Category: Methodology

The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions. Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients. Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.

Source: Jason LA, Holtzman CS, Sunnquist M, Cotler J. The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome. J Health Psychol. 2018 Oct 24:1359105318805819. doi: 10.1177/1359105318805819. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30354489

Defining the minimally clinically important difference of the SF-36 physical function subscale for paediatric CFS/ME: triangulation using three different methods

Abstract:

BACKGROUND: Defining the minimally clinically important difference (MCID) is important for the design and analysis of clinical trials and ensures that findings are clinically meaningful. Studies in adult populations have investigated the MCID of The Short Form 36 physical function sub-scale (SF-36-PFS). However, to our knowledge no studies have defined the MCID of the SF-36-PFS in a paediatric population. We aimed to triangulate findings from distribution, anchor and qualitative methods to identify the MCID of the SF-36-PFS for children and adolescents with CFS/ME.

METHODS: Quantitative methods: We analysed routinely-collected data from a specialist paediatric CFS/ME service in South-West England using: 1) the anchor method, based on Clinical Global Impression (CGI) outcomes at 6 months’ follow-up; 2) the distribution method, based on the standard deviation of baseline SF-36-PFS scores. Qualitative methods: Young people (aged 12-17 years) and parents were asked to complete the SF-36-PFS, marking each question twice: once for where they would currently rate themselves/their child and a second time to show what they felt would be the smallest amount of change for them/their child to feel treatment had made a difference. Semi-structured interviews were designed to explore what factors were deemed important to patients and to what extent an improvement was considered satisfactory. We thematically analysed qualitative interviews from 21 children and their parents.

RESULTS: Quantitative results: Six-month follow-up data were available for 198 children with a mean age of 14 years. Most were female (74%, 146/198) and 95% gave their ethnicity as “White British”. Half the standard deviation of the baseline SF-36-PFS scores was 11.0. “A little better” on the CGI equated to a mean difference on the SF-36-PFS from baseline to 6-month follow-up of 9.0. Qualitative results: Twenty-one children with CFS/ME participated: 16 females (76.2%) with a mean age of 14.4 years. Twenty mothers and two fathers were also interviewed. The median minimal improvement in the SF-36-PFS was 10. Participants indicated that small changes in physical function can lead to important improvements in valued social and family function. Patients and parents were positive about improvement even in the presence of persisting symptoms. Triangulation: The MCID based on the mean score from the three methods was 10.

CONCLUSIONS: Converging evidence indicates future studies in paediatric CFS/ME should use an MCID of 10 on the SF-36-PFS.

Source: Brigden A, Parslow RM, Gaunt D, Collin SM, Jones A, Crawley E. Defining the minimally clinically important difference of the SF-36 physical function subscale for paediatric CFS/ME: triangulation using three different methods. Health Qual Life Outcomes. 2018 Oct 19;16(1):202. doi: 10.1186/s12955-018-1028-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194701/ (Full article)

Chronic fatigue syndrome and quality of life

Abstract:

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a challenging long-term condition (LTC) with complex and fluctuating symptoms. It is heterogeneous in presentation without diagnostic indicators; therefore, in health care encounters, insight must be gained from the patient’s perspective. One indicator of impact can be gained by measuring quality of life (QoL). By applying a patient-reported outcome measure (PROM), professionals can gather insights with direct relevance to the patient questioned. Such a tool can act therapeutically tool to promote holistic and individualized professional interventions and interval measurement can inform commissioning of specialist services.

Standard practice appears not fully to capture the experience of CFS, while a search of the literature turned up QoL patient-reported outcome tools, but failed to reveal a CFS/ME-specific measure. The author explores a valid and reliable PROM that can monitor change and evaluate the UK National Institute of Clinical Excellence rehabilitation program, as delivered by specialist National Health Service units. An alternative, the World Health Organization’s quality-of life instrument (WHOQoL)-Bref26, is reviewed for relevance to the condition, measuring treatment outcomes and the wider debate of measuring QoL in LTCs.

