Cognitive outcomes in late-onset versus adult-onset Multiple Sclerosis.

INTRODUCTION: Recent studies show that cognitive impairment is more prevalent in older patients with Multiple Sclerosis (MS). However, whether this is the result of several years of a chronic disease or specific age-related changes is still unclear. Therefore, we aim to assess the outcomes in both classic and social cognition in late-onset MS (LOMS) and compare them to adult-onset MS (AOMS) when accounting for age and disease duration. METHODS: In this cross-sectional study, a group of 27 LOMS patients (age of disease onset >50 years) was compared with patients with AOMS (age of disease onset between 18 and 50 years). Patients with AOMS were grouped based on age (AOAMS, n = 27) and on disease duration (AODMS, n = 27) in order that these variables are matched with LOMS. Their cognitive performance was evaluated using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and the Revised "Reading the Mind in the Eyes" Test (RMET). Clinical and demographic variables were collected and analysed. RESULTS: In general, both classic and social cognitive performance was inferior in the LOMS group when accounting for age and disease duration. We found a statistically significant negative correlation between age of disease onset and performance in all cognitive domains except for verbal memory. The presence of at least one vascular risk factor (VRF) was associated with slower information-processing speed (SDMT) (p = 0.006) and poorer RMET performance (p = 0.020). DISCUSSION: A later age of MS is associated with worse cognitive functioning possibly due to the loss of neuroplasticity in an already aged brain. CONCLUSION: Patients with LOMS have worse cognitive outcomes than AOMS in both classic and social domains, especially when associated with the presence of VRF. Hence, health care providers and patients should not undervalue the importance of cognitive stimulating activities, management of VFR and socialization in this specific group of patients.

Prevalence and Classification of Pediatric Neuromuscular Disorders in the Central Region of Portugal.

Neuromuscular disorders are a group of rare heterogenous diseases with profound impact on quality of life, for which overall pediatric prevalence has rarely been reported. The purpose of this study was to determine the point prevalence of pediatric neuromuscular disorders and its subcategories in the central region of Portugal. Retrospective case identification was carried out in children with neuromuscular disorders seen between 1998 and 2020 from multiple data sources. Demographics, clinical and molecular diagnoses were registered. On January 1, 2020, the point overall prevalence in the population <18 years of age was 41.20/100 000 (95% confidence interval 34.51-49.19) for all neuromuscular disorders. The main case proportion were genetic disorders (95.7%). We found a relatively higher occurrence of limb-girdle muscular dystrophies, congenital myopathies, and spinal muscular atrophy and a slightly lower occurrence of Duchenne muscular dystrophy, hereditary spastic paraparesis, and acquired neuropathies compared to previous studies in other countries. Molecular confirmation was available in 69.5% of pediatric neuromuscular patients in our cohort.Total prevalence is high in comparison with the data reported in the only previous study on the prevalence of pediatric neuromuscular disorders in our country. Our high definitive diagnostic rate underscores the importance of advances in investigative genetic techniques, particularly new sequencing technologies, in the diagnostic workup of neuromuscular patients.

[Penicillin: from discovery to patenting the large-scale production process]. / Penicilina: da descoberta ao patenteamento do processo de produção em larga escala.

This article examines discoveries, inventions, and innovations related to penicillin by sampling activities to solve technological problems which can be traced by the distribution of scientific articles, government reports, innovations, and patents between 1929 and 1945, and proposes reflection on the importance of scientific progress for national security. The analysis highlights the technological trajectory and outcomes in the area of intellectual property, considering US policy implemented to catalyze innovation and provide institutional conditions to meet national defense needs as an important factor, although this did not necessarily imply a unique solution in other contexts.

A partir de pesquisa sobre a descoberta, a invenção e a inovação relacionadas à penicilina, por amostra de atividades de resolução de problemas tecnológicos rastreada pela distribuição, no período de 1929 a 1945, de trabalhos científicos, relatórios de governo, inovações e patentes, o artigo propõe uma reflexão sobre a importância do progresso científico para a segurança nacional. A análise destaca a trajetória tecnológica e os resultados na área de propriedade intelectual, considerando um fator importante a política implementada nos EUA para catalisar processos de inovação e oferecer condições institucionais para atender às demandas de defesa nacional, o que não significa necessariamente unicidade de solução em outros contextos.

