A REST-based framework to support non-invasive and early coeliac disease diagnosis

The health sector has traditionally been one of the early adopters of databases, from the most simple Electronic Health Record (formerly Computer-Based Patient Record) systems in use in general practice, hospitals and intensive care units to big data, multidata based systems used to support diagnosis and care decisions. In this paper we present a framework to support non-invasive and early diagnosis of coeliac disease. The proposed framework makes use of well-known technologies and techniques, both hardware and software, put together in a novel way. The main goals of our framework are: (1) providing users with a reliable and fast repository of a large amount of data; (2) to make such repository accessible by means of a suitable API in multiple modes, such as intuitive web-based or mobile visual interfaces; (3) to allow for data processing and analysis, as a basis for decision support systems

Uncertainty in economic evaluations:implications for healthcare decisions

Onzekerheid rondom kosteneffectiviteitsanalyse gezondheidszorg in kaart gebracht Wel of niet vergoeden? Die vraag wordt bij nieuwe behandelingen in de gezondheidszorg steeds belangrijker, en daarom spelen kosteneffectiviteitsanalyses een steeds belangrijkere rol. Leyla Mohseninejad verkende in haar promotieonderzoek manieren om de onzekerheid rondom zulke analyses in kaart te brengen en ze vertaalde deze theoretische concepten naar besluitvorming.Mohseninejad legt uit dat een kosteneffectiviteitsanalyse de extra kosten van een nieuwe behandeling koppelt aan de gezondheidswinst ten opzicht van de oude behandeling. Deze berekening wordt bemoeilijkt doordat de kosten en de gezondheidswinst lastig te voorspellen zijn, bijvoorbeeld doordat er gegevens uit verschillende bronnen worden gecombineerd of doordat er gewoonweg nog te weinig gegevens zijn. Dat betekent dat beslissingen die gebaseerd zijn op zo’n analyse, ook onzeker zijn.De promovenda paste enkele theoretische kostenberekeningsmethoden toe op concrete voorbeelden uit de gezondheidszorg, namelijk preventie van depressie door een “e-health”-behandeling, screening op coeliakie (glutenintolerantie) bij mensen met een prikkelbare darm, behandeling van uitgezaaide darmkanker en de behandeling van schimmelinfecties bij mensen met een ernstig verminderde afweer.Ze concludeert onder andere dat het mogelijk is, door een systematische analyse van kosten en opbrengsten in de tijd, om het tijdstip vast te stellen waarop verder verlengen van de evaluatieperiode van een bepaald duur geneesmiddel niet meer opweegt tegen de kosten. Deze resultaten kunnen zorgverzekeraars mogelijk helpen bij het vaststellen van een nieuwe leidraad.Economic evaluations, especially cost-effectiveness analyses, play an increasing role in supporting policy making in health care. In these methods, additional costs and health benefits of a new drug/health intervention are compared to the standard of care. When the additional costs and benefits of the new technology are balanced in a way that the adoption is worthwhile, the health policy can change in favor of the new technology. Different diseases with various specifications and progression stages would need different ways of calculating the long term costs and health effects. However, since any assessment of the effects as well as costs will remain uncertain to some degree, any decision based on cost-effectives will also be uncertain. This uncertainty arises from different sources, and can have an important effect on the results. The objective of this thesis is to explore different ways of handling the uncertainty in economic evaluation of new medical technologies and to extend the methods of the uncertainty analysis. Beside the methodological contribution, I explore different policy options in uncertainty management and contribute to the methods of linking reimbursement of medical products to the collection of additional evidence

Clinical profile and pathogenesis of idiopathic non-cirrhotic intra-hepatic portal hypertension (NCIPH)