Source: Roberts D. Chronic fatigue syndrome and quality of life. Patient Relat Outcome Meas. 2018 Aug 1;9:253-262. doi: 10.2147/PROM.S155642. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078083/ (Full article)

Operationalizing Substantial Reduction in Functioning Among Young Adults with Chronic Fatigue Syndrome

Abstract:

PURPOSE: Chronic fatigue syndrome and myalgic encephalomyelitis are fatiguing illnesses that often result in long-term impairment in daily functioning. In reviewing case definitions, Thrope et al. (Fatigue 4(3):175-188, 2016) noted that the vast majority of case definitions used to describe these illnesses list a “substantial reduction” in activities as a required feature for diagnosis. However, there is no consensus on how to best operationalize the criterion of substantial reduction.

METHOD: The present study used a series of receiver operating curve (ROC) analyses to explore the use of the Medical Outcomes Study Short-Form-36 Health Survey (SF-36), designed by Ware and Shelbourne for operationalizing the substantial reduction criterion in a young adult population (18-29 years old). We compared the sensitivity and specificity of various cutoff scores for the SF-36 subscales and assessed their usefulness in discriminating between a group of young adults with a known diagnosis of chronic fatigue syndrome or myalgic encephalomyelitis (n = 98) versus those without that diagnosis (n = 272).

RESULTS: The four top performing subscales and their associated cutoffs were determined: Physical Functioning ≤ 80, General Health ≤ 47, Role Physical ≤ 25, and Social Functioning ≤ 50. Used in combination, these four cutoff scores were shown to reliably discriminate between the patients and controls in our sample of young adults.

CONCLUSION: The implications of these findings for employing the substantial reduction criterion in both clinical and research settings are discussed.

Source: Gleason KD, Stoothoff J, McClellan D, McManimen S, Thorpe T, Katz BZ, Jason LA.  Operationalizing Substantial Reduction in Functioning Among Young Adults with Chronic Fatigue Syndrome. Int J Behav Med. 2018 Jun 5. doi: 10.1007/s12529-018-9732-1. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29872989

Psychometric properties and factor structure of a shortened version of the Cognitive Behavioural Responses Questionnaire (CBRQ)

Abstract:

OBJECTIVE: Symptoms of chronic fatigue syndrome (CFS) can be perpetuated by cognitive and behavioural responses to the illness. We aimed to determine the factor structure, reliability and validity of the 40-item Cognitive Behavioural Responses Questionnaire (CBRQ) using data gathered from CFS patients. We also propose a short version CBRQ for greater clinical utility.

METHODS: The psychometric analysis was performed on datasets drawn from two sources: a clinical service for CFS patients (N=576) and the PACE randomised controlled trial (RCT) of CFS treatments (N=640). An exploratory factor analysis (EFA) was conducted on the clinical dataset and a confirmatory factor analysis (CFA) was performed on the RCT dataset. Using these results, a short version of the CBRQ was proposed. Reliability, metric invariance across age and sex, and construct validity were assessed.

RESULTS: The EFA (relative Chi-square 2.52; RMSEA 0.051; CFI 0.964; TLI 0.942) and CFA (relative Chi-square 4.029; RMSEA 0.069; CFI 0.901; TLI 0.892) revealed that eight factor models fitted the data well. Satisfactory Cronbach’s alpha values were obtained for the final subscales (≥0.76). The shortened CBRQ was obtained by removing items that cross-loaded onto other factors and/or were the lowest loading items in each factor. The shortened CBRQ contained 18 items which had high factor loadings, good face-validity and reliability (Cronbach’s alpha 0.67-0.88).

CONCLUSIONS: The CBRQ, long and short versions, are reliable and valid scales for measuring cognitive and behavioural responses of patients with CFS. Further research is needed to examine the utility of the CBRQ in other long-term conditions.

