/26549386

 

Myalgic Encephalomyelitis: Symptoms and Biomarkers

Abstract:

Myalgic Encephalomyelitis (ME) continues to cause significant morbidity worldwide with an estimated one million cases in the United States. Hurdles to establishing consensus to achieve accurate evaluation of patients with ME continue, fueled by poor agreement about case definitions, slow progress in development of standardized diagnostic approaches, and issues surrounding research priorities. Because there are other medical problems, such as early MS and Parkinson’s Disease, which have some similar clinical presentations, it is critical to accurately diagnose ME to make a differential diagnosis.

In this article, we explore and summarize advances in the physiological and neurological approaches to understanding, diagnosing, and treating ME. We identify key areas and approaches to elucidate the core and secondary symptom clusters in ME so as to provide some practical suggestions in evaluation of ME for clinicians and researchers.

This review, therefore, represents a synthesis of key discussions in the literature, and has important implications for a better understanding of ME, its biological markers, and diagnostic criteria. There is a clear need for more longitudinal studies in this area with larger data sets, which correct for multiple testing.

 

Source: Jason LA, Zinn ML, Zinn MA. Myalgic Encephalomyelitis: Symptoms and Biomarkers. Curr Neuropharmacol. 2015;13(5):701-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/ (Full article)

 

Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

Abstract:

BACKGROUND: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States.

PURPOSE: To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs.

DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information.

STUDY SELECTION: English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments.

DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus.

DATA SYNTHESIS: Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence).

LIMITATION: Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality.

CONCLUSION: Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.

Comment in

 

Source: Smith ME, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, Fu R, Nelson HD. Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Jun 16;162(12):841-50. doi: 10.7326/M15-0114. http://annals.org/aim/article/2322801/treatment-myalgic-encephalomyelitis-chronic-fatigue-syndrome-systematic-review-national-institutes (Full article)

 

Comments

  • Ellen M Goudsmit 2016 Feb 12 05:56 a.m.

    Postscript 2016. The errors noted were rejected as inaccuracies by the editors and thus my comment (under Haney et al) was not published as a letter or correction. Example, they refused to accept that a trial discussed used two sets of criteria, not just the one listed. And if they had checked the reference given for the London criteria, they would have known that it does not give a list of authors. I was not named, so the citation is factually incorrect. I submit that this attitude to factual errors is inconsistent with good science.

    PermalinkShare

  • Ellen M Goudsmit 2015 Jun 24 10:14 a.m.

    I’ve already noted some of the factual errors and misleading comments in this review online: http://annals.org/article.aspx?articleid=2322800

    Due to the word limit, I could not add that Haney et al named four individuals as authors of the London criteria for ME, despite the fact that their reference, the Westcare Report, did not [1]. The people listed in the review did not write the version published in the Westcare Report and this information has been in the public domain since 1994.

    I was also unable to point out that that Haney et al refer to clinical criteria (e.g., p. 834), when most of the case definitions they discussed were formulated for research.

    The omission of the new research criteria for classic ME is baffling as they have already been cited in the literature, most recently by Jason et al [2]. If people are going to make decisions about ME, or ME/CFS, they need to know what ME is. I suggest readers look online or access the original paper from 2009 [3].

    [1]. The UK Patient Organisations. “London Criteria”. In: Report from The National Task Force on Chronic Fatigue Syndrome (CFS), Post Viral Fatigue Syndrome (PVFS), Myalgic Encephalomyelitis (ME). Bristol: Westcare; 1994. Appendix B, Names, Definitions and Descriptions: p. 96-8. Available from: http://www.actionforme.org.uk/Resources/Action for ME/Documents/get-informed/national task force.pdf

    [2]. Jason, LA., Sunnquist, M., Brown, A and Reed, J. Defining essential features of myalgic encephalomyelitis and chronic fatigue syndrome. Journal of Human Behavior in the Social Environment, 2015, 25, 6, 657-674. Online 6th May. doi:10.1080/10911359.2015.1011256

    [3]. Goudsmit E, Shepherd C, Dancy CP, Howes S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33. Available from: http://shop.bps.org.uk/publications/publications-by-subject/health/health-psychology-update-vol-18-no-1-2009.html

    Alternatively see: http://www.foodsmatter.com/me_and_cfs/cfs_me_causes_general/articles/goudsmit-me-clinical entity-10-12.html

    Revised article (2014): http://www.axfordsabode.org.uk/me/mecrit2014.htm

  • This article was mentioned in a comment by Ellen M Goudsmit 2015 Jul 17 1:24 p.m.

