Differentiation of functional gastrointestinal disorders from healthy volunteers by lactulose hydrogen breath test and test meal

BACKGROUND AND AIM Functional dyspepsia (FD) is a common disorder of gut-brain interaction with incompletely understood pathophysiology. Consequently, heterogeneous expert opinions on diagnostic tests and assessment of treatment efficacies exist. So far, no consensus about the most relevant diagnostic and outcome tool has been reached. In this study, we aimed to analyze the significance of a combined lactulose hydrogen breath test (LHBT) and liquid meal, yet representing a standardized test in irritable bowel syndrome (IBS), in FD. METHODS We analyzed data of 146 FD, 204 IBS patients, and 50 healthy volunteers (HV). All patients underwent LHBT with a meal-drink consisting of 30-g Lactulose and 400-mL Ensure®. Effect of abdominal symptom generation in FD/IBS compared with HV was assessed on a patient-reported Likert-scale. RESULTS There was a significant difference between FD/IBS patients and HV in LHBT-induced abdominal pain (odds ratio [OR] 246.9, 95% confidence interval [CI] 26.6-2290.7; OR 161.2, 95% CI 16.9-1534.8), abdominal bloating (OR 384.8, 95% CI 92.9-2135.4; OR 524.1, 95% CI 114.7-3432.3), borborygmi (OR 9.9, 95% CI 2.2-46.9; OR 17.7, 95% CI 4.7-67.4), nausea only in FD (OR 174.4, 95% CI 15.5-5375.5), and diarrhea in IBS only (OR 25.8, 95% CI 2.0-7012.6). Hydrogen production was not significantly different in FD/IBS and HV. CONCLUSIONS In this study, we demonstrated significant differences in postprandial symptom generation in FD and IBS compared with HV after LHBT. This does not only allow us to discriminate FD/IBS from HV but may also represent a diagnostic and monitoring tool for FD/IBS in the future, including monitoring of treatment effects

White matter matters: a multimodal approach to investigate white matter microstructure and metabolism

White matter connects different brain areas and applies electrical insulation to the neuron’s axons with myelin sheaths in order to enable quick signal transmission. Due to its modulatory properties in signal conduction, white matter plays an essential role in learning, cognition and psychiatric disorders (Fields, 2008a). In respect thereof, the non-invasive investigation of white matter anatomy and function in vivo provides the unique opportunity to explore the most complex organ of our body. Thus, the present thesis aimed to apply a multimodal neuroimaging approach to investigate different white matter properties in psychiatric and healthy populations. On the one hand, white matter microstructural properties were investigated in a psychiatric population; on the other hand, white matter metabolic properties were assessed in healthy adults providing basic information about the brain’s wiring entity. As a result, three research papers are presented here. The first paper assessed the microstructural properties of white matter in relation to a frequent epidemiologic finding in schizophrenia. As a result, reduced white matter integrity was observed in patients born in summer and autumn compared to patients born in winter and spring. Despite the large genetic basis of schizophrenia, accumulating evidence indicates that environmental exposures may be implicated in the development of schizophrenia (A. S. Brown, 2011). Notably, epidemiologic studies have shown a 5–8% excess of births during winter and spring for patients with schizophrenia on the Northern Hemisphere at higher latitudes (Torrey, Miller, Rawlings, & Yolken, 1997). Although the underlying mechanisms are unclear, the seasonal birth effect may indicate fluctuating environmental risk factors for schizophrenia. Thus, exposure to harmful factors during foetal development may result in the activation of pathologic neural circuits during adolescence or young adulthood, increasing the risk of schizophrenia (Fatemi & Folsom, 2009). While white matter development starts during the foetal period and continues until adulthood, its major development is accomplished by the age of two years (Brody, Kinney, Kloman, & Gilles, 1987; Huang et al., 2009). This indicates a vulnerability period of white matter that may coincide with the fluctuating environmental risk factors for schizophrenia. Since microstructural alterations of white matter in schizophrenia are frequently observed, the current study provided evidence for the neurodevelopmental hypothesis of schizophrenia. In the second research paper, the perfusion of white matter showed a positive correlation between white matter microstructure and its perfusion with blood across healthy adults. This finding was in line with clinical studies indicating a tight coupling between cerebral perfusion and WM health across subjects (Amann et al., 2012; Chen, Rosas, & Salat, 2013; Kitagawa et al., 2009). Although relatively little is known about the metabolic properties of white matter, different microstructural properties, such as axon diameter and myelination, might be coupled with the metabolic demand of white matter. Furthermore, the ability to detect perfusion signal in white matter was in accordance with a recent study showing that technical improvements, such as pseudo-continuous arterial spin labeling, enabled the reliable detection of white matter perfusion signal (van Osch et al., 2009). The third paper involved a collaboration within the same department to assess the interrelation between functional connectivity networks and their underlying structural connectivity

