evidence- and practice-based guidance

The authors thank Luı́s Veloso, Daniela Carvalho, and Catarina Oliveira Silva (from CTI, Clinical Trial & Consulting Services) for their assistance with the project.Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren's syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.publishersversionpublishe

Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and Sjögren’s syndrome: evidence- and practice-based guidance

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren’s syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts’ input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS

Determinants of HIV late presentation among men who have sex with men in Portugal (2014–2019): who’s being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.info:eu-repo/semantics/publishedVersio

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.info:eu-repo/semantics/publishedVersio

COOPEDU IV — Cooperação e Educação de Qualidade

O quarto Congresso Internacional de Cooperação e Educação-IV COOPEDU, organizado pelo Centro de Estudos Internacionais (CEI) do Instituto Universitário de Lisboa e pela Escola Superior de Educação e Ciências Sociais do Instituto Politécnico de Leiria decorreu nos dias 8 e 9 de novembro de 2018, subordinado à temática Cooperação e Educação de Qualidade. Este congresso insere-se numa linha de continuidade de intervenção por parte das duas instituições organizadoras e dos elementos coordenadores e este ano beneficiou do financiamento do Instituto Camões, obtido através de um procedimento concursal, que nos permitiu contar com a participação presencial de elementos dos Países Africanos de Língua Portuguesa, fortemente implicados nas problemáticas da Educação e da Formação. Contou também com a participação do Instituto Camões e da Fundação Calouste Gulbenkian, entidades que sistematizaram a sua intervenção nos domínios da cooperação na área da educação nos últimos anos. A opção pela temática da qualidade pareceu aos organizadores pertinente e actual. Com efeito os sistemas educativos dos países que constituem a Comunidade de países de língua portuguesa têm implementado várias reformas mas em vários domínios mantem-se a insatisfação de responsáveis políticos, pedagogos, técnicos sociais face aos resultados obtidos. Aliás o caminho de procura da Qualidade é interminável porque vai a par da aposta na exigência e na promoção da cidadania e responsabilidade social. As comunicações que agora se publicam estão organizadas em dois eixos: o das Políticas da Educação e Formação e o das dimensões em que se traduzem essas políticas. Neste último eixo encontramos fios condutores para agregarmos as comunicações apresentadas

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

Aplicação da densitometria do cristalino baseada no príncipio de scheimpflug na avaliação pré-operatória de catarata nuclear senil

