2013 – Page 5 – American ME and CFS Society

Effects of Time Frame on the Recall Reliability of CFS Symptoms

Abstract:

This study serves as an investigation of the reliability of symptom data as reported by individuals with chronic fatigue syndrome (CFS), across three recall time frames (the past week, the past month, and the past 6 months), and at two assessment points (with 1 week in between each assessment). Multilevel model analyses were used to determine the optimal recall time frame, in terms of test -retest reliability, for each of the Fukuda et al. (1994) case defining symptoms.

Results suggested that the optimal time frame for reliably reporting CFS symptoms was six months for sore throat, lymph node pain, muscle pain, post-exertional malaise, headaches, memory/concentration difficulties, and unrefreshing sleep. For joint pain, the optimal time frame was one month. Researchers who are interested in the assessment of CFS symptoms need to take recall time frame into account, especially when the intended goal is to standardize and improve the methods used to reliably and accurately diagnose this complex illness.

Source: Evans M, Jason LA. Effects of Time Frame on the Recall Reliability of CFS Symptoms. Eval Health Prof. 2015 Sep;38(3):367-81. doi: 10.1177/0163278713497014. Epub 2013 Sep 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874064/ (Full article)

Understanding medical students’ views of chronic fatigue syndrome: a qualitative study

Abstract:

Chronic fatigue syndrome receives little attention in the medical curriculum. This study explores UK medical students’ knowledge of and attitudes towards chronic fatigue syndrome. Semi-structured interviews (average length 22 minutes) were conducted with 21 participants (7 females and 14 males) in years 3 (n = 4), 4 (n = 11) and 5 (n = 6) of their studies. Inductive thematic analysis taking a realist perspective produced three themes: limited knowledge, influences on attitudes and training needs.

Students acquired their knowledge and attitudes largely from informal sources and expressed difficulty understanding chronic fatigue syndrome within a traditional biomedical framework. Incorporating teaching about chronic fatigue syndrome into the medical curriculum within the context of a biopsychosocial understanding of illness could encourage more positive attitudes towards chronic fatigue syndrome.

Source: Stenhoff AL, Sadreddini S, Peters S, Wearden A. Understanding medical students’ views of chronic fatigue syndrome: a qualitative study. J Health Psychol. 2015 Feb;20(2):198-209. doi: 10.1177/1359105313501534. Epub 2013 Sep 20. https://www.ncbi.nlm.nih.gov/pubmed/24058124

Differing leukocyte gene expression profiles associated with fatigue in patients with prostate cancer versus chronic fatigue syndrome

Abstract:

BACKGROUND: Androgen deprivation therapy (ADT) often worsens fatigue in patients with prostate cancer, producing symptoms similar to chronic fatigue syndrome (CFS). Comparing expression (mRNA) of many fatigue-related genes in patients with ADT-treated prostate cancer versus with CFS versus healthy controls, and correlating mRNA with fatigue severity may clarify the differing pathways underlying fatigue in these conditions.

METHODS: Quantitative real-time PCR was performed on leukocytes from 30 fatigued, ADT-treated prostate cancer patients (PCF), 39 patients with CFS and 22 controls aged 40-79, together with ratings of fatigue and pain severity. 46 genes from these pathways were included: (1) adrenergic/monoamine/neuropeptides, (2) immune, (3) metabolite-detecting, (4) mitochondrial/energy, (5) transcription factors.

RESULTS: PCF patients showed higher expression than controls or CFS of 2 immune transcription genes (NR3C1 and TLR4), chemokine CXCR4, and mitochondrial gene SOD2. They showed lower expression of 2 vasodilation-related genes (ADRB2 and VIPR2), 2 cytokines (TNF and LTA), and 2 metabolite-detecting receptors (ASIC3 and P2RX7). CFS patients showed higher P2RX7 and lower HSPA2 versus controls and PCF. Correlations with fatigue severity were similar in PCF and CFS for only DBI, the GABA-A receptor modulator (r=-0.50, p<0.005 and r=-0.34, p<0.05). Purinergic P2RY1 was correlated only with PCF fatigue and pain severity (r=+0.43 and +0.59, p=0.025 and p=0.001).

CONCLUSIONS: PCF patients differed from controls and CFS in mean expression of 10 genes from all 5 pathways. Correlations with fatigue severity implicated DBI for both patient groups and P2RY1 for PCF only. These pathways may provide new targets for interventions to reduce fatigue.

