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Objectives: Early diagnosis and treatment of rheumatoid arthritis (RA) and axial spondylarthritis (axSpA) can limit the impact of disease outcomes. This study evaluated the effectiveness of a referral program on the identification of patients with RA and axSpA. Methods: This was an observational, prospective, randomized (by clusters) study conducted in Portugal to evaluate the impact of the implementation of a set of referral support actions (RSA). The study was divided in two sub-studies, the RA sub-study and the axSpA sub-study. 28 participating primary care units were randomly (by clusters) assigned to RSA or control group (with no intervention). Both RSA and control groups identified and referred patients with suspected RA or axSpA to the rheumatology unit of the reference hospital. The primary objective was to evaluate the correct diagnosis of RA or axSpA cases confirmed by the rheumatologist of the reference hospital. Results: RA-Substudy: A total of 340 patients were recruited (144 in the RSA-exposed group; 196 in the control). RA diagnosis confirmation was 7.3% (95%CI, 2.1-12.5%) in RSA group versus 2.7% (95%CI, 0.0- -5.7%) in control group. RSA effect was positive but moderate (4.6%) and not statistically significant (95% CI, 0.0%-11.8%; p=0.222, adjusted for clustering effect). Rate of confirmed arthritis of any type was 16.9% (n=14/83) in the RSA group and 6.0% (n=5/83) in the control group. This difference was statistically significant and favorable to RSA group (OR=3.2; 95% CI 1.1-9.2; p=0.028). AxSpA-Substudy: A total of 231 patients were recrui - ted (108 in the RSA-exposed group; 123 in the control). AxSpA diagnosis confirmation was 8.7% (95% CI, 2.1-15.4%) in RSA group versus 5.6% (95% CI, 0.0-11.73%) in control group. RSA effect was positive (3.1%) but not statistically significant (95% CI, -7.5- -12.9%; p=0.568, adjusted for clustering effect). Conclusions: This study showed a positive tendency for the RSA program, most relevantly on the diagnosis of patients with any type of arthritis in the RA substudy. It is possible that a referral program more comprehensive than the one herein tested might improve early diagnosis of RA and SpA. [ABSTRACT FROM AUTHOR]

Xanthomonas spp. reduce crop yields and quality worldwide. During infection of their plant hosts, many strains secrete transcription activator-like (TAL) effectors, which enter the host cell nucleus and activate specific corresponding host genes at effector binding elements (EBEs) in the promoter. TAL effectors may contribute to disease by activating the expression of susceptibility genes or trigger resistance associated with the hypersensitive reaction (HR) by activating an executor resistance ( R) gene. The rice bacterial leaf streak pathogen X. oryzae pv. oryzicola (Xoc) is known to suppress host resistance, and no host R gene has been identified against it, despite considerable effort. To further investigate Xoc suppression of host resistance, we conducted a screen of effectors from BLS256 and identified Tal2a as an HR elicitor in rice when delivered heterologously by a strain of the closely related rice bacterial blight pathogen X. oryzae pv. oryzae (Xoo) or by the soybean pathogen X. axonopodis pv. glycines. The HR required the Tal2a activation domain, suggesting an executor R gene. Tal2a activity was differentially distributed among geographically diverse Xoc isolates, being largely conserved among Asian isolates. We identified four genes induced by Tal2a in next-generation RNA sequencing experiments and confirmed them using quantitative real-time reverse transcription-polymerase chain reaction (qPCR). However, neither individual nor collective activation of these genes by designer TAL effectors resulted in HR. A tal2a knockout mutant of BLS256 showed virulence comparable with the wild-type, but plasmid-based overexpression of tal2a at different levels in the wild-type reduced virulence in a directly corresponding way. Overall, the results reveal that host resistance suppression by Xoc plays a critical role in pathogenesis. Further, the dose-dependent avirulence activity of Tal2a and the apparent lack of a single canonical target that accounts for HR point to a novel, activation domain-dependent mode of action, which might involve, for example, a non-coding gene or a specific pattern of activation across multiple targets. [ABSTRACT FROM AUTHOR]

