Assessing severity of illness and outcomes of treatment in children with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME): a systematic review of patient-reported outcome measures (PROMs)

Abstract:

Chronic Fatigue Syndrome or Myalgic Encephalomyelitis (CFS/ME) in children is characterized by persistent or recurrent debilitating fatigue which results in a substantial reduction in activity. There is a growing interest in the use of questionnaires, or patient-reported outcome measures (PROMs), to assess how patients function and feel in relation to their health and associated healthcare. However, guidance for PROM selection for children with CFS/ME does not exist.

We reviewed the quality and acceptability of PROMs used with children with CFS/ME to inform recommendations for practice. We conducted a systematic review of PROMs completed by children with CFS/ME. The quality of the evaluative studies and the reviewed measures were assessed against recommended criteria using an appraisal framework and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. We sought evidence of measurement (reliability, validity, responsiveness, interpretability, data quality) and practical properties (acceptability, relevance, feasibility).

Sixteen articles were included in the review, providing evidence of reliability and/or validity for 13 PROMs. Of these, five were child-specific (one health-related quality-of-life; four emotional well-being) and eight were not (four emotional well-being, three fatigue-specific; and one generic). All measures had limited evidence of measurement properties and no evidence of practical properties.

Recommendations for patient-reported assessment are difficult to make because of limited evidence of the quality and acceptability of PROMs for children with CFS/ME. The appraisal method highlighted significant methodological and quality issues which must be addressed in future research. There is a lack of qualitative evidence describing the outcomes of healthcare that are important to children with CFS/ME, and the relevance or appropriateness of available measures.

Future PROM development and evaluation in this group must seek to involve children collaboratively to ensure that the outcomes that children care about are assessed in an acceptable way.

© 2014 John Wiley & Sons Ltd.

 

Source: Haywood KL, Collin SM, Crawley E. Assessing severity of illness and outcomes of treatment in children with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME): a systematic review of patient-reported outcome measures (PROMs). Child Care Health Dev. 2014 Nov;40(6):806-24. doi: 10.1111/cch.12135. Epub 2014 Mar 24. https://www.ncbi.nlm.nih.gov/pubmed/24661148

 

Predictors of Post-Infectious Chronic Fatigue Syndrome in Adolescents

Abstract:

This study focused on identifying risk factors for adolescent post-infectious chronic fatigue syndrome (CFS), utilizing a prospective, nested case-control longitudinal design in which over 300 teenagers with Infectious Mononucleosis (IM) were identified through primary care sites and followed.

Baseline variables that were gathered several months following IM, included autonomic symptoms, days in bed since IM, perceived stress, stressful life events, family stress, difficulty functioning and attending school, family stress and psychiatric disorders. A number of variables were predictors of post-infectious CFS at 6 months; however, when autonomic symptoms were used as a control variable, only days spent in bed since mono was a significant predictor. Step-wise logistic regression findings indicated that baseline autonomic symptoms as well as days spent in bed since mono, which reflect the severity of illness, were the only significant predictors of those who met CFS criteria at 6 months.

 

Source: Jason LA, Katz BZ, Shiraishi Y, Mears CJ, Im Y, Taylor R. Predictors of Post-Infectious Chronic Fatigue Syndrome in Adolescents. Health Psychol Behav Med. 2014 Jan 1;2(1):41-51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956649/ (Full article)

 

α-1 antitrypsin and chronic fatigue syndrome: a case study from pathophysiology to clinical practice

Abstract:

SUMMARY

BACKGROUND: Several lines of evidence support the involvement of inflammatory and immunologic abnormalities in chronic fatigue syndrome (CFS). Since recent studies have shown that α-1 antitrypsin (AAT) possesses anti-inflammatory properties, the potential therapeutic effect of AAT treatment on CFS has been investigated.

CASE PRESENTATION: A 49-year-old woman diagnosed with CFS was treated with intravenous infusions of a human plasma-derived AAT concentrate (60 mg/kg body weight weekly for 8 consecutive weeks). The patient’s monocyte elastase, a regulator of inflammatory processes, was 1170 U/mg. At completion of treatment, improvement in maximal workload was observed (54.0-71.7% of predicted). Additionally, amelioration in working memory (scores: 83-94) and perceptual organization (scores: 75-83) were detected on the Wechsler Adult Intelligence Scale-III test. Monocyte elastase decreased to a normal range (<150 U/mg). Improvement in functional capacity allowed the patient to work in part-time employment.

CONCLUSION: These findings suggest a possible role for AAT in the treatment of CFS.

