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  • 1
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    Potential performance of a 0 h/1 h algorithm and a single cut-off measure of high-sensitivity troponin T in a diverse population: main results of the IN-HOPE study
    Oxford University Press (OUP) ; 2023
    In:  European Heart Journal: Acute Cardiovascular Care ( 2023-07-14)
    Details
    In: European Heart Journal: Acute Cardiovascular Care, Oxford University Press (OUP), ( 2023-07-14)
    Kurzfassung: Chest pain is a major cause of medical evaluation at emergency department (ED) and demands observation to exclude the diagnosis of acute myocardial infarction (AMI). High-sensitivity cardiac troponin assays used as isolated measure and by 0- and 1-h algorithms are accepted as a rule-in/rule-out strategy, but there is a lack of validation in specific populations. Methods and results The IN-HOspital Program to systematizE Chest Pain Protocol (IN-HOPE study) is a multicentre study that prospectively included patients admitted to the ED due to suspected symptoms of AMI at 16 sites in Brazil. Medical decisions of all patients followed the standard approach of 0 h/3 h protocol, but, in addition, blood samples were also collected at 0 and 1 h and sent to a central laboratory (core lab) to measure high-sensitivity cardiac troponin T (hs-cTnT). To assess the theoretical performance of 0 h/1 h algorithm, troponin & lt; 12 ng/L with a delta & lt; 3 was considered rule-out while a value ≥ 52 or a delta ≥ 5 was considered a rule-in criterion (the remaining were considered as observation group). The main objective of the study was to assess, in a population managed by the 0 h/3 h protocol, the accuracy of 0 h/1 h algorithm overall and in groups with a higher probability of AMI. All patients were followed up for 30 days, and potential events were adjudicated. In addition to the prospective cohort, a retrospective analysis was performed assessing all patients with hs-cTnT measured during the year of 2021 but not included in the prospective cohort, regardless of the indication of the test. A total of 5.497 patients were included (583 in the prospective and 4.914 in the retrospective analysis). The prospective cohort had a mean age of 57.3 (± 14.8) and 45.6% of females with a mean HEART score of 4.0 ± 2.2. By the core lab analysis, 74.4% would be eligible for a rule-out approach (45.3% of them with a HEART score & gt; 3) while 7.3% would fit the rule-in criteria. In this rule-out group, the negative predictive value for index AMI was 100% (99.1–100) overall and regardless of clinical scores. At 30 days, no death or AMI occurred in the rule-out group of both 0/1 and 0/3 h algorithms while 52.4% of the patients in the rule-in group (0 h/1 h) were considered as AMI by adjudication. In the observation group (grey zone) of 0 h/1 h algorithm, GRACE discriminated the risk of these patients better than HEART score. In the retrospective analysis, 1.091 patients had a troponin value of & lt;5 ng/L and there were no cardiovascular deaths at 30 days in this group. Among all 4.914 patients, the 30-day risk of AMI or cardiovascular death increased according to the level of troponin: 0% in the group & lt; 5 ng/L, 0.6% between 5 and 14 ng/L, 2.2% between 14 and 42 ng/L, 6.3% between 42 and 90 ng/L, and 7.7% in the level ≥ 90 ng/L. Conclusion In this large multicentre study, a 0 h/1 h algorithm had the potential to classify as rule-in or rule-out in almost 80% of the patients. The rule-out protocol had high negative predictive value regardless of clinical risk scores. Categories of levels of hs-cTn T also showed good accuracy in discriminating risk of the patients with a very favourable prognosis for cardiovascular death in the group with value & lt; 5 ng/L. ClinicalTrials.gov NCT04756362
    Materialart: Online-Ressource
    ISSN: 2048-8726 , 2048-8734
    URL: Article
    DOI: 10.1093/ehjacc/zuad082
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 2663340-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    National surveillance of Neisseria gonorrhoeae antimicrobial susceptibility and epidemiological data of gonorrhoea patients across Brazil, 2018–20
    Oxford University Press (OUP) ; 2022