Linking brain connectivity across different time scales with electroencephalogram, functional magnetic resonance imaging, and diffusion tensor imaging

Structural and functional connectivity are intrinsic properties of the human brain and represent the amount of cognitive capacities of individual subjects. These connections are modulated due to development, learning, and disease. Momentary adaptations in functional connectivity alter the structural connections, which in turn affect the functional connectivity. Thus, structural and functional connectivity interact on a broad timescale. In this study, we aimed to explore distinct measures of connectivity assessed by functional magnetic resonance imaging and diffusion tensor imaging and their association to the dominant electroencephalogram oscillatory property at rest: the individual alpha frequency (IAF). We found that in 21 healthy young subjects, small intraindividual temporal IAF fluctuations were correlated to increased blood oxygenation level-dependent signal in brain areas associated to working memory functions and to the modulation of attention. These areas colocalized with functionally connected networks supporting the respective functions. Furthermore, subjects with higher IAF show increased fractional anisotropy values in fascicles connecting the above-mentioned areas and networks. Hence, due to a multimodal approach a consistent functionally and structurally connected network related to IAF was observed

Effect of guideline revisions by the Swiss Society of Hypertension on blood pressure control in hypertensive patients from primary care

BACKGROUND Recommendations for blood pressure goals have considerably changed across time, in particular for high-risk patients with diabetes mellitus and/or renal dysfunction. Before 2009, Swiss Society of Hypertension (SSH) guidelines recommended lowering blood pressure to <135/85 mm Hg and after 2009 to <130/80 mm Hg in high-risk patients. It remains unclear whether guideline changes for blood pressure targets are associated with reductions in blood pressure in hypertensive patients treated in primary care. The objective was to report the association between guideline change and blood pressure target achievement, as well as the prevalence of blood pressure target achievement according to guidelines and to identify factors associated with blood pressure target achievement in a Swiss primary care sample of treated hypertensive patients. METHODS We used longitudinal data from the Swiss Hypertension Cohort Study, which was a prospective, observational study conducted by the Centre for Primary Health Care of the University of Basel from 2006 to 2013. General practitioners (GPs) enrolled 1003 patients attending their practice with a pre-existing diagnosis of arterial hypertension or office blood pressure measurement ≥140/90 mm Hg and assessed office blood pressure, cardiovascular risk factors, subclinical organ damage, diabetes mellitus, and established cardiovascular and renal disease. Mixed-effects regression models were used to estimate the associations of (1) the change in hypertension guidelines in 2009 with blood pressure and antihypertensive therapy in high-risk patients, and (2) cardiovascular risk factors with blood pressure target achievement in patients with complicated and uncomplicated hypertension. Models were adjusted for sociodemographic and health-related covariates. Missing data were imputed using a “multiple imputation by chained equation” approach. RESULTS At baseline, hypertensive patients were on average 65.9 ± 12.5 years old and 55% were male. Blood pressure targets were achieved in 47% of patients with uncomplicated hypertension and in 13% of high-risk patients at baseline. In multivariable analyses adjusted for potential confounding factors, a visit by high-risk patients after 2009 was associated with decreased systolic office blood pressure (−5.40 mm Hg, 95% confidence interval [CI] −8.08 to 2.73) and a trend towards an increased use of pharmacological combination therapy (odds ratio [OR] 1.85, 95% CI 0.94 to 3.63; p = 0.073) compared with a visit before 2009. Neither a reduction of diastolic blood pressure nor an increase of blood pressure target achievement in high-risk patients was observed after 2009. High-risk patients were slightly more likely to achieve blood pressure targets at later follow-up visits than at baseline (OR 1.35, 95% CI 0.98 to 1.86; p = 0.068). In patients with uncomplicated hypertension, factors associated with the likelihood to achieve blood pressure goals were the increased use of pharmacological combination therapy (OR 1.19 per combination increase: e.g., dual therapy vs monotherapy, 95% CI 1.02 to 1.40), left ventricular hypertrophy (OR 0.58, 95% CI 0.36 to 0.93), older age (OR 1.19 per 10 years, 95% CI 1.02 to 1.40) and the number of follow-up examinations (OR 1.44 per follow-up visit, 95% CI 1.21 to 1.72). CONCLUSION Overall, blood pressure goal attainment remains low for treated hypertensive patients followed up by primary care physicians in Switzerland. Independent of known confounding factors for blood pressure, the 2009 guideline change in high-risk patients was associated with a reduction in systolic office blood pressure together with an increase in pharmacological combination therapy. These results highlight primary care physicians’ efforts to implement blood pressure guidelines. Further, blood pressure goal attainment was more likely to be achieved in later follow-up visits, indicating that it takes time and regular follow-up visits with the GP to meet blood pressure goals

