Tag: large-scale study

Linear data mining the Wichita clinical matrix suggests sleep and allostatic load involvement in chronic fatigue syndrome

Abstract:

OBJECTIVES: To provide a mathematical introduction to the Wichita (KS, USA) clinical dataset, which is all of the nongenetic data (no microarray or single nucleotide polymorphism data) from the 2-day clinical evaluation, and show the preliminary findings and limitations, of popular, matrix algebra-based data mining techniques.

METHODS: An initial matrix of 440 variables by 227 human subjects was reduced to 183 variables by 164 subjects. Variables were excluded that strongly correlated with chronic fatigue syndrome (CFS) case classification by design (for example, the multidimensional fatigue inventory [MFI] data), that were otherwise self reporting in nature and also tended to correlate strongly with CFS classification, or were sparse or nonvarying between case and control. Subjects were excluded if they did not clearly fall into well-defined CFS classifications, had comorbid depression with melancholic features, or other medical or psychiatric exclusions. The popular data mining techniques, principle components analysis (PCA) and linear discriminant analysis (LDA), were used to determine how well the data separated into groups. Two different feature selection methods helped identify the most discriminating parameters.

RESULTS: Although purely biological features (variables) were found to separate CFS cases from controls, including many allostatic load and sleep-related variables, most parameters were not statistically significant individually. However, biological correlates of CFS, such as heart rate and heart rate variability, require further investigation.

CONCLUSIONS: Feature selection of a limited number of variables from the purely biological dataset produced better separation between groups than a PCA of the entire dataset. Feature selection highlighted the importance of many of the allostatic load variables studied in more detail by Maloney and colleagues in this issue [1] , as well as some sleep-related variables. Nonetheless, matrix linear algebra-based data mining approaches appeared to be of limited utility when compared with more sophisticated nonlinear analyses on richer data types, such as those found in Maloney and colleagues [1] and Goertzel and colleagues [2] in this issue.

 

Source: Gurbaxani BM, Jones JF, Goertzel BN, Maloney EM. Linear data mining the Wichita clinical matrix suggests sleep and allostatic load involvement in chronic fatigue syndrome. Pharmacogenomics. 2006 Apr;7(3):455-65. https://www.ncbi.nlm.nih.gov/pubmed/16610955

 

Gene expression profile exploration of a large dataset on chronic fatigue syndrome

Abstract:

OBJECTIVE: To gain understanding of the molecular basis of chronic fatigue syndrome (CFS) through gene expression analysis using a large microarray data set in conjunction with clinically administrated questionnaires.

METHOD: Data from the Wichita (KS, USA) CFS Surveillance Study was used, comprising 167 participants with two self-report questionnaires (multidimensional fatigue inventory [MFI] and Zung depression scale [Zung]), microarray data, empiric classification, and others. Microarray data was analyzed using bioinformatics tools from ArrayTrack.

RESULTS: Correspondence analysis was applied to the MFI questionnaire to select the 23 samples having either the most or the least fatigue, and to the Zung questionnaire to select the 26 samples having either the most or least depression; ten samples were common, resulting in a total of 39 samples. The MFI and Zung-based CFS/non-CFS (NF) classifications on the 39 samples were consistent with the empiric classification. Two differentially-expressed gene lists were determined, 188 fatigue-related genes and 164 depression-related genes, which shared 24 common genes and involved 11 common pathways. Principal component analysis based on 24 genes clearly separates 39 samples with respect to their likelihood to be CFS. Most of the 24 genes are not previously reported for CFS, yet their functions are consistent with the prevailing model of CFS, such as immune response, apoptosis, ion channel activity, signal transduction, cell-cell signaling, regulation of cell growth and neuronal activity. Hierarchical cluster analysis was performed based on 24 genes to classify 128 (=167-39) unassigned samples. Several of the 11 identified common pathways are supported by earlier findings for CFS, such as cytokine-cytokine receptor interaction and neuroactive ligand-receptor interaction. Importantly, most of the 11 common pathways are interrelated, suggesting complex biological mechanisms associated with CFS.

CONCLUSION: Bioinformatics is critical in this study to select definitive sample groups, analyze gene expression data and gain insight into biological mechanisms. The 24 identified common genes and 11 common pathways could be important in future studies of CFS at the molecular level.