Ongoing outbreak of hepatitis A associated with sexual transmission among men who have sex with men, Portugal, October 2023 to April 2024.

An outbreak of hepatitis A is ongoing in Portugal, with 71 confirmed cases from 7 October 2023 to 24 April 2024. Most cases are male, aged 18-44 years, with many identifying as men who have sex with men (MSM) and reported as suspected sexual transmission. Phylogenetic analysis identified the subgenotype IA, VRD 521-2016 strain, last observed in an MSM-associated multi-country outbreak in 2016 to 2018. We wish to alert colleagues in other countries to investigate potential similar spread.

Penicilina: da descoberta ao patenteamento do processo de produção em larga escala / Penicillin: from discovery to patenting the large-scale production process

Resumo A partir de pesquisa sobre a descoberta, a invenção e a inovação relacionadas à penicilina, por amostra de atividades de resolução de problemas tecnológicos rastreada pela distribuição, no período de 1929 a 1945, de trabalhos científicos, relatórios de governo, inovações e patentes, o artigo propõe uma reflexão sobre a importância do progresso científico para a segurança nacional. A análise destaca a trajetória tecnológica e os resultados na área de propriedade intelectual, considerando um fator importante a política implementada nos EUA para catalisar processos de inovação e oferecer condições institucionais para atender às demandas de defesa nacional, o que não significa necessariamente unicidade de solução em outros contextos.

Abstract This article examines discoveries, inventions, and innovations related to penicillin by sampling activities to solve technological problems which can be traced by the distribution of scientific articles, government reports, innovations, and patents between 1929 and 1945, and proposes reflection on the importance of scientific progress for national security. The analysis highlights the technological trajectory and outcomes in the area of intellectual property, considering US policy implemented to catalyze innovation and provide institutional conditions to meet national defense needs as an important factor, although this did not necessarily imply a unique solution in other contexts.

Hepatitis B vaccination associated with low response in patients with rheumatic diseases treated with biologics.

BACKGROUND: Hepatitis B virus (HBV) vaccination is recommended for non-immunised patients with rheumatic diseases starting biological disease-modifying antirheumatic drugs (bDMARDs). There is some evidence that HBV vaccination is effective in patients under conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), but it is currently unclear whether this also applies to bDMARDs. OBJECTIVES: To assess the efficacy and safety of HBV vaccination in patients with inflammatory arthritides treated with bDMARDs. METHODS: A prospective cohort with inflammatory arthritides treated with bDMARDs, negative for anti-HBs and anti-HBc and never vaccinated for HBV was recruited. Engerix B was administered at 0, 1 and 6 months and anti-HBs was reassessed ≥1 month after last dose. Response was defined as anti-HBs≥10 IU/L and compared against vaccinated healthy controls. Disease flare, serious adverse events and immune-related disorders not previously present were recorded. RESULTS: 62 patients, most treated with TNF inhibitors (TNFi), and 38 controls were recruited. Most patients were taking csDMARDs (67.7%) and were in remission/low disease activity (59.4%). Only 20/62 patients (32.3%) had a positive response to vaccination, in comparison to 36/38 age-matched controls (94.7%, p<0.001). Response was seen in 19/51 patients treated with TNFi (37.3%) and in 1/11 (9.1%) patients treated with non-TNFi (p=0.07), including 1/6 treated with tocilizumab (16.7%). Among TNFi, response rates ranged from 4/22 (18.2%) for infliximab to 8/14 (57.1%) for etanercept. No relevant safety issues were identified. CONCLUSIONS: HBV vaccination response in patients with rheumatic diseases treated with bDMARDs was poorer than expected. Our data reinforce the recommendation for vaccination prior to starting bDMARDs.

Climate change, human migration and health nexus: what do we know about public health implications on a global scale?

