Birgitta Evengård

Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution

BackgroundChronic fatigue syndrome (CFS) is defined by symptoms and disability, has no confirmatory physical signs or characteristic laboratory abnormalities, and the etiology and pathophysiology remain unknown. Difficulties with accurate case ascertainment contribute to this ignorance.MethodsExperienced investigators from around the world who are involved in CFS research met for a series of three day workshops in 2000, 2001 and 2002 intended to identify the problems in application of the current CFS case definition. The investigators were divided into focus groups and each group was charged with a topic. The investigators in each focus group relied on their own clinical and scientific knowledge, brainstorming within each group and with all investigators when focus group summaries were presented. Relevant literature was selected and reviewed independent of the workshops. The relevant literature was circulated via list-serves and resolved as being relevant by group consensus. Focus group reports were analyzed and compiled into the recommendations presented here.ResultsAmbiguities in the current CFS research definition that contribute to inconsistent case identification were identified. Recommendations for use of the definition, standardization of classification instruments and study design issues are presented that are intended to improve the precision of case ascertainment. The International CFS Study Group also identified ambiguities associated with exclusionary and comorbid conditions and reviewed the standardized, internationally applicable instruments used to measure symptoms, fatigue intensity and associated disability.ConclusionThis paper provides an approach to guide systematic, and hopefully reproducible, application of the current case definition, so that case ascertainment would be more uniform across sites. Ultimately, an operational CFS case definition will need to be based on empirical studies designed to delineate the possibly distinct biological pathways that result in chronic fatigue.

Physiological correlates of burnout among women

OBJECTIVES The purpose of this study was to investigate the immune, endocrine, and metabolic correlates of burnout among women. METHODS Forty-three participants with high and 20 participants with low scores for the Shirom-Melamed Burnout Questionnaire were compared in terms of subjective symptoms, job strain, social support, plasma levels of prolactin, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), C-reactive protein (CRP), neopterin, serum levels of dehydroepiandrosterone sulphate (DHEAs), progesterone, estradiol, cortisol, and glycated hemoglobin (HbA1C) in whole blood. RESULTS Besides reporting more job strain, less social support at work, and higher levels of anxiety, depression, vital exhaustion (VE), and sleep impairments, participants with high burnout manifested higher levels of TNF-alpha and HbA1C, independent of confounders including depression. CONCLUSIONS Among women, burnout seems to involve enhanced inflammatory responses and oxidative stress.

Enteropathogens in Adult Patients with Diarrhea and Healthy Control Subjects: A 1-Year Prospective Study in a Swedish Clinic for Infectious Diseases

A 1-year prospective study was conducted to identify enteropathogens in adults with diarrhea (n=851) and in healthy control subjects (n=203) by use of conventional laboratory methods. Virulence factor genes for diarrheagenic Escherichia coli were detected by polymerase chain reaction. Enteropathogens were identified in 56% of patients and 16% of control subjects. The isolation rate was 65% for patients with symptoms for <1 week and for travelers; >1 pathogen was found in 11% of patients. The most frequent enteropathogens were Campylobacter (13% of patients), Clostridium difficile (13%), enterotoxigenic Escherichia coli (8%), Salmonella (7%), Shigella (4%), Blastocystis hominis (4%), calicivirus (3%), rotavirus (3%), enteroaggregative E. coli (2%), Aeromonas (2%), Giardia intestinalis (2%), Cryptosporidium (2%), and astrovirus (2%). Less frequently isolated (< or =1% of patients) were verotoxigenic E. coli, enteropathogenic E. coli, enteroinvasive E. coli, Entamoeba histolytica/Entamoeba dispar, microsporidia, and adenovirus. Fifty percent of the patients were hospitalized, and 43% needed intravenous fluids. The median duration of diarrhea was 14 days. Clinical features were not helpful for predicting the etiology of diarrhea.

Biodiversity redistribution under climate change : Impacts on ecosystems and human well-being

