Serum 25-hydroxy vitamin D levels in chronic fatigue syndrome: a retrospective survey

Abstract:

INTRODUCTION: Patients with chronic fatigue syndrome (CFS) may be at risk of osteoporosis due to their relative lack of physical activity and excessive time spent indoors, leading to reduced vitamin D synthesis. We hypothesized that serum 25-OH vitamin D levels are lower in CFS patients than in the general British population.

SUBJECTS AND METHODS: We performed a retrospective survey of serum 25-OH vitamin D levels in 221 CFS patients. We compared this to a group of patients attending the hospital for other chronic conditions and to a large British longitudinal survey of 45-year old women, using a variety of appropriate statistical approaches.

RESULTS: 25-OH vitamin D levels are moderately to severely suboptimal in CFS patients, with a mean of 44.4 nmol/L (optimal levels >75 nmol/L). These levels are lower and the difference is statistically significant (p<0.0004) than those of the general British population from a recent national survey, but similar to those in patients with other chronic conditions.

CONCLUSIONS: This data supports the recommendation made in recent NICE guidelines that all patients with moderate to severe CFS should be encouraged to obtain adequate sun exposure and eat foods high in vitamin D. Oral or intramuscular vitamin D supplementation should be considered for those whose levels remain suboptimal.

 

Source: Berkovitz S, Ambler G, Jenkins M, Thurgood S. Serum 25-hydroxy vitamin D levels in chronic fatigue syndrome: a retrospective survey. Int J Vitam Nutr Res. 2009 Jul;79(4):250-4. Doi: 10.1024/0300-9831.79.4.250. https://www.ncbi.nlm.nih.gov/pubmed/20209476

 

Chronic fatigue syndrome is associated with metabolic syndrome: results from a case-control study in Georgia

Abstract:

We hypothesized that persons with chronic fatigue syndrome (CFS) would have a higher prevalence of metabolic syndrome compared with well controls, and that unwell persons with insufficient symptoms or fatigue for CFS (termed ISF) would have a prevalence of metabolic syndrome intermediate between those with CFS and the controls. We also sought to examine the relationship between metabolic syndrome and measures of functional impairment, fatigue, and other symptoms.

Our analysis was based on a population-based case-control study conducted in metropolitan, urban, and rural areas of Georgia, United States, between September 2004 and July 2005. There were 111 persons with CFS, 259 with ISF, and 123 controls.

Metabolic syndrome was determined based on having at least 3 of 5 standard risk components (abdominal obesity, high triglycerides, high blood pressure, elevated fasting glucose, and decreased high-density lipids) according to the National Cholesterol Education Program Adult Treatment Panel III definition.

Persons with CFS were 2-fold as likely to have metabolic syndrome (odds ratio = 2.12, confidence interval = 1.06, 4.23) compared with the controls. There was a significant graded relationship between the number of metabolic syndrome factors and CFS; each additional factor was associated with a 37% increase in likelihood of having CFS. The association of ISF with metabolic syndrome was weaker (odds ratio = 1.72, confidence interval = 0.94-3.16).

Among persons with CFS, the number of metabolic syndrome factors was significantly correlated with worse fatigue on a standardized summary measure of fatigue (r = 0.20, P = .04). In conclusion, CFS was associated with metabolic syndrome, which further exacerbated fatigue.

 

Source: Maloney EM, Boneva RS, Lin JM, Reeves WC. Chronic fatigue syndrome is associated with metabolic syndrome: results from a case-control study in Georgia. Metabolism. 2010 Sep;59(9):1351-7. doi: 10.1016/j.metabol.2009.12.019. Epub 2010 Jan 27. https://www.ncbi.nlm.nih.gov/pubmed/20102774

 

A two-year follow-up study of chronic fatigue syndrome comorbid with psychiatric disorders

Abstract:

AIMS: Chronic fatigue syndrome patients often have comorbid psychiatric disorders such as major depressive disorders and anxiety disorders. However, the outcomes of chronic fatigue syndrome and the comorbid psychiatric disorders and the interactions between them are unknown. Therefore, a two-year prospective follow-up study was carried out on chronic fatigue syndrome patients with comorbid psychiatric disorders.

METHODS: A total of 155 patients who met the Japanese case definition of chronic fatigue syndrome were enrolled in this study. Comorbid psychiatric disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria. Patients with comorbid psychiatric disorders received psychiatric treatment in addition to medical therapy for chronic fatigue syndrome. Seventy patients participated in a follow-up interview approximately 24 months later.

