[Interdisciplinary, collaborative D-A-CH (Germany, Austria and Switzerland) consensus statement concerning the diagnostic and treatment of myalgic encephalomyelitis/chronic fatigue syndrome]. / Interdisziplinäres, kollaboratives D-A-CH Konsensus-Statement zur Diagnostik und Behandlung von Myalgischer Enzephalomyelitis/Chronischem Fatigue-Syndrom.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, chronic multisystemic disease which, depending on its severity, can lead to considerable physical and cognitive impairment, loss of ability to work and the need for nursing care including artificial nutrition and, in very severe cases, even death.The aim of this D-A-CH (Germany, Austria, Switzerland) consensus statement is 1) to summarize the current state of knowledge on ME/CFS, 2) to highlight the Canadian Consensus Criteria (CCC) as clinical criteria for diagnostics with a focus on the leading symptom post-exertional malaise (PEM) and 3) to provide an overview of current options and possible future developments, particularly with regard to diagnostics and therapy. The D-A-CH consensus statement is intended to support physicians, therapists and valuer in diagnosing patients with suspected ME/CFS by means of adequate anamnesis and clinical-physical examinations as well as the recommended clinical CCC, using the questionnaires and other examination methods presented. The overview of the two pillars of therapy for ME/CFS, pacing and symptom-relieving therapy options, is intended not only to provide orientation for physicians and therapists, but also to support decision-makers from healthcare policy and insurance companies in determining which therapy options should already be reimbursable by them at this point in time for the indication ME/CFS.

One-year follow-up of young people with ME/CFS following infectious mononucleosis by Epstein-Barr virus.

Background: Infectious mononucleosis after primary infection with Epstein-Barr virus (EBV-IM) has been linked to the development of myalgic encephalomyelitis/chronic fatigue-syndrome (ME/CFS) in children, adolescents, and young adults. Here, we present clinical phenotypes and follow-up data from a first German cohort of young people with ME/CFS following EBV-IM. Methods: 12 adolescents and 13 young adults were diagnosed with IM-triggered ME/CFS at our specialized tertiary outpatient service by clinical criteria requiring post-exertional malaise (PEM) and a history of confirmed EBV primary infection as triggering event. Demographic information, laboratory findings, frequency and severity of symptoms, physical functioning, and health-related quality of life (HRQoL) were assessed and re-evaluated 6 and 12 months later. Results: Young adults displayed more severe symptoms as well as worsening of fatigue, physical and mental functioning, and HRQoL throughout the study, compared to adolescents. After one year, 6/12 (54%) adolescents no longer met the diagnostic criteria for ME/CFS while all young adults continued to fulfill the Canadian consensus criteria. Improvement in adolescents was evident in physical functioning, symptom frequency and severity, and HRQoL, while young adults showed little improvement. EBV serology and EBV DNA load did not correlate with distinct clinical features of ME/CFS, and clinical chemistry showed no evidence of inflammation. Remarkably, the median time from symptom onset to ME/CFS diagnosis was 13.8 (IQR: 9.1-34.9) months. Conclusions: ME/CFS following EBV-IM is a severely debilitating disease often diagnosed late and with limited responses to conventional medical care, especially in adults. Although adolescents may have a better prognosis, their condition can fluctuate and significantly impact their HRQoL. Our data emphasize that biomarkers and effective therapeutic options are also urgently needed to improve medical care and pave the way to recovery.

[When COVID does not heal: post-COVID courses with fatigue and exercise intolerance]. / Wenn COVID nicht aufhört: Post-COVID-Verläufe mit Fatigue und Belastungsintoleranz.

Post-COVID-Syndrome consists of several pathobiologically different entities, ranging from damage to specific organs to new onset autoimmune diseases. This article focuses on post-COVID courses with the leading symptoms of fatigue and exercise intolerance. This category is also known from other infectious diseases and includes myalgic encephalomyelitis/chronic fatigue syndrome.

[Post-COVID syndrome with fatigue and exercise intolerance: myalgic encephalomyelitis/chronic fatigue syndrome]. / Post-COVID-Syndrom mit Fatigue und Belastungsintoleranz: Myalgische Enzephalomyelitis bzw. Chronisches Fatigue-Syndrom.

BACKGROUND: A sizable part of post-COVID syndrome meets the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A doubling of cases of ME/CFS within the next years is therefore projected. OBJECTIVES: Presentation of the current state of knowledge on ME/CFS. MATERIALS AND METHODS: Unsystematic review of the literature and of own contributions in research and patient care. RESULTS AND CONCLUSIONS: ME/CFS is a neuroimmunological disease, mostly infection-induced, usually persisting throughout life. Clinically it is characterized by fatigue lasting at least 6 months and the defining core feature of exercise intolerance (post-exertional malaise, PEM). Exercise intolerance is defined as a worsening of symptoms after (even mild) everyday exertion, which usually begins after several hours or on the following day, is still noticeable at least 14 h after exertion, and often lasts for several days (up to weeks or longer). Furthermore, ME/CFS is characterized by pain, disturbances of sleep, thinking and memory, and dysregulation of the circulatory, endocrine, and immune systems. As a separate clinical entity, ME/CFS should be distinguished from chronic fatigue, which occurs as a symptom of a range of very different diseases. The diagnosis of ME/CFS is made clinically using established international diagnostic criteria and requires careful stepwise diagnosis to exclude other diagnoses. A causal therapy for ME/CFS has not been established; the focus is on symptoms relief, treatment of the often accompanying orthostatic intolerance, and assistance with anticipatory energy management (pacing).

