Tag: Nacul

Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls

Abstract:

Background: People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continue to struggle to have their condition recognised as disabling in the face of public and professional prejudice and discrimination.

Objective: The aim of this study was to compare the functional status and well-being of people with well-characterised ME/CFS with people with multiple sclerosis (PWMS), as well as healthy controls (HCs).

Methods: In this cross-sectional study, we used data collected as part of the UK ME/CFS Biobank to compare actual participant scores from the Medical Outcomes Survey Short Form-36 v2™ (SF-36v2™) between groups, as a proxy for impact of disability, and from a bespoke questionnaire seeking data on employment and income.

Results: People with ME/CFS scored significantly lower than PWMS or HCs in almost all SF-36v2™ areas. Prominent were lower scores for people with ME/CFS in the Physical Component Summary and Role Physical and Social Function domains, while the smallest differences were seen in the Mental Health domain. Responses to the bespoke questionnaire indicated that people with ME/CFS in this study work fewer hours and have lower incomes compared with people in the other two groups.

Conclusions: Using SF-36v2™ scores as a proxy, people with ME/CFS were measurably more disabled than PWMS or HCs in this study population. Furthermore, employment and income data are consistent with loss of functional status. These findings should encourage the health community to recognise the disabling effects of ME/CFS, to advocate for the needs of people with ME/CFS, and to investigate strategies to address the cost of the disease to both individuals and society.

Source: Caroline C. Kingdon, Erinna W. Bowman, Hayley Curran, Luis Nacul, Eliana M. Lacerda. Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls.PharmacoEconomics Open (2018). https://doi.org/10.1007/s41669-018-0071-6  (Full article)

Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome

Excerpt:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterised by unexplained and persistent or recurrent incapacitating fatigue accompanied by a variety of symptoms and substantial reductions in previous levels of occupational, educational, social and/or personal activity [1, 2]. Given the absence of biomarkers for diagnosis, ME/CFS is defined by a combination of symptoms, most of which are non-specific and common to a number of diseases and conditions.

Over 20 case definitions have been proposed, leading to large variations in sensitivity and specificity of diagnosis. These diverse sets of diagnostic criteria and distinct ways in which they have been applied pose significant problems, as research results may vary considerably according to which definition is used. A particular problem occurs when overly inclusive criteria are used, since their lack of specificity may lead to considerable selection bias [3, 4]. Unfortunately, many studies, clinical trials in particular, have used broad case definitions such as the Oxford criteria [5], which requires little more than the presence of persistent significant fatigue for over 6 months and the exclusion of conditions that could explain symptoms, for a diagnosis to be made.

This problem has been highlighted by the Agency for Healthcare Research and Quality (AHRQ) review of evidence for the NIH Pathways to Prevention Workshop [4], which showed significant changes to the interpretation of evidence for treatment, when studies using broad case definitions, such as the Oxford criteria, are excluded from the analysis. The implications for clinical practice suggest that fit-for-all management approaches to ME/CFS, although more applicable to those who fit such broadly inclusive criteria, may be inadequate for patients who fulfil better targeted case definitions.

For patients selected using more restrictive definitions, cognitive behavioural therapy (CBT), graded exercise therapy (GET) and other forms of non-drug management approaches to ME/CFS, are most appropriate as adjunct therapies rather than restorative treatments, when provided by therapists with a good understanding of ME/CFS. These forms of behavioural intervention have been shown to support the well-being and rehabilitation of those suffering from many chronic and disabling conditions [6]. However, it is very important that the use of behaviourally based management strategies does not deter researchers, physicians, and other health professionals from the overarching goal of investigating the causes and pathophysiology of ME/CFS in various sub-groups and the development of specific treatments.

Source: Luis Nacul, PhD, Caroline C. Kingdon, MS, Erinna W Bowman, MSc, Hayley Curran, MS, and Eliana M Lacerda, PhD. Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome.Fatigue. Author manuscript; available in PMC 2017 Dec 14. Published in final edited form as: Fatigue. 2017; 5(1): 1–4. Published online 2017 Jan 8. doi: 10.1080/21641846.2017.1273863 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730342/ (Full article)

How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome has been a controversial diagnosis, resulting in tensions between patients and professionals providing them with care. A major constraint limiting progress has been the lack of a ‘gold standard’ for diagnosis; with a number of imperfect clinical and research criteria used, each defining different, though overlapping, groups of people with myalgic encephalomyelitis or chronic fatigue syndrome. We review basic epidemiological concepts to illustrate how the use of more specific and restrictive case definitions could improve research validity and drive progress in the field by reducing selection bias caused by diagnostic misclassification.