RESULTS: Of the 70 patients with chronic fatigue syndrome, 33 patients were diagnosed as having comorbid psychiatric disorders including 18 major depressive disorders. Sixteen patients with psychiatric disorders and eight patients with major depressive disorders did not fulfill the criteria of any psychiatric disorders at the follow up. As for chronic fatigue syndrome, nine out of the 70 patients had recovered at the follow up. There is no significant influence of comorbid psychiatric disorders on the outcome of chronic fatigue syndrome.

CONCLUSIONS: Chronic fatigue syndrome patients have a relatively high prevalence of comorbid psychiatric disorders, especially major depressive disorders. The outcomes of chronic fatigue syndrome and psychiatric disorders are independent. Therefore treatment of comorbid psychiatric disorders is necessary in addition to the medical treatment given for chronic fatigue syndrome.

 

Source: Matsuda Y, Matsui T, Kataoka K, Fukada R, Fukuda S, Kuratsune H, Tajima S, Yamaguti K, Kato YH, Kiriike N. A two-year follow-up study of chronic fatigue syndrome comorbid with psychiatric disorders. Psychiatry Clin Neurosci. 2009 Jun;63(3):365-73. doi: 10.1111/j.1440-1819.2009.01954.x. http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1819.2009.01954.x/full (Full article)

 

Anxiety in children with CFS/ME

Abstract:

Anxiety symptoms are commonly described in children with chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) but to date there has been little information on the type of anxiety children experience or the relationship between anxiety and school attendance, disability or fatigue.

The aim of this study was to first describe the prevalence and type of anxiety symptoms in children with CFS/ME compared with a normal European population, and secondly to investigate the association of anxiety symptoms with age, gender, school attendance, fatigue, and physical function in paediatric CFS/ME.

Data were prospectively collected on children and young people with CFS/ME referred to a large specialist CFS/ME service. One hundred and sixty-four children with CFS/ME had complete data for the Spence Children’s Anxiety Scale. Teenage girls had the highest rates of total anxiety symptoms with 38% (95% CI 27-49) over the cut off (top 10% of normal European population) and significantly higher rates of symptoms in each subscale.

Younger girls were more likely to score over the cut off in separation anxiety (37%, 19-40) and social phobia (39%, 25-47). There was no evidence of association between total anxiety symptoms and: time at school, time to assessment, pain or age. Associations with fatigue and physical function were attenuated when adjusted for other variables. Although anxiety symptoms are high in CFS/ME, particularly in teenage girls, it does not appear to be associated with school attendance or other measures of disability. Separation anxiety and social phobia were the most clearly elevated in paediatric CFS/ME.

 

Source: Crawley E, Hunt L, Stallard P. Anxiety in children with CFS/ME. Eur Child Adolesc Psychiatry. 2009 Nov;18(11):683-9. doi: 10.1007/s00787-009-0029-4. Epub 2009 May 19. https://www.ncbi.nlm.nih.gov/pubmed/19452195

 

An investigation into the cognitive deficits associated with chronic fatigue syndrome

Abstract:

This study addresses, among other things, the debate as to whether cognitive deficits do occur with a diagnosis of Chronic Fatigue Syndrome (CFS). Previous studies have indicated a potential mismatch between subjective patient ratings of impairment and clinical assessment.

In an attempt to tackle some of the methodological problems faced by previous research in this field, this study recruited a large sample of CFS patients where adequate diagnosis had been made and administered an extensive battery of measures. In doing so this study was able to replicate previous published evidence of clear cognitive impairment in this group and demonstrate also that these deficits occurred independent of psychopathology.

The conclusion drawn is that cognitive impairments can be identified if appropriate measures are used. Furthermore, the authors have shown that performance changes in these measures have been used to assess both efficacy of a treatment regime and rates of recovery.

 

Source: Thomas M, Smith A. An investigation into the cognitive deficits associated with chronic fatigue syndrome. Open Neurol J. 2009 Feb 27;3:13-23. doi: 10.2174/1874205X00903010013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682840/ (Full article)

 

Visible and near-infrared spectral changes in the thumb of patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) patients show a persistent fatigue condition with muscle pain and impairment of concentration, memory, and sleep. Presently, the physiological basis of CFS remains unclear. In this study, spectroscopic differences in the thumb were compared between 103 CFS patients and 122 healthy controls to examine possible changes of levels of oxygenated or deoxygenated hemoglobin.

METHODS: Visible and near-infrared (Vis-NIR) spectroscopy was used to examine possible changes in the region of 600-1100 nm.

