A logistic regression analysis of risk factors in ME/CFS pathogenesis

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease, whose exact cause remains unclear. A wide range of risk factors has been proposed that helps understanding potential disease pathogenesis. However, there is little consistency for many risk factor associations, thus we undertook an exploratory study of risk factors using data from the UK ME/CFS Biobank participants. We report on risk factor associations in ME/CFS compared with multiple sclerosis participants and healthy controls. Methods: This was a cross-sectional study of 269 people with ME/CFS, including 214 with mild/moderate and 55 with severe symptoms, 74 people with multiple sclerosis (MS), and 134 healthy controls, who were recruited from primary and secondary health services. Data were collected from participants using a standardised written questionnaire. Data analyses consisted of univariate and multivariable regression analysis (by levels of proximity to disease onset). Results: A history of frequent colds (OR = 8.26, P <= 0.001) and infections (OR = 25.5, P = 0.015) before onset were the strongest factors associated with a higher risk of ME/CFS compared to healthy controls. Being single (OR = 4.41, P <= 0.001), having lower income (OR = 3.71, P <= 0.001), and a family history of anxiety is associated with a higher risk of ME/CFS compared to healthy controls only (OR = 3.77, P < 0.001). History of frequent colds (OR = 6.31, P < 0.001) and infections before disease onset (OR = 5.12, P = 0.005), being single (OR = 3.66, P = 0.003) and having lower income (OR = 3.48, P = 0.001), are associated with a higher risk of ME/CFS than MS. Severe ME/CFS cases were associated with lower age of ME/CFS onset (OR = 0.63, P = 0.022) and a family history of neurological illness (OR = 6.1, P = 0.001). Conclusions: Notable differences in risk profiles were found between ME/CFS and healthy controls, ME/CFS and MS, and mild-moderate and severe ME/CFS. However, we found some commensurate overlap in risk associations between all cohorts. The most notable difference between ME/CFS and MS in our study is a history of recent infection prior to disease onset. Even recognising that our results are limited by the choice of factors we selected to investigate, our findings are consistent with the increasing body of evidence that has been published about the potential role of infections in the pathogenesis of ME/CFS, including common colds/flu

How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) progresses. The natural history of ME/CFS

We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to singular or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states. Thus, the predominantly neuro-immune manifestations, underlined by a hyper-metabolic state, that characterize early disease, may be followed by various processes leading to multi-systemic abnormalities and related symptoms. This abnormal state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production. These processes do not seem to happen uniformly; although a spiraling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. With time variation in disease presentation, no single ME/CFS case description, set of diagnostic criteria, or molecular feature is currently representative of all patients at different disease stages. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may support future research design and health care interventions for people with ME/CFS

Assessing the Nutritional Impact of an Increase in Orphan Crops in the Kenyan Diet: The Case of Millet

Orphan crops are those crops that did not receive the same attention of the research community as in the case of staples such as wheat, maize, or rice despite their regional and nutritional importance. A relatively recent trend has been promoting their research to improve their productivity and resilience to environmental shocks. However, their impact on consumers’ nutrition has been analysed only considering the crops individually and not in the context of the diet. This is important because an increase in the consumption of one product may trigger changes in the other products that conform to the diet. The purpose of this paper is to assess the potential impact, in terms of food choices and nutrition, of increasing the consumption of orphan crops (represented by millet) in the Kenyan diet. This is carried out using a microeconomic-based methodology, which augments the original consumer problem with a constraint regarding the amount of the orphan crop on the diet. To compute the required elasticities for the method, three demand systems—i.e., for rural, less affluent urban, more affluent urban households—were estimated using the 2015–16 Kenyan Integrated Household Survey and the two-step approach to address the zero consumption for some food categories; the second step was modelled using the Linquad demand model. The results indicate that although the orphan crops have the capacity to improve some of the nutrients (e.g., vitamins and minerals), in net terms, as measured by the aggregated nutritional indicator the improvement is somewhat limited, the improvements occur in the rural and the less affluent population

Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract: Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterised by fatigue and post-exertional malaise. Its pathogenesis is poorly understood. GDF15 is a circulating protein secreted by cells in response to a variety of stressors. The receptor for GDF15 is expressed in the brain, where its activation results in a range of responses. Among the conditions in which circulating GDF15 levels are highly elevated are mitochondrial disorders, where early skeletal muscle fatigue is a key symptom. We hypothesised that GDF15 may represent a marker of cellular stress in ME/CFS. Methods: GDF15 was measured in serum from patients with ME/CFS (n = 150; 100 with mild/moderate and 50 with severe symptoms), “healthy volunteers” (n = 150) and a cohort of patients with multiple sclerosis (n = 50). Results: Circulating GDF15 remained stable in a subset of ME/CFS patients when sampled on two occasions ~ 7 months (IQR 6.7–8.8) apart, 720 pg/ml (95% CI 625–816) vs 670 pg/ml (95% CI 598–796), P = 0.5. GDF15 levels were 491 pg/ml in controls (95% CI 429–553), 546 pg/ml (95% CI 478–614) in MS patients, 560 pg/ml (95% CI 502–617) in mild/moderate ME/CFS patients and 602 pg/ml (95% CI 531–674) in severely affected ME/CFS patients. Accounting for potential confounders, severely affected ME/CFS patients had GDF15 concentrations that were significantly increased compared to healthy controls (P = 0.01). GDF15 levels were positively correlated (P = 0.026) with fatigue scores in ME/CFS. Conclusions: Severe ME/CFS is associated with increased levels of GDF15, a circulating biomarker of cellular stress that appears which stable over several months

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

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.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. Results 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.Published versio

Improving outcomes for people with COPD by developing networks of general practices: evaluation of a quality improvement project in east London

BACKGROUND: Structured care for people with chronic obstructive pulmonary disease (COPD) can improve outcomes. Delivering care in a deprived ethnically diverse area can prove challenging. AIMS: Evaluation of a system change to enhance COPD care delivery in a primary care setting between 2010 and 2013 using observational data. METHODS: All 36 practices in one inner London primary care trust were grouped geographically into eight networks of 4-5 practices, each supported by a network manager, clerical staff and an educational budget. A multidisciplinary group, including a respiratory specialist and the community respiratory team, developed a 'care package' for COPD management, with financial incentives based on network achievements of clinical targets and supported case management and education. Monthly electronic dashboards enabled networks to track and improve performance. RESULTS: The size of network COPD registers increased by 10% in the first year. Between 2010 and 2013 completed care plans increased from 53 to 86.5%, pulmonary rehabilitation referrals rose from 45 to 70% and rates of flu immunisation from 81 to 83%, exceeding London and England figures. Hospital admissions decreased in Tower Hamlets from a historic high base. CONCLUSIONS: Investment of financial, organisational and educational resource into general practice networks was associated with clinically important improvements in COPD care in socially deprived, ethnically diverse communities. Key behaviour change included the following: collaborative working between practices driven by high-quality information to support performance review; shared financial incentives; and engagement between primary and secondary care clinicians

Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis

BACKGROUND: Needs-based resource allocation is fundamental to equitable care provision, which can meet the often-complex, fluctuating needs of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This has posed challenges both for those providing and those seeking support providers, in building shared understanding of the condition and of actions to address it. This qualitative study reports on needs for equity in health and social care expressed by adults living with CFS/ME. METHODS: The participants were 35 adults with CFS/ME in England, purposively selected to provide variation in clinical presentations, social backgrounds and illness experiences. Accounts of experienced needs and needs-related encounters with health and social services were obtained through a focus group (n = 6) and semi-structured interviews (n = 35). These were transcribed and needs related topics identified through data-led thematic analysis. FINDINGS: Participants emphasised needs for personalised, timely and sustained support to alleviate CFS/ME impacts and regain life control, in three thematic areas: (1) Illness symptoms, functional limitations and illness management; (2) practical support and social care; (3) financial support. Access of people with CFS/ME to support from health and social services was seen to be constrained by barriers stemming from social, cultural, organisational and professional norms and practices, further heightened for disadvantaged groups including some ethnic minorities. These reduced opportunities for their illness to be explained or associated functional limitations and social disadvantages to be addressed through social support. Participants sought more understanding of bio-psycho-social aspects of CFS/ME, of felt needs of people with CFS/ME and of human rights and disability rights, for providing person-centred, equitable care. CONCLUSIONS: Changes in attitudes of health practitioners, policy makers and general public and more flexibly organised health and social care provision are needed to address equity issues in support needs expressed by people with CFS/ME, to be underpinned by research-based knowledge and communication, for public and professional education. Policy development should include shared decision-making and coordinated action across organizations working for people with CFS/ME, human rights and disadvantaged groups. Experiences of people with CFS/ME can usefully inform an understanding of equity in their health and social care

Congenital anomalies in low- and middle-income countries: the unborn child of global surgery.