Consequences of shifting species distributions Climate change is causing geographical redistribution of plant and animal species globally. These distributional shifts are leading to new ecosystems and ecological communities, changes that will affect human society. Pecl et al. review these current and future impacts and assess their implications for sustainable development goals. Science, this issue p. eaai9214 BACKGROUND The success of human societies depends intimately on the living components of natural and managed systems. Although the geographical range limits of species are dynamic and fluctuate over time, climate change is impelling a universal redistribution of life on Earth. For marine, freshwater, and terrestrial species alike, the first response to changing climate is often a shift in location, to stay within preferred environmental conditions. At the cooler extremes of their distributions, species are moving poleward, whereas range limits are contracting at the warmer range edge, where temperatures are no longer tolerable. On land, species are also moving to cooler, higher elevations; in the ocean, they are moving to colder water at greater depths. Because different species respond at different rates and to varying degrees, key interactions among species are often disrupted, and new interactions develop. These idiosyncrasies can result in novel biotic communities and rapid changes in ecosystem functioning, with pervasive and sometimes unexpected consequences that propagate through and affect both biological and human communities. ADVANCES At a time when the world is anticipating unprecedented increases in human population growth and demands, the ability of natural ecosystems to deliver ecosystem services is being challenged by the largest climate-driven global redistribution of species since the Last Glacial Maximum. We demonstrate the serious consequences of this species redistribution for economic development, livelihoods, food security, human health, and culture, and we document feedbacks on climate itself. As with other impacts of climate change, species range shifts will leave “winners” and “losers” in their wake, radically reshaping the pattern of human well-being between regions and different sectors and potentially leading to substantial conflict. The pervasive impacts of changes in species distribution transcend single systems or dimensions, with feedbacks and linkages between multiple interacting scales and through whole ecosystems, inclusive of humans. We argue that the negative effects of climate change cannot be adequately anticipated or prepared for unless species responses are explicitly included in decision-making and global strategic frameworks. OUTLOOK Despite mounting evidence for the pervasive and substantial impacts of a climate-driven redistribution of Earth’s species, current global goals, policies, and international agreements fail to account for these effects. With the predicted intensification of species movements and their diverse societal and environmental impacts, awareness of species “on the move” should be incorporated into local, regional, and global assessments as standard practice. This will raise hope that future targets—whether they be global sustainability goals, plans for regional biodiversity maintenance, or local fishing or forestry harvest strategies—can be achievable and that society is prepared for a world of universal ecological change. Human society has yet to appreciate the implications of unprecedented species redistribution for life on Earth, including for human lives. Even if greenhouse gas emissions stopped today, the responses required in human systems to adapt to the most serious effects of climate-driven species redistribution would be massive. Meeting these challenges requires governance that can anticipate and adapt to changing conditions, as well as minimize negative consequences. As the global climate changes, human well-being, ecosystem function, and even climate itself are increasingly affected by the shifting geography of life. Climate-driven changes in species distributions, or range shifts, affect human well-being both directly (for example, through emerging diseases and changes in food supply) and indirectly (by degrading ecosystem health). Some range shifts even create feedbacks (positive or negative) on the climate system, altering the pace of climate change. Distributions of Earth’s species are changing at accelerating rates, increasingly driven by human-mediated climate change. Such changes are already altering the composition of ecological communities, but beyond conservation of natural systems, how and why does this matter? We review evidence that climate-driven species redistribution at regional to global scales affects ecosystem functioning, human well-being, and the dynamics of climate change itself. Production of natural resources required for food security, patterns of disease transmission, and processes of carbon sequestration are all altered by changes in species distribution. Consideration of these effects of biodiversity redistribution is critical yet lacking in most mitigation and adaptation strategies, including the United Nation’s Sustainable Development Goals.

A population-based twin study of functional somatic syndromes

BACKGROUND The mechanisms underlying the co-occurrence of the functional somatic syndromes are largely unknown. No empirical study has explicitly examined how genetic and environmental factors influence the co-morbidity of these syndromes. We aimed to examine how the co-morbidity of functional somatic syndromes is influenced by genetic and environmental factors that are in common to the syndromes. METHOD A total of 31318 twins in the Swedish Twin Registry aged 41-64 years underwent screening interviews via a computer-assisted telephone system from 1998 to 2002. Four functional somatic syndromes (chronic widespread pain, chronic fatigue, irritable bowel syndrome, and recurrent headache) and two psychiatric disorders (major depression and generalized anxiety disorder) were assessed using structured questions based on standard criteria for each illness in a blinded manner. RESULTS Multivariate twin analyses revealed that a common pathway model with two latent traits that were shared by the six illnesses fit best to the womens data. One of the two latent traits loaded heavily on the psychiatric disorders, whereas the other trait loaded on all four of the functional somatic syndromes, particularly chronic widespread pain, but not on the psychiatric disorders. All illnesses except the psychiatric disorders were also affected by genetic influences that were specific to each. CONCLUSIONS The co-occurrence of functional somatic syndromes in women can be best explained by affective and sensory components in common to all these syndromes, as well as by unique influences specific to each of them. The findings clearly suggest a complex view of the multifactorial pathogenesis of these illnesses.

Association between prenatal treatment and clinical manifestations of congenital toxoplasmosis in infancy: A cohort study in 13 European centres

Aim: To determine the effectiveness of prenatal treatment for clinical manifestations of congenital toxoplasmosis. Methods: We prospectively identified 255 live‐born infants with congenital toxoplasmosis using prenatal or neonatal screening. We determined the effect of prenatal treatment on the risks of intracranial or ocular lesions in infancy, accounting for gestational age at maternal seroconversion. Results: Prenatal treatment within 4 wk of seroconversion reduced the risk of intracranial lesions compared with no treatment (odds ratio, OR 0.28; 95% CI: 0.08–0.75), but there was no significant effect when initiated after 4 wk (OR 0.76; 95% CI: 0.35–1.59; overall p‐value 0.19). Compared to spiramycin alone, no treatment doubled the risk of intracranial lesions (OR 2.33; 95% CI: 1.04–5.50), but the risk did not differ with pyrimethamine‐sulphonamide treatment (overall p‐value 0.52). There was no consistent relationship between the type or timing of treatment and the risk of ocular lesions. Gestational age at maternal seroconversion was inversely associated with the risk of intracranial but not ocular lesions.

Chronic fatigue syndrome: new insights and old ignorance

Abstract. Evengård B, Schacterle RS, Komaroff AL (Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden; and Brigham and Women’s Hospital, Harvard Medical School, Boston, USA). Chronic fatigue syndrome: new insights and old ignorance. J Intern Med 1999; 246: 455–469.

Low incidence of toxoplasma infection during pregnancy and in newborns in Sweden

To estimate the burden of disease due to congenital toxoplasmosis in Sweden the incidence of primary infections during pregnancy and birth prevalence of congenital toxoplasmosis in 40,978 children born in two regions in Sweden was determined. Women possibly infected during pregnancy were identified based on: 1, detection of specific IgG based on neonatal screening of the phenylketonuria (PKU) card blood spot followed by retrospective testing of stored prenatal samples to detect women who acquired infection during pregnancy and follow up of their children to 12 months: 2, detection of specific IgM on the PKU blood spot. The birth prevalence of congenital toxoplasmosis was 0.73/10,000 (95 % CI 0.15-2.14) (3/40,978). The incidence of primary infection during pregnancy was 5.1/10,000 (95% CI 2.6-8.9) susceptible pregnant women. The seroprevalence in the southern part was 25.7% and in the Stockholm area 14.0%. The incidence of infection during pregnancy was low, as the birth prevalence of congenital toxoplasmosis. Neonatal screening warrants consideration in view of the low cost and feasibility.

Brain Regions Involved in Fatigue Sensation: Reduced Acetylcarnitine Uptake into the Brain

Fatigue is an indispensable sense for ordering rest. However, the neuronal and molecular mechanisms of fatigue remain unclear. Chronic fatigue syndrome (CFS) with long-lasting fatigue sensation seems to be a good model for studying these mechanisms underlying fatigue sensation. Recently, we found that most patients with CFS showed a low level of serum acetylcarnitine, which well correlated with the rating score of fatigue, and that a considerable amount of acetyl moiety of serum acetylcarnitine is taken up into the brain. Here we show by metabolite analysis of the mouse brain that an acetyl moiety taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate. When we studied the cerebral uptake of acetylcarnitine by using [2-(11)C]acetyl-L-carnitine in 8 patients with CFS and in 8 normal age- and sex-matched controls, a significant decrease was found in several regions of the brains of the patient group, namely, in the prefrontal (Brodmanns area 9/46d) and temporal (BA21 and 41) cortices, anterior cingulate (BA24 and 33), and cerebellum. These findings suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of chronic fatigue patients and that this abnormality might be one of the keys to unveiling the mechanisms of the chronic fatigue sensation.

The epidemiology of chronic fatigue in the Swedish Twin Registry.

BACKGROUND Chronic fatigue syndrome (CFS) remains an idiopathic and controversial entity. METHOD We screened 31405 individual members of the Swedish Twin Registry (aged 42-64 years) for the symptoms of fatiguing illness via a telephone questionnaire. We refined self-reported symptoms via data from several national registries and from physician review of all available medical records in order to approximate closely the dominant case definition of CFS. FINDINGS The 6-month prevalence of CFS-like illness was 2.36% (95% CI 2.19-2.53) and was markedly higher in women than men, odds ratio 3.92 (95% CI 3.24-4.72) with no significant association with age or years of education. There was a highly significant association with occupation that disappeared after accounting for gender. INTERPRETATION CFS-like illness may be more common that previously acknowledged. There is a marked increase in risk by gender. Previous reports that CFS is more prevalent in individuals in certain occupational categories were not confirmed and may have been due to confounding by gender.