Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units

Abstract:

BACKGROUND AND OBJECTIVE: The chronic fatigue syndrome (CFS) is a disabling disorder. Few studies are available in our area on the prevalence and characteristics of CFS. Therefore, we carried out a study of a consecutive series of 824 cases diagnosed in two specialized units.

PATIENTS AND METHODS: We evaluated all of the CFS patients seen from January 2008 to June 2010. We analyzed social and demographic data, employment status, time of clinical evolution, trigger factors and onset, Fukuda and Canadian criteria, associated comorbidities and treatment.

RESULTS: A total of 824 patients were included, 748 (91%) woman, mean age 48±9 years. Average age of onset of symptoms was 35±11 years, time to diagnosis 108±88 month. A precipitating factor was identified in 481 (58%) patients, the onset was gradual in 517 (63%) and 515 (62.5%) were not employed. The most outstanding diagnostic criteria of Fukuda were prolonged generalized fatigue after exercise, sleep disturbance and impairments in concentration and short-term memory. The different groups of symptoms defined by the Canadian consensus showed that CFS is a homogeneous entity. Accompanying comorbidity phenomena were anxiety 691 (83%), sicca syndrome 678 (82%), fibromyalgia 450 (55%). A total of 63% of patients (520) received pharmacological treatment.

CONCLUSIONS: CFS is an illness that preferentially affects young women and results in employment absenteeism. The most relevant clinical features were prolonged generalized fatigue after exercise, neurocognitive impairment and sleep disturbance. In the evaluation of the patient, it is very important to apply the Canadian criteria and to assess comorbidity.

Copyright © 2011 Elsevier España, S.L. All rights reserved.

Comment in: Chronic fatigue syndrome: current situation. [Rev Clin Esp. 2011]

 

Source: Ruiz E, Alegre J, García Quintana AM, Aliste L, Blázquez A, Fernández de Sevilla T. Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units. Rev Clin Esp. 2011 Sep;211(8):385-90. doi: 10.1016/j.rce.2011.02.013. Epub 2011 Jul 27. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/21794854

 

Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care

Abstract:

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or chronic fatigue syndrome (CFS) has been used to name a range of chronic conditions characterized by extreme fatigue and other disabling symptoms. Attempts to estimate the burden of disease have been limited by selection bias, and by lack of diagnostic biomarkers and of agreed reproducible case definitions. We estimated the prevalence and incidence of ME/CFS in three regions in England, and discussed the implications of frequency statistics and the use of different case definitions for health and social care planning and for research.

METHODS: We compared the clinical presentation, prevalence and incidence of ME/CFS based on a sample of 143,000 individuals aged 18 to 64 years, covered by primary care services in three regions of England. Case ascertainment involved: 1) electronic search for chronic fatigue cases; 2) direct questioning of general practitioners (GPs) on cases not previously identified by the search; and 3) clinical review of identified cases according to CDC-1994, Canadian and Epidemiological Case (ECD) Definitions. This enabled the identification of cases with high validity.

RESULTS: The estimated minimum prevalence rate of ME/CFS was 0.2% for cases meeting any of the study case definitions, 0.19% for the CDC-1994 definition, 0.11% for the Canadian definition and 0.03% for the ECD. The overall estimated minimal yearly incidence was 0.015%. The highest rates were found in London and the lowest in East Yorkshire. All but one of the cases conforming to the Canadian criteria also met the CDC-1994 criteria, however presented higher prevalence and severity of symptoms.

CONCLUSIONS: ME/CFS is not uncommon in England and represents a significant burden to patients and society. The number of people with chronic fatigue who do not meet specific criteria for ME/CFS is higher still. Both groups have high levels of need for service provision, including health and social care. We suggest combining the use of both the CDC-1994 and Canadian criteria for ascertainment of ME/CFS cases, alongside careful clinical phenotyping of study participants. This combination if used systematically will enable international comparisons, minimization of bias, and the identification and investigation of distinct sub-groups of patients with possibly distinct aetiologies and pathophysiologies, standing a better chance of translation into effective specific treatments.

