large-scale study – Page 5 – American ME and CFS Society

Depression in paediatric chronic fatigue syndrome

Abstract:

OBJECTIVE: To describe the prevalence of depression in children with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and investigate the relationship between depression in CFS/ME and clinical symptoms such as fatigue, disability, pain and school attendance.

DESIGN: Cross-sectional survey data using the Hospital Anxiety and Depression Scale (HADS) collected at assessment.

SETTING: Specialist paediatric CFS/ME service in the South West.

PATIENTS: Children aged 12-18 years with CFS/ME.

MAIN OUTCOME MEASURE: Depression was defined as scoring >9 on the HADS depression scale.

RESULTS: 542 subjects had complete data for the HADS and 29% (156/542) (95% CI 25% to 33%) had depression. In a univariable analysis, female sex, poorer school attendance, and higher levels of fatigue, disability, pain, and anxiety were associated with higher odds of depression. Age of child and duration of illness were not associated with depression. In a multivariable analysis, the factors most strongly associated with depression were disability, with higher scores on the physical function subscale of the 36 item Short Form (SF-36).

CONCLUSIONS: Depression is commonly comorbid with CFS/ME, much more common than in the general population, and is associated with markers of disease severity. It is important to screen for, identify and treat depression in this population.

Source: Bould H, Collin SM, Lewis G, Rimes K, Crawley E. Depression in paediatric chronic fatigue syndrome. Arch Dis Child. 2013 Jun;98(6):425-8. doi: 10.1136/archdischild-2012-303396. Epub 2013 Apr 25. https://www.ncbi.nlm.nih.gov/pubmed/23619200

Treatment outcome in adults with chronic fatigue syndrome: a prospective study in England based on the CFS/ME National Outcomes Database

Erratum in: QJM. 2013 Jun;106(6):567.

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is relatively common and disabling. Over 8000 patients attend adult services each year, yet little is known about the outcome of patients attending NHS services.

AIM: Investigate the outcome of patients with CFS and what factors predict outcome.

DESIGN: Longitudinal patient cohort.

METHODS: We used data from six CFS/ME (myalgic encephalomyelitis) specialist services to measure changes in fatigue (Chalder Fatigue Scale), physical function (SF-36), anxiety and depression (Hospital Anxiety and Depression Scale) and pain (visual analogue pain rating scale) between clinical assessment and 8-20 months of follow-up. We used multivariable linear regression to investigate baseline factors associated with outcomes at follow-up.

RESULTS: Baseline data obtained at clinical assessment were available for 1643 patients, of whom 834 (51%) had complete follow-up data. There were improvements in fatigue [mean difference from assessment to outcome: -6.8; 95% confidence interval (CI) -7.4 to -6.2; P < 0.001]; physical function (4.4; 95% CI 3.0-5.8; P < 0.001), anxiety (-0.6; 95% CI -0.9 to -0.3; P < 0.001), depression (-1.6; 95% CI -1.9 to -1.4; P < 0.001) and pain (-5.3; 95% CI -7.0 to -3.6; P < 0.001). Worse fatigue, physical function and pain at clinical assessment predicted a worse outcome for fatigue at follow-up. Older age, increased pain and physical function at assessment were associated with poorer physical function at follow-up.

CONCLUSION: Patients who attend NHS specialist CFS/ME services can expect similar improvements in fatigue, anxiety and depression to participants receiving cognitive behavioural therapy and graded exercise therapy in a recent trial, but are likely to experience less improvement in physical function. Outcomes were predicted by fatigue, disability and pain at assessment.

Comment in: RE: ‘Treatment outcome in adults with chronic fatigue syndrome: a prospective study. [QJM. 2014]

Source: Crawley E, Collin SM, White PD, Rimes K, Sterne JA, May MT; CFS/ME National Outcomes Database. Treatment outcome in adults with chronic fatigue syndrome: a prospective study in England based on the CFS/ME National Outcomes Database. QJM. 2013 Jun;106(6):555-65. doi: 10.1093/qjmed/hct061. Epub 2013 Mar 28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665909/ (Full article)

Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome

Abstract:

OBJECTIVES: A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features.

METHODS: A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health-funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing.

