An economic analysis of ischaemic heart disease in Switzerland

Aims Direct and indirect costs of ischaemic heart disease were assessed in Switzerland, for the period 1988-1993, in order to evaluate the economic consequences of more intensive treatment of the disease and of the decreasing mortality from ischaemic heart disease in the working population. Methods and Results A societal perspective was taken for a prevalence-based assessment of the direct (total resources consumed by outpatients and inpatients) and indirect (due to morbidity, invalidity, and premature death, using the human capital approach) costs. The results showed the total costs were 21 million US dollars per 100 000 population in the year 1993 (47% direct, 53% indirect costs). The largest components were the direct costs of inpatient care and indirect costs due to premature death (each approximately 25% of the total). Trends showed a large increase in direct costs (+9% per year, constant dollars). Indirect costs stabilized or decreased slightly due to the reduction of work losses. Conclusions Today's medicine and preventive measures have proven effective for ischaemic heart disease, although such remedies have required increasingly large financial resources. However, society benefits because indirect costs decrease, although this gain does not compensate for all direct cost

Desenvolvimento descentralizado por meio de End-User Development : avaliação tecnológica : relatório de pesquisa

Pesquisa realizada com financiamento do Ministério da Ciência, Tecnologia, Inovações e Comunicações, Projeto de Cooperação “Aprimoramento do Framework de Soluções de Tecnologia da Informação”. Ministério da Ciência, Tecnologia, Inovações e Comunicaçõe

End-User Development (EUD) : desenvolvimento pelo usuário final: conceitos, estratégias e casos de adoção : relatório de pesquisa

Pesquisa realizada com financiamento do Ministério da Ciência, Tecnologia, Inovações e Comunicações, Projeto de Cooperação “Aprimoramento do Framework de Soluções de Tecnologia da Informação”.Ministério da Ciência, Tecnologia, Inovações e Comunicaçõe

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe:a multicentre, prospective observational study

Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.</p

New cellular tools reveal complex epithelial–mesenchymal interactions in hepatocarcinogenesis

To enable detailed analyses of cell interactions in tumour development, new epithelial and mesenchymal cell lines were established from human hepatocellular carcinoma by spontaneous outgrowth in culture. We obtained several hepatocarcinoma (HCC)-, B-lymphoblastoid (BLC)-, and myofibroblastoid (MF)-lines from seven cases. In-depth characterisation included cell kinetics, genotype, tumourigenicity, expression of cell-type specific markers, and proteome patterns. Many functions of the cells of origin were found to be preserved. We studied the impact of the mesenchymal lines on hepatocarcinogenesis by in vitro assays. BLC- and MF-supernatants strongly increased the DNA replication of premalignant hepatocytes. The stimulation by MF-lines was mainly attributed to HGF secretion. In HCC-cells, MF-supernatant had only minor effects on cell growth but enhanced migration. MF-lines also stimulated neoangiogenesis through vEGF release. BLC-supernatant dramatically induced death of HCC-cells, which could be largely abrogated by preincubating the supernatant with TNFβ-antiserum. Thus, the new cell lines reveal stage-specific stimulatory and inhibitory interactions between mesenchymal and epithelial tumour cells. In conclusion, the new cell lines provide unique tools to analyse essential components of the complex interplay between the microenvironment and the developing liver cancer, and to identify factors affecting proliferation, migration and death of tumour cells, neoangiogenesis, and outgrowth of additional malignancy