RESULTS: Vis-NIR spectra showed sharp peaks at 694, 970 and 1060 nm and broad peaks in the regions of 740-760 and 830-850 nm. As these peaks are possibly related to oxyhemoglobin, cytochrome c oxidase and water, levels of these factors were compared between the two groups. Statistical analysis of the absorbance of Vis-NIR spectra showed a significant decrease in water content, a significant increase in oxyhemoglobin content, and a significant increase in the oxidation of heme a+a(3) and copper in cytochrome c oxidase in CFS patients.

CONCLUSIONS: These changes imply accelerated blood flow and energy metabolism in the thumbs of CFS patients.

 

Source: Sakudo A, Kato YH, Tajima S, Kuratsune H, Ikuta K. Visible and near-infrared spectral changes in the thumb of patients with chronic fatigue syndrome. Clin Chim Acta. 2009 May;403(1-2):163-6. doi: 10.1016/j.cca.2009.02.010. Epub 2009 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/19248775

 

Barriers to healthcare utilization in fatiguing illness: a population-based study in Georgia

Abstract:

BACKGROUND: The purpose of this study was to determine the prevalence of barriers to healthcare utilization in persons with fatiguing illness and describe its association with socio-demographics, the number of health conditions, and frequency of healthcare utilization. Furthermore, we sought to identify what types of barriers interfered with healthcare utilization and why they occurred.

METHODS: In a cross-sectional population-based survey, 780 subjects, 112 of them with chronic fatigue syndrome (CFS), completed a healthcare utilization questionnaire. Text analysis was used to create the emerging themes from verbatim responses regarding barriers to healthcare utilization. Multiple logistic regression was performed to examine the association between barriers to healthcare utilization and other factors.

RESULTS: Forty percent of subjects reported at least one barrier to healthcare utilization. Of 112 subjects with CFS, 55% reported at least one barrier to healthcare utilization. Fatiguing status, reported duration of fatigue, insurance, and BMI were significant risk factors for barriers to healthcare utilization. After adjusting for socio-demographics, medication use, the number of health problems, and frequency of healthcare utilization, fatiguing status remained significantly associated with barriers to healthcare utilization.

Subjects with CFS were nearly 4 times more likely to forego needed healthcare during the preceding year than non-fatigued subjects while those with insufficient fatigue (ISF) were nearly 3 times more likely.Three domains emerged from text analysis on barriers to healthcare utilization: 1) accessibility; 2) knowledge-attitudes-beliefs (KABs); and, 3) healthcare system. CFS and reported duration of fatigue were significantly associated with each of these domains. Persons with CFS reported high levels of healthcare utilization barriers for each domain: accessibility (34%), healthcare system (25%), and KABs (19%). In further examination of barrier domains to healthcare utilization, compared to non-fatigued persons adjusted ORs for CFS having “accessibility”, “KAB” and “Healthcare System” barrier domains decreased by 40%, 30%, and 19%, respectively.

CONCLUSION: Barriers to healthcare utilization pose a significant problem in persons with fatiguing illnesses. Study results suggested two-fold implications: a symptom-targeted model focusing on symptoms associated with fatigue; and an interactive model requiring efforts from patients and providers to improve interactions between them by reducing barriers in accessibility, KABs, and healthcare system.

 

Source: Lin JM, Brimmer DJ, Boneva RS, Jones JF, Reeves WC. Barriers to healthcare utilization in fatiguing illness: a population-based study in Georgia. BMC Health Serv Res. 2009 Jan 20;9:13. doi: 10.1186/1472-6963-9-13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651135/ (Full article)

 

Association of peripheral inflammatory markers with chronic fatigue in a population-based sample

Abstract:

Alterations in the innate immune response may contribute to the pathogenesis of chronic fatigue syndrome (CFS). However, studies have been limited by small sample sizes, use of patients from tertiary care settings, inappropriate selection of controls, and failure to control for confounding demographic, medical and behavioral factors independently associated with immune activity. It is also not known whether specific symptoms account for observed associations between CFS and the innate immune response.

To address these limitations, the current study examined plasma concentrations of high-sensitivity c-reactive protein (hs-CRP), white blood cell count (WBC) and a combined inflammation factor in a large population-based sample. Log-transformed mean plasma concentrations of hs-CRP were increased in subjects with CFS (n=102) and in subjects with unwellness symptoms that did not meet diagnostic criteria for CFS (defined as “insufficient fatigue” [ISF]) (n=240) when compared to subjects who were well (n=115). Log transformed WBC was increased in ISF and was increased at a trend level in CFS. The combined inflammation factor was increased in both CFS and ISF. Subjects with CFS and ISF did not differ on any of the inflammation measures.