OBJECTIVE: to address the nexus among climate change, migration, and health at global and Italian levels. DESIGN: narrative review. SETTING AND PARTICIPANTS: comprehensive, critical, and objective analysis of the current knowledge on the topic by searching online databases. MAIN OUTCOME MEASURES: evidence from the literature examining health issues associated with migration in the context of climate change. RESULTS: anthropogenic climate change has recently influenced the scale and patterns of human mobility, not only as a driver of migration, but also by interacting with and amplifying the effects of migration determinants, including health determinants. Despite research focusing on the distinct relationship between climate change and migration, as well as climate change and health, little attention has been paid to the nexus among climate change, migration, and health. Evidence available examining various health issues associated with migration in the context of climate change include changing patterns of infectious diseases and their risks, rising cases of malnutrition, trauma and injuries, changing patterns of noncommunicable diseases, impact on mental health. Inadequacy of access to health services due to the weakening and overstretching health systems also plays an important role. In a country like Italy, even if the immediate threats posed by climate change differ from one area to another, these threats are already exacerbating the country's existing infrastructure deficiencies, industrial pollution, and hydrogeological and seismic vulnerability. In addition, Italy has historically been a destination country of immigrant afflux through different migration routes. It is possible that the consequences of climate change in Sub-Saharan Africa will drive a growing number of people to cross the sea to reach Europe, specifically Italy. Conclusions: climate change, human migration, and health should be considered as an interconnected and complex issue. A shift to climate resilient health systems' is a useful precautionary measure as it aims to strengthen multiple aspects of national and sub-national health systems, regardless of the extent to which climate-related migration might occur.

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.

BACKGROUND AND OBJECTIVES: COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19. METHODS: This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). RESULTS: Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60). DISCUSSION: Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis. TRIAL REGISTRATION INFORMATION: The study was registered under ClinicalTrials.gov identifier NCT04895462.

Meeting the health needs of displaced people fleeing Ukraine: Drawing on existing technical guidance and evidence.

The invasion of Ukraine has unleashed a humanitarian crisis and the impact is devastating for millions displaced in Ukraine and for those fleeing the country. Receiving countries in Europe are reeling with shock and disbelief and trying at the same time to grapple with the reality of providing for a large, unplanned, unprecedented number of refugees mainly women and children on the move. Several calls for actions, comments and statements express outrage, the risks, and the impending consequences to life and health. There is a need to constantly assess the situation on the ground, identify priorities for health and provide guidance regarding how these needs could be addressed. Therefore, the Lancet Migration European Regional Hub conducted rapid interviews with key informants to identify these needs, and in collaboration with the World Health Organization Health and Migration Programme, summarized how these could be addressed. This viewpoint provides a summary of the situation in receiving countries and the technical guidance required that could be useful for providing assistance in the current refugee crisis.

Posttranslational modifications of proteins are key features in the identification of CSF biomarkers of multiple sclerosis.

BACKGROUND: Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system (CNS) characterized by demyelination and concomitant axonal loss. The lack of a single specific test, and the similarity to other inflammatory diseases of the central nervous system, makes it difficult to have a clear diagnosis of multiple sclerosis. Therefore, laboratory tests that allows a clear and definite diagnosis, as well as to predict the different clinical courses of the disease are of utmost importance. Herein, we compared the cerebrospinal fluid (CSF) proteome of patients with multiple sclerosis (in the relapse-remitting phase of the disease) and other diseases of the CNS (inflammatory and non-inflammatory) aiming at identifying reliable biomarkers of multiple sclerosis. METHODS: CSF samples from the discovery group were resolved by 2D-gel electrophoresis followed by identification of the protein spots by mass spectrometry. The results were analyzed using univariate (Student's t test) and multivariate (Hierarchical Cluster Analysis, Principal Component Analysis, Linear Discriminant Analysis) statistical and numerical techniques, to identify a set of protein spots that were differentially expressed in CSF samples from patients with multiple sclerosis when compared with other two groups. Validation of the results was performed in samples from a different set of patients using quantitative (e.g., ELISA) and semi-quantitative (e.g., Western Blot) experimental approaches. RESULTS: Analysis of the 2D-gels showed 13 protein spots that were differentially expressed in the three groups of patients: Alpha-1-antichymotrypsin, Prostaglandin-H2-isomerase, Retinol binding protein 4, Transthyretin (TTR), Apolipoprotein E, Gelsolin, Angiotensinogen, Agrin, Serum albumin, Myosin-15, Apolipoprotein B-100 and EF-hand calcium-binding domain-containing protein. ELISA experiments allowed validating part of the results obtained in the proteomics analysis and showed that some of the alterations in the CSF proteome are also mirrored in serum samples from multiple sclerosis patients. CSF of multiple sclerosis patients was characterized by TTR oligomerization, thus highlighting the importance of analyzing posttranslational modifications of the proteome in the identification of novel biomarkers of the disease. CONCLUSIONS: The model built based on the results obtained upon analysis of the 2D-gels and in the validation phase attained an accuracy of about 80% in distinguishing multiple sclerosis patients and the other two groups.