    See:Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. [Ann Intern Med. 2015.]

  • Lily Chu 2016 Aug 24 04:39 a.m.

    In response to public comments, Dr. Smith and her colleagues have conducted sensitivity analyses on the data, assessing the impact of CBT and GET on various outcomes when only subjects fitting Oxford criteria are considered versus when subjects fitting non-Oxford case definitions (i.e. 1994 Fukuda) are considered. They concluded in an Addendum to the original report that:

    “Our sensitivity analysis would result in a downgrading of our strength of evidence on several outcomes which can be attributed to the decrease in power, dominance of one large trial, or lack of trials using criteria other than the Oxford (Sharpe, 1991) case definition for inclusion. Blatantly missing from this body of literature are trials evaluating effectiveness of interventions in the treatment of individuals meeting case definitions for ME or ME/CFS.”

    Almost all patients are diagnosed in the United States and most countries using the Fukuda criteria. The United Kingdom is the only region that uses the Oxford criteria on a regular basis. This means that clinicians need to be aware of low strength of evidence or the lack of evidence behind CBT and GET when considering this treatment for their ME/CFS patients.

    The full revised report may be read at: https://effectivehealthcare.ahrq.gov/ehc/products/586/2004/chronic-fatigue-report-160728.pdf

Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

Abstract:

BACKGROUND: 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.

PURPOSE: To review methods to diagnose ME/CFS in adults and identify research gaps and needs for future research.

DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; and reference lists.

STUDY SELECTION: English-language studies describing methods of diagnosis of ME/CFS and their accuracy.

DATA EXTRACTION: 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.

DATA SYNTHESIS: 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.

LIMITATIONS: Studies were heterogeneous and were limited by size, number, applicability, and methodological quality. Most methods were tested in highly selected patient populations.

CONCLUSION: 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.

 

Source: Haney E, Smith ME, McDonagh M, Pappas M, Daeges M, Wasson N, Nelson HD. Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Jun 16;162(12):834-40. doi: 10.7326/M15-0443. http://annals.org/aim/article/2322800/diagnostic-methods-myalgic-encephalomyelitis-chronic-fatigue-syndrome-systematic-review-national (Full article)

Comments

  • Ellen M Goudsmit 2015 Dec 02

    Sad to note today that the journal chose to publish letters, favouring opinion above the correction of factual errors. How can science progress if editors collude in the perpetuation of inaccuracies and myths? Who will know that there ARE research criteria for ME as described by Ramsay? That there are helpful alternatives to CBT and GET?

    Postscript 2016. The editors decided not to publish the comment as a letter in the journal as they rejected the view that there were factual errors. Thus while I was not a co-author of the criteria cited in the article, and I’m not named in the reference given, listing me as a co-author is not a ‘factual error’ in their eyes. Nor is the claim that a trial I discussed selected patients using two sets of criteria, not just the one referred to in the article. In my view, this failure to correct errors and misleading information is inconsistent with good science.

  • Ellen M Goudsmit 2015 Jul 17

    As someone who has studied myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) since the 1980s, I appreciate the work completed by The National Institutes of Health Pathways to Prevention Workshops on what is now known as ME/CFS. Unfortunately, some of the information in the two reviews is inaccurate, incomplete and misleading (1,2). For example, in the report on diagnostic methods, the reviewers included the London criteria for ME but gave details in the table based on a version written by a layperson, rather than the four individuals cited in their reference (3). Moreover, they did not consider the updated criteria for ME (4), although one of the authors had emailed the panel on two separate occasions during the consultation phase to alert them to their existence.

