Continuing medical education challenges in chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) affects at least 4 million people in the United States, yet only 16% of people with CFS have received a diagnosis or medical care for their illness. Educating health care professionals about the diagnosis and management of CFS may help to reduce population morbidity associated with CFS.

METHODS: This report presents findings over a 5-year period from May 2000 to June 2006 during which we developed and implemented a health care professional educational program. The objective of the program was to distribute CFS continuing education materials to providers at professional conferences, offer online continuing education credits in different formats (e.g., print, video, and online), and evaluate the number of accreditation certificates awarded.

RESULTS: We found that smaller conference size (OR = 80.17; 95% CI 8.80, 730.25), CFS illness related target audiences (OR = 36.0; 95% CI 2.94, 436.34), and conferences in which CFS research was highlighted (OR = 4.15; 95% CI 1.16, 14.83) significantly contributed to higher dissemination levels, as measured by visit rates to the education booth. While print and online courses were equally requested for continuing education credit opportunities, the online course resulted in 84% of the overall award certificates, compared to 14% for the print course. This remained consistent across all provider occupations: physicians, nurses, physician assistants, and allied health professionals.

CONCLUSION: These findings suggest that educational programs promoting materials at conferences may increase dissemination efforts by targeting audiences, examining conference characteristics, and promoting online continuing education forums.

 

Source: Brimmer DJ, McCleary KK, Lupton TA, Faryna KM, Reeves WC. Continuing medical education challenges in chronic fatigue syndrome. BMC Med Educ. 2009 Dec 2;9:70. doi: 10.1186/1472-6920-9-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795739/ (Full article)

 

An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome

Abstract:

BACKGROUND: The diagnosis of chronic fatigue syndrome (CFS) in research studies requires the exclusion of subjects with medical and psychiatric conditions that could confound the analysis and interpretation of results. This study compares illness parameters between individuals with CFS who have and those who do not have exclusionary conditions.

METHODS: We used a population-based telephone survey of randomly selected individuals, followed by a clinical evaluation in the study metropolitan, urban, and rural counties of Georgia, USA. The medical and psychiatric histories of the subjects were examined and they underwent physical and psychiatric examinations and laboratory screening. We also employed the multidimensional fatigue inventory (MFI), the medical outcomes survey short form-36 (SF-36) and the US Centres for Disease Control and Prevention symptom inventory (SI).

RESULTS: Twenty-nine percent (1,609) of the 5623 subjects who completed the detailed telephone interview reported exclusionary diagnoses and we diagnosed an exclusionary condition in 36% of 781 clinically evaluated subjects. Both medical and psychiatric exclusionary conditions were more common in women, blacks and participants from rural areas. Subjects with and without exclusions had similar levels of fatigue and impairment as measured by the MFI and SF-36; those with CFS-like illness (not meeting the formal CFS definition) were more likely to have an exclusionary diagnosis. After adjusting for demographics, body mass index, fatigue subscales, SF-36 subscales and CFS symptoms, CFS-like illness did not remain significantly associated with having an exclusionary diagnosis.

CONCLUSION: Medical and psychiatric illnesses associated with fatigue are common among the unwell. Those who fulfill CFS-like criteria need to be evaluated for potentially treatable conditions. Those with exclusionary conditions are equally impaired as those without exclusions.

Comment in: Chronic fatigue syndrome: identifying zebras amongst the horses. [BMC Med. 2009]

 

Source: Jones JF, Lin JM, Maloney EM, Boneva RS, Nater UM, Unger ER, Reeves WC. An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome. BMC Med. 2009 Oct 12;7:57. doi: 10.1186/1741-7015-7-57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768736/ (Full article)

 

Electroencephalographic correlates of Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Unremitting fatigue and unrefreshing sleep, hallmark traits of Chronic Fatigue Syndrome (CFS), are also pathognomonic of sleep disorders. Yet, no reproducible perturbations of sleep architecture, multiple sleep latency times or Epworth Sleepiness Scores are found to be associated consistently with CFS. This led us to hypothesize that sleep homeostasis, rather than sleep architecture, may be perturbed in CFS. To probe this hypothesis, we measured and compared EEG frequencies associated with restorative sleep between persons with CFS and matched controls, both derived from a population-based sample.

METHODS: We evaluated overnight polysomnography (PSG) in 35 CFS and 40 control subjects. PSG records were manually scored and epochs containing artifact removed. Fast Fourier Transformation was utilized to deconstruct individual EEG signals into primary frequency bands of alpha, delta, theta, sigma, and beta frequency domains. The spectral power of each frequency domain for each sleep state was compared between persons with CFS and matched controls.

RESULTS: In persons with CFS, delta power was diminished during slow wave sleep, but elevated during both stage 1 and REM. Alpha power was reduced during stage 2, slow wave, and REM sleep. Those with CFS also had significantly lower theta, sigma, and beta spectral power during stage 2, Slow Wave Sleep, and REM.

