Combinations of Service Use Types of People With Early Cognitive Disorders

Objectives Understanding which persons most likely use particular combinations of service types is important as this could lead to a better understanding of care pathways. The aim of this study is to identify combinations of service use within a sample of community-dwelling people with mild cognitive impairment (MCI) and dementia and identify factors related to these service use combinations. Methods A latent class analysis performed at baseline on a merged dataset (n = 530) was used to classify care recipients based on following service use types: general practitioner visits, physiotherapist visits, hospital outpatient specialist visits, emergency room visits, hospital inpatient visits with stay over, day care visits, use of domestic homecare, use of personal homecare, and informal care on (instrumental) activities of daily living. Multinomial logistic regression was performed to identify factors associated with service use combinations using clinical characteristics of the care recipient and demographic characteristics of the care recipient and caregiver. Results Three service use classes were identified; a formal homecare class (10% of participants), an informal care class (46% of participants), and a low user class (44% of participants). Factors increasing the likelihood of being in the formal homecare class compared with the low service use class included a diagnosis of MCI or dementia, activities of daily living impairment, older age of the care recipient, and care recipient not living together with the caregiver. Conclusions Besides a diagnosis of MCI or dementia, other factors (activities of daily living impairment, age, and living situation) were associated with service use. We recommend using these factors alongside the diagnostic label for care indication

Effectiveness of dementia follow-up care by memory clinics or general practitioners: randomised controlled trial

Objective To examine the effectiveness of post-diagnosis dementia treatment and coordination of care by memory clinics compared with general practitioners

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089

Prophylactic Intra-Uterine β-Cyclodextrin Administration during Intra-Uterine Ureaplasma parvum Infection Partly Prevents Liver Inflammation without Interfering with the Enterohepatic Circulation of the Fetal Sheep

Chorioamnionitis can lead to inflammation and injury of the liver and gut, thereby predisposing patients to adverse outcomes such as necrotizing enterocolitis (NEC). In addition, intestinal bile acids (BAs) accumulation is causally linked to NEC development. Plant sterols are a promising intervention to prevent NEC development, considering their anti-inflammatory properties in the liver. Therefore, we investigated whether an intra-amniotic (IA) Ureaplasma parvum (UP) infection affected the liver and enterohepatic circulation (EHC) and evaluated whether an IA administered plant sterol mixture dissolved in β-cyclodextrin exerted prophylactic effects. An ovine chorioamnionitis model was used in which liver inflammation and the EHC were assessed following IA UP exposure in the presence or absence of IA prophylactic plant sterols (a mixture of β-sitosterol and campesterol dissolved in β-cyclodextrin (carrier)) or carrier alone. IA UP exposure caused an inflammatory reaction in the liver, histologically seen as clustered and conflated hepatic erythropoiesis in the parenchyma, which was partially prevented by IA administration of sterol + β-cyclodextrin, or β-cyclodextrin alone. In addition, IA administration of β-cyclodextrin prior to UP caused changes in the expression of several hepatic BAs transporters, without causing alterations in other aspects of the EHC. Thereby, the addition of plant sterols to the carrier β-cyclodextrin did not have additional effects

Co-expressed immune and metabolic genes in visceral and subcutaneous adipose tissue from severely obese individuals are associated with plasma HDL and glucose levels: a microarray study

<p>Abstract</p> <p>Background</p> <p>Excessive accumulation of body fat, in particular in the visceral fat depot, is a major risk factor to develop a variety of diseases such as type 2 diabetes. The mechanisms underlying the increased risk of obese individuals to develop co-morbid diseases are largely unclear.</p> <p>We aimed to identify genes expressed in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) that are related to blood parameters involved in obesity co-morbidity, such as plasma lipid and glucose levels, and to compare gene expression between the fat depots.</p> <p>Methods</p> <p>Whole-transcriptome SAT and VAT gene expression levels were determined in 75 individuals with a BMI >35 kg/m². Modules of co-expressed genes likely to be functionally related were identified and correlated with BMI, plasma levels of glucose, insulin, HbA_1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol.</p> <p>Results</p> <p>Of the approximately 70 modules identified in SAT and VAT, three SAT modules were inversely associated with plasma HDL-cholesterol levels, and a fourth module was inversely associated with both plasma glucose and plasma triglyceride levels (p < 5.33 × 10^-5). These modules were markedly enriched in immune and metabolic genes. In VAT, one module was associated with both BMI and insulin, and another with plasma glucose (p < 4.64 × 10^-5). This module was also enriched in inflammatory genes and showed a marked overlap in gene content with the SAT modules related to HDL. Several genes differentially expressed in SAT and VAT were identified.</p> <p>Conclusions</p> <p>In obese subjects, groups of co-expressed genes were identified that correlated with lipid and glucose metabolism parameters; they were enriched with immune genes. A number of genes were identified of which the expression in SAT correlated with plasma HDL cholesterol, while their expression in VAT correlated with plasma glucose. This underlines both the singular importance of these genes for lipid and glucose metabolism and the specific roles of these two fat depots in this respect.</p

