Revealing causal heterogeneity using time series analysis of ambulatory assessments: application to the association between depression and physical activity after myocardial infarction

Objective: Studies in psychosomatic medicine are characterized by analyses that typically compare groups. This nomothetic approach leads to conclusions that apply to the average group member but not necessarily to individual patients. Idiographic studies start at the individual patient and are suitable to study associations that differ between time points or between individuals. We illustrate the advantages of the idiographic approach in analyzing ambulatory assessments, taking the association between depression and physical activity after myocardial infarction as an example. Methods: Five middle-aged men who had myocardial infarction with mild to moderate symptoms of depression were included in this study. Four of these. participants monitored their physical activity and depressive symptoms during a period of 2 to 3 months using a daily self-registration form. The time series of each individual participant were investigated using vector autoregressive modeling, which enables the analysis of temporal dynamics between physical activity and depression. Results: We found causal heterogeneity in the association between depression and physical activity. Participants differed in the predominant direction of effect, which was either from physical activity to depression (n = 1,85 observations, unstandardized effect size = -0.183, p=.03) or from depression to physical activity (n = 2, 65 and 59 observations, unstandardized effect sizes = -0.038 and -0.381, p<.001 and p=.04). Also, the persistency of effects differed among individuals. Conclusions: Vector autoregressive models are suitable in revealing causal heterogeneity and can be easily used to analyze ambulatory assessments. We suggest that these models might bridge the gap between science and clinical practice by translating epidemiological results to individual patients

Fatal Attraction: Interactions between antigen-presenting cells and islets of Langerhans in the pathogenesis of autoimmune diabetes

The onset of diabetes mellitus is characterized by various symptoms, all the result of a disturbed glucose metabolism. The main symptoms are thirst and an excessive production of urine. The disturbed glucose metabolism underlying these symptoms is due to an absolute deficiency of insulin secretion (type 1 diabetes mellitus), a reduction in its biological effectiveness (type 2 diabetes mellitus) or a combination of these factors. Type 1 diabetes mellitus is predominantly manifesting in children, and needs to be treated by life-long exogenous insulin administration to prevent high blood glucose levels. Type 2 diabetes mellitus occurs classically in adults, and is relatively milder in its appearance; usually, exogenous insulin administration is not required. This thesis concerns type 1 (ins

What do guidelines and systematic reviews tell us about the management of medically unexplained symptoms in primary care?

Medically unexplained symptoms (MUS) are symptoms for which the origin remains unclear despite adequate history taking, physical examination, and additional investigations.1 An estimated 3–11% of patients visiting general practice repeatedly consult their GP for MUS.2,3 MUS exist along a continuum ranging from self-limiting symptoms, to recurrent and persistent symptoms, through to symptom disorders.4 Although there are various terms for the condition, for example unexplained physical symptoms, functional symptoms, or somatoform symptoms, we have chosen to use MUS in this article because this is the most frequently used term. This review aims to address current problems with the management of undifferentiated MUS; specific syndromes within the MUS spectrum, such as chronic fatigue syndrome and irritable bowel syndrome, are excluded from discussion. Patients with persistent MUS suffer from their symptoms, are functionally impaired, and are at risk of potentially harmful additional testing and treatment.5 Furthermore, these patients commonly express dissatisfaction with the medical care they receive during their illness.6 They feel stigmatised and not taken seriously.7 GPs often experience patients with persistent MUS as difficult and frustrating to manage.8 In addition, MUS are associated with reduced health-related quality of life, higher healthcare and social costs, and costs associated with lost productivity.9,10 The effects of many treatment strategies have been studied in recent decades. However, not all interventions are acceptable or feasible in routine primary care. In the light of the central role of the GP in managing MUS, we will discuss the importance of consultation skills and the effects of specific treatments in primary care. We will do this by way of a narrative review using available national guidelines and Cochrane Reviews in this field

Systemic and Local Corticosteroid Use Is Associated with Reduced Executive Cognition, and Mood and Anxiety Disorders

Background: Use of local corticosteroids, especially the inhaled types, has increasingly been associated with systemic uptake and consequent adverse effects. In this study, we assessed the associations between the use of different corticosteroid types with cognitive and neuropsychiatric adverse effects related to high glucocorticoid exposure. Methods: In 83,592 adults (mean age 44 years, 59% women) of the general population (Lifelines Cohort Study), we analyzed the relationship between corticosteroid use with executive cognitive functioning (Ruff Figural Fluency Test), and presence of mood and anxiety disorders (Mini-International Neuropsychiatric Interview survey). We performed additional exploration for effects of physical quality of life (QoL; RAND-36), and inflammation (high-sensitive C-reactive protein [CRP]). Results: Cognitive scores were lower among corticosteroid users, in particular of systemic and inhaled types, when compared to nonusers. Users of inhaled types showed lower cognitive scores irrespective of physical QoL, psychiatric disorders, and high-sensitive CRP. Overall corticosteroid use was also associated with higher likelihood for mood and anxiety disorders. Users of inhaled corticosteroids were more likely to have mood disorders (OR 1.40 [95% CI 1.19-1.65], p < 0.001) and anxiety disorders (OR 1.19 [95% CI 1.06-1.33], p = 0.002). These findings were independent of physical QoL. A higher likelihood for mood disorders was also found for systemic users whereas nasal and dermal corticosteroid users were more likely to have anxiety disorders. Conclusions: Commonly used local corticosteroids, in particular inhaled types, and systemic corticosteroids are associated with reduced executive cognitive functioning and a higher likelihood of mood and anxiety disorders in the general adult population

The European Training Network ETUDE (Encompassing Training in fUnctional Disorders across Europe) : a new research and training program of the EURONET-SOMA network recruiting 15 early stage researchers

Contains fulltext : 232532.pdf (Publisher’s version ) (Open Access

Methodology of the DCCSS later fatigue study: a model to investigate chronic fatigue in long-term survivors of childhood cancer

Background A debilitating late effect for childhood cancer survivors (CCS) is cancer-related fatigue (CRF). Little is known about the prevalence and risk factors of fatigue in this population. Here we describe the methodology of the Dutch Childhood Cancer Survivor Late Effect Study on fatigue (DCCSS LATER fatigue study). The aim of the DCCSS LATER fatigue study is to examine the prevalence of and factors associated with CRF, proposing a model which discerns predisposing, triggering, maintaining and moderating factors. Triggering factors are related to the cancer diagnosis and treatment during childhood and are thought to trigger fatigue symptoms. Maintaining factors are daily life- and psychosocial factors which may perpetuate fatigue once triggered. Moderating factors might influence the way fatigue symptoms express in individuals. Predisposing factors already existed before the diagnosis, such as genetic factors, and are thought to increase the vulnerability to develop fatigue. Methodology of the participant inclusion, data collection and planned analyses of the DCCSS LATER fatigue study are presented. Results Data of 1955 CCS and 455 siblings was collected. Analysis of the data is planned and we aim to start reporting the first results in 2022. Conclusion The DCCSS LATER fatigue study will provide information on the epidemiology of CRF and investigate the role of a broad range of associated factors in CCS. Insight in associated factors for fatigue in survivors experiencing severe and persistent fatigue may help identify individuals at risk for developing CRF and may aid in the development of interventions.Diabetes mellitus: pathophysiological changes and therap

Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram

The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up

Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25x10-6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3x10 -9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH