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

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

Risk factors for default from tuberculosis treatment in HIV-infected individuals in the state of Pernambuco, Brazil: a prospective cohort study

BACKGROUND: Concomitant treatment of Human Immunodeficiency Virus (HIV) infection and tuberculosis (TB) presents a series of challenges for treatment compliance for both providers and patients. We carried out this study to identify risk factors for default from TB treatment in people living with HIV. METHODS: We conducted a cohort study to monitor HIV/TB co-infected subjects in Pernambuco, Brazil, on a monthly basis, until completion or default of treatment for TB. Logistic regression was used to calculate crude and adjusted odds ratios, 95% confidence intervals and P-values. RESULTS: From a cohort of 2310 HIV subjects, 390 individuals (16.9%) who had started treatment after a diagnosis of TB were selected, and data on 273 individuals who completed or defaulted on treatment for TB were analyzed. The default rate was 21.7% and the following risk factors were identified: male gender, smoking and CD4 T-cell count less than 200 cells/mm3. Age over 29 years, complete or incomplete secondary or university education and the use of highly active antiretroviral therapy (HAART) were identified as protective factors for the outcome. CONCLUSION: The results point to the need for more specific actions, aiming to reduce the default from TB treatment in males, younger adults with low education, smokers and people with CD4 T-cell counts < 200 cells/mm3. Default was less likely to occur in patients under HAART, reinforcing the strategy of early initiation of HAART in individuals with TB

LER/DORT na terceira década da reestruturação bancária: novos fatores associados?

OBJETIVO: Estimar a prevalência de casos sugestivos de LER/DORT e fatores associados três décadas após a reestruturação bancária. MÉTODOS: Estudo transversal com 356 funcionários de 27 agências bancárias das redes pública e privada de Porto Alegre, RS, entre abril e agosto de 2009. Foi utilizada análise estatística bruta e ajustada pelo modelo de Regressão de Poisson com variância robusta, conduzida por modelo hierárquico em três níveis, incorporando-se a estrutura do delineamento e ajuste para os conglomerados. Os resultados foram estratificados por porte da agência e dicotomizados (≥ 25 e < 25 funcionários). RESULTADOS: A prevalência de casos sugestivos de LER/DORT foi menor nos homens (RP = 0,62 IC95% 0,47;0,81). Trabalhadores com idade entre 26 e 45 anos (RP = 2,51 IC95% 1,02;6,14) apresentaram maior prevalência do desfecho. Indivíduos com pós-graduação (RP = 0,45 IC95% 0,22;0,90) e tempo na função entre 5,1 e 15 anos (RP = 0,62 IC95% 0,47;0,81) apresentaram fator de proteção para os casos sugestivos de LER/DORT. Ao estratificar as análises por porte, nas agências com 25 funcionários ou menos, idade, renda e tempo na função permaneceram associados, enquanto nas agências com mais de 25 funcionários, sexo e escolaridade associaram-se ao desfecho. CONCLUSÕES: Aspectos importantes no adoecimento por LER/DORT entre bancários parecem hoje ser diferentes dos historicamente conhecidos. Atenção maior à organização do trabalho e às estratégias de gestão deveria ser considerada na elaboração de programas de prevenção de adoecimento no trabalho bancário.OBJECTIVE: To estimate the prevalence of cases suggestive of repetitive strain injury/work-related musculoskeletal disorders (RSI/WRMSD), three decades after restructuring of banking. METHODS: This was a cross-sectional study on 356 employees in 27 bank branches of public and private banks in Porto Alegre, Southern Brazil, between April and August 2009. After crude statistical analysis, adjustments were made using a Poisson regression model with robust variance and a thre elevel hierarchy that incorporated the design structure and adjustments for the clusters. The results were stratified according to the size of the bank branch and were dichotomized (> 25; ≤ 25 employees). RESULTS: The prevalence of cases suggestive of RSI/WRMSD was lower among the men (PR = 0.62; 95%CI: 0.47-0.81). Workers aged 26 to 45 years (PR = 2.51; 95%CI 1.02;6.14) presented greater prevalence of this outcome. Individuals with postgraduate qualifications (PR = 0.45; 95%CI 0.22;0.90) and length of time in the job between 5.1 and 15 years (PR = 0.62; 95%CI 0.47;0.81) presented protection against RSI/WRMSD. On stratifying the analyses according to size, it was found that age, income and length of time in the job remained associated in branches with 25 employees or fewer, while in branches with more than 25 employees, sex and schooling level were associated with the outcome. CONCLUSIONS: The characteristics of importance in relation to bank employees who become ill due to RSI/WRMSD seem to be different today from those that were known historically. Greater attention to organizing work and management strategies should be taken into consideration in drawing up illness prevention programs for banking work