DISCUSSION: Employing quantitative EEG analysis we demonstrate reduced spectral power of cortical delta activity during SWS. We also establish reduced spectral power of cortical alpha activity, with the greatest reduction occurring during REM sleep. Reductions in theta, beta, and sigma spectral power were also apparent.

CONCLUSION: Unremitting fatigue and unrefreshing sleep, the waking manifestations of CFS, may be the consequence of impaired sleep homeostasis rather than a primary sleep disorder.

 

Source: Decker MJ, Tabassum H, Lin JM, Reeves WC. Electroencephalographic correlates of Chronic Fatigue Syndrome. Behav Brain Funct. 2009 Oct 6;5:43. doi: 10.1186/1744-9081-5-43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765956/ (Full article)

 

Use of medications by people with chronic fatigue syndrome and healthy persons: a population-based study of fatiguing illness in Georgia

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating condition of unknown etiology and no definitive pharmacotherapy. Patients are usually prescribed symptomatic treatment or self-medicate. We evaluated prescription and non-prescription drug use among persons with CFS in Georgia and compared it to that in non-fatigued Well controls and also to chronically Unwell individuals not fully meeting criteria for CFS.

METHODS: A population-based, case-control study. To identify persons with possible CFS-like illness and controls, we conducted a random-digit dialing telephone screening of 19,807 Georgia residents, followed by a detailed telephone interview of 5,630 to identify subjects with CFS-like illness, other chronically Unwell, and Well subjects. All those with CFS-like illness (n = 469), a random sample of chronically Unwell subjects (n = 505), and Well individuals (n = 641) who were age-, sex-, race-, and geographically matched to those with CFS-like illness were invited for a clinical evaluation and 783 participated (48% overall response rate). Clinical evaluation identified 113 persons with CFS, 264 Unwell subjects with insufficient symptoms for CFS (named ISF), and 124 Well controls; the remaining 280 subjects had exclusionary medical or psychiatric conditions, and 2 subjects could not be classified. Subjects were asked to bring all medications taken in the past 2 weeks to the clinic where a research nurse viewed and recorded the name and the dose of each medication.

RESULTS: More than 90% of persons with CFS used at least one drug or supplement within the preceding two weeks. Among users, people with CFS used an average of 5.8 drugs or supplements, compared to 4.1 by ISF and 3.7 by Well controls. Persons with CFS were significantly more likely to use antidepressants, sedatives, muscle relaxants, and anti-acids than either Well controls or the ISF group. In addition, persons with CFS were significantly more likely to use pain-relievers, anti-histamines and cold/sinus medications than were Well controls.

CONCLUSION: Medical care providers of patients with chronic fatigue syndrome should be aware of polypharmacy as a problem in such patients, and the related potential iatrogenic effects and drug interactions.

 

Source: Boneva RS, Lin JM, Maloney EM, Jones JF, Reeves WC. Use of medications by people with chronic fatigue syndrome and healthy persons: a population-based study of fatiguing illness in Georgia. Health Qual Life Outcomes. 2009 Jul 20;7:67. doi: 10.1186/1477-7525-7-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731740/ (Full article)

 

Psychiatric comorbidity in persons with chronic fatigue syndrome identified from the Georgia population

Abstract:

OBJECTIVE: To compare the prevalence of psychiatric disorders in persons with chronic fatigue syndrome (CFS) identified from the general population and a chronically ill group of people presenting with subsyndromic CFS-like illness (“insufficient symptoms or fatigue” (ISF)). Previous studies in CFS patients from primary and tertiary care clinics have found high rates of psychiatric disturbance, but this may reflect referral bias rather than true patterns of comorbidity with CFS.

METHODS: We used random digit dialing to identify unwell individuals. A detailed telephone interview identified those with CFS-like illness. These individuals participated in a 1-day clinical evaluation to confirm CFS or ISF status. We identified 113 cases of CFS and 264 persons with ISF. To identify current and lifetime psychiatric disorders, participants completed the Structured Clinical Interview for DSM-IV.

RESULTS: Sixty-four persons (57%) with CFS had at least one current psychiatric diagnosis, in contrast to 118 persons (45%) with ISF. One hundred one persons (89%) with CFS had at least one lifetime psychiatric diagnosis compared with 208 persons (79%) with ISF. Of note, only 11 persons (9.8%) with CFS and 25 persons (9.5%) with ISF reported having seen a mental healthcare specialist during the past 6 months.

CONCLUSIONS: Our findings indicate that current and lifetime psychiatric disorders commonly accompany CFS in the general population. Most CFS cases with comorbid psychiatric conditions had not sought appropriate help during the past 6 months. These results demonstrate an urgent need to address psychiatric disorders in the clinical care of CFS cases.