The ecology of medical care in Switzerland: prevalence of illness in the community and healthcare utilisation in Switzerland

INTRODUCTION The allocation and equal distribution of healthcare resources is one of the major challenges of today. Therefore, a framework to analyse the prevalence of illness in the community and the use of various sources of healthcare is crucial. The aim of the study was to evaluate the health-seeking behaviour of 1025 individuals in Switzerland in a 2-month period in 2018. METHODS Population-based, cross-sectional health survey with a multistage, stratified cluster design. The LINK Institute interviewed a representative sample of the adult Swiss population (age ≥18 years, stratified by language region: German-, French- and Italian-speaking, 70, 25 and 5%, respectively) by telephone. There were two interview rounds to account for potential seasonal variations, in May (n = 506) and November 2018 (n = 516). The health-seeking behaviour of these individuals during the previous 2 months was analysed. RESULTS In total, data of 1025 individuals were analysed: 51% females, median age 52 years (range 18−85). During the preceding 2 months, per 1000 adults, 546 had at least one symptom, 184 reported several symptoms, 243 sought medical advice, 164 first contacted their general practitioner, 81 directly contacted a specialist in a private practice, 16 were self-admitted to an accident and emergency department, 17 firstly contacted a pharmacy and 6 contacted an alternative medicine healthcare provider. In total, 21 persons were admitted to a hospital, of whom 8 underwent surgical procedures, 18 were at first transferred to a regular ward and 3 required intensive care unit services. Because of their current health problem, 387 individuals took medication and 259 bought their medication themselves. The vast majority (95%) of subjects was registered with a general practitioner. CONCLUSIONS This study represented an attempt to map the healthcare utilisation of the Swiss population. These results may be useful for further delineation of healthcare policies and medical education to meet the demand and needs of people in Switzerland. They indicate that general practitioners are the most important healthcare resource in Switzerland. Compared with specialists, they provide twice as much health advice at less costs. To optimise the health care system in Switzerland, we suggest to allocate resources where they are most needed

Repeatability analysis of global and local metrics of brain structural networks

Computational network analysis provides new methods to analyze the human connectome. Brain structural networks can be characterized by global and local metrics that recently gave promising insights for diagnosis and further understanding of neurological, psychiatric and neurodegenerative disorders. In order to ensure the validity of results in clinical settings the precision and repeatability of the networks and the associated metrics must be evaluated. In the present study, nineteen healthy subjects underwent two consecutive measurements enabling us to test reproducibility of the brain network and its global and local metrics. As it is known that the network topology depends on the network density, the effects of setting a common density threshold for all networks were also assessed. Results showed good to excellent repeatability for global metrics, while for local metrics it was more variable and some metrics were found to have locally poor repeatability. Moreover, between subjects differences were slightly inflated when the density was not fixed. At the global level, these findings confirm previous results on the validity of global network metrics as clinical biomarkers. However, the new results in our work indicate that the remaining variability at the local level as well as the effect of methodological characteristics on the network topology should be considered in the analysis of brain structural networks and especially in networks comparisons

White matter correlates of the disorganized speech dimension in schizophrenia

Disorganized speech is related to functional abnormalities in schizophrenia. To test the association between formal thought disorders (FTDs) and white matter microstructure, we applied a behavioral rating and diffusion tensor imaging in 61 patients with schizophrenia spectrum disorders. The Bern Psychopathology Scale was used to rate the dimension of language abnormalities ranging from negative FTDs, basically unaltered speech, to positive FTDs. Tract-based spatial statistics indicated increased fractional anisotropy in left hemispheric pathways of the language system in patients with negative FTDs. Thus, altered white matter properties in relevant fiber tracts may represent vulnerability to specific formal thought disorders

Microstructure and Cerebral Blood Flow within White Matter of the Human Brain: A TBSS Analysis.

BACKGROUND White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects. METHODS Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years). RESULTS CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects. CONCLUSION The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation