Systematic review of randomized controlled trials for CFS/ME

Posted on 01/29/2020 by wames

Systematic review of randomized controlled trials for chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME), by Do-Young Kim, Jin-Seok Lee, Samuel-Young Park, Soo-Jin Kim & Chang-Gue Son in Journal of Translational Medicine vol 18, no. 7 (2020)

 

Research abstract:

Background:
Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date.

Methods:
RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes.

Results:
Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%).

Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C12U) and CoQ10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility.

Conclusions:
This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.

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The prevalence of pediatric ME/CFS in a community‑based sample

Posted on 01/28/2020 by wames

The prevalence of pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome  in a community‑based sample, by Leonard A Jason, Ben Z Katz, Madison Sunnquist, Chelsea Torres, Joseph Cotler & Shaun Bhatia in Child & Youth Care Forum, 23 January 2020 [doi.org/10.1007/s10566-019-09543-3]

 

Research abstract:

Background:
Most pediatric prevalence studies of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have been based upon data from tertiary care centers, a process known for systematic biases such as excluding youth of lower socioeconomic status and those less likely to have access to health care. In addition, most pediatric ME/CFS epidemiologic studies have not included a thorough medical and psychiatric examination. The purpose of this study was to determine the prevalence of pediatric ME/CFS from an ethnically and sociodemographically diverse community-based random sample.

Method:
A sample of 10,119 youth aged 5–17 from 5622 households in the Chicagoland area were screened. Following evaluations, a team of physicians made final diagnoses. Youth were given a diagnosis of ME/CFS if they met criteria for three selected case definitions. A probabilistic, multi-stage formula was used for final prevalence calculations.

Results:
The prevalence of pediatric ME/CFS was 0.75%, with a higher percentage being African American and Latino than Caucasian. Of the youth diagnosed with ME/CFS, less than 5% had been previously diagnosed with the illness.

Conclusions:
Many youth with the illness have not been previously diagnosed with ME/CFS. These findings point to the need for better ways to identify and diagnose youth with this illness.

Read full paper

Press release: Study finds many youth living with undiagnosed chronic fatigue syndrome

DePaul researchers unmask misunderstood chronic illness

Simon McGrath: Leonard Jason research finds that many young people have ME/CFS

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Health-related quality of life in patients with ME/CFS: an Australian cross-sectional study

Posted on 01/27/2020 by wames

Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study, by N Eaton-Fitch, SC Johnston, P Zalewski, D Staines & S Marshall-Gradisnik in Quality of Life Research, 22 January 2020

 

Research abstract:

Background:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and debilitating disorder associated with significant disruptions in daily life including. This study aimed to examine the impact of sociodemographic and patient symptom characteristics on health-related quality of life (HRQoL) of Australians with ME/CFS.

Methods:
Self-reported data collected from 480 individuals diagnosed with ME/CFS were obtained between August 2014 and August 2018. This cross-sectional survey analysed sociodemographic, symptom characteristics and HRQoL according to the 36-Item Health Survey (SF-36). Multivariate linear regression models were used to determine ME/CFS symptoms associated with eight domains of HRQoL.

Results:
Reported HRQoL was significantly impaired in ME/CFS patients across all domains compared with the general population. Scores were the lowest for physical role (4.11 ± 15.07) and energy/fatigue (13.54 ± 13.94). Associations with females, higher body mass index (BMI), employment status, cognitive difficulties, sensory disturbances and cardiovascular symptoms were observed in the physical functioning domain. Impaired pain domain scores were associated with high BMI, annual visits to their general practitioner, flu-like symptoms and fluctuations in body temperature. Reduced well-being scores were associated with smoking status, psychiatric comorbidity, cognitive difficulties, sleep disturbances and gastrointestinal difficulties.

Conclusion:
This study provides evidence that ME/CFS has a profound and negative impact on HRQoL in an Australian cohort.

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Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with CFS

Posted on 01/27/2020 by wames

Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome, by Scott J Fatt, Jessica E Beilharz, Michael Joubert, Chloe Wilson, Andrew R Lloyd, Uté Vollmer-Conna, Erin Cvejic in Clin Sleep Med. Vol 16, no. 1  Jan 2020 [https://doi.org/10.5664/jcsm.8114]

 

Research abstract:

Study objectives:
Physiological dearousal characterized by an increase in parasympathetic nervous system activity is important for good-quality sleep. Previous research shows that nocturnal parasympathetic activity (reflected by heart rate variability [HRV]) is diminished in individuals with chronic fatigue syndrome (CFS), suggesting hypervigilant sleep. This study investigated differences in nocturnal autonomic activity across sleep stages and explored the association of parasympathetic activity with sleep quality and self-reported physical and psychological wellbeing in individuals with CFS.