The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure.

Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a specific and distinctive profile of clinical features, the disease remains an enigma because causal explanation of the pathobiological matrix is lacking. Several potential disease mechanisms have been identified, including immune abnormalities, inflammatory activation, mitochondrial alterations, endothelial and muscular disturbances, cardiovascular anomalies, and dysfunction of the peripheral and central nervous systems. Yet, it remains unclear whether and how these pathways may be related and orchestrated. Here we explore the hypothesis that a common denominator of the pathobiological processes in ME/CFS may be central nervous system dysfunction due to impaired or pathologically reactive neuroglia (astrocytes, microglia and oligodendrocytes). We will test this hypothesis by reviewing, in reference to the current literature, the two most salient and widely accepted features of ME/CFS, and by investigating how these might be linked to dysfunctional neuroglia. From this review we conclude that the multifaceted pathobiology of ME/CFS may be attributable in a unifying manner to neuroglial dysfunction. Because the two key features - post exertional malaise and decreased cerebral blood flow - are also recognized in a subset of patients with post-acute sequelae COVID, we suggest that our findings may also be pertinent to this entity.

[What role do children in school and kindergarten settings play in transmitting SARS-CoV-2? An evidence-based perspective]. / Welche Rolle spielen Kinder in Schulen und Kindertagesstätten bei der Übertragung von SARS-CoV-2? ­ Eine evidenzbasierte Perspektive.

Are children and adolescents relevant disease vectors when it comes to the transmission of SARS-CoV-2? Moreover, do they play a role as relevant disease vectors in a school or kindergarten setting? These questions could not be sufficiently answered at the beginning of the pandemic. Consequently, schools and childcare facilities were closed to stop the spread of SARS-CoV­2. Over the past few months, researchers have gained a more detailed understanding of the overall pandemic situation. The SARS-CoV­2 infection rate in children below 10 years of age in 2020 has been substantially lower than in adults. In addition, it showed that children had a milder course of disease.Although a majority of the analyses performed in schools and childcare facilities revealed that the virus is transmitted in these facilities, these transmissions did not, however, have a considerable influence on the overall rate of new infections. Despite these findings, German politicians continue to advocate for the closure of childcare facilities, including schools, to fight the pandemic, whereas many specialist societies such as the German Society for Pediatric Infectious Diseases (DGPI) have emphasized that such closures should be the measure of last resort in combating the pandemic. The same message is also conveyed by a German evidence-based S3 guideline established by an interdisciplinary expert group that had already put forward clear recommendations for high incidences in the general population at the beginning of February 2021, indicating that school closures were only required in exceptional cases.In this article, we would like to outline the situation based on the currently available data, try to predict the future, and discuss the circumstances necessary to realize normal classroom teaching without accepting the risk of an uncontrolled spread of SARS-CoV­2.

Deformational plagiocephaly: The case for an evolutionary mismatch.

Lay Summary: In industrialized societies some babies develop flattening of the back part of their head. It is thought that this comes from sleeping supine, which has been shown to be the safest option for babies. However, this explanation cannot be correct from an evolutionary standpoint: why should safe sleep come at the cost of a misshaped head? Babies in industrialized societies are generally healthy. The medical problems they may be afflicted with are usually well understood. Deformational plagiocephaly presents a notable exception. In many industrialized countries, one in six babies shows posterior flattening of the skull-a feature noteworthy from an evolutionary perspective as the well rounded cranium is part of the 'Kindchenschema' evolved to secure care for the infant. It is commonly held that the deformation of the posterior cranium occurs as a consequence of the supine sleep position, now advocated as the safest sleep position for babies by medical experts. This explanation, however, does not fare well in the light of evolutionary theory: why should safe sleep come at the cost of a social handicap? Here, we present an alternative hypothesis that is grounded on evolutionary mismatch theory and exemplifies how evolutionary reasoning can help clarify medical conditions relevant to today's public health.

Deformational plagiocephaly in normal infants: a systematic review of causes and hypotheses.