 

Source: Fang H, Xie Q, Boneva R, Fostel J, Perkins R, Tong W. Gene expression profile exploration of a large dataset on chronic fatigue syndrome. Pharmacogenomics. 2006 Apr;7(3):429-40. https://www.ncbi.nlm.nih.gov/pubmed/16610953

 

How relevant are exercise capacity measures for evaluating treatment effects in chronic fatigue syndrome? Results from a prospective, multidisciplinary outcome study

Abstract:

OBJECTIVE: To evaluate the outcome of a multidisciplinary treatment programme for patients with chronic fatigue syndrome, including health-related quality of life (HRQoL) and psychosocial variables, and exercise capacity measures.

DESIGN: A six-month prospective outcome study.

SETTING: University outpatient rehabilitation clinic; group setting.

SUBJECTS: One hundred and sixteen women fulfilling chronic fatigue syndrome criteria.

INTERVENTIONS: Cognitive behaviourally and graded exercise-based strategies; emphasis on adaptive lifestyle changes.

MEASURES: Short Form General Health Survey (SF-36); Symptom Checklist (SCL-90); Causal Attribution List (CAL); Self-Efficacy Scale (SE); maximum progressive bicycle ergometer test with respiratory gas analysis; and isokinetic leg strength test, before and after treatment.

RESULTS: The total group significantly improved on nearly all reported HRQoL/psychosocial variables. Changes in exercise capacity measures were rather modest and did not correlate or only weakly correlated with HRQoL/psychosocial variables. Subgroup analyses indicated that less fit patients improved significantly more on exercise capacity measures than their more fit counterparts. Patients who were fitter at baseline scored better on pretreatment HRQoL/psychosocial variables, but both subgroups improved similarly on these variables.

CONCLUSIONS: Health-related quality of life and psychosocial functioning in patients with chronic fatigue syndrome improves after a six-month cognitive behaviourally and graded exercise-based multidisciplinary treatment programme. Increase in exercise capacity measures is not a necessary condition for reported improvements, except for less fit patients.

 

Source: Pardaens K, Haagdorens L, Van Wambeke P, Van den Broeck A, Van Houdenhove B. How relevant are exercise capacity measures for evaluating treatment effects in chronic fatigue syndrome? Results from a prospective, multidisciplinary outcome study. Clin Rehabil. 2006 Jan;20(1):56-66. https://www.ncbi.nlm.nih.gov/pubmed/16502751

 

Sub-typing CFS patients on the basis of ‘minor’ symptoms

Abstract:

The diagnosis of chronic fatigue syndrome (CFS), an illness characterized by medically unexplained fatigue, depends on a clinical case definition representing one or more pathophysiological mechanisms. To prepare for studies of these mechanisms, this study sought to identify subtypes of CFS.

In 161 women meeting 1994 criteria for CFS, principal components analysis of the 10 ‘minor’ symptoms of CFS produced three factors interpreted to indicate musculoskeletal, infectious and neurological subtypes. Extreme scores on one or more of these factors characterized about 2/3 of the sample. Those characterized by the neurological factor were at increased risk of reduced scores on cognitive tests requiring attention, working memory, long-term memory or rapid performance.

In addition, the neurological subtype was associated with reduced levels of function. Those characterized by the musculoskeletal factor were at increased risk for the diagnosis of fibromyalgia (chronic widespread pain and mechanical allodynia) and reduced physical function. Those characterized by the infectious factor were less likely to evidence co-occurring fibromyalgia, and showed lesser risk of functional impairment.

The prevalence of disability was increased in those with the highest scores on any of the subtypes, as well as in those with high scores on multiple factors. Depression and anxiety, while frequently present, were not more prevalent in any particular subtype, and did not increase with the severity of specific symptom reports. Results suggest that subtypes of CFS may be identified from reports of the minor diagnostic symptoms, and that these subtypes demonstrate construct validity.

 

Source: Janal MN, Ciccone DS, Natelson BH. Sub-typing CFS patients on the basis of ‘minor’ symptoms. Biol Psychol. 2006 Aug;73(2):124-31. Epub 2006 Feb 10. https://www.ncbi.nlm.nih.gov/pubmed/16473456

 

Twin analyses of chronic fatigue in a Swedish national sample

Abstract:

BACKGROUND: Chronic fatigue has infrequently been studied in twins. Data from twin studies can inform clinical and research approaches to the management and etiology of human complex traits.

