Identifying common enablers and barriers in European health information systems

European countries possess unique health information systems (HISs) and face similar health system challenges. Investigating common enablers and barriers across Europe pinpoint where HISs need improvements to address these challenges. This study aims to identify common enablers and barriers for optimal functioning of HISs across the European Union and associated countries, and to interpret what this means for the further development of HISs in Europe. A qualitative thematic analysis was carried out based on nine countries HISs assessments. Two main observations are made. Firstly, regardless of the differences between HISs, each HIS had its strengths and weaknesses and often the same barriers and enablers arose. Secondly, barriers were identified in all HIS areas. The five most important barriers are (i) fragmentation of data sources, limited accessibility, use and re-use of data, (ii) barriers in the implementation of EHR-systems, (iii) governance issues related to unclear responsibilities, discontinuous financing and weak intra-and inter-sectorial collaboration, (iv) legal gaps and General Data Protection Regulation (mis)interpretation, and (v) limited skilled staff. The enablers identified in this study lead to potential solutions to address these. Solutions can be implemented by national initiatives, but there is considerable added value in a joint European approach. Several international initiatives provide opportunities to improve HISs, but these need to be strengthened and better geared towards tackling the identified barriers. (C) 2021 The Authors. Published by Elsevier B.V

Capacity building in European health information systems:The InfAct peer assessment methodology

Background A Health Information System (HIS) assessment is an evaluation of the functioning of the main elements that compose a national HIS. Assessors from nine countries performed peer assessments of each other’s national HIS in the Joint Action on Health Information (InfAct). The aim of this study is to evaluate the advantages and disadvantages of the InfAct peer assessment methodology as well as the different steps involved in this assessment process. Methods Each peer assessment included a preparatory desk report, a country visit with semi-structured interviews with local stakeholders, a final report and a follow-up stakeholder meeting. A qualitative content analysis of the peer HIS assessment was performed based on 12 semi-structured interviews. Results The main advantage of the assessments is its informal atmosphere, high degree of objectiveness and its networking opportunities. Disadvantages are its informal request format and setting for recommendation uptake. The peer assessment helped the assessors to broaden their understanding of the assessed and their own HISs, to gain knowledge on how to carry out an HIS assessment and to practice their organization, communication, reporting and negotiation skills. All steps of the HIS assessment are essential and each contributes to the enriching experience of the participants. Conclusion The InfAct peer HIS assessment methodology strengthened capacity in national HISs by building up the knowledge and expertise in participating countries and as such addressed health information inequalities. This study confirms the value and relatively easy to implement methodology, and therefore recommends its wide and more systematic application across Europe

A clinically applicable molecular classification of oncocytic cell thyroid nodules

Whole chromosome instability with near-whole genome haploidization (GH) and subsequent endoreduplication is considered a main genomic driver in the tumorigenesis of oncocytic cell thyroid neoplasms (OCN). These copy number alterations (CNA) occur less frequently in oncocytic thyroid adenoma (OA) than in oncocytic carcinoma (OCA), suggesting a continuous process. The current study described the CNA patterns in a cohort of 30 benign and malignant OCN, observed using a next-generation sequencing (NGS) panel that assesses genome-wide loss of heterozygosity (LOH) and chromosomal imbalances using 1500 single-nucleotide polymorphisms (SNPs) across all autosomes and the X chromosome in DNA derived from cytological and histological samples. Observed CNA patterns were verified using multiparameter DNA flow cytometry with or without whole-genome SNP array analysis and lesser-allele intensity-ratio (LAIR) analysis. On CNA–LOH analysis using the NGS panel, GH-type CNA were observed in 4 of 11 (36%) OA and in 14 of 16 OCA (88%). Endoreduplication was suspected in 8 of 16 (50%) OCA, all with more extensive GH-type CNA (P &lt; 0.001). Reciprocal chromosomal imbalance type CNA, characterized by (imbalanced) chromosomal copy number gains and associated with benign disease, were observed in 6 of 11 (55%) OA and one equivocal case of OCA. CNA patterns were different between the histopathological subgroups (P &lt; 0.001). By applying the structured interpretation and considerations provided by the current study, CNA–LOH analysis using an NGS panel that is feasible for daily practice may be of great added value to the widespread application of molecular diagnostics in the diagnosis and risk stratification of OCN.</p

[¹⁸F]FDG Uptake and Expression of Immunohistochemical Markers Related to Glycolysis, Hypoxia, and Proliferation in Indeterminate Thyroid Nodules