Source: Ryan EG, Vitoratou S, Goldsmith KA, Chalder T. Psychometric properties and factor structure of a shortened version of the Cognitive Behavioural Responses Questionnaire (CBRQ). Psychosom Med. 2017 Oct 10. doi: 10.1097/PSY.0000000000000536. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29023262

Defining and measuring recovery from myalgic encephalomyelitis and chronic fatigue syndrome: the physician perspective

Abstract:

Purpose: To inform an operationalised definition of recovery from myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) for research and practice. Without a consensus on defining and measuring recovery, there will continue to be controversy amongst researchers, clinicians, and patients when interpreting treatment outcomes.

Method: This study explores physicians’ views on recovery from ME and CFS. We conducted semi-structured interviews with 10 physician participants who are experts in the ME and CFS field. Our deductive thematic analysis, using a realist perspective, provided a framework for differentiating recovery and significant improvement.

Results: Physicians conceptualised recovery as complete symptom remission and a return to premorbid functioning (adjusted for with age), whereas they viewed significant improvement as a substantial reduction in symptoms with considerable functional gains, where patients may operate in daily life but still must cope or be treated.

Conclusions: Our findings provide recommendations and approaches for measuring: daily functioning, symptomatology, quality of life, and physical functioning.

  • Implications for rehabilitation
  • Physicians viewed recovery as complete symptom remission and a return to premorbid functioning (adjusted for with age).
  • Recovery from myalgic encephalomyelitis and chronic fatigue syndrome should be viewed as multidimensional, considering patients’ daily life, psychosocial functioning, and overall physical functioning.
  • These findings can improve practitioner-client interactions, as they provide recommendations for measuring recovery in research and practice.

Source: Andrew R. Devendorf, Carly T. Jackson, Madison Sunnquist & Leonard A. Jason. Defining and measuring recovery from myalgic encephalomyelitis and chronic fatigue syndrome: the physician perspective. Disability and Rehabilitation. Published online: 05 Oct 2017

A robust, single-injection method for targeted, broad-spectrum plasma metabolomics

Abstract:

BACKGROUND: Metabolomics is a powerful emerging technology for studying the systems biology and chemistry of health and disease. Current targeted methods are often limited by the number of analytes that can be measured, and/or require multiple injections.

METHODS: We developed a single-injection, targeted broad-spectrum plasma metabolomic method on a SCIEX Qtrap 5500 LC-ESI-MS/MS platform. Analytical validation was conducted for the reproducibility, linearity, carryover and blood collection tube effects. The method was also clinically validated for its potential utility in the diagnosis of chronic fatigue syndrome (CFS) using a cohort of 22 males CFS and 18 age- and sex-matched controls.

RESULTS: Optimization of LC conditions and MS/MS parameters enabled the measurement of 610 key metabolites from 63 biochemical pathways and 95 stable isotope standards in a 45-minute HILIC method using a single injection without sacrificing sensitivity. The total imprecision (CVtotal) of peak area was 12% for both the control and CFS pools. The 8 metabolites selected in our previous study (PMID: 27573827) performed well in a clinical validation analysis even when the case and control samples were analyzed 1.5 years later on a different instrument by a different investigator, yielding a diagnostic accuracy of 95% (95% CI 85-100%) measured by the area under the ROC curve.

CONCLUSIONS: A reliable and reproducible, broad-spectrum, targeted metabolomic method was developed, capable of measuring over 600 metabolites in plasma in a single injection. The method might be a useful tool in helping the diagnosis of CFS or other complex diseases.