 

Source: Nacul LC, Lacerda EM, Pheby D, Campion P, Molokhia M, Fayyaz S, Leite JC, Poland F, Howe A, Drachler ML. Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care. BMC Med. 2011 Jul 28;9:91. doi: 10.1186/1741-7015-9-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170215/ (Full article)

 

The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers

Abstract:

BACKGROUND: Diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome or ME/CFS is largely based on clinical history, and exclusion of identifiable causes of chronic fatigue. Characterization of cases and the impact of interventions have been limited due to clinical heterogeneity and a lack of reliable biomarkers for diagnosis and outcome measures. People with ME/CFS (PWME) often report high levels of disability, which are difficult to measure objectively. The well being of family members and those who care for PWME are also likely to be affected. This study aimed to investigate the functional status and well being of PWME and their lay carers, and to compare them with people with other chronic conditions.

METHODS: We used a cross sectional design to study 170 people aged between 18 and 64 years with well characterized ME/CFS, and 44 carers, using SF-36 v2™. Mean physical and mental domains scores (scales and component summaries) were calculated and compared internally and externally with reference standards for the general population and for population groups with 10 chronic diseases.

: SF-36 scores in PWME were significantly reduced, especially within the physical domain (mean norm-based Physical Component Summary (PCS) score = 26.8), but also within the mental domain (mean norm-based score for Mental Component Summary (MCS) = 34.1). The lowest and highest scale scores were for “Role-Physical” (mean = 25.4) and “Mental Health” (mean = 36.7) respectively. All scores were in general lower than those for the general population and diseased-specific norms for other diseases. Carers of those with ME/CFS tended to have low scores in relation to population norms, particularly within the mental domain (mean = 45.4).

CONCLUSIONS: ME/CFS is disabling and has a greater impact on functional status and well being than other chronic diseases such as cancer. The emotional burden of ME/CFS is felt by lay carers as well as by people with ME/CFS. We suggest the use of generic instruments such as SF-36, in combination of other objective outcome measurements, to describe patients and assess treatments.

 

Source: Nacul LC, Lacerda EM, Campion P, Pheby D, Drachler Mde L, Leite JC, Poland F, Howe A, Fayyaz S, Molokhia M. The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers. BMC Public Health. 2011 May 27;11:402. doi: 10.1186/1471-2458-11-402. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123211/ (Full article)

 

Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial

Abstract:

BACKGROUND: Trial findings show cognitive behaviour therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome, but patients’ organisations have reported that these treatments can be harmful and favour pacing and specialist health care. We aimed to assess effectiveness and safety of all four treatments.

METHODS: In our parallel-group randomised trial, patients meeting Oxford criteria for chronic fatigue syndrome were recruited from six secondary-care clinics in the UK and randomly allocated by computer-generated sequence to receive specialist medical care (SMC) alone or with adaptive pacing therapy (APT), CBT, or GET. Primary outcomes were fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks after randomisation, and safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes. We used longitudinal regression models to compare SMC alone with other treatments, APT with CBT, and APT with GET. The final analysis included all participants for whom we had data for primary outcomes. This trial is registered at http://isrctn.org, number ISRCTN54285094.

FINDINGS: We recruited 641 eligible patients, of whom 160 were assigned to the APT group, 161 to the CBT group, 160 to the GET group, and 160 to the SMC-alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3·4 (95% CI 1·8 to 5·0) points lower for CBT (p = 0·0001) and 3·2 (1·7 to 4·8) points lower for GET (p = 0·0003), but did not differ for APT (0·7 [-0·9 to 2·3] points lower; p = 0·38). Compared with SMC alone, mean physical function scores were 7·1 (2·0 to 12·1) points higher for CBT (p = 0·0068) and 9·4 (4·4 to 14·4) points higher for GET (p = 0·0005), but did not differ for APT (3·4 [-1·6 to 8·4] points lower; p=0·18). Compared with APT, CBT and GET were associated with less fatigue (CBT p = 0·0027; GET p = 0·0059) and better physical function (CBT p=0·0002; GET p<0·0001). Subgroup analysis of 427 participants meeting international criteria for chronic fatigue syndrome and 329 participants meeting London criteria for myalgic encephalomyelitis yielded equivalent results. Serious adverse reactions were recorded in two (1%) of 159 participants in the APT group, three (2%) of 161 in the CBT group, two (1%) of 160 in the GET group, and two (1%) of 160 in the SMC-alone group.

