Category: Methodology

Urinary and plasma organic acids and amino acids in chronic fatigue syndrome

Abstract:

Previous work by others have suggested the occurrence of one or more chemical or metabolic ‘markers’ for ME/CFS including specific amino acids and organic acids and a number of unidentified compounds (CFSUM1, CFSUM2). We have shown elsewhere that CFSUM1 is partially derivatised pyroglutamic acid and CFSUM2 partially derivatised serine and have suggested and demonstrated that the analytical methods used were unsuitable to identify or to accurately quantify urinary metabolites. We have now made a detailed analysis of plasma and urinary amino acids and of urinary organic acids from patients with ME/CFS and from three control groups.

Fasting blood plasma and timed urine samples were obtained from 31 patients with CFS, 31 age and sex-matched healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Plasma and urinary amino acids and urinary organic acids were determined using established and validated methods and data compared by statistical analysis. None of the previously reported abnormalities in urinary amino acids or of organic acids could be confirmed.

Results however provide some evidence in patients with ME/CFS for underlying inflammatory disease and for reduced intramuscular collagen with a lowered threshold for muscle micro-injury. These factors in combination may provide a basis for the fatigue and muscle pain that are the major symptoms in these patients.

 

Source: Jones MG, Cooper E, Amjad S, Goodwin CS, Barron JL, Chalmers RA. Urinary and plasma organic acids and amino acids in chronic fatigue syndrome. Clin Chim Acta. 2005 Nov;361(1-2):150-8. http://www.ncbi.nlm.nih.gov/pubmed/15992788

 

Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution

Abstract:

BACKGROUND: A recent article by Reeves et al. on the identification and resolution of ambiguities in the 1994 chronic fatigue syndrome (CFS) research case definition recommended the Checklist Individual Strength, the Chalder Fatigue Scale, and the Krupp Fatigue Severity Scale for evaluating fatigue in CFS studies. To be able to discriminate between various levels of severe fatigue, extreme scoring on the individual items of these questionnaires must not occur too often.

METHODS: We derived an expression that allows us to compute a lower bound for the number of items with the maximum item score for a given study from the reported mean scale score, the number of reported subjects, and the properties of the fatigue rating scale. Several CFS studies that used the recommended fatigue rating scales were selected from literature and analyzed to verify whether abundant extreme scoring had occurred.

RESULTS: Extreme scoring occurred on a large number of the items for all three recommended fatigue rating scales across several studies. The percentage of items with the maximum score exceeded 40% in several cases. The amount of extreme scoring for a certain scale varied from one study to another, which suggests heterogeneity in the selected subjects across studies.

CONCLUSION: Because all three instruments easily reach the extreme ends of their scales on a large number of the individual items, they do not accurately represent the severe fatigue that is characteristic for CFS. This should lead to serious questions about the validity and suitability of the Checklist Individual Strength, the Chalder Fatigue Scale, and the Krupp Fatigue Severity Scale for evaluating fatigue in CFS research.

Comment on: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. [BMC Health Serv Res. 2003]

 

Source: Stouten B. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res. 2005 May 13;5:37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1175848/ (Full article)

 

Development of a functional ability scale for children and young people with myalgic encephalopathy (ME)/chronic fatigue syndrome (CFS)

Abstract:

The numerous symptoms and unpredictable pattern of myalgic encephalopathy (ME) make it difficult to describe, especially for children. It was left to carers to guess what the child could achieve each day, often leading to over/underestimates. A functional ability scale was needed, which measured from 0 to 100 percent able and that children and young people themselves designed.

A new scale was developed from the Moss Ability Scale using the critique of 251 children and young people from the Association of Young People with ME (AYME). Responding to the shift in emphasis towards patients taking an active role in their own care, it was felt these young people would know whether the scale measured what it had set out to measure, and were asked questions on the face and content validity of the scale. There was a 99 percent agreement between the young people that the final scale was ‘workable’ or better.

