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

Inflammation Dynamically Regulates Steroid Hormone Metabolism and Action within Macrophages in Rheumatoid Arthritis

Rationale: In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages. Methods: Bulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures. Results: RNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11β-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11β-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17,), whilst 11β-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11β-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes. Conclusions: This study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.<br/

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