INTERPRETATION: CBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition.

FUNDING: UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Comment in:

 

Source: White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O’Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M; PACE trial management group. Collaborators (19). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36. doi: 10.1016/S0140-6736(11)60096-2. Epub 2011 Feb 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065633/ (Full article)

 

A national cross-sectional survey of diagnosed sufferers of myalgic encephalomyelitis/chronic fatigue syndrome: pathways to diagnosis, changes in quality of life and service priorities

Abstract:

BACKGROUND: The diagnosis and treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is subject to debate.

AIMS: To measure the time to diagnosis and services accessed.

METHOD: A national cross-sectional study. A profile and service utilisation questionnaire, information on the pathways to diagnosis, the WHOQoL Brief and a listing of priorities of the needs of participants were used. Individuals were invited to participate if they had a medical diagnosis of ME/CFS.

RESULTS: A total of 211 surveys were returned. Prior to diagnosis sufferers accessed on average 4.5 services after their initial consultation. The mean time to diagnosis was 3.7 years but time ranged from 0 to 34 years. Quality of life deteriorated post-onset. The priority for future service provision was increased understanding and diagnosis of ME/CFS by the medical profession.

CONCLUSION: In order to alleviate the burden on the sufferer there is a greater need for education on this condition.

 

Source: Comiskey C, Larkan F. A national cross-sectional survey of diagnosed sufferers of myalgic encephalomyelitis/chronic fatigue syndrome: pathways to diagnosis, changes in quality of life and service priorities. Ir J Med Sci. 2010 Dec;179(4):501-5. doi: 10.1007/s11845-010-0585-0. Epub 2010 Sep 26. https://www.ncbi.nlm.nih.gov/pubmed/20872086

 

A Comparison of Immune Functionality in Viral versus Non-Viral CFS Subtypes

Abstract:

Participants with CFS were grouped into viral and non-viral onset fatigue categories and assessed for differential immunological marker expression. Peripheral Blood Mononuclear Cells were assessed for differential phenotypic expression of surface adherence glycoproteins on circulating lymphocytes. The flow cytometric analysis employed fluorescent monoclonal antibody labeling.

The viral in comparison to the non-viral group demonstrated significant elevations in several Th1 type subsets including: the percentage and number of CD4+ cells, the percentage and number of CD2+CD26+ cells, the percentage and number of CD2+CD4+CD26+ cells, the percentage and number of CD4+ CD26+ cells, and the percentage of Th2 naïve cells (CD4+ CD45RA+CD62L+).

Of the remaining significant findings, the non viral group demonstrated significant elevations in comparison to the viral group for the following Th1 type subsets: the percentage of CD8+ cells, the percentage of T-cytotoxic suppressor cells (CD3+8+), and the percentage and number of Th1 memory cells (CD8+CD45RA-CD62L-).

The viral group demonstrated a pattern of activation that differed from that of the group with a non-viral etiology, as evidenced by an elevated and out of range percentage and number of CD4+ cells, the percentage of CD2+CD26+, and the percentage of Th2 naïve cells (CD4+CD45RA+CD62L+). Both groups demonstrated reduced and out of range Natural Killer Cell Cytotoxicity and percentage of B-1 cells (CD5+CD19).

In addition, both groups demonstrated an elevated and out of range percentage of CD2+CD8+CD26+, percentage of the Th1 memory subset (CD4+CD45RA-CD62L-), the percentage of Th1 memory and naïve cells (CD8+CD45RA-CD62L-, CD8+CD45RA+CD62L-), the percentage and number of Th2 memory cells (CD4+CD45RA-CD62L+), and the percentage of Th2 memory and naïve cells (CD8+CD45RA-CD62L+, CD8+CD45RA+CD62L+).