Purpose: The current study explored the association between 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake and the quantitative expression of immunohistochemical markers related to glucose metabolism, hypoxia, and cell proliferation in benign and malignant thyroid nodules of indeterminate cytology. Procedures: Using a case–control design, 24 patients were selected from participants of a randomized controlled multicenter trial (NCT02208544) in which [18F]FDG-PET/CT and thyroid surgery were performed for Bethesda III and IV nodules. Three equally sized groups of [18F]FDG-positive malignant, [18F]FDG-positive benign, and [18F]FDG-negative benign nodules were included. Immunohistochemical staining was performed for glucose transporters (GLUT) 1, 3, and 4; hexokinases (HK) 1 and 2; hypoxia-inducible factor-1 alpha (HIF1α; monocarboxylate transporter 4 (MCT4); carbonic anhydrase IX (CA-IX); vascular endothelial growth factor (VEGF); sodium-iodide symporter (NIS); and Ki-67. Marker expression was scored using an immunoreactive score. Unsupervised cluster analysis was performed. The immunoreactive score was correlated to the maximum and peak standardized uptake values (SUVmax, SUVpeak) and SUVmax ratio (SUVmax of nodule/background SUVmax of contralateral, normal thyroid) of the [18F]FDG-PET/CT using the Spearman’s rank correlation coefficient and compared between the three groups using Kruskal–Wallis tests. Results: The expression of GLUT1, GLUT3, HK2, and MCT4 was strongly positively correlated with the SUVmax, SUVpeak, and SUVmax ratio. The expression of GLUT1 (p = 0.009), HK2 (p = 0.02), MCT4 (p = 0.01), and VEGF (p = 0.007) was statistically significantly different between [18F]FDG-positive benign nodules, [18F]FDG-positive thyroid carcinomas, and [18F]FDG-negative benign nodules. In both [18F]FDG-positive benign nodules and [18F]FDG-positive thyroid carcinomas, the expression of GLUT1, HK2, and MCT4 was increased as compared to [18F]FDG-negative benign nodules. VEGF expression was higher in [18F]FDG-positive thyroid carcinomas as compared to [18F]FDG-negative and [18F]FDG-positive benign nodules. Conclusions: Our results suggest that [18F]FDG-positive benign thyroid nodules undergo changes in protein expression similar to those in thyroid carcinomas. To expand the understanding of the metabolic changes in benign and malignant thyroid nodules, further research is required, including correlation with underlying genetic alterations.</p

Natural and cryptic peptides dominate the immunopeptidome of atypical teratoid rhabdoid tumors

BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive CNS tumors of infancy and early childhood. Hallmark is the surprisingly simple genome with inactivating mutations or deletions in the SMARCB1 gene as the oncogenic driver. Nevertheless, AT/RTs are infiltrated by immune cells and even clonally expanded T cells. However, it is unclear which epitopes T cells might recognize on AT/RT cells. METHODS: Here, we report a comprehensive mass spectrometry (MS)-based analysis of naturally presented human leukocyte antigen (HLA) class I and class II ligands on 23 AT/RTs. MS data were validated by matching with a human proteome dataset and exclusion of peptides that are part of the human benignome. Cryptic peptide ligands were identified using Peptide-PRISM. RESULTS: Comparative HLA ligandome analysis of the HLA ligandome revealed 55 class I and 139 class II tumor-exclusive peptides. No peptide originated from the SMARCB1 region. In addition, 61 HLA class I tumor-exclusive peptide sequences derived from non-canonically translated proteins. Combination of peptides from natural and cryptic class I and class II origin gave optimal representation of tumor cell compartments. Substantial overlap existed with the cryptic immunopeptidome of glioblastomas, but no concordance was found with extracranial tumors. More than 80% of AT/RT exclusive peptides were able to successfully prime CD8(+) T cells, whereas naturally occurring memory responses in AT/RT patients could only be detected for class II epitopes. Interestingly, >50% of AT/RT exclusive class II ligands were also recognized by T cells from glioblastoma patients but not from healthy donors. CONCLUSIONS: These findings highlight that AT/RTs, potentially paradigmatic for other pediatric tumors with a low mutational load, present a variety of highly immunogenic HLA class I and class II peptides from canonical as well as non-canonical protein sources. Inclusion of such cryptic peptides into therapeutic vaccines would enable an optimized mapping of the tumor cell surface, thereby reducing the likelihood of immune evasion

Towards a sustainable EU health information system infrastructure: A consensus driven approach.

Health information in the EU is characterised by diversity and fragmentation of health information infrastructures. A well-defined and sustainable EU health information system infrastructure is lacking. The potential of a European Research Infrastructure Consortium on Health Information for Research and Evidence-based Policy (HIREP-ERIC) to take up this role is investigated