Source: Nacul L, Lacerda EM, Kingdon CC, Curran H, Bowman EW. How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies? J Health Psychol. 2017 Mar 1:1359105317695803. doi: 10.1177/1359105317695803. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28810428

The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis

Abstract:

The UK ME/CFS Biobank was launched in August 2011 following extensive consultation with professionals and patient representatives. The bioresource aims to enhance research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), related to pathophysiology, biomarkers and therapeutic approaches. The cohort includes 18–60 year olds, encompassing 284 clinically-confirmed ME/CFS cases, 60 neurologist-diagnosed multiple sclerosis (MS) cases, and 135 healthy individuals. The Biobank contains blood samples, aliquoted into serum, plasma, peripheral blood mononuclear cells (PBMC), red blood cells/granulocyte pellet, whole blood, and RNA (totalling 29,863 aliquots). Extensive dataset (700 clinical and socio-demographic variables/participant) enables comprehensive phenotyping. Potential reuse is conditional to ethical approval.

Source: Eliana M Lacerda , Erinna W Bowman, Jacqueline M Cliff, Caroline C Kingdon, Elizabeth C King, Ji-Sook Lee, Taane G Clark, Hazel M Dockrell, Eleanor M Riley, Hayley Curran, Luis Nacul. The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis. Open Journal of Bioresources. 4(1), p.4. DOI: http://doi.org/10.5334/ojb.28 http://openbioresources.metajnl.com/articles/10.5334/ojb.28/ (Full article)

Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS

Abstract:

BACKGROUND: There are considerable phenotypic and neuroimmune overlaps between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). While the precise aetiologies of both MS and ME/CFS are unclear, evidence suggests that deterioration in cognitive function is widely prevalent in patients with either condition. Little is known about differing risk factors or exposures, which may lead to severe cognitive or sleep symptoms. This study aims to gauge the extent of cognitive and sleep symptoms in ME/CFS and MS patients participating in the UK ME/CFS Biobank and identify the characteristics of those experiencing severe symptoms.

METHODS: This was a cross-sectional study of 395 UK ME/CFS Biobank participants, recruited from primary care and the community, using similar standardised protocols, and matched by age, sex and geographical area. Data were collected from participants using a standardized written questionnaire at clinical visits. Cognitive symptoms included problems with short-term memory, attention, and executive function. Sleep symptoms included unrefreshing sleep and poor quality or inadequate duration of sleep. All participants reported symptoms based on an ordinal severity scale. Multivariable logistic regression was carried out in the ME/CFS group to investigate socio-demographic factors associated with severe symptoms.

RESULTS: All cognitive and sleep symptoms were more prevalent in the ME/CFS group, with 'trouble concentrating' (98.3%) the most commonly reported symptom. Severe symptoms were also more commonly reported in the ME/CFS group, with 55% reporting 'severe, unrefreshing sleep'. Similarly, in the MS group, the most commonly reported severe symptoms were sleep-related. Logistic regression analysis revealed that ME/CFS patients aged over 50 years were more than three times as likely to experience severe symptoms than those younger than 30 (OR 3.23, p = 0.031). Current smoking was associated with severe symptoms, increasing the risk by approximately three times (OR 2.93, p = 0.003) and those with household incomes of more than £15,000 per year were less likely to experience severe symptoms compared to those earning less than this (OR 0.31, p = 0.017).

CONCLUSIONS:Cognitive and sleep symptoms are more common in ME/CFS patients than in MS patients and healthy controls, providing further support for existing evidence of central nervous system abnormalities in ME/CFS. Our findings suggest that people with ME/CFS who are smokers, or have a low income, are more likely to report severe cognitive and sleep symptoms. Future research should aim to develop strategies to prevent the progression of severe cognitive and sleep symptoms through early interventions that prioritise patients identified as being at highest risk.

Source: Jain V, Arunkumar A, Kingdon C, Lacerda E, Nacul L. Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS. BMC Neurol. 2017 Jun 20;17(1):117. doi: 10.1186/s12883-017-0896-0. https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-017-0896-0 (Full article)

Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol

Abstract:

BACKGROUND: Our aim, having previously investigated through a qualitative study involving extensive discussions with experts and patients the issues involved in establishing and maintaining a disease specific brain and tissue bank for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), was to develop a protocol for a UK ME/CFS repository of high quality human tissue from well characterised subjects with ME/CFS and controls suitable for a broad range of research applications. This would involve a specific donor program coupled with rapid tissue collection and processing, supplemented by comprehensive prospectively collected clinical, laboratory and self-assessment data from cases and controls.