Risk of COVID-19 in Health Professionals: A Case-Control Study, Portugal.

Introduction: Health professionals face higher occupational exposure to SARS-CoV-2. We aimed to estimate the risk of COVID-19 test positivity in health professionals compared to non-health professionals. Methods: We conducted a test-negative case-control study using Portuguese national surveillance data (January to May 2020). Cases were suspected cases who tested positive for SARS-CoV-2; controls were suspected cases who tested negative. We used multivariable logistic regression modelling to estimate the odds ratio of a positive COVID-19 test (RT-PCR; primary outcome), comparing health professionals and non-health professionals (primary exposure), and adjusting for the confounding effect of demographic, clinical, and epidemiological characteristics, and the modification effect of the self-reported epidemiological link (i.e., self-reported contact with a COVID-19 case or person with COVID-19-like symptoms). Results: Health professionals had a 2-fold higher risk of a positive COVID-19 test result (aOR = 1.89, 95% CI 1.69-2.11). However, this association was strongly modified by the self-report of an epidemiological link such that, among cases who did report an epidemiological link, being a health professional was a protective factor (aOR = 0.90, 95% CI 0.82-0.98). Conclusion: Our findings suggest that health professionals might be primarily infected by unknown contacts, plausibly in the healthcare setting, but also that their occupational exposure does not systematically translate into a higher risk of transmission. We suggest that this could be interpreted in light of different types and timing of exposure, and variability in risk perception and associated preventive behaviours.

Introdução: Os profissionais de saúde têm uma maior exposição profissional à SARS-CoV-2. O objetivo era estimar o risco de testar positivo para SARS-CoV-2 em profissionais de saúde. Métodos: Foi realizado um estudo testenegativo caso-controlo utilizando os dados de vigilância epidemiológica nacional (Janeiro­Maio 2020). Casos foram definidos como casos suspeitos que testaram positivo para SARS-CoV-2 (RTPCR), e os controlos como casos suspeitos que testaram negativo. Foi aplicado um modelo de regressão logística multivariável para estimar o odds ratio de teste positivo para SARS-CoV-2, comparando profissionais de saúde e não profissionais de saúde, ajustado para as características demográficas, clínicas e epidemiológicas, e a modificação de efeito com o autorrelato duma ligação epidemiológica (i.e., contacto auto-reportado com um caso COVID-19 ou uma pessoa com sintomas semelhantes aos da COVID-19). Resultados: Os profissionais de saúde tiveram um risco duas vezes maior de testar positivo para SARS-CoV-2 (aOR = 1.89, 95% CI 1.69­2.11). No entanto, esta associação era fortemente modificada pelo autorrelato de uma ligação epidemiológica, de tal forma que entre os casos que relataram uma ligação epidemiológica, ser profissional de saúde revelou-se fator de proteção (aOR = 0.90, 95% CI 0.82­0.98). Conclusão: Os nossos resultados sugerem que os profissionais de saúde podem estar infetados principalmente por contactos desconhecidos, plausivelmente em instituições de saúde, e a exposição profissional não se traduz sistematicamente num maior risco de transmissão. Isto poderá ser interpretado à luz de diferentes tipos e tempos de exposição, e da variabilidade na perceção do risco e dos comportamentos preventivos associados.