Source: Li K, Naviaux JC, Bright AT, Wang L, Naviaux RK. A robust, single-injection method for targeted, broad-spectrum plasma metabolomics. Metabolomics. 2017;13(10):122. doi: 10.1007/s11306-017-1264-1. Epub 2017 Sep 4. https://www.ncbi.nlm.nih.gov/pubmed/28943831

Cognitive behaviour therapy and objective assessments in chronic fatigue syndrome

Abstract:

Most evaluations of cognitive behavioural therapy to treat people with chronic fatigue syndrome/myalgic encephalomyelitis rely exclusively on subjective self-report outcomes to evaluate whether treatment is effective. Few studies have used measures appropriate to assessing whether cognitive behavioural therapy changes in more objective measures. A review of studies incorporating objective measures suggests that there is a lack of evidence that cognitive behavioural therapy produces any improvement in a patient’s physical capabilities or other objective measures such as return to work. Future studies of chronic fatigue syndrome/myalgic encephalomyelitis should include some objective assessments as primary outcomes. If this is to include activity monitors, we first need a sound baseline dataset.

Source: Graham McPhee. Cognitive behaviour therapy and objective assessments in chronic fatigue syndrome. Journal of Health Psychology. First Published June 19, 2017. http://journals.sagepub.com/doi/abs/10.1177/1359105317707215 

The assessment of fatigue: Psychometric qualities and norms for the Checklist individual strength

Abstract:

OBJECTIVE: The Checklist Individual Strength (CIS) measures four dimensions of fatigue: Fatigue severity, concentration problems, reduced motivation and activity. On the fatigue severity subscale, a cut-off score of 35 is used. This study 1) investigated the psychometric qualities of the CIS; 2) validated the cut-off score for severe fatigue and 3) provided norms.

METHODS: Representatives of the Dutch general population (n=2288) completed the CIS. The factor structure was investigated using an exploratory factor analysis. Internal consistency and test-retest reliability were determined. Concurrent validity was assessed in two additional samples by correlating the CIS with other fatigue scales (Chalder Fatigue Questionnaire, MOS Short form-36 Vitality subscale, EORTC QLQ-C30 fatigue subscale). To validate the fatigue severity cut-off score, a Receiver Operating Characteristics analysis was performed with patients referred to a chronic fatigue treatment centre (n=5243) and a healthy group (n=1906). Norm scores for CIS subscales were calculated for the general population, patients with chronic fatigue syndrome (CFS; n=1407) and eight groups with other medical conditions (n=1411).

RESULTS: The original four-factor structure of the CIS was replicated. Internal consistency (α=0.84-0.95) and test-retest reliability (r=0.74-0.86) of the subscales were high. Correlations with other fatigue scales were moderate to high. The 35 points cut-off score for severe fatigue is appropriate, but, given the 17% false positive rate, should be adjusted to 40 for research in CFS.

CONCLUSION: The CIS is a valid and reliable tool for the assessment of fatigue, with a validated cut-off score for severe fatigue that can be used in clinical practice.

Copyright © 2017. Published by Elsevier Inc.

Source: Worm-Smeitink M, Gielissen M, Bloot L, van Laarhoven HWM, van Engelen BGM, van Riel P, Bleijenberg G, Nikolaus S, Knoop H. The assessment of fatigue: Psychometric qualities and norms for the Checklist individual strength. J Psychosom Res. 2017 Jul;98:40-46. doi: 10.1016/j.jpsychores.2017.05.007. Epub 2017 May 8. https://www.ncbi.nlm.nih.gov/pubmed/28554371

The problem of bias in behavioural intervention studies: Lessons from the PACE trial

Abstract:

Geraghty’s recent editorial on the PACE trial for chronic fatigue syndrome has stimulated a lively discussion. Here, I consider whether the published claims are justified by the data. I also discuss wider issues concerning trial procedures, researcher allegiance and participant reporting bias. Cognitive behavioural therapy and graded exercise therapy had modest, time-limited effects on self-report measures, but little effect on more objective measures such as fitness and employment status. Given that the trial was non-blinded, and the favoured treatments were promoted to participants as ‘highly effective’, these effects may reflect participant response bias. In non-blinded trials, the issue of reporting biases deserves greater attention in future.

 

Source: Carolyn Wilshire. The problem of bias in behavioural intervention studies: Lessons from the PACE trial. Journal of Health Psychology. First published date: March-23-2017. http://journals.sagepub.com/doi/full/10.1177/1359105317700885 (Full article)