Implementation Status of the Proposal for a Regulation of the European Health Data Space in Portugal: Are We Ready for It?

The European Health Data Space (EHDS) proposal aims to establish a set of rules and governance frameworks to promote the use of electronic health data for both primary and secondary purposes. This study aims at analysing the implementation status of the EHDS proposal in Portugal, particularly the points concerning the primary use of health data. The proposal was scanned for the points that gave member states a direct responsibility to implement actions, and a literature review and interviews were conducted to assess the implementation status of these policies in Portugal This study found that Portugal is well advanced in the implementation of policies concerning the rights of natural persons in relation to the primary use of their personal health data, but also identified challenges, which include the lack of a common interoperability framework for the exchange of electronic health data.

Structure and electronic properties of a benzene-water solution.

Electronic properties of benzene in water were investigated by a sequential quantum mechanical/molecular dynamics approach. Emphasis was placed on the analysis of the structure, polarization effects, and ionization spectrum. By adopting a polarizable model for both benzene and water the structure of the benzene-water solution is in good agreement with data from first principles molecular dynamics. Further, strong evidence that water molecules acquire enhanced orientational order near the benzene molecule is found. Upon hydration, the quadrupole moment of benzene is not significantly changed in comparison with the gas-phase value. We are also reporting results for the dynamic polarizability of benzene in water. Our results indicate that the low energy behaviour of the dynamic polarizability of gas-phase and hydrated benzene is quite similar. Outer valence Green's function calculations for benzene in liquid water show a splitting of the gas-phase energy levels associated with the 1e(1g)(π), 2e(2g), and 2e(1u) orbitals upon hydration. Lifting of the orbitals degeneracy and redshift of the outer valence bands is related to symmetry breaking of the benzene structure in solution and polarization effects from the surrounding water molecules.

Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients.

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.

Commercial green tea from Portugal: Comprehensive microbiologic analyses.

In recent times green tea (GT) consumption has increased, due to the numerous studies that indicate a wide variety of health benefits following its regular consumption. The aim of this study was to assess the bioburden (bacteria and fungi) of bulk and bags of GT marketed in Lisbon and to obtain a more refined fungal burden characterization, including azole resistance profile. The bacteriota in tea bags before boiling ranged from lower than the detection limit to 1770 CFU.g-1, whereas in brew samples ranged from lower than the detection limit to 54.55 CFU.mL-1. In bulk samples before boiling ranged from lower than the detection limit to 2636 CFU.g-1, while after boiling ranged from lower than the detection limit to 72.73 CFU.mL-1. Fungal contamination on tea bags before boiling ranged from lower than the detection limit to 66.67 CFU.g-1 and after boiling, all samples presented results lower than the detection limit. Concerning bulk samples before boiling ranged from lower than the detection limit to 96.97 CFU.g-1, whereas after boiling ranged from lower the detection limit to 30.3 CFU.mL-1. Before boiling, the most common fungal species in the bagged tea (90.91 CFU.g-1; 45.45%) and bulk samples (66.67 CFU.g-1; 91.67%) was Aspergillus section Nigri. Fungal diversity was higher on bulk samples than in tea bags. Aspergillus section Nigri and Rhizopus sp. growth was observed mostly on itraconazole-supplemented Sabouraud dextrose agar media, which require further investigation. Aspergillus sections Fumigati and Nidulantes were detected by using real time PCR, but not in the GT samples in which they were identified through culture-based methods. A significantly reduction of bacterial contamination after boiling was observed, however fungal contamination with toxigenic potential was observed before and after boiling. Future research work needs to characterize in detail the mycotoxins contamination to allow a risk-benefit assessment to estimate the human health benefits and risks following tea consumption and to support policy-actions, if and when needed. The results also suggest that the conditions how tea is packed can influence the fungal diversity and this variable should be further investigated.