Genomes of the rice ( Oryza sativa) xylem and mesophyll pathogens Xanthomonas oryzae pv. oryzae ( Xoo) and pv. oryzicola ( Xoc) encode numerous secreted transcription factors called transcription activator-like ( TAL) effectors. In a few studied rice varieties, some of these contribute to virulence by activating corresponding host susceptibility genes. Some activate disease resistance genes. The roles of X. oryzae TAL effectors in diverse rice backgrounds, however, are poorly understood., Xoo TAL effectors that promote infection by activating SWEET sucrose transporter genes were expressed in TAL effector-deficient X. oryzae strain X11-5A, and assessed in 21 rice varieties. Some were also tested in Xoc on variety Nipponbare. Several Xoc TAL effectors were tested in X11-5A on four rice varieties., Xoo TAL effectors enhanced X11-5A virulence on most varieties, but to varying extents depending on the effector and variety. SWEET genes were activated in all tested varieties, but increased virulence did not correlate with activation level. SWEET activators also enhanced Xoc virulence on Nipponbare. Xoc TAL effectors did not alter X11-5A virulence., SWEET-targeting TAL effectors contribute broadly and non-tissue-specifically to virulence in rice, and their function is affected by host differences besides target sequences. Further, the utility of X11-5A for characterizing individual TAL effectors in rice was established. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Current epidemiological data on heart failure (HF) in Portugal derives from studies conducted two decades ago. The main aim of this study is to determine HF prevalence in the Portuguese population. Using current standards, this manuscript aims to describe the methodology and research protocol applied., Methods: The Portuguese Heart Failure Prevalence Observational Study (PORTHOS) is a large, three-stage, population-based, nationwide, cross-sectional study. Community-dwelling citizens aged 50 years and older will be randomly selected via stratified multistage sampling. Eligible participants will be invited to attend a screening visit at a mobile clinic for HF symptom assessment, anthropomorphic assessment, N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, one-lead electrocardiogram (ECG) and a sociodemographic and health-related quality of life questionnaire (EQ-5D). All subjects with NT-proBNP ≥125 pg/mL or with a prior history of HF will undergo a diagnostic confirmatory assessment at the mobile clinic composed of a 12-lead ECG, comprehensive echocardiography, HF questionnaire (KCCQ) and blood sampling. To validate the screening procedure, a control group will undergo the same diagnostic assessment. Echocardiography results will be centrally validated, and HF diagnosis will be established according to the European Society of Cardiology HF guidelines. A random subsample of patients with an equivocal HF with preserved ejection fraction diagnosis based on the application of the Heart Failure Association preserved ejection fraction diagnostic algorithm will be invited to undergo an exercise echocardiography., Conclusions: Through the application of current standards, appropriate methodologies, and a strong research protocol, the PORTHOS study will determine the prevalence of HF in mainland Portugal and enable a comprehensive characterization of HF patients, leading to a better understanding of their clinical profile and health-related quality of life., (Copyright © 2023 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The implementation of models capable of improving referral quality, limiting the growth of waiting lists in hospitals, and ensuring the best possible treatment and follow-up of the psoriatic patient is of the utmost importance., Material and Methods: A panel of Family Physicians and Dermatologists discussed and created a simple and effective algorithm of referral for patients with psoriasis., Results: The proposed algorithm starts when the Family Physician suspects of psoriasis. In case of diagnostic doubt, the patient should be referred to Dermatology. In case of a confirmed diagnosis, the Family Physician should assess the patient's severity and responder profile, evaluate comorbidities and assess the presence of psoriatic arthritis. If psoriasis is mild, topical treatments should be initiated, and if there is no clinical improvement or worsening of the disease, the patient should be referred to Dermatology. If psoriasis is moderate to severe, is located in high impact locations, or in pediatric age, the patient should be referred to Dermatology. In order to enable shared management in terms of follow-up and treatment of these patients, it is critical that the Family Physician has the necessary knowledge regarding the systemic treatments used in psoriasis and their side effects., Discussion and Conclusion: Only a shared management of the psoriatic patient can allow for the best treatment and follow-up of these patients, a more rational use of available medical resources, thus giving the patient the best possible quality of life.

Background: Despite the widespread treatments for osteoarthritis (OA), data on treatment patterns, adequacy of pain relief, and quality of life are limited. The prospective multinational Survey of Osteoarthritis Real World Therapies (SORT) was designed to investigate these aspects., Objectives: To analyze the characteristics and the patient reported outcomes of the Portuguese dataset of SORT at the start of observation., Methods: Patients ≥50 years with primary knee OA who were receiving oral or topical analgesics were eligible. Patients were enrolled from seven healthcare centers in Portugal between January and December 2011. Pain and function were evaluated using the Brief Pain Inventory (BPI) and WOMAC. Quality of life was assessed using the 12-Item Short Form Health Survey (SF-12). Inadequate pain relief (IPR) was defined as a score >4/10 on item 5 of the BPI., Results: Overall, 197 patients were analyzed. The median age was 67.0 years and 78.2% were female. Mean duration of knee OA was 6.2 years. IPR was reported by 51.3% of patients. Female gender (adjusted odds ratio - OR 2.15 [95%CI 1.1, 4.5]), diabetes (OR 3.1 [95%CI 1.3, 7.7]) and depression (OR 2.24 [95%CI 1.2, 4.3]) were associated with higher risk of IPR. Patients with IPR reported worst outcomes in all dimensions of WOMAC (p<0.001) and in all eight domains and summary components of SF-12 (p<0.001)., Conclusions: Our findings indicate that improvements are needed in the management of pain in knee OA in order to achieve better outcomes in terms of pain relief, function and quality of life., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