    In:  JAC-Antimicrobial Resistance Vol. 4, No. 4 ( 2022-07-04)
    Details
    In: JAC-Antimicrobial Resistance, Oxford University Press (OUP), Vol. 4, No. 4 ( 2022-07-04)
    Kurzfassung: To (i) describe the nationwide antimicrobial susceptibility of Neisseria gonorrhoeae (NG) isolates cultured across Brazil in 2018–20 and compare it with NG antimicrobial resistance data from 2015–16, and (ii) present epidemiological data of the corresponding gonorrhoea patients in 2018–20. Methods Twelve representative sentinel sites cultured NG isolates from men with urethral discharge. Susceptibility to eight antimicrobials was examined using agar dilution method, according to WHO standards. The consenting participants were invited to provide epidemiological data. Results In total, 633 NG isolates (one isolate per participant) were analysed, and 449 (70.9%) questionnaires were answered. Heterosexual (68.2%) and homosexual (23.1%) sexual orientations were common, and most prevalent types of unprotected sexual intercourse were vaginal insertive (69.9%), oral giving (56.6%) and anal insertive (47.4%). The levels of in vitro NG resistance to ciprofloxacin, tetracycline, benzylpenicillin, azithromycin, cefixime, gentamicin, spectinomycin and ceftriaxone were 67.3%, 40.0%, 25.7%, 10.6%, 0.3%, 0%, 0% and 0%, respectively. Compliance with the recommended first-line ceftriaxone 500 mg plus azithromycin 1 g therapy was high (90.9%). Conclusions Compared with 2015–16, ciprofloxacin resistance has remained high and azithromycin and cefixime resistance rates have increased in Brazil. Resistance remained lacking to ceftriaxone, gentamicin and spectinomycin, which all are gonorrhoea treatment options. The increasing azithromycin resistance in Brazil and internationally may threaten the future use of azithromycin in dual regimens for treatment of gonorrhoea. Consequently, continued and enhanced quality-assured surveillance of gonococcal AMR, and ideally also treatment failures and including WGS, is imperative in Brazil and worldwide.
    Materialart: Online-Ressource
    ISSN: 2632-1823
    URL: Article
    DOI: 10.1093/jacamr/dlac076
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2022
    ZDB Id: 2973194-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Multifunctional T cell response in convalescent patients two years after ZIKV infection
    Oxford University Press (OUP) ; 2020
    In:  Journal of Leukocyte Biology Vol. 108, No. 4 ( 2020-10-01), p. 1265-1277
    Details
    In: Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 108, No. 4 ( 2020-10-01), p. 1265-1277
    Kurzfassung: Zika is an important emerging infectious disease in which the role of T cells remains elusive. This study aimed to evaluate the phenotype of multifunctional T cells in individuals 2 yr after exposure to Zika virus (ZIKV). We used a library of 671 synthetic peptides covering the whole polyprotein of ZIKV in pools corresponding to each viral protein (i.e., capsid, membrane precursor or prM, envelope, NS1 [nonstructural protein], NS2A + NS2B, NS3, NS4A + NS4B, and NS5) to stimulate PBMCs from individuals previously exposed to ZIKV. We observed an increased frequency of ZIKV-specific IFNγ, IL-17A, TNF, and IL-10 production by T cell populations. IFNγ and TNF production were especially stimulated by prM, capsid, or NS1 in CD8+ T cells and by capsid or prM in CD4+ T cells. In addition, there was an increase in the frequency of IL-10+ CD8+ T cells after stimulation with prM, capsid, NS1, NS3, or NS5. Multifunctional properties were observed in ZIKV-specific T cells responding especially to prM, capsid, NS1 or, to a smaller extent, NS3 antigens. For example, we found a consistent IFNγ + TNF+ CD8+ T cell population in response to most virus antigens and CD4+ and CD8+ T cells that were IFNγ + IL-17A+ and IL-17A+IL-10+, which could also produce TNF, in response to capsid, prM, NS1, or NS3 stimulation. Interestingly, CD8+ T cells were more prone to a multifunctional phenotype than CD4+ T cells, and multifunctional T cells were more efficient at producing cytokines than single-function cells. This work provides relevant insights into the quality of ZIKV-specific T cell responses and ZIKV immunity.
