Loss to follow-up in registries of rheumatic patients treated with biologics : a potential information bias in assessing pharmacovigilance and efficacy outcomes

© 2001-2021 Sociedade Portuguesa de Reumatologia.Background: The information associated with loss to follow-up (LFU) patients may affect real-world data evaluation of the use of biologics that is not being adequately captured in registries. Methods: We identified all patients(Pts) treated with biologics in our center who had no visits registered for more than 6 months, in the Rheumatic Diseases Portuguese Register, Reuma.pt. We retrieved baseline information from Reuma.pt and from the hospital electronic clinical record. We then performed a telephonic interview to characterize the reasons for LFU at our day care unit. For Pts unable to be contacted by telephone a letter of invitation to an appointment at the hospital was sent. Results: From a total of 794 Ptsregistered in Reuma.pt at our center with active biologic therapy 227 did not have any information registered in the last 6 months. Of this, 36 Pts were on biologic therapy prescribed by other departments and maintained follow-up in these departments. 102 Pts had suspended biologic administration by medical indication and this information was registered in the hospital electronic clinical records but not updated in Reuma.pt. For 89 Pts no information could be retrieved from either the hospital electronic clinical record or Reuma.pt and we classified these Pts as true LFU. 26 of these LFU Pts were being followed up in another Rheumatology center. 26 of the LFU Pts died. 11 Pts had an adverse effect. 4 Pts of the LFU were considering to be in remission. We were not able to contact 15 of the LFU pts. Conclusion: Identifying LFU Pts and clarifying the reason for the loss of data in a register contributes to a better knowledge on strategies to discontinue biologics in stable pts, to a better pharmacovigilance of adverse effects and to more efficiency in data capture by registries. Due to data protection reasons it was impossible to have access to the Pts's death certificates.info:eu-repo/semantics/publishedVersio

Rheumatology practice amidst the COVID-19 pandemic : a pragmatic view

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.The coronavirus disease 2019 (COVID-19) pandemic has come with many challenges for healthcare providers and patients alike. In addition to the direct burden it has placed on societies and health systems, it had a significant impact in the care of patients with chronic diseases, as healthcare resources were deployed to fight the crisis, and major travel and social restrictions were adopted. In the field of rheumatology, this has required notable efforts from departments and clinicians to adapt to the novel status quo and assure the follow-up of patients with rheumatic and musculoskeletal diseases. In the present viewpoint, we provide a practical approach to tackle this reality. Key measures include setting up preventive team management strategies, optimising communication with patients and reorganising patient care in all its dimensions. We then anticipate the nuances of rheumatology practice as restrictive measures are progressively lifted, while an effective vaccine is still pending. This includes the need to reimpose the same strategy as further waves unfold. Finally, we look ahead and address the lessons we can incorporate into post-COVID-19 rheumatology.info:eu-repo/semantics/publishedVersio

Genomic epidemiology of carbapenemase producing Klebsiella pneumoniae strains at a northern Portuguese hospital enables the detection of a misidentified Klebsiella variicola KPC-3 producing strain

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The evolutionary epidemiology, resistome, virulome and mobilome of thirty-one multidrug resistant Klebsiella pneumoniae clinical isolates from the northern Vila Real region of Portugal were characterized using whole-genome sequencing and bioinformatic analysis. The genomic population structure was dominated by two main sequence types (STs): ST147 (n = 17; 54.8%) and ST15 (n = 6; 19.4%) comprising four distinct genomic clusters. Two main carbapenemase coding genes were detected (blaKPC-3 and blaOXA-48) along with additional extended-spectrum β-lactamase coding loci (blaCTX-M-15, blaSHV-12, blaSHV-27, and blaSHV-187). Moreover, whole genome sequencing enabled the identification of one Klebsiella variicola KPC-3 producer isolate previously misidentified as K. pneumoniae, which in addition to the blaKPC-3 carbapenemase gene, bore the chromosomal broad spectrum β-lactamase blaLEN-2 coding gene, oqxAB and fosA resistance loci. The blaKPC-3 genes were located in a Tn4401b transposon (K. variicolan = 1; K. pneumoniaen = 2) and Tn4401d isoform (K. pneumoniaen = 28). Overall, our work describes the first report of a blaKPC-3 producing K. variicola, as well as the detection of this species during infection control measures in surveillance cultures from infected patients. It also highlights the importance of additional control measures to overcome the clonal dissemination of carbapenemase producing clones.This work was supported in part by UID/DTP/04138/2019 and UIDB/04033/2020 from Fundação para a Ciência e Tecnologia (FCT), Portugal.info:eu-repo/semantics/publishedVersio