BACKGROUND: Deformational plagiocephaly (DP) is one of the most prevalent abnormal findings in infants and a frequent reason for parents to seek paediatric advice. OBJECTIVE: To systematically review the literature and identify evidence and hypotheses on the aetiology and determinants of DP in otherwise healthy infants. DESIGN: Systematic keyword search in all major biomedical databases to identify peer-reviewed publications reporting (a) empirical research or (b) hypotheses on the aetiology of DP in healthy, term infants. 3150 studies published between 1985 and 2016 and containing relevant keywords were screened. In a two-pronged approach, results were summarised separately for the body of empirical work (22 studies) and the body of hypotheses (110 articles). REVIEW FINDINGS: Only a few empirical studies have examined risk factors in non-selected patient populations on a higher grade methodological level. The most commonly reported risk factors were: male gender, supine sleep position, limited neck rotation or preference in head position, first-born child, lower level of activity and lack of tummy time. Agreement between empirical studies was poor for most exposures, including supine sleep position, tummy time and use of car seats. The articles reporting hypotheses on the aetiology of DP cover a wide field of environmental and biological factors, but include little suggestions as to the potential influence of the everyday care environment of the baby. CONCLUSIONS AND RELEVANCE: The evidence on the aetiology of DP is fragmentary and heterogeneous. In addition, factors possibly relevant to the development of DP have not been appreciated in the scientific discussion.

A participatory physical activity intervention in preschools: a cluster randomized controlled trial.

BACKGROUND: Previous studies on physical activity interventions in preschools have reported limited effectiveness. Participatory community-based approaches hold promise for increasing intervention effectiveness and involving parents as key stakeholders in a sustainable way. PURPOSE: To assess whether a participatory parent-focused approach using parents as agents of behavioral change enhances the efficacy of a preschool physical activity (PA) intervention. DESIGN: Two-armed, cluster-RCT with preschool as unit of randomization and children as unit of analysis. SETTING/PARTICIPANTS: 39 South German preschools applying for an existing state-sponsored PA program with 826 children (52% boys, aged 5.0±0.2 years), with 441 allocated to the intervention arm. INTERVENTION: Control preschools received a state-sponsored program consisting of twice-weekly gym classes over 6 months. In intervention preschools, this program was augmented by motivating parents to develop and implement their own project ideas for promoting children's PA. MAIN OUTCOME MEASURES: Primary outcomes included mean accelerometry counts and time spent in moderate- to vigorous-intensity PA or sedentary behavior. Secondary outcomes were BMI, percentage body fat, quality of life, sleep quality, and general health. Outcomes were measured at baseline and at 6 and 12 months in both study arms (time period: 2008-2010). Using an intention-to-treat-analysis, linear multilevel regression models assessed change over time and across study arms, adjusted for age, gender, season, and preschool location. Analysis was conducted in 2011. RESULTS: In 15 intervention preschools, parents implemented 25 PA projects. Compared with controls, intervention arm children were 11 minutes less sedentary per day (95% CI=5.39, 17.01, p=0.014); had significantly more mean accelerometry counts (1.4 counts/15 seconds [95% CI=0.22, 2.54], p=0.019); and showed benefits in perceived general health and quality of life. All other outcomes showed no difference between study arms. CONCLUSIONS: A participatory preschool intervention focusing on parents as agents of behavioral change may be able to promote PA and reduce sedentary behavior in preschoolers. These benefits may go beyond the effects of existing nonparticipatory interventions. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov NCT00987532.

A participatory parent-focused intervention promoting physical activity in preschools: design of a cluster-randomized trial.

BACKGROUND: With rates of childhood obesity increasing, physical activity (PA) promotion especially in young children has assumed greater importance. Given the limited effectiveness of most interventions to date, new approaches are needed. The General Systems theory suggests that involving parents as intervention targets may be effective in fostering healthier life styles in children. We describe the development of a parent-focused participatory intervention and the procedures used to evaluate its effectiveness in increasing daily PA in preschoolers. METHODS/DESIGN: Thirty-seven South German preschools were identified for this study and agreed to participate. Using a two-armed, controlled cluster-randomized trial design we test a participatory intervention with parents as the primary target group and potential agents of behavioural change. Specifically, the intervention is designed to engage parents in the development, refinement and selection of project ideas to promote PA and in incorporating these ideas into daily routines within the preschool community, consisting of children, teachers and parents. Our study is embedded within an existing state-sponsored programme providing structured gym lessons to preschool children. Thus, child-based PA outcomes from the study arm with the parent-focused intervention and the state-sponsored programme are compared with those from the study arm with the state-sponsored programme alone. The evaluation entails baseline measurements of study outcomes as well as follow-up measurements at 6 and 12 months. Accelerometry measures PA intensity over a period of six days, with the mean over six days used as the primary outcome measure. Secondary outcomes include childrens' BMI, a sum of averaged skin fold thickness measurements across multiple sites, and PA behaviour. Longitudinal multilevel models are used to assess within-subject change and between-group differences in study outcomes, adjusted for covariates at the preschool and individual levels. Teacher qualitative interviews monitor the intervention implementation process. DISCUSSION: Participatory approaches that actively involve parents have the potential to promote PA in ways that might be better tailored to local needs and more sustainable. Our mixed methods approach to assess the intervention efficacy and implementation employing both quantitative and qualitative measures within a cluster-randomized controlled trial may serve as a framework for evaluating public health interventions in preschool settings. TRIAL REGISTRATION: clinicaltrials.gov No: NCT00987532.