These findings imply that the homeostatic mechanism responsible for the regulation of the Th1 (cell mediated) and Th2 (humoral) immune responses is disturbed in CFS. The implications of these findings are discussed.

 

Source: Porter N, Lerch A, Jason LA, Sorenson M, Fletcher MA, Herrington J. A Comparison of Immune Functionality in Viral versus Non-Viral CFS Subtypes. J Behav Neurosci Res. 2010 Jun 1;8(2):1-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951052/ (Full article)

 

Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial

Abstract:

OBJECTIVE: To evaluate the effectiveness of home delivered pragmatic rehabilitation-a programme of gradually increasing activity designed collaboratively by the patient and the therapist-and supportive listening-an approach based on non-directive counselling-for patients in primary care with chronic fatigue syndrome/myalgic encephalomyelitis or encephalitis (CFS/ME).

DESIGN: Single blind, randomised, controlled trial.

SETTING: 186 general practices across the north west of England between February 2005 and May 2007.

PARTICIPANTS: 296 patients aged 18 or over with CFS/ME (median illness duration seven years) diagnosed using the Oxford criteria.

INTERVENTIONS: Participants were randomly allocated to pragmatic rehabilitation, supportive listening, or general practitioner treatment as usual. Both therapies were delivered at home in 10 sessions over 18 weeks by one of three adult specialty general nurses who had received four months’ training, including supervised practice, in each of the interventions. GP treatment as usual was unconstrained except that patients were not to be referred for systematic psychological therapies during the treatment period. Main outcome measures The primary clinical outcomes were fatigue and physical functioning at the end of treatment (20 weeks) and 70 weeks from recruitment compared with GP treatment as usual. Lower fatigue scores and higher physical functioning scores denote better outcomes.

RESULTS: A total of 257 (87%) of the 296 patients who entered the trial were assessed at 70 weeks, the primary outcome point. Analysis was on an intention to treat basis, with robust treatment effects estimated after adjustment for missing data using probability weights. Immediately after treatment (at 20 weeks), patients allocated to pragmatic rehabilitation (n=95) had significantly improved fatigue (effect estimate -1.18, 95% confidence interval -2.18 to -0.18; P=0.021) but not physical functioning (-0.18, 95% CI -5.88 to +5.52; P=0.950) compared with patients allocated to treatment as usual (n=100). At one year after finishing treatment (70 weeks), there were no statistically significant differences in fatigue or physical functioning between patients allocated to pragmatic rehabilitation and those on treatment as usual (-1.00, 95% CI -2.10 to +0.11; P=0.076 and +2.57, 95% CI 3.90 to +9.03; P=0.435). At 20 weeks, patients allocated to supportive listening (n=101) had poorer physical functioning than those allocated to treatment as usual (-7.54, 95% CI -12.76 to -2.33; P=0.005) and no difference in fatigue. At 70 weeks, patients allocated to supportive listening did not differ significantly from those allocated to treatment as usual on either primary outcome.

CONCLUSIONS: For patients with CFS/ME in primary care, pragmatic rehabilitation delivered by trained nurse therapists improves fatigue in the short term compared with unconstrained GP treatment as usual, but the effect is small and not statistically significant at one year follow-up. Supportive listening delivered by trained nurse therapists is not an effective treatment for CFS/ME.

Trial registration International Standard Randomised Controlled Trial Number IRCTN74156610.