New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death

New fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing the 7-position of the thieno[3,2-blpyridine, using copper (C-O) or palladium (C N) catalyzed couplings, respectively, of the 7-bromothieno[3,2-blpyridine, also prepared, with ortho, meta and para fluoro or methoxy phenols and anilines. The compounds obtained were evaluated for their growth inhibitory activity on the human tumor cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HCI15 (colon carcinoma), HepG2 (hepatocellular carcinoma) and HeLa (cervical carcinoma). The most active compounds, a di(hetero)arylether with a methoxy group in the meta position relative to the ether function and two di(hetero)arylamines with a methoxy group either in the ortho or in the meta position relative to the NH, were further tested at their GI(50) concentrations on NCI-H460 cells causing pronounced alterations in the cell cycle profile and a strong and significant increase in the programmed death of these cells. The fluorinated and the other methoxylated compounds did not show important activity, presenting high GI(50) values in all the cell lines tested. Furthermore, the hepatotoxicity of the compounds was assessed using porcine liver primary cells (PLP2), established by some of us. Results showed that one of the most active compounds was not toxic to the non-tumor cells at their GI(50) concentrations showing to be the most promising as antitumoral.The authors would like to thank to the Foundation for the Science and Technology (PCT Portugal) for financial support through the NMR Portuguese network (Bruker 400 Avance III-Univ Minho); to FCT and FEDER-COMPETE/QREN/EU for financial support through the research unities PEst-C/QUI/UI686/2011 and PEst-OE/AGR/UI0690/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-Doctoral grants attributed to R.C.C. (SFRH/BPD/68344/2010) and R.T.L. (SRH/BPD/68787/2010). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT

Contribution for new genetic markers of rheumatoid arthritis activity and severity : sequencing of the tumor necrosis factor-alpha gene promoter

© 2007 Fonseca et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedThe objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.This work was supported by grant POCTI/SAU-ESP/59111/2004 from Fundação Ciência e Tecnologia.info:eu-repo/semantics/publishedVersio

Genomic epidemiological analysis of Klebsiella pneumoniae from Portuguese hospitals reveals insights into circulating antimicrobial resistance.

Klebsiella pneumoniae (Kp) bacteria are an increasing threat to public health and represent one of the most concerning pathogens involved in life-threatening infections and antimicrobial resistance (AMR). To understand the epidemiology of AMR of Kp in Portugal, we analysed whole genome sequencing, susceptibility testing and other meta data on 509 isolates collected nationwide from 16 hospitals and environmental settings between years 1980 and 2019. Predominant sequence types (STs) included ST15 (n = 161, 32%), ST147 (n = 36, 7%), ST14 (n = 26, 5%) or ST13 (n = 26, 5%), while 31% of isolates belonged to STs with fewer than 10 isolates. AMR testing revealed widespread resistance to aminoglycosides, fluoroquinolones, cephalosporins and carbapenems. The most common carbapenemase gene was blaKPC-3. Whilst the distribution of AMR linked plasmids appears uncorrelated with ST, their frequency has changed over time. Before year 2010, the dominant plasmid group was associated with the extended spectrum beta-lactamase gene blaCTX-M-15, but this group appears to have been displaced by another carrying the blaKPC-3 gene. Co-carriage of blaCTX-M and blaKPC-3 was uncommon. Our results from the largest genomics study of Kp in Portugal highlight the active transmission of strains with AMR genes and provide a baseline set of variants for future resistance monitoring and epidemiological studies

A Lei da Mediação de Conflitos: estudos sobre a sua aplicação

Financiamento de MEDLaw - FCT UIDB/04112/2020.Os dez anos de vigência da Lei da Mediação em Portugal constituíram o mote para a compilação nesta obra de diversos estudos empírico-dogmáticos sobre a sua aplicação, analisando-se questões prementes como a voluntariedade ou obrigatoriedade da mediação, a executoriedade do acordo de mediação e a Convenção de Singapura, as exigências processuais e a suspensão dos prazos de prescrição e caducidade com o recurso à mediação, a organização associativa dos mediadores e a importância da sua formação, o funcionamento dos sistemas públicos de mediação, bem como novas áreas de aplicação da mediação, em especial no domínio administrativo e na recuperação extrajudicial de empresas, e ainda a relevância do desenvolvimento científico sobre este meio de resolução de conflitos. Ao regulamentar num único diploma, pela primeira vez no nosso ordenamento jurídico, a mediação pública e privada, a Lei n.º 29/2013, de 19 de abril, constituiu um marco legislativo. Dez anos volvidos, importava refletir sobre a sua aplicação prático-jurídica, norteados pelo objetivo de promover o estudo e a efetiva implementação da mediação de conflitos em Portugal. Esta obra constitui o output desenvolvido no âmbito do projeto de investigação MEDLAW, com o apoio da Fundação para a Ciência e Tecnologia, no âmbito do financiamento base atribuído ao polo de Leiria do Instituto Jurídico Portucalense, com a ref. UIDB/04112/2020.info:eu-repo/semantics/publishedVersio

Thinness, overweight, and obesity in 6‐ to 9‐year‐old children from 36 countries: The World Health Organization European Childhood Obesity Surveillance Initiative - COSI 2015-2017