In the entire subject population, the physical component summary score (PCS), but not the mental component summary score (MCS), from the Medical Outcomes Study Short Form-36 (SF-36) was negatively associated with each of the inflammation measures. Depressive symptoms were also associated with increased log hs-CRP. After adjustment for age, sex, race, location of residence, BMI, depressive status and immune-modulating medications, subjects classified as ISF continued to demonstrate increased log hs-CRP, WBC and elevations on the inflammation factor when compared to well controls; however, associations between CFS and log hs-CRP and the inflammation factor were no longer statistically significant. After adjustment, PCS score also remained independently associated with each of the inflammation measures.

These findings support a role for innate immune activation in unexplained fatigue and unwellness, but do not suggest that immune activation is specific to CFS.

Comment in: Chronic fatigue syndrome and the immune system: “findings in search of meanings”. [Brain Behav Immun. 2009]

 

Source: Raison CL, Lin JM, Reeves WC. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun. 2009 Mar;23(3):327-37. doi: 10.1016/j.bbi.2008.11.005. Epub 2008 Dec 11. https://www.ncbi.nlm.nih.gov/pubmed/19111923

 

Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings?

Abstract:

OBJECTIVE: The validity of the diagnosis of chronic fatigue syndrome and related chronic fatigue states remains controversial, particularly in psychiatry. This project utilized international epidemiological and clinical research data to test construct validity across diagnostic categories, health-care settings and countries. Relevant demographic, symptom and diagnostic data were obtained from 33 studies in 21 countries. The subjects had fatigue lasting 1-6 months (prolonged fatigue), or >6 months (chronic fatigue), or met diagnostic criteria for chronic fatigue syndrome.

METHOD: Common symptom domains were derived by factor analytic techniques. Mean scores on each symptom factor were compared across diagnostic categories, health-care settings and countries.

RESULTS: Data were obtained on 37,724 subjects (n = 20,845 female, 57%), including from population-based studies (n = 15,749, 42%), studies in primary care (n = 19 472, 52%), and secondary or specialist tertiary referral clinics (n = 2503, 7%). The sample included 2013 subjects with chronic fatigue, and 1958 with chronic fatigue syndrome. A five-factor model of the key symptom domains was preferred (‘musculoskeletal pain/fatigue’, ‘neurocognitive difficulties’, ‘inflammation’, ‘sleep disturbance/fatigue’ and ‘mood disturbance’) and was comparable across subject groups and settings. Although the core symptom profiles were similar, some differences in symptoms were observed across diagnostic categories, health-care settings and between countries.

CONCLUSIONS: The construct validity of chronic fatigue and chronic fatigue syndrome is supported by an empirically derived factor structure from existing international datasets.

 

 

Source: Hickie I, Davenport T, Vernon SD, Nisenbaum R, Reeves WC, Hadzi-Pavlovic D, Lloyd A; International Chronic Fatigue Syndrome Study Group. Collaborators (28) Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings? Aust N Z J Psychiatry. 2009 Jan;43(1):25-35. Doi: 10.1080/00048670802534432. https://www.ncbi.nlm.nih.gov/pubmed/19085525

 

Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy

Abstract:

OBJECTIVE: To investigate factors associated with school attendance and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME).

DESIGN: Cross-sectional study.

SETTING: Regional specialist CFS/ME service.

PATIENTS: Children and young people aged under 18 years.

OUTCOME MEASURES: Self-reported school attendance and physical function measured using the physical function subscale of the Short Form 36.

METHODS: Linear and logistic regression analysis of data from self-completed assessment forms on children attending a regional specialist service between 2004 and 2007. Analyses were done in two groups of children: with a completed Spence Children’s Anxiety Scale (SCAS) and with a completed Hospital Anxiety and Depression Scale (HADS).

RESULTS: Of 211 children with CFS/ME, 62% attended 40% of school or less. In children with completed SCAS, those with better physical function were more likely to attend school (adjusted odds ratio (OR) 1.70; 95% CI 1.36 to 2.13). This was also true for those with completed HADS (adjusted OR 2.05; 95% CI 1.4 to 3.01). Increasing fatigue and pain and low mood were associated with worse physical function. There was no evidence that anxiety, gender, age at assessment, family history of CFS/ME or time from onset of symptoms to assessment in clinic were associated with school attendance or physical function.

IMPLICATIONS: Paediatricians should recognise that reduced school attendance is associated with reduced physical function rather than anxiety. Improving school attendance in children with CFS/ME should focus on evidence-based interventions to improve physical function, particularly concentrating on interventions that are likely to reduce pain and fatigue.

 

Source: Crawley E, Sterne JA. Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy. Arch Dis Child. 2009 Oct;94(10):752-6. doi: 10.1136/adc.2008.143537. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19001477