Comment in:

Pragmatic rehabilitation for chronic fatigue syndrome. [BMJ. 2010]

Nurse-delivered, home-based pragmatic rehabilitation has a short-term effect on improving fatigue in people with chronic fatigue syndrome compared with usual GP care, but effects were not sustained at 1 year. [Evid Based Nurs. 2010]

 

Source: Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Riste L, Richardson G, Lovell K, Dunn G; Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group and 23 Collaborators. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ. 2010 Apr 23;340:c1777. doi: 10.1136/bmj.c1777. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859122/ (Full article)

 

U.S. healthcare providers’ knowledge, attitudes, beliefs, and perceptions concerning Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating illness with particular difficulties for healthcare providers because there are no diagnostic signs or laboratory tests and because management aims to merely improve symptoms. Further complicating management, healthcare providers’ awareness concerning CFS has not been rigorously assessed. The present study aimed to ascertain United States (U.S.) healthcare providers’ awareness of CFS and to assess their knowledge, attitudes, and beliefs (KAB) related to diagnosis and management of the illness. This information forms the foundation for developing CFS educational strategies.

METHODS: We combined convenience and probability samples to measure CFS KAB among healthcare providers. In the convenience sample, 1,255 healthcare providers (81% response rate) from 13 professional conferences completed a 12-item form. Descriptive statistics were reported for 9 KAB item responses and chi-square tests were performed for examining their association with giving a diagnosis of CFS. We used principal component analysis to construct multidimensional subscales and perform a general linear model to examine factors associated with subscales. The probability sample involved data on 15 CFS-specific questions from 2006 and 2007 DocStyles web-based panel surveys collected from 2,750 physicians (average response rate 55%). We calculated descriptive and chi-square statistics. The significance was set at two-tailed with the alpha level of 0.05.

RESULTS: Healthcare providers in both samples were aware of CFS and exhibited a high level of knowledge. Overall, 96% of respondents in the DocStyles (probability) sample had heard about CFS. Healthcare providers in the conference (convenience) sample demonstrated good KAB scores; physicians’ scores were highest on KAB scales and lowest in perception. Nurses’ scores were lowest in knowledge. More than 40% of physicians reported ever giving a CFS diagnosis and in the DocStyles (probability) sample more than 80% of physicians correctly identified CFS symptoms. Physicians reported professional journals, the Internet, and continuing education programs as the top 3 sources from which they obtain CFS information.

CONCLUSIONS: Findings from these combined samples fill a gap in the evidence-base of U.S. healthcare providers’ and knowledge, attitudes, and beliefs concerning CFS. Importantly, respondents in both samples expressed similar knowledge, attitudes, beliefs and perceptions. Awareness was high and negative attitudes were low. The primary areas for future education should address diagnosis and management of CFS and should be delivered through those venues providers indicated they primarily use. Data from this study provide a benchmark for evaluation the success of these future efforts.

 

Source: Brimmer DJ, Fridinger F, Lin JM, Reeves WC. U.S. healthcare providers’ knowledge, attitudes, beliefs, and perceptions concerning Chronic Fatigue Syndrome. BMC Fam Pract. 2010 Apr 21;11:28. doi: 10.1186/1471-2296-11-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875206/ (Full article)

 

Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary-referral centre in Norway

Abstract:

BACKGROUND: We aimed to compare patients reporting acute infection with those reporting no infection at onset of chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: This study includes 873 patients with CFS referred to a tertiary centre on average 4.8 years after symptom onset. Assessment was by both observer query and self-reports. Antibody analyses against infectious agents including Epstein-Barr virus and enterovirus were performed in a majority of patients.

RESULTS: Females comprised 75.3% of the patient group, and the mean age was 33 years. Initial infection was reported by 77%. There was no difference as to antibody analyses. Logistic regression showed that initial infection was independently associated with acute onset of fatigue, improvement of fatigue at referral, and the following symptoms at referral: fever, tender lymph nodes, and myalgia.

CONCLUSION: CFS patients with initial infection as a precipitating factor more often report acute onset of fatigue, more frequent accompanying symptoms, and more frequent improvement on referral than do patients without initial infection.

 

Source: Naess H, Sundal E, Myhr KM, Nyland HI. Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary-referral centre in Norway. In Vivo. 2010 Mar-Apr;24(2):185-8. https://www.ncbi.nlm.nih.gov/pubmed/20363992

 

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