Methods:
Twenty-four patients with medically diagnosed CFS, and 24 matched healthy control individuals participated. Electroencephalography and HRV were recorded during sleep in participants’ homes using a minimally invasive ambulatory device. Questionnaires were used to measure self-reported wellbeing and sleep quality.

Results:
Sleep architecture in patients with CFS differed from that of control participants in slower sleep onset, more awakenings, and a larger proportion of time spent in slow-wave sleep (SWS). Linear mixed-model analyses controlling for age revealed that HRV reflecting parasympathetic activity (normalized high frequency power) was reduced in patients with CFS compared to control participants, particularly during deeper stages of sleep.

Poorer self-reported wellbeing and sleep quality was associated with reduced  during deeper sleep, but not during wake before sleep, rapid eye movement sleep, or with the proportion of time spent in SWS.

Conclusions:
Autonomic hypervigilance during the deeper, recuperative stages of sleep is associated with poor quality sleep and self-reported wellbeing. Causal links need to be confirmed but provide potential intervention opportunities for the core symptom of unrefreshing sleep in CFS.

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Development of a conceptual framework to underpin a health-related quality of life outcome measure in paediatric CFS/ME: prioritisation through card ranking

Posted on 01/23/2020 by wames

Development of a conceptual framework to underpin a health-related quality of life outcome measure in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME): prioritisation through card ranking, by Roxanne M. Parslow, Nina Anderson, Danielle Byrne, Kirstie L Haywood, Alison Shaw & Esther Crawley in Quality of Life Research (2020)

Research abstract:

Purpose:
Chronic fatigue syndrome (CFS)/myalgic encephalopathy (ME) is relatively common in children and is disabling at an important time in their development. This study aimed to develop a conceptual framework of paediatric CFS/ME using the patient-perspective to ensure that the content of a new outcome measure includes the outcomes most important to young people.

Methods:
We developed a child-centred interactive card ranking exercise that included health-related quality of life (HRQoL) outcomes identified from a previous review of the literature as well as qualitative work. Adolescents and their parents selected and ranked the outcomes most important to them and discussed each outcome in further detail. Adolescents were purposively sampled from a single specialist paediatric CFS/ME service in England. Interviews were audio recorded and transcribed verbatim, and thematic framework analysis was used to develop the final conceptual framework.

Results:
We interviewed 43 participants in which there are 21 adolescents, 12–17 years of age with mild–moderate CFS/ME and their parents (20 mothers and 2 fathers). ‘Symptoms’, ‘tiredness’, ‘payback and crashing’ and ‘activities and hobbies’ were ranked most important to improve by both children and parents. Children ranked ‘school’ higher than parents and parents ranked ‘mood’ higher than children.

A youth- specific CFS/ME conceptual framework of HRQoL was produced that included 4 outcome domains and 11 subdomains: sleep, tiredness, problems concentrating, individual symptoms, fluctuation and payback, daily and general activities, participation in school, leisure and social life, mood, anxiety and self-esteem.

Conclusions:
An interactive card ranking exercise worked well for adolescents aged 12–17 to elicit the most important outcomes to them and explore each domain in further detail. We developed a final conceptual framework of HRQoL that forms the basis of a new paediatric patient-reported outcome measure (PROM) in CFS/ME.

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Changes in circulating microRNA after recumbent isometric yoga practice by patients with ME/CFS

Posted on 01/22/2020 by wames

Changes in circulating microRNA after recumbent isometric yoga practice by patients with myalgic encephalomyelitis/chronic fatigue syndrome: an explorative pilot study, by Shu Takakura, Takakazu Oka & Nobuyuki Sudo in BioPsychoSocial Medicine vol 13, no. 29 (Dec 2019)

 

Research abstract:

Background:
Yoga is a representative mind-body therapy. Our previous studies have demonstrated that isometric yoga (i.e. yoga programs that we developed so individuals can practice yoga poses with a self-adjustable isometric load) reduces the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, the underlying mechanisms remain unclear. Several studies have suggested that the micro-ribonucleic acid (miRNA) expression of ME/CFS patients is different from that of healthy subjects. However, it has not to date been determined if the practice of isometric yoga can affect miRNA expression. Therefore, we sought to investigate if isometric yoga is associated with changes in the expression levels of serum miRNA of patients with ME/CFS.

Methods:
The study included nine patients with ME/CFS who failed to show satisfactory improvement after at least 6 months of treatment administered at our hospital. Patients practiced recumbent isometric yoga for 3 months; they met with a yoga instructor every 2 to 4 weeks and participated in daily in-home sessions. The effect of recumbent isometric yoga on fatigue was assessed by comparing pre- and post-intervention scores on the Japanese version of the 11-item Chalder fatigue scale (CFQ 11). Patient blood samples were drawn pre- and post-intervention, just prior to practicing recumbent isometric yoga with an instructor. The serum was used for miRNA array analysis with known human miRNAs.