    The second review (2) encourages further research on subgroups and outcomes other than fatigue and function but did not identify one of the few controlled studies which had employed such a design (5). For instance, in the Appendix, Table 1 lists the programme evaluated by Goudsmit and colleagues under ‘counseling and behavioural therapies’, and describes the treatment as ‘counseling’. It also states that patients were selected using the Oxford criteria, that the duration of follow-up was six months and that the outcomes were function and fatigue.

    In fact, the trial evaluated a physician-led multi-component programme comprising medical care, information on the illness, diet and relaxation, as well as advice on activity management and some counselling (5). It was conducted in the naturalistic setting of an NHS hospital clinic, patients were diagnosed using criteria for post-viral fatigue syndrome as well as the Oxford criteria, and data were available for a number of symptoms including cognitive impairment, as well as other variables. Fatigue improved as noted in the review but the latter did not convey that 82% of the patients rated themselves as ‘better’, that 23% were well enough to be discharged at six months and that the improvements were maintained at 1 year. Given the missing details, the study’s rating as ‘poor’ is understandable.

    The reviewers concluded that “more definitive studies comparing participants meeting different case definitions, including ME… are needed to fill research gaps”. It was therefore disappointing that they did not recognise the positive aspects of a study that used a different case definition and assessed a range of symptoms, not just fatigue.

    1. Haney E, Smith MEB, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Diagnostic methods for myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162: 834-40. [PMID: 26075754] doi:10.7326/M15-0443
    2. Smith MEB, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162:841-
    3. [PMID: 26075755] doi:10.7326/M15-0114
    4. Dowsett E, Goudsmit E, Macintyre A, Shepherd C. London Criteria for myalgic encephalomyelitis. In: Report from The National Task Force on Chronic Fatigue Syndrome (CFS), Post Viral Fatigue Syndrome (PVFS), Myalgic Encephalomyelitis (ME). Westcare. 1994. 96-98. Available from: http://www.actionforme.org.uk/Resources/Action for ME/Documents/get-informed/national task force.pdf
    5. Goudsmit E, Shepherd C, Dancy CP, Howes S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33. Available from: http://shop.bps.org.uk/publications/publications-by-subject/health/health-psychology-update-vol-18-no-1-2009.html
    6. Goudsmit EM, Ho-Yen DO, Dancey CP. Learning to cope with chronic illness. Efficacy of a multi-component treatment for people with chronic fatigue syndrome. Patient Educ Couns. 2009;77:231–6. [PMID: 19576714 ] doi:10.1016/j.pec.2009.05.015

    Ellen M Goudsmit PhD FBPsS

    Comment also on Annals of Internal Medicine website under Haney et al.

 

Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues

Abstract:

There is an increasing interest in understanding the biological mechanism underpinning fibromyalgia (FM) and chronic fatigue syndrome (CFS). Despite the presence of mixed findings in this area, a few biological systems have been consistently involved, and the increasing number of studies in the field is encouraging. This chapter will focus on inflammatory and oxidative stress pathways and on the neuroendocrine system, which have been more commonly examined.

Chronic inflammation, together with raised levels of oxidative stress and mitochondrial dysfunction, has been increasingly associated with the manifestation of symptoms such as pain, fatigue, impaired memory, and depression, which largely characterise at least some patients suffering from CFS and FM.

Furthermore, the presence of blunted hypothalamic-pituitary-adrenal axis activity, with reduced cortisol secretion both at baseline and in response to stimulation tests, suggests a role for the hypothalamic-pituitary-adrenal axis and cortisol in the pathogenesis of these syndromes. However, to what extent these systems’ abnormalities could be considered as primary or secondary factors causing FM and CFS has yet to be clarified.

© 2015 S. Karger AG, Basel.