Predictors of response to TNF blockers in patients with polyarticular psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease with a broad clinical spectrum. PsA can affect the axial skeleton, peripheral joints, entheses, synovial sheaths of tendons, skin, nails and extra-articular organs. Tumour necrosis factor alpha blockers (TNF blockers) were a breakthrough development in the treatment of PsA. Identifying predictors of response to biological therapies in patients with PsA is of utmost importance, especially in view of the costs and potential side effects of these agents. The aims of the present study were to determine baseline predictive factors of response to biological therapies, at 3 and 6 months, in PsA patients with polyarticular involvement (with or without axial involvement). Data were collected from the Rheumatic Diseases Portuguese Register (Reuma.pt). Eligible patients had to be anti-TNF-naive at baseline and to have at least 3 months of follow-up after the beginning of TNF blocker therapy. Only patients with information on at least one of the response measures (at 3 or 6 months of follow-up) were included in the analysis. Univariable logistic regression analysis of potential baseline predictors of European League Against Rheumatism (EULAR) good clinical response, EULAR good/moderate response, 28-joint Disease Activity Score with three variables including the erythrocyte sedimentation rate (DAS28-3V-ESR) remission and Health Assessment Questionnaire (HAQ) response were performed. Multivariable logistic regression using a forward selection procedure was used until the best-fit model was obtained, taking confounding effects into account. A total of 180 patients were eligible for the study (mean age 52 years, 54% women). In multivariable analysis at 3 months, females were less likely to attain a good EULAR response [OR=0.082 (95% CI=0.024, 0.278)], a DAS28-3V-ESR remission [OR=0.083 (95% CI=0.017, 0.416)], a moderate or good EULAR response [OR=0.091 (95% CI=0.011, 0.091)] and a HAQ response [OR=0.074 (95% CI=0.009, 0.608)]. At 6 months, female gender was also less likely to achieve a good EULAR response [OR=0.060 (95% CI=0.011, 0.325)], DAS28-3V-ESR remission [OR=0.060 (95% CI=0.012, 0.297)], and a HAQ response [OR=0.138 (95% CI= 0.029, 0.654)]. In this study we found that gender was the most consistent predictor of response to TNF blocker therapy in patients with polyarticular PsA, with females having a lower probability of response compared to males. These findings suggest that gender-related biochemical, hormonal and psychological factors could play an important role in the response to TNF blocker therapy in PsA.

Utilization of Subcutaneous Methotrexate in Rheumatoid Arthritis Patients After Failure or Intolerance to Oral Methotrexate: A Multicenter Cohort Study.

INTRODUCTION: Low-dose weekly methotrexate (MTX) is the mainstay in the therapy of rheumatoid arthritis (RA). It can be given via oral, intramuscular or subcutaneous (SC) route. This study sought to determine the real-world pattern of treatment with SC MTX in Portuguese adult patients with active RA. METHODS: Utilization of Metoject(®) in Rheumatoid Arthritis (UMAR) was a non-interventional, cohort multicenter study with retrospective data collection. Eligible patients had active RA, at least 18 years of age, and started SC MTX treatment in 2009 or 2010 after failure or intolerance to oral MTX. Data were collected from patient's clinical records. Both non-parametric and parametric survival methods were used to obtain a detailed understanding of SC MTX treatment duration. RESULT: Fifty patients were included, of which only 9 discontinued SC MTX during the study follow-up period. The probability of discontinuation after 1, 2, and 3 years of treatment of SC MTX treatment is expected to be 6.10%, 8.50%, and 23.20%, respectively. The extrapolated median duration of SC MTX using an exponential model was 106.4 months/8.87 years. Mean dose of SC MTX was 18.36 mg. The reasons for treatment discontinuation were occurrence of adverse events in six patients and lack of efficacy in three. CONCLUSION: The long treatment duration of SC MTX highlights its excellent tolerability compared to oral MTX, especially concerning the frequent adverse gastrointestinal events of MTX. Furthermore, long MTX treatment duration provides the opportunity to postpone or even avoid expensive therapies with biologics. The results obtained from the UMAR study provide important information for the utilization and public financing of SC MTX in Portugal.

Poncet's disease: a symmetric seronegative polyarthritis with enthesopathy refractory to the therapy.

Poncet's disease is a reactive polyarthritis associated to active tuberculosis (TB), with excluded presence of mycobacterium in the joints and bones affected, and no other cause for the clinical arthritis. It is a frequently forgotten entity, especially in countries with low tuberculosis prevalence. It is described a case report of a man of Guinea-Bissau that presented symmetrical generalized polyarthralgias and hands swelling, clinical sacroiliítis and multiple enthesopathies. Serum and urinary biochemical testing were normal. Immunologic studies were negative and serum levels of angiotensin-converting enzyme and calcium were normal. Sexual transmitted diseases were excluded. The initial diagnose was undifferentiated polyarthritis or reactive arthritis. A persistent and refractory monoarthritis of the right wrist demanded a direct and cultural exam of the synovial fluid, synovial biopsy and protein chain reaction for TB that were negative. After he developed right wrist arthritis with purulent synovial fluid positive to TB in the direct exam and the detection of M. tuberculosis in the cultural exam. Granula was found in his chest radiograph. He was diagnosed a Poncet's disease reactive to a pulmonary TB infection.

[Eosinophilic fasciitis and aplastic anemia]. / Fasceíte eosinofílica e aplasia medular.

Eosinophilic fasciitis is a rare rheumatic condition characterized by inflammatory thickening of the skin and fascia, peripheral eosinophilia, elevated erythrocyte sedimentation rate and hypergammaglobulinemia. Internal organ involvement is uncommon. It is often difficult to diagnose eosinophilic fasciitis and its course may be variable. Glucocorticoids are most commonly used in the treatment but in many cases they are ineffective, requiring combined immunosuppressive treatment. Several cases of eosinophilic fasciitis and serious haematological disorders such as immune thrombocytopenia, Hodgkin's disease and aplastic anaemia have been described. The authors report an atypical severe case of eosinophilic fasciitis complicated by aplastic anaemia non responsive to treatment.