NOTCH3 mutations in a cohort of Portuguese patients within CADASIL spectrum phenotype.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease. It is caused by mutations in the NOTCH3 gene, which encodes a membranebound receptor protein with three main distinct functional domains. Thus far, several different NOTCH3 mutations, most of them cysteine altering variants, have been described and although they tend to cluster in certain exons, their distribution varies in different geographically populations. Therefore, in this study, we describe the mutation analysis of NOTCH3 gene in 24 Portuguese families with small vessel disease suspected to have CADASIL from the central region of Portugal. The genetic analysis revealed 15 different heterozygous variants, eight pathogenic cysteine altering variants, six cysteine sparing variants and one nonsense variant, located mainly in the exons 4, 8 and 11. Thus, in our population, the genetic testing should initially be focused on these exons. In addition, the genetic findings broaden the mutational and clinical spectrum of CADASIL related phenotype and provide additional evidences for genetic counseling and clinical management.

Community socioeconomic deprivation and SARS-CoV-2 infection risk: findings from Portugal.

BACKGROUND: Socioeconomic differences have been observed in the risk of acquiring infectious diseases, but evidence regarding SARS-CoV-2 remains sparse. Hence, this study aimed to investigate the association between SARS-CoV-2 infection risk and socioeconomic deprivation, exploring whether this association varied according to different phases of the national pandemic response. METHODS: A cross-sectional study was conducted. Data routinely collected for patients with a laboratorial result recorded in SINAVE®, between 2 March and 14 June 2020, were analysed. Socioeconomic deprivation was assessed using quintiles of the European Deprivation Index (Q1-least deprived to Q5-most deprived). Response phases were defined as before, during and after the national State of Emergency. Associations were estimated using multilevel analyses. RESULTS: The study included 223 333 individuals (14.7% were SARS-CoV-2 positive cases). SARS-CoV-2 infection prevalence ratio increased with deprivation [PR(Q1)=Ref; PR(Q2)=1.37 (95% CI 1.19-1.58), PR(Q3)=1.48 (95% CI 1.26-1.73), PR(Q4)=1.73 (95% CI 1.47-2.04), PR(Q5)=2.24 (95% CI 1.83-2.75)]. This was observed during the State of Emergency [PR(Q5)=2.09 (95% CI 1.67-2.62)] and more pronounced after the State of Emergency [PR(Q5)= 3.43 (95% CI 2.66-4.44)]. CONCLUSION: The effect of socioeconomic deprivation in the SARS-CoV-2 infection risk emerged after the implementation of the first State of Emergency in Portugal, and became more pronounced as social distancing policies eased. Decision-makers should consider these results when deliberating future mitigation measures.

Clinical and hospitalisation predictors of COVID-19 in the first month of the pandemic, Portugal.

COVID-19 mainly presents as a respiratory disease with flu-like symptoms, however, recent findings suggest that non-respiratory symptoms can occur early in the infection and cluster together in different groups in different regions. We collected surveillance data among COVID-19 suspected cases tested in mainland Portugal during the first wave of the pandemic, March-April 2020. A multivariable logistic-regression analysis was performed to ascertain the effects of age, sex, prior medical condition and symptoms on the likelihood of testing positive and hospitalisation. Of 25,926 COVID-19 suspected cases included in this study, 5,298 (20%) tested positive. Symptoms were grouped into ten clusters, of which two main ones: one with cough and fever and another with the remainder. There was a higher odds of a positive test with increasing age, myalgia and headache. The odds of being hospitalised increased with age, presence of fever, dyspnoea, or having a prior medical condition although these results varied by region. Presence of cough and other respiratory symptoms did not predict COVID-19 compared to non-COVID respiratory disease patients in any region. Dyspnoea was a strong determinant of hospitalisation, as well as fever and the presence of a prior medical condition, whereas these results varied by region.

Mumps outbreak among fully vaccinated school-age children and young adults, Portugal 2019/2020.