 

Source: Romano GF, Tomassi S, Russell A, Mondelli V, Pariante CM. Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues. Adv Psychosom Med. 2015;34:61-77. doi: 10.1159/000369085. Epub 2015 Mar 30. https://www.ncbi.nlm.nih.gov/pubmed/25832514

 

Gray matter volumes in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by profound fatigue with uncertain pathologic mechanism. Neuroimage may be an important key to unveil the central nervous system (CNS) mechanism in CFS. Although most of the studies found gray matter (GM) volumes reduced in some brain regions in CFS, there are many factors that could affect GM volumes in CFS, including chronic pain, stress, psychiatric disorder, physical activity, and insomnia, which may bias the results. In this paper, through reviewing recent literatures, we discussed these interferential factors, which overlap with the symptoms of CFS.

 

Source: Tang LW, Zheng H, Chen L, Zhou SY, Huang WJ, Li Y, Wu X. Gray matter volumes in patients with chronic fatigue syndrome. Evid Based Complement Alternat Med. 2015;2015:380615. doi: 10.1155/2015/380615. Epub 2015 Feb 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352504/ (Full article)

 

The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVES: The present paper aimed at reviewing literature data on the inflammatory hypothesis of mood spectrum, as well as the overlapping features with some chronic rheumatologic disorders, in particular fibromyalgia and chronic fatigue syndrome.

METHODS: A literature search was carried out for English papers published in the years 2000-2014, while using the following words: mood spectrum, depression, bipolar disorders, fibromyalgia, chronic fatigue syndrome, neurotransmitters, inflammation, neuroinflammation, cytokines.

RESULTS: Overlapping features were highlighted between mood spectrum, fibromyalgia and chronic fatigue syndrome suggesting common underlying mechanisms at pathophysiological level involving both central nervous and the immune systems.

CONCLUSIONS: Taken together, the literature would suggest that the borders between different medical domains should be reconsidered in the light of common processes linking them.

 

Source: Dell’Osso L, Bazzichi L, Baroni S, Falaschi V, Conversano C, Carmassi C, Marazziti D. The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome. Clin Exp Rheumatol. 2015 Jan-Feb;33(1 Suppl 88):S109-16. Epub 2015 Mar 18. https://www.ncbi.nlm.nih.gov/pubmed/25786052

 

Sleep Disturbances in Pediatric Chronic Fatigue Syndrome: A Review of Current Research

Abstract:

OBJECTIVE: Children and adolescents with chronic fatigue syndrome (CFS) frequently report sleep disturbances. However, little is known about the nature and severity of sleep disturbance and factors associated with sleep problems in pediatric CFS. The purpose of this review was to synthesize and critically appraise existing literature relating to sleep disturbances in pediatric CFS.

METHODS: Embase, CINAHL, PsychINFO, PubMed. and Medline databases were searched to retrieve all studies that included an assessment of sleep in pediatric CFS. Two reviewers independently assessed eligibility, extracted data, and systematically assessed reporting quality.

RESULTS: Six studies were included and these were mostly case-controlled designs. Findings varied across studies; however, most studies found that children and adolescents with CFS had significantly more sleep disturbances when compared to healthy controls. Significant methodological variations and limitations were apparent.

CONCLUSIONS: This review suggests that children and adolescents with CFS experience sleep disturbances. However, results need to be interpreted cautiously given the limited evidence available and its overall low quality. More research is required to elucidate the nature and extent of sleep disturbance in pediatric CFS and should focus on (1) identifying the specific types, causes, and severity of sleep disturbances; (2) the specific consequences of sleep disturbances; and (3) the most effective interventions for sleep problems in this population.

© 2015 American Academy of Sleep Medicine.

 

Source: Snodgrass K, Harvey A, Scheinberg A, Knight S. Sleep Disturbances in Pediatric Chronic Fatigue Syndrome: A Review of Current Research. J Clin Sleep Med. 2015 Jul 15;11(7):757-64. doi: 10.5664/jcsm.4854. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481060/ (Full article)