 

Source: Alegre J, Camprubí S, García-Quintana A. α-1 antitrypsin and chronic fatigue syndrome: a case study from pathophysiology to clinical practice.Pain Manag. 2013 Mar;3(2):119-22. doi: 10.2217/pmt.12.84. https://www.ncbi.nlm.nih.gov/pubmed/24645995

 

The role of hypocortisolism in chronic fatigue syndrome

Abstract:

BACKGROUND: There is accumulating evidence of hypothalamic-pituitary-adrenal (HPA) axis hypofunction in chronic fatigue syndrome (CFS). However, knowledge of this hypofunction has so far come exclusively from research in adulthood, and its clinical significance remains unclear. The objective of the current study was to assess the role of the HPA-axis in adolescent CFS and recovery from adolescent CFS.

METHOD: Before treatment, we compared the salivary cortisol awakening response of 108 diagnosed adolescent CFS patients with that of a reference group of 38 healthy peers. Salivary cortisol awakening response was measured again after 6 months of treatment in CFS patients.

RESULTS: Pre-treatment salivary cortisol levels were significantly lower in CFS-patients than in healthy controls. After treatment recovered patients had a significant rise in salivary cortisol output attaining normalization, whereas non-recovered patients improved slightly, but not significantly. The hypocortisolism found in CFS-patients was significantly correlated to the amount of sleep. Logistic regression analysis showed that an increase of one standard deviation in the difference between pre- and post-treatment salivary cortisol awakening response was associated with a 93% higher odds of recovery (adjusted OR 1.93 (1.18 to 3.17), p=0.009). Pre-treatment salivary cortisol did not predict recovery.

CONCLUSIONS: Hypocortisolism is associated with adolescent CFS. It is not pre-treatment cortisol but its change to normalization that is associated with treatment success. We suggest that this finding may have clinical implications regarding the adaptation of future treatment strategies.

Copyright © 2014 Elsevier Ltd. All rights reserved.

 

Source: Nijhof SL, Rutten JM, Uiterwaal CS, Bleijenberg G, Kimpen JL, Putte EM. The role of hypocortisolism in chronic fatigue syndrome. Psychoneuroendocrinology. 2014 Apr;42:199-206. doi: 10.1016/j.psyneuen.2014.01.017. Epub 2014 Jan 30. https://www.ncbi.nlm.nih.gov/pubmed/24636516

 

Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study

Abstract:

Chronic Fatigue Syndrome (CFS) represents a disabling condition characterized by persistent mental and physical fatigue, bodily discomfort and cognitive difficulties. To date the neural bases of CFS are poorly understood; however, mono-aminergic abnormalities, sleep-wake cycle changes and prefrontal dysfunctions are all thought to play a role in the development and maintenance of this condition.

Here we explored in a group of 62 CFS subjects the impact on fatigue levels of agomelatine, an antidepressant with agonist activity at melatonin receptors (MT1 and MT2) and antagonist activity at serotoninergic 2C receptors (5HT2C). To tease out the relative effects of MT-agonism and 5HT2C antagonism on fatigue, we compared agomelatine 50mg u.i.d. with sustained release melatonin 10mg u.i.d. in the first 12-week-long phase of the study, and then switched all melatonin-treated subjects to agomelatine in the second 12-week-long phase of the study.

Agomelatine treatment, but not melatonin, was associated with a significant reduction of perceived fatigue and an increase in perceived quality of life. Moreover the switch from melatonin to agomelatine was associated with a reduction of fatigue levels. Agomelatine was well tolerated by all enrolled subjects. Our data, albeit preliminary, suggest that agomelatine treatment could represent a novel useful approach to the clinical care of subjects with CFS.

Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

 

Source: Pardini M, Cordano C, Benassi F, Mattei C, Sassos D, Guida S, Serrati C, Primavera A, Amore M, Cocito L, Emberti Gialloreti L. Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study. Eur Neuropsychopharmacol. 2014 Jun;24(6):939-44. doi: 10.1016/j.euroneuro.2014.02.010. Epub 2014 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/24636462

 

Non-REM sleep EEG power distribution in fatigue and sleepiness

Abstract:

OBJECTIVES: The aim of this study is to contribute to the sleep-related differentiation between daytime fatigue and sleepiness.

METHODS: 135 subjects presenting with sleep apnea-hypopnea syndrome (SAHS, n=58) or chronic fatigue syndrome (CFS, n=52) with respective sleepiness or fatigue complaints and a control group (n=25) underwent polysomnography and psychometric assessments for fatigue, sleepiness, affective symptoms and perceived sleep quality. Sleep EEG spectral analysis for ultra slow, delta, theta, alpha, sigma and beta power bands was performed on frontal, central and occipital derivations.