 

Source: Moss J. Development of a functional ability scale for children and young people with myalgic encephalopathy (ME)/chronic fatigue syndrome (CFS). J Child Health Care. 2005 Mar;9(1):20-30. http://www.ncbi.nlm.nih.gov/pubmed/15684437

 

Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome

Abstract:

PURPOSE: To establish an inexpensive, simple method of predicting peak oxygen uptake (VO2peak) in patients fulfilling the 1994 Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome (CFS).

DESIGN: A retrospective observational study.

SETTING: An outpatient tertiary care chronic fatigue clinic.

SUBJECTS: Two hundred and forty consecutive patients fulfilling the 1994 CDC criteria for CFS.

INTERVENTIONS: Heart rate, metabolic and ventilatory parameters were measured continuously during a maximal exercise stress test on a bicycle ergometer. Using the equation peak oxygen uptake = 13.1 x peak workload +284 (used by Mullis et al., Br J Sports Med 1999; 33: 352-56), VO2peak was predicted from the peak workload of a maximal exercise capacity test. Pearson correlation coefficient and linear regression analysis were used to establish the most accurate way to predict VO2peak.

RESULTS: Percentage error encountered when comparing actual measured VO2peak with predicted value was 17.3% (+/-10.0). A strong correlation between VO2peak and peak workload was observed (r= 0.89, p < 0.001). A regression analysis established the relation as VO2peak = 10.47 x peak workload +284.1, where VO2peak is given in ml/min and peak workload in W (error in prediction = 11.0+/-9.5%).

CONCLUSIONS: Monitoring of the peak workload during a maximal, graded bicycle ergometric test suffices to predict the VO2peak. When predicting VO2peak the used operational definition for the diagnosis of CFS could be taken into account. Compared with the equation used by Mullis et al., peak workload is multiplied by 10.47 in order to predict peak oxygen uptake in CDC-defined CFS patients.

 

Source: Nijs J, De Meirleir K. Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome. Clin Rehabil. 2004 Nov;18(7):785-92. http://www.ncbi.nlm.nih.gov/pubmed/15573835

 

The feeling of fatigue–fatigue severity by unidimensional versus composite questionnaires

Abstract:

The authors’ purpose in this study was to compare the perception of fatigue severity as measured by different fatigue questionnaires. The authors evaluated 3 groups of patients in a cross-sectional study: chronic fatigue syndrome (CFS, n = 20), non-CFS fatigue (n = 20), and familial Mediterranean fever (FMF n = 25). In addition, the authors tracked 7 patients with CFS longitudinally for severity of fatigue.

The severity of fatigue-related symptoms was assessed with 2 questionnaires: the unidimensional Chalder’s Fatigue Severity Scale (CH) and the composite Fatigue Impact Scale (FI) which has 3 subscales–cognitive, physical, and social–and a total score.

In the cross-sectional study, correlations between CH and FI cognitive scores were r = .78 (p < .0001), CH versus FI physical scores r = .603 (p < .0001), CH versus FI social scores r = .66 (p < .0001), and CH versus FI total scores r = .74 (p < .0001).

In the longitudinal survey of CFS patients, the authors compared 30 questionnaires revealing correlations of CH versus FI cognitive scores r = .64 (p = .0004), CH versus FI physical r = .68 (p = .0001), CH versus FI social r = .87 (p < .0001), and CH versus FI total r = .90 (p < .0001).

Fatigue severity as assessed by the unidimensional CH scale and the composite FI scale is comparable. The simple CH scale may be adequate for the assessment of the feeling of fatigue, in general, and for monitoring the severity of fatigue in CFS, in particular.

 

Source: Naschitz JE, Rozenbaum M, Shaviv N, Fields MC, Enis S, Babich JP, Manor H, Yeshurun D, Sabo E, Rosner I. The feeling of fatigue–fatigue severity by unidimensional versus composite questionnaires. Behav Med. 2004 Winter;29(4):167-72. http://www.ncbi.nlm.nih.gov/pubmed/15369197

 

Decreased fractal correlation in diurnal physical activity in chronic fatigue syndrome

Abstract:

OBJECTIVES: Our objectives were to study the temporal correlation of physical activity time series in patients with chronic fatigue syndrome (CFS) during normal daily life and to examine if it could identify the altered physical activity in these patients.