RESULTS: CFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P < 0.0001), less fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS-D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values.

CONCLUSIONS: The presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate.

Comment in: Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning. [J Intern Med. 2013]

Source: Lewis I, Pairman J, Spickett G, Newton JL. Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. J Intern Med. 2013 May;273(5):501-10. doi: 10.1111/joim.12022. Epub 2013 Jan 7. http://onlinelibrary.wiley.com/doi/10.1111/joim.12022/full (Full article)

A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a severely debilitating disease of unknown pathogenesis consisting of a variety of symptoms including severe fatigue. The objective of the study was to examine the efficacy and safety of a TLR-3 agonist, rintatolimod (Poly I: C(12)U), in patients with debilitating CFS/ME.

METHODS AND FINDINGS: A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites. The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET). Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS), Activities of Daily Living (ADL), and Vitality Score (SF 36). Subjects receiving rintatolimod for 40 weeks improved intra-patient placebo-adjusted ET 21.3% (p = 0.047) from baseline in an intention-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo-adjusted ET improvement to 28% (p = 0.022). The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies. The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048). Placebo subjects crossed-over to receive rintatolimod demonstrated an intra-patient improvement in ET performance at 24 weeks of 39% (p = 0.04). Rintatolimod at 400 mg twice weekly was generally well-tolerated.

CONCLUSIONS/SIGNIFICANCE: Rintatolimod produced objective improvement in ET and a reduction in CFS/ME related concomitant medication usage as well as other secondary outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov NCT00215800.

Source: Strayer DR, Carter WA, Stouch BC, Stevens SR, Bateman L, Cimoch PJ, Lapp CW, Peterson DL; Chronic Fatigue Syndrome AMP-516 Study Group, Mitchell WM.Collaborators (12). A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome. PLoS One. 2012;7(3):e31334. doi: 10.1371/journal.pone.0031334. Epub 2012 Mar 14.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303772/ (Full article)

Alternative diagnoses to chronic fatigue syndrome in referrals to a specialist service: service evaluation survey

Abstract:

OBJECTIVE: To assess the accuracy of diagnoses made by referrers to a chronic fatigue syndrome (CFS) service.

DESIGN: Retrospective service evaluation surveys of both rejected referral letters and medical case-notes after full clinical assessment.

SETTING: A specialist CFS clinic in London, UK.

PARTICIPANTS: In the first survey, we assessed rejected referral letters between March 2007 and September 2008. In the second survey, we ascertained the primary diagnosis made in case-notes of 250 consecutive new patients assessed between April 2007 and November 2008.

MAIN OUTCOME MEASURES: Reasons for rejection of referrals and primary diagnosis in those assessed.

RESULTS: In the first survey, 154 out of 418 referrals (37%) were rejected. Of these, 77 out of the available 127 referrals (61%) had a likely alternative diagnosis. In the second survey of clinically assessed patients, 107 (43%) had alternative medical/psychiatric diagnoses, while 137 out of 250 (54%) patients received a diagnosis of CFS. The commonest alternative medical diagnoses of those assessed were sleep disorders and the commonest alternative psychiatric diagnosis was depressive illness. Altogether 184 of 377 (49%) patients had alternative diagnoses to CFS.

CONCLUSIONS: Half of all the referred patients to a specialist CFS clinic had alternative medical and psychiatric diagnoses. Specialist medical assessment for patients with unexplained, disabling, chronic fatigue needs to incorporate both medical and psychiatric assessments.

Source: Devasahayam A, Lawn T, Murphy M, White PD. Alternative diagnoses to chronic fatigue syndrome in referrals to a specialist service: service evaluation survey. JRSM Short Rep. 2012 Jan;3(1):4. doi: 10.1258/shorts.2011.011127. Epub 2012 Jan 12.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269106/ (Full article)

Validation of the three-factor model of the PSQI in a large sample of chronic fatigue syndrome (CFS) patients

Abstract:

OBJECTIVE: To evaluate whether a 3-factor model of the Pittsburgh Sleep Quality Index (PSQI) scale would fit the constellation of sleep disturbances in patients with a diagnosis of chronic fatigue syndrome (CFS).