RESULTS: Patient groups presented with impaired subjective sleep quality and higher affective symptom intensity. CFS patients presented with highest fatigue and SAHS patients with highest sleepiness levels. All groups showed similar total sleep time. Subject groups mainly differed in sleep efficiency, wake after sleep onset, duration of light sleep (N1, N2) and slow wave sleep, as well as in sleep fragmentation and respiratory disturbance. Relative non-REM sleep power spectra distributions suggest a pattern of power exchange in higher frequency bands at the expense of central ultra slow power in CFS patients during all non-REM stages. In SAHS patients, however, we found an opposite pattern at occipital sites during N1 and N2.

CONCLUSIONS: Slow wave activity presents as a crossroad of fatigue and sleepiness with, however, different spectral power band distributions during non-REM sleep. The homeostatic function of sleep might be compromised in CFS patients and could explain why, in contrast to sleepiness, fatigue does not resolve with sleep in these patients. The present findings thus contribute to the differentiation of both phenomena.

Copyright © 2014 Elsevier Inc. All rights reserved.

 

Source: Neu D, Mairesse O, Verbanck P, Linkowski P, Le Bon O. Non-REM sleep EEG power distribution in fatigue and sleepiness. J Psychosom Res. 2014 Apr;76(4):286-91. doi: 10.1016/j.jpsychores.2014.02.002. Epub 2014 Feb 17. https://www.ncbi.nlm.nih.gov/pubmed/24630178

 

Chronic fatigue syndrome is associated with the risk of fracture: a nationwide cohort study

Abstract:

PURPOSE: Chronic fatigue syndrome (CFS) is a complex disorder that is associated with unreasonable persistent fatigue. CFS has also been reported to be a possible risk factor for osteopathy. We propose that CFS might be associated with an increased risk of fracture.

METHODS: We used the National Health Insurance Research Database to conduct a prospective cohort study, identifying 3744 patients with a CFS diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 780.71) and 14 976 patients without CFS until 2006, with follow-up observed until the end of 2010.

RESULTS: The incidence rate of fracture was higher in the CFS cohort than in the non-CFS cohort (17.44 vs. 14.53 per 1000 person-year, respectively), with an adjusted hazard ratio of 1.14 (95% confidence interval = 1.00-1.30). The risks of fracture between CFS and non-CFS were shown without comorbidity for each would be elevated than with other comorbidities, particularly in osteoporosis. The patients without osteoporosis in the CFS cohort exhibited a 1.16-fold higher risk of fracture than did those in the non-CFS cohort.

CONCLUSIONS: We propose that CFS-related fracture might not be associated with osteoporosis. The mechanism for developing CFS-related fracture remains unclear; however, we recommend noticing the prevention of fracture for CFS patients before clarifying the aetiology of CFS-related fracture.

© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

 

Source: Chen CS, Lin WM, Yang TY, Chen HJ, Kuo CN, Kao CH. Chronic fatigue syndrome is associated with the risk of fracture: a nationwide cohort study. QJM. 2014 Aug;107(8):635-41. doi: 10.1093/qjmed/hcu037. Epub 2014 Mar 11. https://www.ncbi.nlm.nih.gov/pubmed/24619129

 

Impacts on chronic fatigue syndrome of qi deficiency syndrome and T cell subgroups in patients treated with acupuncture at selective time

Abstract:

OBJECTIVE: To verify the clinical efficacy on chronic fatigue syndrome of qi deficiency syndrome treated with acupuncture at selective time and explore the effect mechanism.

METHODS: Eighty patients were randomized into a selective-time-acupuncture group and an acupuncture group, 40 cases in each one. Qihai (CV 6), Guanyuan (CV 4), Hegu (LI 4), Taichong (LR 3), Sanyinjiao (SP 6) and Zusanli (ST 36) were selected in the two groups. In the selective-time-acupuncture group, acupuncture was used at 9:00am to 11:00am. In the acupuncture group, acupuncture was used at any time except in the range from 9:00am to 11:00am. No any manipulation was applied after the arrival of needling sensation. The treatment was given once every day, 10 day treatment made one session and two sessions of treatment were required. The fatigue scale was adopted to evaluate the efficacy before and after treatment in the patients of the two groups. The ratios among CD3+, CD4+ and CD8+ T cells in the peripheral blood were detected before ad b a after treatment.