INTRODUCTION: Idiopathic non-cirrhotic intra-hepatic portal hypertension (NCIPH) is a disorder characterised by occlusion of small intra-hepatic portal venous radicles (3rd/ 4th order branches). It is thus a cause of pre-sinusoidal intra-hepatic portal hypertension. NCIPH is clinically characterised by portal hypertension (gastro-oesophageal varices and subsequent bleeding), hypersplenism (low blood counts secondary to peripheral destruction) and liver functions that deteriorate, albeit much later in comparison to cirrhosis1, 2. A proportion of NCIPH patients develop liver failure and require liver transplant. Even the explant liver at the time of transplant grossly gives the appearance of cirrhosis1. AIM OF THE STUDY: The studies will explore the natural history and pathogenesis of idiopathic non-cirrhotic intra-hepatic portal hypertension (NCIPH). We also plan to study the associated disorders in patients with NCIPH. Case definition of NCIPH : For all the studies, diagnosis of NCIPH will be based on the following published criteria : 1. Portal hypertension – evidenced by gastro-oesophageal varices on upper gastrointestinal endoscopy. 2. Patent portal vein (inflow) and hepatic venous outflow tract on Doppler of the intra-abdominal vessels. 3. Absence of known aetiology of chronic liver disease – e.g. Hepatitis B/ C virus, alcohol intake etc. 4. Absence of cirrhosis or advanced fibrosis (bridging fibrosis) on liver biopsy. 5. Absence of any aetiology known to cause portal venous lesions similar to NCIPH – e.g. sarcoidosis, congenital hepatic fibrosis etc. OBJECTIVES: 1. To study the clinical profile, natural history and prognostic factors of patients with NCIPH. 2. To explore pathogenic mechanisms involved in NCIPH. 3. To study the associated disorders in patients with NCIPH. SUMMARY AND CONCLUSION: 1. Non-cirrhotic intra-hepatic portal hypertension (NCIPH) remains a common cause of portal hypertension in 21st century India. 2. The overall prognosis in these patients remains good, but these patients are prone to compensation, heptocellular carcinoma and portal vein thrombosis. 3. Imbalance of von-Willebrand factor and its cleaving protease (ADAMTS-13), despite normal liver function, suggestsa possibility of micro-angiopathy involving small portal venous radicles as the pathogenetic mechanism involved in NCIPH causation. 4. Over-representation for gut disorders, often non-specific inflammaton which is clinically silent, suggests the important role of GI tract in the pathogenesis of NCIPH. This may also partly explain the increased prevalence of NCIPH in India, esp. in the lower socio-economic strata. 5. Continued ingestion of arsenic contaminated groundwater may be one of the pathogenic mechanisms in NCIPH, esp. in patients hailing from regions near ganges

Machine Learning Analysis of the Human Infant Gut Microbiome Identifies Influential Species in Type 1 Diabetes

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Diabetes is a disease that is closely linked to genetics and epigenetics, yet mechanisms for clarifying the onset and/or progression of the disease have sometimes not been fully managed. In recent years and due to the large number of recent studies, it is known that changes in the balance of the microbiota can cause a high battery of diseases, including diabetes. Machine Learning (ML) techniques are able to identify complex, non-linear patterns of expression and relationships within the data set to extract intrinsic knowledge without any biological assumptions about the data. At the same time, mass sequencing techniques allow us to obtain the metagenomic profile of an individual, whether it is a body part, organ or tissue, and thus identify the composition of a given microbe. The great increase in the development of both technologies in their respective fields of study leads to the logical union of both to try to identify the bases of a complex disease such as diabetes. To this end, a Random Forest model has been developed at different taxonomic levels, obtaining results above 0.80 in AUC for families and above 0.98 at species level, following a strict experimental design to ensure that results are compared under equal conditions. It is identified how, in infants, the species Bacteroides uniformis, Bacteroides dorei and Bacteroides thetaiotaomicron are reduced in the microbiota of those with T1D, while, the populations of Prevotella copri increase slightly and that of Bacteroides vulgatus is much higher. Finally, thanks to the more specific metagenomic signature at species level, a model has been generated to predict those seroconverted patients not previously diagnosed with diabetes but who have expressed at least two of the autoantibodies analysed.This work was supported by the “Collaborative Project in Genomic Data Integration (CICLOGEN)” PI17/01826 funded by the Carlos III Health Institute from the Spanish National plan for Scientific and Technical Research and Innovation 2013–2016 and the European Regional Development Funds (FEDER)—“A way to build Europe”. and the General Directorate of Culture, Education and University Management of Xunta de Galicia, Spain (Ref. ED431D 2017/16), the “Galician Network for Colorectal Cancer Research, Spain” (Ref. ED431D 2017/23) and Competitive Reference Groups, Spain (Ref. ED431C 2018/49). The funding body did not have a role in the experimental design; data collection, analysis and interpretation; and writing of this manuscript. CITIC, as Research Center accredited by Galician University System, is funded by “Consellería de Cultura, Educación e Universidades from Xunta de Galicia, Spain”, supported in an 80% through ERDF Funds, Spain, ERDF Operational Programme Galicia 2014–2020, and the remaining 20% by “Secretaría Xeral de Universidades, Spain” (Grant ED431G 2019/01). The funding body did not have a role in the experimental design; data collection, analysis and interpretation; and writing of this manuscript. The calculations were performed on resources provided by the Spanish Ministry of Economy and Competitiveness via funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13-3503) and the European Regional Development Funds (FEDER) . Funding for open access charge: Universidade da Coruña/CISUGXunta de Galicia; ED431D 2017/16Xunta de Galicia; ED431D 2017/23Xunta de Galicia; ED431C 2018/49Xunta de Galicia; ED431G 2019/0