METHODS: Fractal scaling exponents of diurnal and nocturnal physical activity time series in 10 CFS patients and 6 healthy control subjects (CON) were calculated by the detrended fluctuation analysis (DFA) and the wavelet transform modulus maxima (WTMM) method. We hypothesized that, due to their illness- and/or fatigue-induced resting episodes, altered physical activity patterns in CFS patients might be observed at the interruption of activity bursts. Thus, we further developed a new method, the wavelet transform negative modulus maxima (WTNMM) method, which could evaluate the temporal correlation at the interruption of activities. We compared the fractal scaling exponents for CFS and CON by each method.

RESULTS: Both for CFS and CON, we found the fractal time structures in their diurnal physical activity records for at least up to 35 minutes. No group difference was found in nocturnal activities. The WTNMM method revealed that, in diurnal activities, CFS patients had significantly (p < 0.01) smaller fractal scaling exponent (0.87 +/- 0.03) compared to controls (1.01 +/- 0.03). Such a difference was identified neither by the DFA nor WTMM method.

CONCLUSIONS: CFS patients had more abrupt interruptions of voluntary physical activity during diurnal periods in normal daily life, probed by the decreased correlation in the negative modulus maxima of the wavelet-transformed activity data, possibly due to their exaggerated fatigue.

 

Source: Ohashi K, Bleijenberg G, van der Werf S, Prins J, Amaral LA, Natelson BH, Yamamoto Y. Decreased fractal correlation in diurnal physical activity in chronic fatigue syndrome. Methods Inf Med. 2004;43(1):26-9. http://www.ncbi.nlm.nih.gov/pubmed/15026831

 

Psychometric properties of the Dutch Chronic Fatigue Syndrome–Activities and Participation Questionnaire (CFS-APQ)

Abstract:

BACKGROUND AND PURPOSE: The Chronic Fatigue Syndrome-Activities and Participation Questionnaire (CFS-APQ) is a recently developed disease-specific assessment tool for monitoring activity limitations and participation restrictions in patients with chronic fatigue syndrome (CFS). In this study, the convergent validity, content validity, and test-retest reliability of data obtained with the Dutch-language version of the questionnaire were examined.

SUBJECTS AND METHODS: One hundred eleven consecutive patients with CFS were enrolled, of whom 47 fulfilled all inclusion criteria. The subjects were first asked to rate their pain, fatigue, and ability to concentrate using 3 visual analog scales, to list at least 5 activities that had become difficult to perform due to their complaints, and to complete the CFS-APQ. Furthermore, subjects were asked to complete a modified version of the CFS-APQ at home and return it to the investigators. The content of the questionnaire was reviewed using the World Health Organization’s International Classification of Impairments, Disability and Health (ICIDH) beta II draft. Spearman rank correlation coefficients (R) were used for the convergent validity analysis, and intraclass correlation coefficients were computed for the assessment of the test-retest data.

RESULTS: Overall scores on the CFS-APQ correlated with the scores from the visual analog scales for pain (R=.51, P<.001) and fatigue (R=.50, P<.001). The majority of the responses (157 out of 183 answers [85.8%]) to the request to “list difficult activities” matched the content of the CFS-APQ. Using the ICIDH beta II draft, 21 out of 26 questions were found to address activities, and the remaining 5 questions measured the participation level. The Cronbach alpha coefficient was.94, and intraclass correlation coefficients for test-retest reliability of the overall scores were >or= .95 (P<.001).

DISCUSSION AND CONCLUSION: The results substantiate the convergent validity, content validity, and reliability of the CFS-APQ scores for patients with CFS.