METHODS: Consecutive CFS patients filled out the PSQI. Scores from this self-report questionnaire were examined with exploratory and confirmatory factor analysis (CFA).

RESULTS: 413 CFS patients were included for analysis in this study. CFA showed that the 7 PSQI component scores clustered into the 3 factors reported by Cole et al. (2006), i.e. Sleep Efficiency, Perceived Sleep Quality and Daily Disturbances. In contrast with the single-factor and all 2-factor models, all factor loadings were significant, and all goodness-of-fit values were acceptable.

CONCLUSION: In CFS, the PSQI operates as a 3-factor scoring model as initially seen in healthy and depressed older adults. The separation into 3 discrete factors suggests the limited usefulness of the global PSQI as a single factor for the assessment of subjective sleep quality, as also evidenced by a low Cronbach’s alpha (0.64) in this patient sample.

Source: Mariman A, Vogelaers D, Hanoulle I, Delesie L, Tobback E, Pevernagie D. Validation of the three-factor model of the PSQI in a large sample of chronic fatigue syndrome (CFS) patients. J Psychosom Res. 2012 Feb;72(2):111-3. doi: 10.1016/j.jpsychores.2011.11.004. Epub 2011 Dec 22. https://www.ncbi.nlm.nih.gov/pubmed/22281451

Factor analysis of the Beck Depression Inventory-II with patients with chronic fatigue syndrome

Abstract:

This study examined the properties of the Beck Depression Inventory-II (BDI-II) in a sample of 111 patients with chronic fatigue syndrome (CFS). Exploratory factor analysis identified two factors. The mean score for the Somatic-Affective factor was significantly higher than the Cognitive factor. Convergent and discriminant validity were assessed for BDI-II total score, the two factor scores, and the BDI for Primary Care (BDI-PC). The BDI-PC and Cognitive factor demonstrated superior validity. Results suggest patients endorse BDI-II somatic items that overlap with CFS symptoms at a high rate. Factor scores should be evaluated separately, or the BDI-PC should be utilized with this population.

Source: Brown M, Kaplan C, Jason L. Factor analysis of the Beck Depression Inventory-II with patients with chronic fatigue syndrome. J Health Psychol. 2012 Sep;17(6):799-808. doi: 10.1177/1359105311424470. Epub 2011 Nov 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655435/ (Full article)

The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database

Abstract:

BACKGROUND: Few studies have investigated factors associated with discontinuation of employment in patients with CFS/ME or quantified its impact on productivity.

METHODS: We used patient-level data from five NHS CFS/ME services during the period 01/04/2006-31/03/2010 collated in the UK CFS/ME National Outcomes Database. We used logistic regression to identify factors associated with discontinuation of employment. We estimated UK-wide productivity costs using patient-level data on duration of illness before assessment by a CFS/ME service, duration of unemployment, age, sex and numbers of patients, in conjunction with Office for National Statistics income and population data.

RESULTS: Data were available for 2,170 patients, of whom 1,669 (76.9%) were women. Current employment status was recorded for 1,991 patients (91.8%), of whom 811 patients (40.7%) were currently employed and 998 (50.1%) had discontinued their employment “because of fatigue-related symptoms”. Older age, male sex, disability, fatigue, pain, and duration of illness were associated with cessation of employment. In a multivariable model, age, male sex, and disability remained as independent predictors. Total productivity costs among the 2,170 patients due to discontinuation of employment in the years preceding assessment by a specialist CFS/ME service (median duration of illness=36 months) were £49.2 million. Our sample was equivalent to 4,424 UK adults accessing specialist services each year, representing productivity costs to the UK economy of £102.2 million. Sensitivity analyses suggested a range between £75.5-£128.9 million.

CONCLUSIONS: CFS/ME incurs huge productivity costs amongst the small fraction of adults with CFS/ME who access specialist services.

Source: Collin SM, Crawley E, May MT, Sterne JA, Hollingworth W; UK CFS/ME National Outcomes Database. Collaborators (8) The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database. BMC Health Serv Res. 2011 Sep 15;11:217. doi: 10.1186/1472-6963-11-217. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184626/ (Full article)

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.

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)