METHOD: The authors obtained telephone interview data on current chronic fatigue from 31406 individuals twins in the Swedish Twin Registry (aged 42-64 years, 75.68% response rate), from both members of 12407 pairs and from one member of 6592 pairs. Of the complete pairs, 3269 pairs were monozygotic, 9010 pairs dizygotic, and 128 pairs of unknown zygosity. Structural equation twin modeling was used to estimate the latent genetic architecture of varying definitions of fatiguing illness.

RESULTS: Estimates of additive genetic effects, shared environmental effects, and individual-specific environmental effects were similar in males and females. No definition of current fatiguing illness (ranging from any fatigue to CFS-like illness) was strikingly distinctive. Individual-specific effects were the predominant source of variation, followed by modest genetic influences. We could not exclude a small but conceptually important contribution of shared environmental effects.

CONCLUSIONS: Current fatiguing illness appears to be a complex trait resulting from both environmental and genetic sources of variation without pronounced differences by gender.

 

Source: Sullivan PF, Evengård B, Jacks A, Pedersen NL. Twin analyses of chronic fatigue in a Swedish national sample. Psychol Med. 2005 Sep;35(9):1327-36. http://www.ncbi.nlm.nih.gov/pubmed/16168155

 

The epidemiology of chronic fatigue in the Swedish Twin Registry

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) remains an idiopathic and controversial entity.

METHOD: We screened 31405 individual members of the Swedish Twin Registry (aged 42-64 years) for the symptoms of fatiguing illness via a telephone questionnaire. We refined self-reported symptoms via data from several national registries and from physician review of all available medical records in order to approximate closely the dominant case definition of CFS.

FINDINGS: The 6-month prevalence of CFS-like illness was 2.36% (95% CI 2.19-2.53) and was markedly higher in women than men, odds ratio 3.92 (95% CI 3.24-4.72) with no significant association with age or years of education. There was a highly significant association with occupation that disappeared after accounting for gender.

INTERPRETATION: CFS-like illness may be more common that previously acknowledged. There is a marked increase in risk by gender. Previous reports that CFS is more prevalent in individuals in certain occupational categories were not confirmed and may have been due to confounding by gender.

 

Source: Evengård B, Jacks A, Pedersen NL, Sullivan PF. The epidemiology of chronic fatigue in the Swedish Twin Registry. Psychol Med. 2005 Sep;35(9):1317-26. http://www.ncbi.nlm.nih.gov/pubmed/16168154

 

Prevalence of chronic fatigue and chronic fatigue syndrome in Korea: community-based primary care study

Abstract:

There have been many epidemiological and clinical researches on chronic fatigue (CF) and chronic fatigue syndrome (CFS) since the 1990s, but such studies have been quite limited in Korea. The aim of this study was to investigate the point prevalence of CF and CFS in patients who visited community-based eight primary care clinics in Korea. The study subjects were 1,648 patients aged 18 yr and over who visited one of eight primary care clinics in Korea between the 7th and 17th of May 2001. The physicians determined the status of the subjects through fatigue-related questionnaires, medical history, physical examination, and laboratory tests. The subjects were categorized into no fatigue, prolonged fatigue, CF and then CF were further classified to medically explained CF (Physical CF and Psychological CF) and medically unexplained CF (CFS and idiopathic chronic fatigue). The point prevalence of CF and CFS were 8.4% (95% CI 7.1-9.7%) and 0.6% (95% CI 0.2-1.0%). Medically explained CF was 80.5% of CF, of which 57.1% had psychological causes. The clinical characteristics of CFS were distinguished from explained CF. CF was common but CFS was rare in community-based primary care settings in Korea.

 

Source: Kim CH, Shin HC, Won CW. Prevalence of chronic fatigue and chronic fatigue syndrome in Korea: community-based primary care study. J Korean Med Sci. 2005 Aug;20(4):529-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782143/ (Full article)

 

The definition of disabling fatigue in children and adolescents

Abstract:

BACKGROUND: Disabling fatigue is the main illness related reason for prolonged absence from school. Although there are accepted criteria for diagnosing chronic fatigue in adults, it remains uncertain as to how best to define disabling fatigue and Chronic Fatigue Syndrome (CFS) in children and adolescents. In this population-based study, the aim was to identify children who had experienced an episode of disabling fatigue and examine the clinical and demographic differences between those individuals who fulfilled a narrow definition of disabling fatigue and those who fulfilled broader definitions of disabling fatigue.