Comment in: Criteria used to define chronic fatigue syndrome questioned. [Psychosom Med. 2010]

 

Source: Nater UM, Lin JM, Maloney EM, Jones JF, Tian H, Boneva RS, Raison CL, Reeves WC, Heim C. Psychiatric comorbidity in persons with chronic fatigue syndrome identified from the Georgia population. Psychosom Med. 2009 Jun;71(5):557-65. doi: 10.1097/PSY.0b013e31819ea179. Epub 2009 May 4. https://www.ncbi.nlm.nih.gov/pubmed/19414619

 

Chronic fatigue syndrome and high allostatic load: results from a population-based case-control study in Georgia

Abstract:

OBJECTIVE: To confirm the association of chronic fatigue syndrome (CFS) with high allostatic load (AL) level, examine the association of subsyndromal CFS with AL level, and investigate the effect of depression on these relationships and the association of AL with functional impairment, fatigue, symptom severity, fatigue duration, and type of CFS onset. AL represents the cumulative physiologic effect of demands to adapt to stress.

METHODS: Population-based case-control study of 83 persons with CFS, 202 persons with insufficient symptoms or fatigue for CFS (ISF), and 109 well controls living in Georgia. Unconditional logistic regression was used to generate odds ratios (ORs) as measures of the association of AL with CFS.

RESULTS: Relative to well controls, each 1-point increase in allostatic load index (ALI) was associated with a 26% increase in likelihood of having CFS (OR(adjusted) = 1.26, 95% Confidence Interval (CI) = 1.00, 1.59). This association remained in the presence and absence of depression (OR(adjusted) = 1.35, CI = 1.07, 1.72; OR(adjusted) = 1.35, CI = 1.10, 1.65). Compared with the ISF group, each 1-point increase in ALI was associated with a 10% increase in likelihood of having CFS (OR(adjusted) = 1.10, CI = 0.93, 1.31). Among persons with CFS, the duration of fatigue was inversely correlated with ALI (r = -.26, p = .047).

CONCLUSIONS: Compared with well controls, persons with CFS were significantly more likely to have a high AL. AL increased in a gradient across well, ISF, and CFS groups.

 

Source: Maloney EM, Boneva R, Nater UM, Reeves WC. Chronic fatigue syndrome and high allostatic load: results from a population-based case-control study in Georgia. Psychosom Med. 2009 Jun;71(5):549-56. doi: 10.1097/PSY.0b013e3181a4fea8. Epub 2009 May 4. https://www.ncbi.nlm.nih.gov/pubmed/19414615 (Full article)

 

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)

 

Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction

Abstract:

CONTEXT: Childhood trauma appears to be a potent risk factor for chronic fatigue syndrome (CFS). Evidence from developmental neuroscience suggests that early experience programs the development of regulatory systems that are implicated in the pathophysiology of CFS, including the hypothalamic-pituitary-adrenal axis. However, the contribution of childhood trauma to neuroendocrine dysfunction in CFS remains obscure.

OBJECTIVES: To replicate findings on the relationship between childhood trauma and risk for CFS and to evaluate the association between childhood trauma and neuroendocrine dysfunction in CFS.

DESIGN, SETTING, AND PARTICIPANTS: A case-control study of 113 persons with CFS and 124 well control subjects identified from a general population sample of 19 381 adult residents of Georgia.

MAIN OUTCOME MEASURES: Self-reported childhood trauma (sexual, physical, and emotional abuse; emotional and physical neglect), psychopathology (depression, anxiety, and posttraumatic stress disorder), and salivary cortisol response to awakening.

RESULTS: Individuals with CFS reported significantly higher levels of childhood trauma and psychopathological symptoms than control subjects. Exposure to childhood trauma was associated with a 6-fold increased risk of CFS. Sexual abuse, emotional abuse, and emotional neglect were most effective in discriminating CFS cases from controls. There was a graded relationship between exposure level and CFS risk. The risk of CFS conveyed by childhood trauma further increased with the presence of posttraumatic stress disorder symptoms. Only individuals with CFS and with childhood trauma exposure, but not individuals with CFS without exposure, exhibited decreased salivary cortisol concentrations after awakening compared with control subjects.

CONCLUSIONS: Our results confirm childhood trauma as an important risk factor of CFS. In addition, neuroendocrine dysfunction, a hallmark feature of CFS, appears to be associated with childhood trauma. This possibly reflects a biological correlate of vulnerability due to early developmental insults. Our findings are critical to inform pathophysiological research and to devise targets for the prevention of CFS.

 

Source: Heim C, Nater UM, Maloney E, Boneva R, Jones JF, Reeves WC. Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction. Arch Gen Psychiatry. 2009 Jan;66(1):72-80. doi: 10.1001/archgenpsychiatry.2008.508. https://www.ncbi.nlm.nih.gov/pubmed/19124690

 

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