Results:
The average CFQ 11 score decreased significantly (from 25.3 ± 5.5 to 17.0 ± 5.8, p <  0.0001) after practicing recumbent isometric yoga for 3 months. The miRNA microarray analysis revealed that four miRNAs were significantly upregulated, and 42 were downregulated after the intervention period.

Conclusions:
This explorative pilot study is the first to demonstrate changes in the serum levels of several miRNAs after regular practice of recumbent isometric yoga. These miRNAs might represent biomarkers for the fatigue-relieving effects of isometric yoga of patients with ME/CFS.

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The impact of a Structured Exercise Programme upon cognitive function in CFS patients

Posted on 01/21/2020 by wames

The impact of a structured exercise programme upon cognitive function in Chronic Fatigue Syndrome patients, by Paweł Zalewski, Sławomir Kujawski, Malwina Tudorowska, Karl Morten, Małgorzata Tafil-Klawe, Jacek J. Klawe, James Strong, Fernando Estevez-Lopez, Modra Murovska, Julia L. Newton and the European Network on ME/CFS (EUROMENE) in Brain Sciences Vol 10, #1, p 4, Dec 2019

 

Research abstract:

Background:
Cognitive function disturbance is a frequently described symptom of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). In this study, the effects of a structured exercise programme (SEP) upon cognitive function in ME/CFS patients was examined.

Methods:
Out of the 53 ME/CFS patients initiating SEP 34 (64%) completed the 16 week programme. Cognitive function was assessed using a computerized battery test consisting of a Simple Reaction Time (SRT) (repeated three times) and Choice Reaction Time (CRT) measurements, a Visual Attention Test (VAT) and a Delayed Matching to Sample (DMS) assessment.

Results:
Statistically significant improvement was noted in the third attempt to SRT in reaction time for correct answers, p=0.045, r=0.24. Moreover, significant improvement was noted in VAT reaction time, number of correct answers and errors committed, p=0.02, omega=0.03, p=0.007, r=0.34 and p=0.004, r=0.35, respectively. Non-significant changes were noted in other cognitive tests.

Conclusions:
A substantial number of participants were unwilling or unable to complete the exercise programme. ME/CFS patients able to complete the SEP showed improved visual attention both in terms of reaction time and correctness of responses and processing speed of simple visual stimuli.

Comment on Science4ME blog:

69 patients identified with Fukuda diagnosis, only 34 were able to complete C-PET and exercise program. No control group. A range of cognitive tests on the 34 showed some improvement in average performance after the activity program on a few of the tests relating to reaction time and accuracy, but the results were not significant when corrected for multiple comparisons. Despite this, the authors claim exercise is effective in improving cognitive function for some CFS patients.

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Low-dose naltrexone as a treatment for CFS

Posted on 01/21/2020 by wames

Low-dose naltrexone as a treatment for chronic fatigue syndrome, by Monica Jane Bolton, Bryan Paul Chapman, Harm Van Marwijk, in BMJ Case Reports, Vol 13, #1, January 6, 2020

 

Research abstract:

Naltrexone is used as an off-label treatment in low doses for several chronic immune-modulated disorders in many countries. Although only small-scale clinical trials have been performed, these suggest efficacy in several diseases including Crohn’s disease, fibromyalgia and Gulf War Illness. Despite numerous internet reports of response to low-dose naltrexone (LDN), no clinical trials exist in people with chronic fatigue syndrome.

This condition is characterised by chronic profound fatigue, postexertional malaise, pain and autonomic and neurocognitive disturbances.

This series of three case reports compiled by people with long-term ill-health due to chronic fatigue syndrome shows the range of responses they observed when taking LDN, from life changing to a reduction in some symptoms only. Treatment doses ranged from 4 to 12 mg.

Clinical trials may be warranted to explore the potential use of naltrexone in people with these debilitating illnesses which currently have no licensed treatments available.

From discussion:

The mechanism of action for naltrexone at low dose in this disease group is unknown. It is possibly due to rebound of endorphins following short-term suppression or to direct action suppressing inflammation induced by microglia.39–41 There have been no formal dosing studies of naltrexone at low dose in any disorder. Therefore, although the dose of 3–4.5 mg is established in clinical practice, some practitioners use 9 mg (Klimas, personal communication, 2017) or higher(42) in chronic fatigue syndrome. Causality and dosing need further study.

…Internet reports suggest side effects can be troublesome initially, particularly increased fatigue and headaches.44 Two double-blind, placebo-controlled studies in people with fibromyalgia found no difference in tolerability between LDN and placebo but an increased frequency of vivid dreams and headaches.27 28 Recent work in Norway has found that individuals may experience fewer side effects if starting naltrexone at 6 mg, even if the final dose taken is lower than this (personal communication Brian Haviland 2018).