Genetic and epigenetic regulation of gene expression in fetal and adult human livers

Background: The liver plays a central role in the maintenance of homeostasis and health in general. However, there is substantial inter-individual variation in hepatic gene expression, and although numerous genetic factors have been identified, less is known about the epigenetic factors. Results: By analyzing the methylomes and transcriptomes of 14 fetal and 181 adult livers, we identified 657 differentially methylated genes with adult-specific expression, these genes were enriched for transcription factor binding sites of HNF1A and HNF4A. We also identified 1,000 genes specific to fetal liver, which were enriched for GATA1, STAT5A, STAT5B and YY1 binding sites. We saw strong liver-specific effects of single nucleotide polymorphisms on both methylation levels (28,447 unique CpG sites (meQTL)) and gene expression levels (526 unique genes (eQTL)), at a false discovery rate (FDR) <0.05. Of the 526 unique eQTL associated genes, 293 correlated significantly not only with genetic variation but also with methylation levels. The tissue-specificities of these associations were analyzed in muscle, subcutaneous adipose tissue and visceral adipose tissue. We observed that meQTL were more stable between tissues than eQTL and a very strong tissue-specificity for the identified associations between CpG methylation and gene expression. Conclusions: Our analyses generated a comprehensive resource of factors involved in the regulation of hepatic gene expression, and allowed us to estimate the proportion of variation in gene expression that could be attributed to genetic and epigenetic variation, both crucial to understanding differences in drug response and the etiology of liver diseases

Unraveling the Regulatory Mechanisms Underlying Tissue-Dependent Genetic Variation of Gene Expression

It is known that genetic variants can affect gene expression, but it is not yet completely clear through what mechanisms genetic variation mediate this expression. We therefore compared the cis-effect of single nucleotide polymorphisms (SNPs) on gene expression between blood samples from 1,240 human subjects and four primary non-blood tissues (liver, subcutaneous, and visceral adipose tissue and skeletal muscle) from 85 subjects. We characterized four different mechanisms for 2,072 probes that show tissue-dependent genetic regulation between blood and non-blood tissues: on average 33.2% only showed cis-regulation in non-blood tissues; 14.5% of the eQTL probes were regulated by different, independent SNPs depending on the tissue of investigation. 47.9% showed a different effect size although they were regulated by the same SNPs. Surprisingly, we observed that 4.4% were regulated by the same SNP but with opposite allelic direction. We show here that SNPs that are located in transcriptional regulatory elements are enriched for tissue-dependent regulation, including SNPs at 3′ and 5′ untranslated regions (P = 1.84×10−5 and 4.7×10−4, respectively) and SNPs that are synonymous-coding (P = 9.9×10−4). SNPs that are associated with complex traits more often exert a tissue-dependent effect on gene expression (P = 2.6×10−10). Our study yields new insights into the genetic basis of tissue-dependent expression and suggests that complex trait associated genetic variants have even more complex regulatory effects than previously anticipated

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Cost-effectiveness of one year dementia follow-up care by memory clinics or general practitioners: economic evaluation of a randomised controlled trial

Contains fulltext : 125289.pdf (publisher's version ) (Open Access)OBJECTIVE: To evaluate the cost-effectiveness of post-diagnosis dementia treatment and coordination of care by memory clinics compared to general practitioners' care. METHODS: A multicentre randomised trial with 175 community dwelling patients newly diagnosed with mild to moderate dementia, and their informal caregivers, with twelve months' follow-up. Cost-effectiveness was evaluated from a societal point of view and presented as incremental cost per quality adjusted life year. To establish cost-effectiveness, a cost-utility analysis was conducted using utilities based on the EQ-5D. Uncertainty surrounding the incremental cost-effectiveness ratio (difference in costs divided by difference in effects) was calculated by bootstrapping from the original data. RESULTS: Compared to general practitioners' care, treatment by the memory clinics was on average euro1024 (95% CI: -euro7723 to euro5674) cheaper, and showed a non-significant decrease of 0.025 (95% CI: -0.114 to 0.064) quality adjusted life years. The incremental cost-effectiveness point estimate from the bootstrap simulation was euro 41 442 per QALY lost if one would use memory clinic care instead of general practitioner care. CONCLUSION: No evidence was found that memory clinics were more cost-effective compared to general practitioners with regard to post-diagnosis treatment and coordination of care of patients with dementia in the first year after diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00554047