Source: Light KC, Agarwal N, Iacob E, White AT, Kinney AY, VanHaitsma TA, Aizad H, Hughen RW, Bateman L, Light AR. Differing leukocyte gene expression profiles associated with fatigue in patients with prostate cancer versus chronic fatigue syndrome. Psychoneuroendocrinology. 2013 Dec;38(12):2983-95. doi: 10.1016/j.psyneuen.2013.08.008. Epub 2013 Sep 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848711/ (Full article)

Exercise and sleep deprivation do not change cytokine expression levels in patients with chronic fatigue syndrome

Abstract:

A major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysregulation, thought to be reflected in upregulated proinflammatory cytokines leading to the symptoms that are characteristic of this illness. Because the symptoms worsen with physical exertion or sleep loss, we hypothesized that we could use these stressors to magnify the underlying potential pathogenic abnormalities in the cytokine systems of people with CFS.

We conducted repeat blood sampling for cytokine levels from healthy subjects and CFS patients during both postexercise and total sleep deprivation nights and assayed for protein levels in the blood samples, mRNA activity in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. We found that these environmental manipulations did not produce clinically significant upregulation of proinflammatory cytokines. These data do not support an important role of immune dysregulation in the genesis of stress-induced worsening of CFS.

Source: Nakamura T, Schwander S, Donnelly R, Cook DB, Ortega F, Togo F, Yamamoto Y, Cherniack NS, Klapholz M, Rapoport D, Natelson BH. Exercise and sleep deprivation do not change cytokine expression levels in patients with chronic fatigue syndrome. Clin Vaccine Immunol. 2013 Nov;20(11):1736-42. doi: 10.1128/CVI.00527-13. Epub 2013 Sep 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837776/ (Full article)

The protocol for a randomised controlled trial comparing intermittent and graded exercise to usual care for chronic fatigue syndrome patients

Abstract:

BACKGROUND: Chronic Fatigue Syndrome is a debilitating disorder with an unknown aetiology but suspected multifactorial origins. Common “triggers” include severe viral infections and emotional stress. Recent studies have also found evidence of immune dysfunction and elevated inflammatory cytokines in CFS patients, but there has been considerable variation in the outcome measures and magnitude of these studies. Currently, there is no cure for CFS but treatments include rest, specialist medical care, cognitive behavioural therapy, and graded (self-paced) exercise. To date, several studies have examined the efficacy of graded exercise with or without Cognitive Behavioural Therapy, with some success for patients. However, improvements in functional capacity have not necessarily correlated with improvements in immune function, fatigue or other symptoms. This 12-week pilot trial compares graded and intermittent exercise to normal care, measuring physiological outcomes, fatigue levels, immune function and wellness.

METHODS/DESIGN: 90 patients aged between 16 to 60 years, who meet the diagnostic criteria for CFS and have been diagnosed by their medical practitioner, will be randomly recruited into groups consisting of Intermittent exercise, Graded exercise and usual care (Control). The outcomes will be measured pre-study (Week 0) and post-study (Week 13). Primary outcomes are VO2peak, anaerobic threshold, peak power, levels of fatigue, immune cell (CD3+CD4+, CD3+CD8+, CD19+, CD 16+CD56+) concentrations and activation. Secondary outcomes include onset of secondary CFS symptoms (e.g. fever, swollen lymph nodes), wellness, mood and sleep patterns. Primary analysis will be based on intention to treat using logistic regression models to compare treatments. Quantitative data will be analysed using repeated measures ANOVA with a linear model, and Cohen’s effect size. Qualitative data such as participants’ responses (e.g. changes in mood and other reactions) following the exercise modalities will be read and sections demarcated. A code will be applied to each segment. A prevalence of codes will be considered thematically.

DISCUSSION: The results of the trial will provide information about the efficacy of intermittent and graded exercise compared to usual care (rest and lifestyle recommendations), contributing to the evidence for best-practice CFS management.

TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12612001241820.

Source: Broadbent S, Coutts R. The protocol for a randomised controlled trial comparing intermittent and graded exercise to usual care for chronic fatigue syndrome patients. BMC Sports Sci Med Rehabil. 2013 Aug 30;5(1):16. doi: 10.1186/2052-1847-5-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848853/ (Full article)

Acupuncture for chronic fatigue syndrome: a randomized, sham-controlled trial with single-blinded design

Abstract:

CONTEXT: Given that the etiology of chronic fatigue syndrome (CFS) is believed to be multidimensional, interventions generally have been nonspecific and typically produce only mild to moderate effects. In medical practice, treatment for CFS remains largely symptomatic. Preliminary evidence of the efficacy of acupuncture for CFS is available, but the field has lacked high-quality trials.

OBJECTIVE: The research team conducted the study to determine the efficacy of acupuncture for CFS.

DESIGN: A two-arm, randomized, controlled, singleblinded design was adopted.

SETTING: The study took place in a teaching laboratory at the School of Chinese Medicine at the University of Hong Kong, Hong Kong, China.

PARTICIPANTS: Recruited through press publicity in Hong Kong, 127 individuals–40 men and 87 women–participated in the study. Intervention Through careful implementation of sham acupuncture in the control group (CG), the study blinded all participants with regard to their experimental or control status. The treatment regime was 2 sessions/wk for 4 consecutive wk.

OUTCOME MEASURES: Measures of fatigue (Chalder’s Fatigue Scale), health-related quality of life (SF-12), and general mental health (GH Q-12) were taken at baseline and upon completion of treatment.

RESULTS: Ninety-nine participants completed the interventions, with 50 and 49 participants in the experimental group (EG) and CG respectively. Repeated measures ANOVA revealed a significant decrease in physical (F(1,93) = 4.327; P = .040) and mental fatigue (F(1,96) = 10.451; P = .002) and improvement in the physical component score of SF-12 (F(1,93) = 4.774; P = .031). Considerable effects with Cohen’s d were observed in the sham-control group: 0.92, 0.78, and 0.38 for the three scores, respectively. These positive effects could have included some therapeutic effects due to pressure on the acupuncture points from the sham needles in addition to normal placebo effects. The EG showed moderate net effect sizes with Cohen’s d: 0.52, 0.63, and 0.54 for the three outcome measures, respectively.

CONCLUSION: Despite considerable positive effects for the CG, the EG demonstrated significant net-effect sizes at a moderate magnitude in physical and mental fatigue and in the physical component of health-related quality of life. The impacts on general mental health outcomes appeared to be smaller.

Source: Ng SM, Yiu YM. Acupuncture for chronic fatigue syndrome: a randomized, sham-controlled trial with single-blinded design. Altern Ther Health Med. 2013 Jul-Aug;19(4):21-6. https://www.ncbi.nlm.nih.gov/pubmed/23981369

Differences in physical functioning between relatively active and passive patients with Chronic Fatigue Syndrome

Abstract:

OBJECTIVE: According to the Cognitive behavioral therapy (CBT) protocol for patients with Chronic Fatigue Syndrome (CFS), therapists are advised to categorize patients in relatively active and passive patients. However, evidence to support the differences in physical functioning between these subgroups is limited. Using the baseline data from a multicentre randomized controlled trial (FatiGo), the differences in actual and perceived physical functioning between active and passive patients with CFS were evaluated.

METHODS: Sixty patients, who received CBT during the FatiGo trial were included. Based on the expert opinion and using the definitions of subgroups defined in the CBT protocols, the therapist categorized the patient. Data from an activity monitor was used to calculate actual physical functioning, physical activity, daily uptime, activity fluctuations and duration of rest during daily life. Perceived physical functioning was assessed by measuring physical activity, physical functioning and functional impairment with the Checklist Individual Strength, Short Form-36 and Sickness-Impact Profile 8.

RESULTS: Relatively active patients have a significantly higher daily uptime and show significantly less fluctuations in activities between days. Passive patients experience a significantly lower level of physical functioning and feel more functionally impaired in their mobility. However, no significant differences were found in the other actual or perceived physical functioning indices.

CONCLUSIONS: A clear difference in actual and perceived physical functioning between relatively active and passive patients with CFS as judged by their therapists could not be found. Future research is needed to form a consensus on how to categorize subgroups of patients with CFS.

Source: Vos-Vromans DC, Huijnen IP, Köke AJ, Seelen HA, Knottnerus JA, Smeets RJ. Differences in physical functioning between relatively active and passive patients with Chronic Fatigue Syndrome. J Psychosom Res. 2013 Sep;75(3):249-54. doi: 10.1016/j.jpsychores.2013.05.001. Epub 2013 Jun 2. https://www.ncbi.nlm.nih.gov/pubmed/23972414

Does neuropsychological test performance predict outcome of cognitive behavior therapy for Chronic Fatigue Syndrome and what is the role of underperformance?

Abstract:

OBJECTIVE: A subgroup of patients with Chronic Fatigue Syndrome (CFS) has cognitive impairments, reflected by deviant neuropsychological test performance. However, abnormal test scores can also be caused by suboptimal effort. We hypothesized that worse neuropsychological test performance and underperformance were related to each other and to a smaller reduction in fatigue, functional impairments, physical limitations and higher dropout rates following cognitive behavior therapy (CBT) for CFS.

METHODS: Data were drawn from a previous trial, in which CFS patients were randomized to two conditions; 1) guided self-instruction and additional CBT (n=84) or 2) waiting period followed by regular CBT for CFS (n=85). Underperformance was assessed using the Amsterdam Short Term Memory Test (<84). To test neuropsychological test performance, the Symbol Digit Modalities Task, a simple reaction time task and a choice reaction time task were used. Interaction effects were determined between underperformance and neuropsychological test performance on therapy outcomes.

RESULTS: Underperformance was associated to worse neuropsychological test performance, but there were no significant interaction effects of these two factors by therapy on fatigue severity, functional impairments and physical limitations, but there was a significant main effect of underperformance on functional impairments, physical limitations and dropout rates.