Tese de Doutoramento em MedicinaOpacification of the crystalline lens is a commonly observed agerelated process and contributes for visual acuity and contrast sensitivity degradation. Cataract surgery is considered to be the most performed surgical procedure worldwide, accounting for about 22 million interventions. In Portugal, about 75.000 cataract surgeries are performed each year. The most widely used clinical method to assess the crystalline lens opacification is the Lens Opacities Classification System III grading system. Scheimpflug imaging enables objective lens densitometry evaluation, which is not susceptible to observer variability and is considered to be a more sensitive and repeatable approach. An extensive literature review related to this topic revealed that objective assessment of cataract with Scheimpflug imaging offers a considerable opportunity for various scientific researches, especially regarding the functional status of the crystalline lens and cataract surgery planning. Several factors compromise the comparison of results and conclusions of previous research studies, such as different densitometric evaluation methods and metrics. The relative absence of studies analyzing a relationship between crystalline lens densitometry and its functional state is also noted, especially when considering ray-tracing aberrometry. This PhD thesis pretend to analyze the application of Scheimpflug imaging in the preoperative evaluation of age-related nuclear cataracts, regarding functional status of the crystalline lens based on ray-tracing wavefront analysis and phacodynamics prediction. In this thesis, we have confirmed that Scheimpflugbased lens densitometry presented a strong association with aging, corrected distance visual acuity decrease, and slit lamp evaluation. A significant and positive relationship was also described between the Scheimpflug-based lens densitometry variables and the internal high-order aberrations, including coma and trefoil. We also studied the relationship between the Scheimpflug-based lens densitometry and a new parameter (Dysfunctional Lens Index) based on raytracing wavefront findings. Regarding phacodynamics, we selected different lens densitometric modes to analyze the hardness of the nucleus that were described and used in previous studies. Our results revealed that parameters derived from specific modes, such as three-dimensional and region of interest modes, yielded the highest correlations coefficients with the ultrasound energy consumed during phacoemulsification. In another study, we also demonstrated that the Dysfunctional Lens Index and the Scheimpflug-derived average density based on three-dimensional presented a similar relationship with phacodynamics. Our findings presented in this thesis suggest that Scheimpflug-based lens densitometry is useful for demonstrating the functional status of the crystalline lens. Scheimpflug-based densitometry also showed to be useful concerning phacodynamics prediction. The data presented also warns for the proper use of the lens densitometry software, regarding selection and placement of the densitometry template, as well as the density metric adopted.A opacificação do cristalino é um processo relacionado com a idade e contribui para a degradação da acuidade visual e da sensibilidade ao contraste. A cirurgia de catarata é considerada o procedimento cirúrgico mais realizado em todo o mundo, contabilizando cerca de 22 milhões de intervenções. Em Portugal, aproximadamente 75.000 cirurgias de catarata são realizadas anualmente. O método clínico mais amplamente utilizado para avaliar a opacificação do cristalino é o sistema de classificação Lens Opacities Classification System III. O princípio de Scheimpflug permite a avaliação objetiva da densitometria do cristalino, que não é suscetível à variabilidade do observador e é considerada uma abordagem mais sensível e reprodutível. Uma extensa revisão da literatura relacionada com este tópico revelou que a avaliação objetiva da catarata com esta tecnologia oferece uma oportunidade considerável para inúmeras pesquisas científicas, especialmente no que se refere ao estado funcional do cristalino e ao planeamento cirúrgico. Vários fatores comprometem a comparação de resultados e conclusões de pesquisas anteriores, tais como diferentes métodos de avaliação e parâmetros de densitometria. A ausência relativa de estudos que analisam a relação entre a densitometria do cristalino e o seu estado funcional também é evidente, especialmente quando se considera a aberrometria por traçado de raios. Esta tese de doutoramento tem como objetivo analisar a aplicação da imagem Scheimpflug na avaliação pré-operatória de cataratas nucleares senis, no que diz respeito ao estado funcional do cristalino com base na análise de frente de onda por traçado de raios e na previsão da energia ultrassónica consumida durante a facoemulsificação. Confirmamos que a densitometria do cristalino baseada na imagem de Scheimpflug apresentou forte associação com o envelhecimento, a diminuição da melhor acuidade visual corrigida e a avaliação da lâmpada de fenda. Uma relação significativa e positiva também foi descrita entre as variáveis de densitometria baseada no princípio de Scheimpflug e as aberrações de alta ordem internas, incluindo o coma e o trefoil. Também estudamos a relação entre a densitometria do cristalino e um novo parâmetro (Dysfunctional Lens Index) baseado em achados da frente de onda por traçado de raios. Quanto à facodinâmica, foram selecionados diferentes modos densitométricos do cristalino para analisar a dureza do núcleo, os quais tinham sido descritos e utilizados em estudos anteriores. Os nossos resultados revelaram que os parâmetros derivados de certos modos de análise, tais como os modos tridimensional e de região de interesse, obtiveram os maiores coeficientes de correlação com a energia ultrassónica consumida durante a facoemulsificação. Noutro estudo, também demonstramos que o Dysfunctional Lens Index e a densidade média baseada na análise densitométrica tridimensional apresentaram uma relação similar com a facodinâmica. Os resultados apresentados nesta tese sugerem que a densitometria do cristalino baseado no princípio de Scheimpflug é útil para demonstrar o seu estado funcional. Esta tecnologia também mostrou ser útil em relação à previsão da facodinâmica. Os dados apresentados alertam para o uso adequado do programa de densitometria do cristalino, quanto à seleção e colocação do modelo de densitometria e, os parâmetros de densidade adotados

Integration of Scheimpflug-Based corneal tomography and biomechanical assessments for enhancing ectasia detection