METHODS: Participants (aged 8-17 years) were identified from a population-based twin register. Parent report was used to identify children who had ever experienced a period of disabling fatigue. Standardised telephone interviews were then conducted with the parents of these affected children. Data on clinical and demographic characteristics, including age of onset, gender, days per week affected, hours per day spent resting, absence from school, comorbidity with depression and a global measure of impairment due to the fatigue, were examined. A narrow definition was defined as a minimum of 6 months disabling fatigue plus at least 4 associated symptoms, which is comparable to the operational criteria for CFS in adults. Broader definitions included those with at least 3 months of disabling fatigue and 4 or more of the associated symptoms and those with simply a minimum of 3 months of disabling fatigue. Groups were mutually exclusive.

RESULTS: Questionnaires were returned by 1468 families (65% response rate) and telephone interviews were completed on 99 of the 129 participants (77%) who had experienced fatigue. There were no significant differences in demographic and clinical characteristics or levels of impairment between those who fulfilled the narrower definition and those who fulfilled the broader definitions. The only exception was the reported number of days per week that the child was affected by the fatigue. All groups demonstrated evidence of substantial impairment associated with the fatigue.

CONCLUSION: Children and adolescents who do not fulfil the current narrow definition of CFS but do suffer from disabling fatigue show comparable and substantial impairment. In primary care settings, a broader definition of disabling fatigue would improve the identification of impaired children and adolescents who require support.

 

Source: Fowler T, Duthie P, Thapar A, Farmer A. The definition of disabling fatigue in children and adolescents. BMC Fam Pract. 2005 Aug 9;6:33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1192794/ (Full article)

 

Effect of psychiatric disorders on outcome of cognitive-behavioural therapy for chronic fatigue syndrome

Abstract:

Psychiatric disorders have been associated with poor outcome in individuals with chronic fatigue syndrome (CFS). This study examines the impact of psychiatric disorders on outcome of cognitive-behavioural therapy (CBT). Psychiatric diagnoses were assessed with a structured psychiatric interview in a CBT trial of 270 people with CFS. Lifetime and current psychiatric disorders were found in 50 and 32% respectively. No significant differences in fatigue severity and functional impairment following treatment were found between participants with and without psychiatric diagnoses.

 

Source: Prins J, Bleijenberg G, Rouweler EK, van der Meer J. Effect of psychiatric disorders on outcome of cognitive-behavioural therapy for chronic fatigue syndrome. Br J Psychiatry. 2005 Aug;187:184-5. http://bjp.rcpsych.org/content/187/2/184.long (Full article)

 

Psychometric properties of the CDC Symptom Inventory for assessment of chronic fatigue syndrome

Abstract:

OBJECTIVES: Validated or standardized self-report questionnaires used in research studies and clinical evaluation of chronic fatigue syndrome(CFS) generally focus on the assessment of fatigue. There are relatively few published questionnaires that evaluate case defining and other accompanying symptoms in CFS. This paper introduces the self-report CDC CFS Symptom Inventory and analyzes its psychometric properties.

METHODS: One hundred sixty-four subjects (with CFS, other fatiguing illnesses and non fatigued controls) identified from the general population of Wichita, Kansas were enrolled. Evaluation included a physical examination, a standardized psychiatric interview, three previously validated self-report questionnaires measuring fatigue and illness impact (Medical Outcomes Survey Short-Form-36 [MOS SF-36], Multidimensional Fatigue Inventory [MFI], Chalder Fatigue Scale), and the CDC CFS Symptom Inventory. Based on theoretical assumptions and statistical analyses, we developed several different Symptom Inventory scores and evaluated them on their ability to differentiate between participants with CFS and non-fatigued controls.

RESULTS: The Symptom Inventory had good internal consistency and excellent convergent validity. A Total score (all symptoms), Case Definition score (CFS case defining symptoms) and Short Form score (6 symptoms with minimal correlation) differentiated CFS cases from controls. Furthermore, both the Case Definition and Short Form scores distinguished people with CFS from fatigued subjects who did not meet criteria for CFS.

CONCLUSION: The Symptom Inventory appears to be a reliable and valid instrument to assess symptoms that accompany CFS. It is a positive addition to existing instruments measuring fatigue because it allows other dimensions of the illness to be assessed. Further research is needed to confirm and replicate the current findings in a normative population.

 

Source: Wagner D, Nisenbaum R, Heim C, Jones JF, Unger ER, Reeves WC. Psychometric properties of the CDC Symptom Inventory for assessment of chronic fatigue syndrome. Popul Health Metr. 2005 Jul 22;3:8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1183246/ (Full article)