    Materialart: Online-Ressource
    ISSN: 0741-5400 , 1938-3673
    URL: Article
    DOI: 10.1002/JLB.4MA0520-708R
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2020
    ZDB Id: 2026833-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Liver X Receptor Activation Impairs Neutrophil Functions and Aggravates Sepsis
    Oxford University Press (OUP) ; 2020
    In:  The Journal of Infectious Diseases Vol. 221, No. 9 ( 2020-04-07), p. 1542-1553
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 221, No. 9 ( 2020-04-07), p. 1542-1553
    Kurzfassung: Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in several metabolic development and inflammatory disorders. Although neutrophils express both LXR-α and LXR-β, the consequences of their activation, particularly during sepsis, remain unknown. Methods We used the model of cecal ligation and puncture (CLP) to investigate the role of LXR activation during sepsis. Results In this study, we verified that LXR activation reduces neutrophil chemotactic and killing abilities in vitro. Mice treated with LXR agonists showed higher sepsis-induced mortality, which could be associated with reduced neutrophil infiltration at the infectious foci, increased bacteremia, systemic inflammatory response, and multiorgan failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load, and multiorgan dysfunction. More important, neutrophils from septic patients showed increased ABCA1 messenger ribonucleic acid levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared with cells from healthy individuals. Conclusions Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome.
    Materialart: Online-Ressource
    ISSN: 0022-1899 , 1537-6613
    URL: Article
    DOI: 10.1093/infdis/jiz635
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2020
    ZDB Id: 1473843-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    969. Gamification for Infectious Diseases Medical Education: Creating a Videogame to Teach COVID 19 Diagnosis and Treatment to Medical Students
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. Supplement_1 ( 2021-12-04), p. S576-S577
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S576-S577
    Kurzfassung: Brazillian authorities reported a total of 16.3 million cases and 454.000 deaths during COVID-19 pandemic in Brazil by may 2021. It became necessary to educate healthcare professionals on diagnosis and treatment of the syndrome. Game based learning surfaced as an effective alternative, since it promotes critical thinking and problem solving skills. A team of Brazilian and Peruvian students, physicians, designers and programmers gathered to create a decision based computer game that simulates a hospital scenario and allows medical students to analise, make decisions and receive feedback. This work describes the creative process and showcase the initial version of the software. Methods Professors and students of Medicine, Information Technology (IT), Design and Architecture from Brazil and Peru assembled a team in order to develop the computer game. Clinical cases were created by the medical students and professors, comprising medical procedures for the treatment and management of COVID 19, and a video game script was developed exploring gamification principles of challenge, objectivity, persistence, failure, reward and feedback. Algorithms (image 1) were created, under supervision of professors of Medicine, to define possible courses of action and outcomes (e.g. gain or loss of points, improvement or worsening of the patient). Students of Design created artistic elements, and IT students programmed with a game engine software. This fluxogram, written in portuguese, describes in detail all the possible courses of actions that can be exercised by the player. It is created by a team of Professors of Medicine and medical students, in accordance with evidence-based guidelines. Primarily, this document guides the programmers and designers throughout the development phase of the game. Results Initially, an expandable minimum viable product was obtained. The game, visualized on image 2, consists in a non-playable character and a playable character (i.e. doctor), with a scenario and a dialogue script simulating a clinical examination of a COVID 19 patient. The player can interact with certain elements within the game, e.g. the computer and other characters, to retrieve test results or start dialogues with relevant information. Hospital scenario and dialogue window between doctor (player in black) and patient (non playable character) are displayer in the game engine software (Unity 2D). On the bottom half of the screen, the dialogue box allows the player to collect the patient’s medical history. The player can interact with certain elements to obtain relevant information to make decision and progress in the game. Conclusion The game allows medical students to practice diagnosis and treatment of COVID 19. Future versions will include assessment reports of player’s actions, and a new score system will be implemented. New diseases will be incorporated in the gameplay to match the variety of scenarios offered by real hospitals and patients. Artificial intelligence will be employed to optimize gameplay, feedback and learning. Disclosures All Authors: No reported disclosures
    Materialart: Online-Ressource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofab466.1164
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial
    Oxford University Press (OUP) ; 2021
    In:  Clinical Infectious Diseases Vol. 72, No. 9 ( 2021-05-04), p. e373-e381
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 72, No. 9 ( 2021-05-04), p. e373-e381
    Kurzfassung: Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. Methods A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. Results From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. Conclusions The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. Clinical Trials Registration NCT04343729.
    Materialart: Online-Ressource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciaa1177
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2002229-3
    Standort Signatur Einschränkungen Verfügbarkeit
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