 

Source: Nijs J, Vaes P, McGregor N, Van Hoof E, De Meirleir K. Psychometric properties of the Dutch Chronic Fatigue Syndrome–Activities and Participation Questionnaire (CFS-APQ). Phys Ther. 2003 May;83(5):444-54. http://ptjournal.apta.org/content/83/5/444.long (Full article)

 

Validation of a telephone cognitive assessment test battery for use in chronic fatigue syndrome

Abstract:

We compared a computerized version of the Cognitive Drug Research (CDR) cognitive assessment test battery and a completely automated telephone version of the same battery. These assessed aspects of attention, working memory and long-term memory. Both methods were used to assess the cognitive performance of a cohort of 30 people with confirmed chronic fatigue syndrome (CFS) and a group of 30 healthy controls matched for age and education.

The CFS group had significantly slower reaction times on all four cognitive measures on both the computerized and telephone tests. The mood data followed similar patterns in the computer and telephone assessments. The results from both forms of the test battery confirmed the pattern and severity of cognitive impairment in CFS. Furthermore, the two methods of testing were similarly sensitive in detecting cognitive deficits. The incapacitating nature of CFS may cause problems for researchers if the restrictions to mobility affect the representativeness of the study group. The findings of the present study support the use of a fully automated telephone cognitive testing system for detecting deficits in CFS.

 

Source: McCue P, Scholey AB, Herman C, Wesnes KA. Validation of a telephone cognitive assessment test battery for use in chronic fatigue syndrome.  J Telemed Telecare. 2002;8(6):337-43. http://www.ncbi.nlm.nih.gov/pubmed/12537921

 

The Mid-Atlantic Twin Registry

Abstract:

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of twin pairs ascertained from birth records and school system records of Virginia, North Carolina, and South Carolina. The MATR was formed in 1997 with the merging of the Virginia and North Carolina Twin Registries, and it expanded to include South Carolina when access to twin birth records in that state was granted in 1998. Registered twins (“participants”) number more than 51,000, with approximately 46,000 of these individuals representing complete pairs. Roughly two-thirds of MATR participants are over age 18, with a mean age of approximately 35 years. These participants have primarily been drawn from the more than 170,000 identical and fraternal twin pairs born in the three states between 1913 and 2000. Twins and their family members have participated in numerous research projects, ranging from general health surveys to studies on specific health topics such as cardiovascular disease; depression and anxiety; seizures; behavioral development; pregnancy complications; conduct disorder; drug use, abuse, and dependence; cleft lip/palate; obesity; and chronic fatigue syndrome. The MATR has established a privacy policy and strict standard operating procedures to protect the confidentiality of participant data. The MATR considers a limited number of qualified requests per year from investigators interested in recruiting MATR participants into their research studies.

 

Source:  Anderson LS, Beverly WT, Corey LA, Murrelle L. The Mid-Atlantic Twin Registry. Twin Res. 2002 Oct;5(5):449-55. http://www.ncbi.nlm.nih.gov/pubmed/12537875

 

The Swedish Twin Registry in the third millennium

Abstract:

Since the Swedish Twin Registry was first established in the late 1950s to study the importance of smoking and alcohol consumption on cancer and cardiovascular diseases, it has been expanded and updated on several occasions. The focus has similarly broadened to most common complex diseases. The content of the database is described, ongoing projects based on the registry are summarized, and we review some of the principal findings on aging, cancer and cardiovascular disease that have come from the registry. Ongoing efforts and future plans for the STR are discussed. Among others, we plan blood collection and genotyping to study the genetic bases of complex diseases, a first contact ever with the cohorts born after 1958, and in-depth studies of selected diseases, such as Parkinson’s disease and chronic fatigue syndrome.

 

Source: Pedersen NL, Lichtenstein P, Svedberg P. The Swedish Twin Registry in the third millennium. Twin Res. 2002 Oct;5(5):427-32. http://www.ncbi.nlm.nih.gov/pubmed/12537870