RESULTS: In the acupuncture group, the total score of fatigue and the score of physical fatigue were reduced after treatment as compared with those before treatment (all P<0.05). In the selective-time -acupuncture group, the total score of fatigue, the s core of physical fatigue and the score of mental fatigue after treatment were reduced obviously as compared with those hefore treatment (all P<0. 01). The improvements in the scores of the selective-time-acupuncture group were superior to the acupuncture group (all P<0. 05). The ratio of CD3+ and CD8+ T cells was increased obviously after treatment in the two groups (all P<0. 05) and the ratio of CD4+ and CD8+ T cells was reduced obviously in the selective-time-acupuncture group (P<0. 05), which was better than that in the acupuncture group (all P<0.05). The total effective rate was 95.0% (38/40) in the selective-time-acupuncture group, which was better than 80.0% (32/40) in the acupuncture group (P<0.05).

CONCLUSION: The acupuncture therapy at selective time is effective in the treatment of chronic fatigue syndrome of qi deficiency syndrome, which is especially better at relieving mental fatigue. The effect of this therapy is achieved probably by improving the immune function via the regulation of the ratios among CD3+, CD4+ and CD8+ T cells.

 

Source: Ling JY, Shen L, Liu Q, Wang LY. Impacts on chronic fatigue syndrome of qi deficiency syndrome and T cell subgroups in patients treated with acupuncture at selective time. Zhongguo Zhen Jiu. 2013 Dec;33(12):1061-4. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/24617226

 

Overcoming the barriers to the diagnosis and management of chronic fatigue syndrome/ME in primary care: a meta synthesis of qualitative studies

Abstract:

BACKGROUND: The NICE guideline for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) emphasises the need for an early diagnosis in primary care with management tailored to patient needs. However, GPs can be reluctant to make a diagnosis and are unsure how to manage people with the condition.

METHODS: A meta synthesis of published qualitative studies was conducted, producing a multi-perspective description of barriers to the diagnosis and management of CFS/ME, and the ways that some health professionals have been able to overcome them. Analysis provided second-order interpretation of the original findings and developed third-order constructs to provide recommendations for the medical curriculum.

RESULTS: Twenty one qualitative studies were identified. The literature shows that for over 20 years health professionals have reported a limited understanding of CFS/ME. Working within the framework of the biomedical model has also led some GPs to be sceptical about the existence of the condition. GPs who provide a diagnosis tend to have a broader, multifactorial, model of the condition and more positive attitudes towards CFS/ME. These GPs collaborate with patients to reach agreement on symptom management, and use their therapeutic skills to promote self care.

CONCLUSIONS: In order to address barriers to the diagnosis and management of CFS/ME in primary care, the limitations of the biomedical model needs to be recognised. A more flexible bio-psychosocial approach is recommended where medical school training aims to equip practitioners with the skills needed to understand, support and manage patients and provide a pathway to refer for specialist input.

 

Source: Bayliss K, Goodall M, Chisholm A, Fordham B, Chew-Graham C, Riste L, Fisher L, Lovell K, Peters S, Wearden A. Overcoming the barriers to the diagnosis and management of chronic fatigue syndrome/ME in primary care: a meta synthesis of qualitative studies. BMC Fam Pract. 2014 Mar 7;15:44. doi: 10.1186/1471-2296-15-44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973969/ (Full article)

 

Malfunctioning of the autonomic nervous system in patients with chronic fatigue syndrome: a systematic literature review

Abstract:

INTRODUCTION: It is hypothesised that the autonomic nervous system responds differently to various stressors in patients with chronic fatigue syndrome (CFS) compared with healthy controls. The goal is to systematically review the scientific literature addressing the functioning of the autonomic nervous system in patients with CFS.

MATERIALS AND METHODS: All studies that were identified through electronic databases (PubMed and Web of Science) were screened for eligibility based on the selection criteria and assessed (two independent raters) for methodological quality using a methodological checklist for case-control studies.

RESULTS: Twenty-seven case-control studies were included. The methodological quality varied between 50% and 71·4%. Some studies showed different responses to head-up tilt and other autonomous testing.

CONCLUSION: Although comparison between the included case-control studies was difficult, we can conclude that there are differences in autonomous response between patients with CFS and healthy controls. The heart rate dynamic response during the head-up tilt test differs between patients with CFS and healthy controls, supporting the increased prevalence of postural orthostatic tachycardia syndrome. The autonomic response can be useful for the diagnosis of CFS.

© 2014 Stichting European Society for Clinical Investigation Journal Foundation.

 

Source: Van Cauwenbergh D, Nijs J, Kos D, Van Weijnen L, Struyf F, Meeus M. Malfunctioning of the autonomic nervous system in patients with chronic fatigue syndrome: a systematic literature review. Eur J Clin Invest. 2014 May;44(5):516-26. doi: 10.1111/eci.12256. https://www.ncbi.nlm.nih.gov/pubmed/24601948