Surgically correctable congenital anomalies cause a substantial burden of global morbidity and mortality. These anomalies disproportionately affect children in low- and middle-income countries (LMICs) due to sociocultural, economic, and structural factors that limit the accessibility and quality of pediatric surgery. While data from LMICs are sparse, available evidence suggests that the true human and financial cost of congenital anomalies is grossly underestimated and that pediatric surgery is a cost-effective intervention with the potential to avert significant premature mortality and lifelong disability

Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with unknown aetiology, Myalgic encephalomyelitis unclear pathophysiology and with no diagnostic test or biomarker available. Many patients report their ME/CFS began after an acute infection, and subsequent increased frequency of infections, such as colds or influenza, is common. These factors imply an altered immunological status exists in ME/CFS, in at least a proportion of patients, yet previous studies of peripheral immunity have been discrepant and inconclusive. The UK ME/CFS Biobank, which has collected blood samples from nearly 300 clinically-confirmed ME/CFS patients, enables large-scale studies of immunological function in phenotypically well-characterised participants. In this study, herpes virus serological status and T cell, B cell, NK cell and monocyte populations were investigated in 251 ME/CFS patients, including 54 who were severely affected, and compared with those from 107 healthy participants and with 46 patients with Multiple Sclerosis. There were no differences in seroprevalence for six human herpes viruses between ME/CFS and healthy controls, although seroprevalence for the Epstein-Barr virus was higher in multiple sclerosis patients. Contrary to previous reports, no significant differences were observed in NK cell numbers, subtype proportions or in vitro responsiveness between ME/CFS patients and healthy control participants. In contrast, the T cell compartment was altered in ME/CFS, with increased proportions of effector memory CD8+ T cells and decreased proportions of terminally differentiated effector CD8+ T cells. Conversely, there was a significantly increased proportion of mucosal associated invariant T cells (MAIT) cells, especially in severely affected ME/CFS patients. These abnormalities demonstrate that an altered immunological state does exist in ME/CFS, particularly in severely affected people. This may simply reflect ongoing or recent infection, or may indicate future increased susceptibility to infection. Longitudinal studies of ME/CFS patients are needed to help to determine cause and effect and thus any potential benefits of immuno-modulatory treatments for ME/CFS

Association analysis between symptomology and herpesvirus IgG antibody concentrations in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis

Data availability statement: The data set used in this study is freely available from the United Kingdom ME/CFS biobank upon application.Supplementary data are available online at https://www.sciencedirect.com/science/article/pii/S2405844023054580?via%3Dihub#appsec2 .Copyright © 2023 The Authors. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS) are two complex and multifactorial diseases whose patients experience persistent fatigue, cognitive impairment, among other shared symptoms. The onset of these diseases has also been linked to acute herpesvirus infections or their reactivations. In this work, we re-analyzed a previously-described dataset related to IgG antibody responses to 6 herpesviruses (CMV – cytomegalovirus; EBV – Epstein-Barr virus; HHV6 – human herpesvirus-6; HSV1 and HSV2 – herpes simplex virus-1 and -2, respectively; VZV – varicella-zoster virus) from the United Kingdom ME/CFS biobank. The primary goal was to report the underlying symptomology and its association with herpesvirus IgG antibodies using data from 4 disease-trigger-based subgroups of ME/CFS patients (n = 222) and patients with MS (n = 46). The secondary objective was to assess whether serological data could distinguish ME/CFS and its subgroup from MS using a SuperLearner (SL) algorithm. There was evidence for a significant negative association between temporary eye insight disturbance and CMV antibody concentrations and for a significant positive association between bladder problems and EBV antibody concentrations in the MS group. In the ME/CFS or its subgroups, the most significant antibody-symptom association was obtained for increasing HSV1 antibody concentration and brain fog, a finding in line with a negative impact of HSV1 exposure on cognitive outcomes in both healthy and disease conditions. There was also evidence for a higher number of significant antibody-symptom associations in the MS group than in the ME/CFS group. When we combined all the serological data in an SL algorithm, we could distinguish three ME/CFS subgroups (unknown disease trigger, non-infection trigger, and an infection disease trigger confirmed in the lab at the time of the event) from the MS group. However, we could not find the same for the remaining ME/CFS group (related to an unconfirmed infection disease). In conclusion, IgG antibody data explains more the symptomology of MS patients than the one of ME/CFS patients. Given the fluctuating nature of symptoms in ME/CFS patients, the clinical implication of these findings remains to be determined with a longitudinal study. This study is likely to ascertain the robustness of the associations during natural disease course.This research was funded by: FCT - Fundação para a Ciência e Tecnologia, Portugal, ref. grant: SFRH/BD/149758/2019 (J.M.), and UIDB/00006/2020 (T.D.D., J.M., H.M., NS); the Polish National Agency for Academic Exchange (NAWA), ref. grant: PPN/ULM/2020/1/00069/U/00001 (N.S.). The UKMEB was established with a joint grant from the charities ME Association (including continuing support), ME Research UK and Action for ME, as well as private donors. Research reported in this manuscript was supported by the National Institutes of Health (NIH) under award number 2R01AI103629