In 2015-2017, the fourth round of the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative (COSI) was conducted in 36 countries. National representative samples of children aged 6–9 (203,323) were measured by trained staff, with similar equipment and using a standardized protocol. This paper assesses the children's body weight status and compares the burden of childhood overweight, obesity, and thinness in Northern, Eastern, and Southern Europe and Central Asia. The results show great geographic variability in height, weight, and body mass index. On average, the children of Northern Europe were the tallest, those of Southern Europe the heaviest, and the children living in Central Asia the lightest and the shortest. Overall, 28.7% of boys and 26.5% of girls were overweight (including obesity) and 2.5% and 1.9%, respectively, were thin according to the WHO definitions. The prevalence of obesity varied from 1.8% of boys and 1.1% of girls in Tajikistan to 21.5% and 19.2%, respectively, in Cyprus, and tended to be higher for boys than for girls. Levels of thinness, stunting, and underweight were relatively low, except in Eastern Europe (for thinness) and in Central Asia. Despite the efforts to halt it, unhealthy weight status is still an important problem in the WHO European Region.The authors gratefully acknowledge support from a grant from the Russian Government in the context of the WHO European Office for the Prevention and Control of NCDs. Data collection in the countries was made possible through funding from the following: Albania: WHO through the Joint Programme on Children, Food Security and Nutrition “Reducing Malnutrition in Children,” funded by the Millennium Development Goals Achievement Fund, and the Institute of Public Health; Austria: Federal Ministry of Social Affairs, Health, Care and Consumer Protection, Republic of Austria; Bulgaria: Ministry of Health, National Center of Public Health and Analyses, WHO Regional Office for Europe; Croatia: Ministry of Health, Croatian Institute of Public Health and WHO Regional Office for Europe; Czechia: Ministry of Health of the Czech Republic, grants AZV MZČR 17-31670 A and MZČR – RVO EÚ 00023761; Cyprus: not available; Denmark: Danish Ministry of Health; Estonia: Ministry of Social Affairs, Ministry of Education and Research (IUT 42-2), WHO Country Office, and National Institute for Health Development; Finland: Finnish Institute for Health and Welfare; France: Santé publique France, the French Agency for Public Health; Georgia: WHO; Greece: International Hellenic University and Hellenic Medical Association for Obesity; Hungary: WHO Country Office for Hungary; Ireland: Health Service Executive; Italy: Ministry of Health and Italian National Institute of Health; Kazakhstan: Ministry of Health of the Republic of Kazakhstan and WHO Country Office; Kyrgyzstan: World Health Organization; Latvia: Ministry of Health, Centre for Disease Prevention and Control; Lithuania: Science Foundation of Lithuanian University of Health Sciences and Lithuanian Science Council and WHO; Malta: Ministry of Health; Montenegro: WHO and Institute of Public Health of Montenegro; North Macedonia: funded by the Government of North Macedonia through National Annual Program of Public Health and implemented by the Institute of Public Health and Centers of Public Health in the country. WHO country office provided support for training and data management; Norway: Ministry of Health and Norwegian Institute of Public Health; Poland: National Health Programme, Ministry of Health; Portugal: Ministry of Health Institutions, the National Institute of Health, Directorate General of Health, Regional Health Directorates and the kind technical support from the Center for Studies and Research on Social Dynamics and Health (CEIDSS); Romania: Ministry of Health; Russian Federation: WHO; San Marino: Health Ministry, Educational Ministry, Social Security Institute and Health Authority; Serbia: World Health Organization (Ref. File 2015-540940); Slovakia: Biennial Collaborative Agreement between WHO Regional Office for Europe and Ministry of Health SR; Slovenia: Ministry of Education, Science and Sport of the Republic of Slovenia within the SLOfit surveillance system; Spain: Spanish Agency for Food Safety and Nutrition (AESAN); Sweden: Public Health Agency of Sweden; Tajikistan: WHO Country Office in Tajikistan and Ministry of Health and Social Protection; Turkmenistan: WHO Country Office in Turkmenistan and Ministry of Health; Turkey: Turkish Ministry of Health and World Bank.info:eu-repo/semantics/publishedVersio

A search for resonances decaying into a Higgs boson and a new particle X in the XH→qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson ($H$) and a new particle ($X$) is reported, utilizing 36.1 fb$^{-1}$ of proton-proton collision data at $\sqrt{s} =$ 13 TeV collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle $X$ is assumed to decay to a pair of light quarks, and the fully hadronic final state $XH \rightarrow q\bar q'b\bar b$ is analysed. The search considers the regime of high $XH$ resonance masses, where the $X$ and $H$ bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of $XH$ mass versus $X$ mass is scanned for evidence of a signal, over a range of $XH$ resonance mass values between 1 TeV and 4 TeV, and for $X$ particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of $XH$ and $X$ masses, on the production cross-section of the $XH\rightarrow q\bar q'b\bar b$ resonance

Study of ordered hadron chains with the ATLAS detector

La lista completa de autores que integran el documento puede consultarse en el archivo