Patients’ perspective

Case 2
After 25 years of living with the devastating effects of myalgic encephalomyelitis, I was struggling to cope with the limited options for symptom and pain management. Having had many bad reactions to medications, I was hesitant to try a medication that would affect my immune system so I started out at an extremely low dose and slowly increased dosage. While the dreaming was at times disturbing, the positive changes gave me a hope for improvement I had not had in many years. The subsequent improvements have led to a much higher quality of life and I would like to see this medication as an approved option for others in my situation.

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A cross-national comparison of ME & CFS at tertiary care settings from the US & Spain

Posted on 01/20/2020 by wames

A Cross-National Comparison of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome at Tertiary Care Settings from the US and Spain, by Shaun Bhatia, Nicole Olczyk, Leonard A. Jason, Jose Alegre, Judith Fuentes-Llanos, Jesus Castro-Marrero in American Journal of Social Sciences and Humanities Vol. 5, No. 1, 104-115, 2020

 

Highlights of this paper:

  • Cross-cultural comparative studies serve as exemplars highlighting the challenges associated with assessing differences in symptoms, functional limitations, and work disability when using variant case definitions for ME and CFS. 
  • Using a single case definition, differences were observed on an array of symptoms and functional impairments from individuals with ME and CFS recruited at tertiary centers from the US and Spain. 
  • Disparity in ME and CFS symptomatology and impairment between the US and Spain may be attributed to differences in disability policy, perception of ME and CFS, and access to specialist care.

Research abstract:

Cross-national comparative studies are useful for describing the unique characteristics of complex illnesses, and can reveal culture-specific traits of disease frequency/severity and healthcare. Though myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) are debilitating conditions found all over the world, few studies have examined their characteristics across different countries. T

he purpose of this study was to compare the levels of functional impairment and symptomatology in patients with ME and CFS at tertiary referral hospitals in the US and Spain.

Four hundred twenty potentially eligible participants (N = 235 from the US and N = 185 from Spain) who met the 1994 Fukuda et al. definition for CFS were enrolled. Both samples completed the medical outcomes study 36-item short-form health survey (SF-36) as a proxy for impairment, and the DePaul Symptom Questionnaire (DSQ) for patient symptomatology. ANCOVA and, where appropriate, MANCOVA tests were used to compare the SF-36 and DSQ items for illness characteristics between the samples.

The patients from Spain demonstrated significantly worse functioning than those from the US in the SF-36 domains of physical functioning, bodily pain, general health functioning, role emotional, and mental health functioning. The Spanish sample also was also more symptomatic across all the DSQ-items, most significantly in the pain and neuroendocrine domains.

These findings may be due to differences between the US and Spain regarding disability policy, perception of ME and CFS, and access to specialist care.

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Reduced heart rate variability predicts fatigue severity in individuals with CFS/ME

Posted on 01/16/2020 by wames

Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis, by Rosa María Escorihuela, Lluís Capdevila, Juan Ramos Castro, María Cleofé Zaragozà, Sara Maurel, José Alegre & Jesús Castro-Marrero in Journal of Translational Medicine volume 18, Article number: 4 (2020)

 

Abstract:

Background:
Heart rate variability (HRV) is an objective, non-invasive tool to assessing autonomic dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). People with CFS/ME tend to have lower HRV; however, in the literature there are only a few previous studies (most of them inconclusive) on their association with illness-related complaints. To address this issue, we assessed the value of different diurnal HRV parameters as potential biomarker in CFS/ME and also investigated the relationship between these HRV indices and self-reported symptoms in individuals with CFS/ME.

Methods:
In this case–control study, 45 female patients who met the 1994 CDC/Fukuda definition for CFS/ME and 25 age- and gender-matched healthy controls underwent HRV recording-resting state tests. The intervals between consecutive heartbeats (RR) were continuously recorded over three 5-min periods. Time- and frequency-domain analyses were applied to estimate HRV variables. Demographic and clinical features, and self-reported symptom measures were also recorded.

Results:
CFS/ME patients showed significantly higher scores in all symptom questionnaires (p < 0.001), decreased RR intervals (p < 0.01), and decreased HRV time- and frequency-domain parameters (p < 0.005), except for the LF/HF ratio than in the healthy controls. Overall, the correlation analysis reached significant associations between the questionnaires scores and HRV time- and frequency-domain measurements (p < 0.05). Furthermore, separate linear regression analyses showed significant relationships between self-reported fatigue symptoms and mean RR (p = 0.005), RMSSD (p = 0.0268) and HFnu indices (p = 0.0067) in CFS/ME patients, but not in healthy controls.

Conclusions:
Our findings suggest that ANS dysfunction presenting as increased sympathetic hyperactivity may contribute to fatigue severity in individuals with ME/CFS. Further studies comparing short- and long-term HRV recording and self-reported outcome measures with previous studies in larger CFS/ME cohorts are urgently warranted.

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