CONCLUSION: Underperformance or neuropsychological test performance was not related to the change in fatigue, functional impairments, and physical limitations following CBT for CFS. However, underperforming patients did drop out more often. Therapists should pay attention to beliefs and behavioral or environmental factors that might maintain underperformance and increase the risk of dropout.

Comment in

Source: Goedendorp MM, van der Werf SP, Bleijenberg G, Tummers M, Knoop H. Does neuropsychological test performance predict outcome of cognitive behavior therapy for Chronic Fatigue Syndrome and what is the role of underperformance? J Psychosom Res. 2013 Sep;75(3):242-8. doi: 10.1016/j.jpsychores.2013.07.011. Epub 2013 Jul 26. https://www.ncbi.nlm.nih.gov/pubmed/23972413

The process of cognitive behaviour therapy for chronic fatigue syndrome: which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue?

Abstract:

OBJECTIVE: Cognitive behaviour therapy (CBT) can significantly reduce fatigue in chronic fatigue syndrome (CFS), but little is known about the process of change taking place during CBT. Based on a recent treatment model (Wiborg et al. J Psych Res 2012), we examined how (changes in) cognitions and behaviour are related to the decrease in fatigue.

METHODS: We included 183 patients meeting the US Centers for Disease Control criteria for CFS, aged 18 to 65 years, starting CBT. We measured fatigue and possible process variables before treatment; after 6, 12 and 18 weeks; and after treatment. Possible process variables were sense of control over fatigue, focusing on symptoms, self-reported physical functioning, perceived physical activity and objective (actigraphic) physical activity. We built multiple regression models, explaining levels of fatigue during therapy by (changes in) proposed process variables.

RESULTS: We observed large individual variation in the patterns of change in fatigue and process variables during CBT for CFS. Increases in the sense of control over fatigue, perceived activity and self-reported physical functioning, and decreases in focusing on symptoms explained 20 to 46% of the variance in fatigue. An increase in objective activity was not a process variable.

CONCLUSION: A change in cognitive factors seems to be related to the decrease in fatigue during CBT for CFS. The pattern of change varies considerably between patients, but changes in process variables and fatigue occur mostly in the same period.

Source: Heins MJ, Knoop H, Burk WJ, Bleijenberg G. The process of cognitive behaviour therapy for chronic fatigue syndrome: which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue? J Psychosom Res. 2013 Sep;75(3):235-41. doi: 10.1016/j.jpsychores.2013.06.034. Epub 2013 Jul 19. http://www.jpsychores.com/article/S0022-3999(13)00266-3/fulltext (Full article)

Response to Derek Enlander

Sir,

Derek Enlander’s comments refer to Table 4 in our paper1 which describes the association of baseline characteristics with change in physical function at follow-up. It does not describe the outcome which can be found in Table 2. This shows an improvement in fatigue (−6.8; 95% CI −7.4 to −6.2; P < 0.001), physical function (4.4, 95% CI 3.0 to 5.8; P < 0.001), anxiety, depression and pain at follow-up.

In addition, as we state in the methods, the scores from the different inventories were re-scaled, so that a regression coefficient of 1 represents a 10% change in the score. Hence, the coefficient of −0.47 (95% CI −0.58 to −0.36) for the mean change in (re-scaled) SF-36 physical function per unit (re-scaled) Chalder Fatigue score at baseline, indicates that each 10% increment in baseline Chalder Fatigue (i.e. 3.3 points on the original 0 to 33 scale) is associated with a mean change of −4.7 points (95% CI −5.8 to −3.6 points) on the original 0 to 100 SF-36 scale at follow-up. Similarly, the coefficient of 0.81 (95% CI 0.75 to 0.87) for the mean change in (re-scaled) SF-36 physical function per unit (re-scaled) SF-36 score at baseline, indicates that each 10% increment in baseline physical function (i.e. 10 points on the original 0 to 100 SF-36 scale) is associated with a mean change of 8.1 points (95% CI 7.5 to 8.7 points) on the original 0 to 100 SF-36 scale at follow-up.

In summary, our paper shows that patients showed improvements in fatigue, physical disability, anxiety, depression and pain. Table 4 referred to by Derek Enlander show that worse fatigue and disability at assessment predict a worse outcome for disability at follow-up.

You can read the rest of this comment here: https://academic.oup.com/qjmed/article/107/3/247/1569245/Response-to-Derek-Enlander

Comment on

RE: ‘Treatment outcome in adults with chronic fatigue syndrome: a prospective study. [QJM. 2014]

Source: Crawley E. Response to Derek Enlander. QJM. 2014 Mar;107(3):247. doi: 10.1093/qjmed/hct171. Epub 2013 Aug 22. https://academic.oup.com/qjmed/article/107/3/247/1569245/Response-to-Derek-Enlander (Full article)