Heart failure is a syndrome with high prevalence, morbidity and mortality, but awareness of the disease is poor among the general public and policy makers. This document, which was prepared by a group of experts consisting of cardiologists, internists and general practitioners, aims to set out in detail the problem of heart failure in Portugal at several levels: burden of the disease, diagnosis, treatment and monitoring. To this aim, different aspects of the management of the various stages of the disease are identified and discussed in detail, covering both outpatients and hospitalized patients. In order to optimize the medical care provided to these patients, various short-, medium- and long-term solutions and strategies are put forward that have the potential to improve the integration and use of available resources. The intention is to highlight strategies that are not based on a single model but can be adapted to different regional circumstances, in order to increase awareness and improve management of heart failure in Portugal., (Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Despite the widespread treatments for Osteoarthritis (OA), data on treatment patterns, adequacy of pain relief, and quality of life are limited. The prospective multinational Survey of Osteoarthritis Real World Therapies (SORT) was designed to investigate these aspects., Objectives: To analyze the characteristics and the patient reported outcomes of the Portuguese dataset of SORT at the start of observation., Methods: Patients ≥ 50 years with primary knee OA who were receiving oral or topical analgesics were eligible. Patients were enrolled from seven healthcare centers in Portugal between January and December 2011. Pain and function were evaluated using the Brief Pain Inventory (BPI) and WOMAC. Quality of life was assessed using the 12-Item Short Form Health Survey (SF-12). Inadequate Pain Relief (IPR) was defined as a score>4/10 on item 5 of the BPI., Results: Overall, 197 patients were analyzed. The median age was 67.0 years and 78.2% were female. Mean duration of knee OA was 6.2 years. IPR was reported by 51.3% of patients. Female gender (adjusted odds ratio - OR 2.15 [95%CI 1.1, 4.5]), diabetes (OR 3.1 [95%CI 1.3, 7.7]) and depression (OR 2.24 [95%CI 1.2, 4.3]) were associated with higher risk of IPR. Patients with IPR reported worst outcomes in all dimensions of WOMAC (p<0.001) and in all eight domains and summary components of SF-12 (p<0.001)., Conclusions: Our findings indicate that improvements are needed in the management of pain in knee OA in order to achieve better outcomes in terms of pain relief, function and quality of life., (Copyright © 2016. Published by Elsevier Editora Ltda.)

Background: The access to healthcare and treatment by rheumatoid arthritis (RA) patients, particularly to biologics, differs significantly among European countries.We aimed to explore the views and experiences of Portuguese healthcare stakeholders on key barriers which limit the access to treatment, and ultimately to biologics, by RA patients and to find potential solutions (leverage points) to overcome the identified barriers., Methods: This was a qualitative research consisting of semi-structured face-to-face interviews with key stakeholders in RA framework. Thirty four individuals from eight groups of stakeholders were interviewed: rural and urban general practitioners (GPs), rheumatologists, hospital managers, hospital pharmacists, budget holders, representatives from the Portuguese Rheumatology Society and the RA Patient Association. Interviews were conducted between May and June 2011. Conventional content analysis with research triangulation was used., Results: The key barriers identified were related to the accessibility to primary healthcare services, difficulties in RA diagnosis among GPs, inefficient referral to secondary healthcare and controlled process of biologics prescription in public hospitals. The leverage points identified included the improvement of epidemiological and clinical knowledge about RA in Portugal, a better understanding of the disease among patients and GPs, the clarification of biologics benefits among budget holders and a raised awareness of the current treatment guidelines. In order to further address the leverage points, the following key initiatives were proposed: optimization of RA national registry; dissemination of information on rheumatic symptoms in primary care facilities and among the general public; increase interaction between rheumatologists and GPs through clinical discussions of successfully treated patients or workshops; broader utilization of disease diagnosis and monitoring tools, such as DAS28, and implementation of hospital-based research to collect real-world data., Conclusions: Most of the key barriers limiting the access to treatment, including biologics, in RA in Portugal are upstream of rheumatology practice. Our findings suggest that future actions should be focused on the primary care level to improve referral to rheumatologists. In addition, the collection of real-world data seems essential to characterise the RA population, to improve disease management and to increase compliance with current treatment guidelines.

Dabigatran etexilate is a novel, oral, reversible, direct thrombin inhibitor that constitutes a major breakthrough for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Dabigatran was the first new oral anticoagulant approved in Europe and became available in Portugal, for stroke prevention in nonvalvular AF, earlier than in most European countries. This paper is the joint effort of a panel of experts from different specialties and provides information on the use of dabigatran, in anticipation of the challenges that will come with increased usage.