On 16-17 January 2020, four suspected mumps cases were reported to the local Public Health Authorities with an epidemiological link to a local school and football club. Of 18 suspected cases identified, 14 were included in this study. Laboratory results confirmed mumps virus as the cause and further sequencing identified genotype G. Our findings highlight that even with a high MMR vaccine coverage, mumps outbreaks in children and young adults can occur. Since most of the cases had documented immunity for mumps, we hypothesise that waning immunity or discordant mumps virus strains are likely explanations for this outbreak.

Outcomes on Social and Classic Cognition in adults with Pediatric-onset Multiple Sclerosis.

BACKGROUND: Cognitive impairment affecting classic and social domains has been consistently reported in patients with Multiple Sclerosis (MS). However, little is known about the cognitive outcomes, particularly on social cognition, in adults with pediatric-onset multiple sclerosis (POMS). OBJECTIVES: To compare the performance in classic and social cognitive domains between adults with POMS and adult-onset MS (AOMS). METHODS: A group of 30 patients with POMS (age onset <18 years) was compared with age-matched (AOAMS, n=30) and disease duration-matched (AODMS, n= 30) patients who developed MS after the age of 18 years. Cognitive performance was assessed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and Theory of Mind (ToM) tests. RESULTS: Cognitive impairment was more prevalent in POMS patients (40% vs. 16.7%, p=0.045), independently of age or disease duration, affecting more severely information-processing speed and visual memory domains. No statistically significant differences were found in ToM performance between patients with POMS and AOMS. When analyzing ToM performance according to age of disease onset (≤15 years; 15-20 years; ≥20 years), patients with disease onset ≤15 years old had significantly lower scores on ToM tests when compared to the other groups. CONCLUSION: Patients with POMS were more prone to develop impairment on classic cognitive domains than on ToM ability, when compared with AOMS patients. The interference of POMS with critical neurodevelopmental periods, specific for each cognitive domain, may explain different outcomes at adulthood on social and classic cognition.

Protective effects of cognitive and brain reserve in multiple sclerosis: Differential roles on social cognition and 'classic cognition'.

BACKGROUND: According to cognitive reserve (CR) and brain reserve (BR) theories, lifetime intellectual enrichment and maximal brain volume protect against cognitive decline. OBJECTIVE: To examine the effects of CR and BR on social cognition in multiple sclerosis (MS), and compare it with 'classic cognition'. METHODS: We included 60 MS patients and 60 healthy controls matched on age, sex, and education. Education was used has a proxy of CR and intracranial volume (ICV) as a proxy of BR. Participants underwent Theory of Mind (ToM) testing (Eyes Test, Videos Test), comprehensive neuropsychological assessment and 3Tesla brain MRI. Cortical and subcortical grey matter (GM) volumes were calculated. RESULTS: We found positive effects of education and ICV on general cognitive status and ToM performance, respectively. Higher education moderated the impact of subcortical GM atrophy on 'classic' cognitive status (R2=0.219, p=<0.001). Conversely, greater ICV attenuated the impact of cortical GM atrophy on Eyes Test (R2=0.158, p=0.002) and Videos Test (R2=0.198, p=0.001). Stratification for disease duration showed that the protective effect of education/ICV occurred in early stages of disease (<10 years). CONCLUSION: CR and BR have differential protective roles in MS, with BR having a positive effect on social cognition and CR on 'classic' cognitive domains.

Burden and Trends of Severe Rotavirus Infections and Allcause Acute Gastroenteritis Hospital Episodes in Children Under Five Years Old in Mainland Portugal.

INTRODUCTION: Rotavirus infections are a leading cause of severe acute gastroenteritis in children under five years old. In December 2019, Portugal announced the inclusion of the rotavirus vaccine, already available for private purchase, in the National Immunization Program. We present the first nationwide analysis of the burden and trends of rotavirus and acute gastroenteritis hospital episodes in children under five years old in mainland Portugal (2014 - 2017). MATERIAL AND METHODS: We used the hospital morbidity database and the Death Certificate Information System to identify hospital episodes and deaths of rotavirus and acute gastroenteritis based on the codes of the International Classification of Diseases. We described the number and rates of hospital episodes disaggregated by age group, sex, geographical units, and the seasonality and trends over the study period. RESULTS: On average, during the study period, there were 1985 annual hospital episodes among children under five years old. The annual rate was 48.0/10 000 children (95% CI 46.9 - 49.0). Rates were consistently higher in younger children, and 67.8% episodes occurred in children under 24 months. We found a seasonal pattern with a major peak in the early spring. DISCUSSION: Our results were consistent with the current knowledge on rotavirus and acute gastroenteritis hospital episodes in Europe. Additional studies are needed to identify the risk factors and high-risk groups for hospital attendance. CONCLUSION: Rotavirus and acute gastroenteritis hospital episodes in children under five years old in mainland Portugal represent an important health and economic burden. In the future, monitoring this burden and these trends in relation with rotavirus vaccine coverage could be useful in order to assess the impact of the vaccination programme on the change in hospital episodes.