The Economic Burden of Gluten-Free Products and the Potential of Dietary Inhibitors of Transglutaminase-2

Celiac disease (CD) is a chronic immune-mediated disease of the small intestine caused by the ingestion of gluten. Gluten presents to the intestine largely intact where it is deamidated by Transglutaminase-2 (TG2), increasing affinity for Human Leukocyte Antigen DQ2 (HLA-DQ2) and forming a complex that elicits an inflammatory response ultimately leading to villous atrophy. The only current treatment is strict adherence to a gluten-free diet, though TG2 inhibition is an attractive therapy due its central role in CD pathogenesis. Cocoa contains procyanidin-B2, theobromine and caffeine and may be capable of inhibiting TG2-induced intestinal inflammation and reduce CD symptoms. Procyanidin-B2 rich cocoa extracts reduced TG2 levels by up to 77% in vitro using Caco-2 cells. Significant TG2 inhibition was seen when cocoa extracts contained at least 8.5 μM procyanidin-B2 (p\u3c0.05). Other CD inflammatory biomarkers including COX-2 and IL-15 were also significantly decreased in the presence of cocoa extracts. Serum cytokines IL-6, IL-8 and IL-1β are commonly used to monitor CD and were analyzed using ELISA to confirm the inhibition of inflammatory biomarkers. This study shows promising results for use of a bioactive-rich cocoa product as a dietary inhibitor of TG2 that can be used with wheat-based products as an alternative therapy in CD

Diagnosis and Treatment of Small Bowel Disorders

Over the last few decades, remarkable progress has been made in understanding the aetiology and pathophysiology of diseases and many new theories emphasize the importance of the small bowel ‘ecosystem’ in the pathogenesis of acute and chronic illness. Emerging factors such as microbiome, stem cells, innate intestinal immunity and the enteric nervous system along with mucosal and endothelial barriers have key role in the development of gastrointestinal and extra-intestinal diseases. Therefore, the small intestine is considered key player in metabolic disease development, including diabetes mellitus, and other diet-related disorders such as celiac and non-celiac enteropathies. Another major field is drug metabolism and its interaction with microbiota. Moreover, the emergence of gut-brain, gut-liver and gut-blood barriers points toward the important role of small intestine in the pathogenesis of common disorders, such as liver disease, hypertension and neurodegenerative disease. However, the small bowel remains an organ that is difficult to fully access and assess and accurate diagnosis often poses a clinical challenge. Eventually, the therapeutic potential remains untapped. Therefore, it is due time to direct our interest towards the small intestine and unravel the interplay between small-bowel and other gastrointestinal (GI) and non-GI related maladies