PURPOSE: To present the Tomographic and Biomechanical Index (TBI), which combines Scheimpflugbased corneal tomography and biomechanics for enhancing ectasia detection. METHODS: Patients from different continents were retrospectively studied. The normal group included 1 eye randomly selected from 480 patients with normal corneas and the keratoconus group included 1 eye randomly selected from 204 patients with keratoconus. There were two groups: 72 ectatic eyes with no surgery from 94 patients with very asymmetric ectasia (VAE-E group) and the fellow eyes of these patients with normal topography (VAE-NT group). Pentacam HR and Corvis ST (Oculus Optikgerate GmbH, Wetzlar, Germany) parameters were analyzed and combined using different artificial intelligence methods. The accuracies for detecting ectasia of the Belin/Ambresio Deviation (BAD-D) and Corvis Biomechanical Index (CBI) were compared to the TBI, considering the areas under receiver operating characteristic curves (AUROCs). RESULTS: The random forest method with leave-oneout cross-validation (RF/LOOCV) provided the best artificial intelligence model. The AUROC for detecting ectasia (keratoconus, VAE-E, and VAE-NT groups) of the TBI was 0.996, which was statistically higher (DeLong et al., P < .001) than the BAD-D (0.956) and CBI (0.936). The TBI cut-off value of 0.79 provided 100% sensitivity for detecting clinical ectasia (keratoconus and VAE-E groups) with 100% specificity. The AUROCs for the TBI, BAD-D, and CBI were 0.985, 0.839, and 0.822 in the VAE-NT group (DeLong et al., P <.001). An optimized TBI cut-off value of 0.29 provided 90.4% sensitivity with 96% specificity in the VAE-NT group. CONCLUSIONS: The TBI generated by the RF/LOOCV provided greater accuracy for detecting ectasia than other techniques. The TBI was sensitive for detecting subclinical (fruste) ectasia among eyes with normal topography in very asymmetric patients. The TBI may also confirm unilateral ectasia, potentially characterizing the inherent ectasia susceptibility of the cornea, which should be the subject of future studies.Dr. Ambrosio, Dr. P. Vinciguerra, and Dr. Roberts are consultants for, Dr. Buhren has received lecture fees from, and Dr. Elsheikh has received research funding from Oculus Optikgerate GmbH (Wetzlar, Germany). The remaining authors have no financial or proprietary interest in the materials presented herein.info:eu-repo/semantics/publishedVersio

Sociodemographic, Clinical, and Behavioral Factors Associated with Sexual Transmitted Infection among HIV-1 Positive Migrants in Portugal: Are There Differences between Sexes?

Introduction: Sexually transmitted infections (STIs) continue to occur at high levels. According to the WHO, each year there are an estimated 374 million new infections with syphilis, gonorrhea, chlamydia, and trichomoniasis. STIs are associated with an increased risk of acquiring HIV infection. Migrants are reportedly highly affected by STIs. Objectives: This study aims to characterize factors associated with STIs in a population of HIV-positive migrants living in Portugal. Methodology: This is a cross-sectional observational study of 265 newly diagnosed HIV-1 positive migrants, who were defined as individuals born outside Portugal. This group of people were part of the BESTHOPE study that was developed in 17 Portuguese hospitals between September 2014 and December 2019, and included information collected through sociodemographic and behavioral questionnaires filled in by the migrant patients, clinical questionnaires filled in by the clinicians and HIV-1 genomic sequences generated through resistance testing (Sanger sequencing). A multivariable statistical analysis was used to analyze the association between sociodemographic characteristics, sexual behaviors, HIV testing and sexual infections. Results: Most HIV-1 positive individuals included in the study were men (66.8%) and aged between 25 and 44 years old (59.9%). Men had a higher proportion of STIs when compared to women (40.4% vs. 14.0%) and the majority of men reported homosexual contacts (52.0%). Most men reported having had two or more occasional sexual partners in the previous year (88.8%) and 50.9% reported always using condoms with occasional partners, while 13.2% never used it. For regular partners, only 29.5% of the women reported using condoms, compared to 47.3% of men. Other risk behaviors for acquiring HIV, such as tattooing and performing invasive medical procedures, were more prevalent in men (38.0% and 46.2%, respectively), when compared to women (30.4% and 45.1% respectively) and 4.7% of men reported having already shared injectable materials, with no data for comparison in the case for women. Additionally, 23.9% of women reported having had a blood transfusion while only 10.3% of men reported having had this medical procedure. Meanwhile, 30.9% of the individuals reported having been diagnosed with some type of STI in the last 12 months. In addition, 43.3% of individuals that answered a question about hepatitis reported to be infected with hepatitis B, while 13.0% reported having hepatitis C infection. According to the multivariable analysis, the only transmission route was significantly associated with reports of previous STI infection: men who have sex with men (MSM) were 70% more likely to have been diagnosed with an STI in the past 12 months compared to the heterosexual route. Conclusion: HIV-1 infected men were more likely to report previous STIs than women. On the other hand, most migrant women had a regular sexual partner and never or only sometimes used condoms. This somewhat discrepant findings suggest that gender inequalities may make women unable to negotiate safe sexual practices, resulting in increased susceptibility to infection. However, since migrant women report less STIs, we cannot exclude that these STIs may remain undiagnosed. The implementation of safer sex awareness campaigns for condom use and screening for STIs in women is crucial. On the other hand, health education campaigns for STI knowledge need to be implemented for both MSM and women and their partners