Introdução: As infeções por rotavírus são uma das principais causas de gastroenterite aguda grave em crianças com menos de cinco anos. Em dezembro de 2019, foi anunciada a inclusão da vacina contra rotavírus, já disponível no mercado privado, no Programa Nacional de Vacinação. Esta é a primeira análise nacional da carga e tendência dos episódios hospitalares de rotavírus e gastroenterite aguda grave em crianças com menos de cinco anos em Portugal continental (2014 - 2017). Material e Métodos: Utilizou-se a base de dados de morbilidade hospitalar e o sistema de informação de certificados de óbito para identificar episódios hospitalares e mortes por rotavírus e gastroenterite aguda grave, a partir de códigos da classificação internacional de doenças. Descreveu-se o número e as taxas de episódios hospitalares, desagregadas por grupo etário, sexo, geografia, e a sazonalidade e tendências ao longo do período em estudo. Resultados: Em média, houve 1985 episódios hospitalares anuais em crianças com menos de cinco anos. A taxa anual foi de 48,0/ 10 000 crianças (95% IC 46,9 - 49,0). A taxa de hospitalização foi consistentemente mais elevada em crianças mais jovens, e 67,8% dos episódios ocorreram em crianças com menos de 24 meses. Relativamente à sazonalidade, encontrámos um pico no início da Primavera. Discussão: Os resultados foram consistentes com os conhecimentos atuais sobre rotavírus e episódios hospitalares de gastroenterite aguda grave na Europa. São necessários estudos adicionais para identificar os fatores e grupos de risco de infeções graves. Conclusão: Em Portugal Continental, os episódios hospitalares de rotavírus e gastroenterite aguda grave em crianças de idade inferior a cinco anos têm um impacto negativo relevante na saúde e na economia. No futuro, e na perspetiva da introdução da vacinação para o rotavírus, estes indicadores serão relevantes para monitorizar o impacto do programa de vacinação na diminuição dos episódios hospitalares.

Biologic disease-modifying anti-rheumatic drugs and patient-reported outcomes in axial SpA: a systematic review and a call for action.

This paper is to assess the efficacy of different biologic DMARDs (bDMARDs) on several patient-reported outcomes (PROs) in randomized controlled trials (RCT) in axial spondyloarthritis (axSpA). A systematic literature review (SLR) was performed. MEDLINE (May 1, 2018) was used with the filters "published in the last 10 years" and "humans." The PICO criteria used were Patients: adults with radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA); Intervention: any bDMARD; Compararator: placebo (PBO)/any different drug; Outcome: the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Ankylosing Spondylitis Quality of Life (ASQoL), the EuroQol-5D (EQ-5D), the Short Form 36 Health Survey physical component summary (SF36-PCS), the Short Form 36 Health Survey mental component summary (SF36-MCS), and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). After screening 84 initial references and manually selecting other 9, 24 publications, assessing TNF inhibitors (TNFi) or IL17A inhibitors (IL17Ai) were selected. Four RCTs quantified the minimal clinical important difference (MCID) between treatment arms. Most of the RCTs compared the mean difference of PROs between different timepoints. Overall, the treatment arm was superior to the comparator. PROs were often underreported or highly heterogeneously presented. MCID was seldom mentioned. There is a need to raise the standard of care on SpA by aiming at remission and PRO associated improvements. In order to achieve this goal, the target must be clearly defined, reported, and tested.