FINDINGS: We reviewed the operations of existing tissue banks from published literature and from their internal protocols and standard operating procedures (SOPs). On this basis, we developed the protocol presented here, which was designed to meet high technical and ethical standards and legal requirements and was based on recommendations of the MRC UK Brain Banks Network. The facility would be most efficient and cost-effective if incorporated into an existing tissue bank. Tissue collection would be rapid and follow robust protocols to ensure preservation sufficient for a wide range of research uses. A central tissue bank would have resources both for wide-scale donor recruitment and rapid response to donor death for prompt harvesting and processing of tissue.

CONCLUSION: An ME/CFS brain and tissue bank could be established using this protocol. Success would depend on careful consideration of logistic, technical, legal and ethical issues, continuous consultation with patients and the donor population, and a sustainable model of funding ideally involving research councils, health services, and patient charities. This initiative could revolutionise the understanding of this still poorly-understood disease and enhance development of diagnostic biomarkers and treatments.

 

Source: Nacul L, O’Donovan DG, Lacerda EM, Gveric D, Goldring K, Hall A, Bowman E, Pheby D. Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol. BMC Res Notes. 2014 Jun 18;7:370. doi: 10.1186/1756-0500-7-370. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076507/ (Full article)

 

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)

 

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adults: a qualitative study of perspectives from professional practice

Abstract:

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) can cause profound and prolonged illness and disability, and poses significant problems of uncertainty for healthcare professionals in its diagnosis and management. The aim of this qualitative study was to explore the nature of professional ‘best practice’ in working with people with CFS/ME.

METHODS: The views and experiences of health care practitioners (HCPs) were sought, who had been judged by people with CFS/ME themselves to have been particularly helpful and effective. Qualitative semi-structured interviews following a topic guide were carried out with six health care practitioners. Interviews were audio-recorded, transcribed and subject to thematic analysis.

RESULTS: Five main themes were developed: 1) Diagnosis; 2) Professional perspectives on living with CFS/ME; 3) Interventions for treatment and management; 4) Professional values and support for people with CFS/ME and their families; 5) Health professional roles and working practices. Key findings related to: the diagnostic process, especially the degree of uncertainty which may be shared by primary care physicians and patients alike; the continued denial in some quarters of the existence of CFS/ME as a condition; the variability, complexity, and serious impact of the condition on life and living; the onus on the person with CFS/ME to manage their condition, supported by HCPs; the wealth of often conflicting and confusing information on the condition and options for treatment; and the vital role of extended listening and trustful relationships with patients.

CONCLUSIONS: While professional frustrations were clearly expressed about the variability of services both in primary and specialist care and continuing equivocal attitudes to CFS/ME as a condition, there were also strong positive messages for people with CFS/ME where the right services are in place. Many of the findings from these practitioners seen by their patients as helping them more effectively, accord with the existing literature identifying the particular importance of listening skills, respect and trust for establishing a therapeutic relationship which recognises key features of the patient trajectory and promotes effective person-centred management of this complex condition. These findings indicate the need to build such skills and knowledge more systematically into professional training informed by the experience of specialist services and those living with the condition.

 

Source: Horton SM, Poland F, Kale S, Drachler Mde L, de Carvalho Leite JC, McArthur MA, Campion PD, Pheby D, Nacul L. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adults: a qualitative study of perspectives from professional practice. BMC Fam Pract. 2010 Nov 15;11:89. doi: 10.1186/1471-2296-11-89. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994803/ (Full article)

 

Exploring the feasibility of establishing a disease-specific post-mortem tissue bank in the UK: a case study in ME/CFS

Abstract:

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a condition, the aetiology of which remains controversial, and there is still no consensus on its nature and determination. It has rarely been studied in post-mortem examinations, despite increasing evidence of abnormalities from neuroimaging studies.

AIM: To ascertain the feasibility of developing a national post-mortem ME/CFS tissue bank in the UK, to enhance studies on aetiology and pathogenesis, including cell and tissue abnormalities associated with the condition.

METHODS: The case study was carried out combining qualitative methods, ie, key informant interviews, focus group discussions with people with ME/CFS, and a workshop with experts in ME/CFS or in tissue banking.

RESULTS AND CONCLUSIONS: The study results suggest that the establishment of the post-mortem ME/CFS tissue bank is both desirable and feasible, and would be acceptable to the possible tissue donors, provided that some issues were explicitly addressed.

 

Source: Lacerda EM, Nacul L, Pheby D, Shepherd C, Spencer P. Exploring the feasibility of establishing a disease-specific post-mortem tissue bank in the UK: a case study in ME/CFS. J Clin Pathol. 2010 Nov;63(11):1032-4. doi: 10.1136/jcp.2010.082032. Epub 2010 Oct 5. https://www.ncbi.nlm.nih.gov/pubmed/20924033