Until recently, the treatment of people with hemophilia A and inhibitors (PwHAi) was based on the use of bypassing agents (BPA). However, the advent of emicizumab as prophylaxis has demonstrated ...promising results.
We aimed to compare the bleeding endpoints between PwHAi on BPA and those on emicizumab prophylaxis.
Systematic review of interventions and meta-analysis conducted at the Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
The CENTRAL, MEDLINE, Scopus, and LILACS databases were searched on February 21, 2023. Two authors conducted the literature search, publication selection, and data extraction. The selected publications evaluated the bleeding endpoints between PwHAi on emicizumab prophylaxis and those on BPA prophylaxis. The risk of bias was evaluated according to the Joanna Briggs Institute criteria. A meta-analysis was performed to determine the annualized bleeding rate (ABR) for treated bleeds.
Five publications (56 PwHAi) were selected from the 543 retrieved records. Overall, bleeding endpoints were lower during emicizumab prophylaxis than during BPA prophylaxis. All the publications had at least one risk of bias. The only common parameter for the meta-analysis was the ABR for treated bleeds. During emicizumab prophylaxis, the ABR for treated bleeds was lower than during BPA prophylaxis (standard mean difference: -1.58; 95% confidence interval -2.50, -0.66, P = 0.0008; I2 = 68.4%, P = 0.0031).
Emicizumab was superior to BPA in bleeding prophylaxis in PwHAi. However, both the small population size and potential risk of bias should be considered when evaluating these results.
CRD42021278726, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278726.
Background
Immune tolerance induction (ITI) is the treatment of choice for eradication of anti‐factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and ...high‐responding inhibitor (PwHA‐HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI (∆tinhi‐ITI) is debatable.
Objective
The aim of this study was to evaluate this association among a large cohort of severe PwHA‐HRi.
Methods
Severe (factor VIII activity level <1%) PwHA‐HRi on ITI (n = 142) were enrolled in 15 hemophilia treatment centers. PwHA‐HRi were treated according to the Brazilian ITI Protocol. ITI outcomes were defined as success (i.e., recovered responsiveness to exogenous FVIII) and failure (i.e., no responsiveness to exogenous FVIII and requirement of bypassing agents to control bleeding).
Results
Median ages at inhibitor detection and at ITI start were 3.2 years (interquartile range IQR, 1.6–8.1) and 6.9 years IQR, 2.6–20.1), respectively. PwHA‐HRi were stratified according to ∆tinhi‐ITI quartiles: first (0.0–0.6 year), second (>0.6–1.7 year), third (>1.7–9.2 years), and fourth quartile (>9.2–24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders.
Conclusion
In conclusion, delayed ITI start is not associated with failure of ITI in PwHA‐HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hemophilia is well known in males, but poorly recognized in hemophilia carriers, who may have a hemorrhagic tendency, and the symptoms may be frequent and severe. Few studies have been done ...evidencing this bleeding in female carriers of the hemophilia gene.
To verify the prevalence of hemorrhagic symptoms in HC, compared to women in the general population.
The articles published between October 1996 and November 2016 were searched in the PubMed, Scielo, Lilacs, Web of Science, Scopus and Cochrane Central databases.
Seventy-five articles were found in electronic databases and 2 additional articles, through manual search in journal summaries and bibliographical references of other review articles. There is a limitation as to the number of studies that explore the association between the risk of hemorrhagic events and HC A or B. Among the few existing studies, there is a methodological difference, evidenced by control groups with distinct recruitments, divergent questionnaires and non-standardized concepts.
This review verified the existence of a higher prevalence of hemorrhagic symptoms in the HC in some outcomes, however, due to the limitations of the few studies found, there is still insufficient evidence to state that the HC has a greater hemorrhagic tendency in relation to the general population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Routine use of the script concordance test (SCT) is not common in Brazilian universities. This study aimed to analyze application of the SCT in the medical school of a Brazilian university.
...Quantitative, analytical and descriptive study in the medical school of a Brazilian university.
A total of 159/550 students participated. The test comprised ten clinical cases within internal medicine, with five items per case, rated on a five-point Likert scale. The test was scored in accordance with a marking key that had been validated by a reference panel.
In the pre-clinical and clinical phases, the mean scores were 51.6% and 63.4% of the maximum possible scores, respectively. Comparison of the means of the responses among all the years showed that there were significant differences in 40% of the items. The panel marked all the possible answers in five items, while in one item, all the panelists marked a single answer. Cronbach's alpha was 0.64. The results indicated that the more senior students performed better. Construction of an SCT with discriminative questions was not easy. The low reliability index may have occurred due to: a) problems with the construction of the questions; b) limitations of the reference panel; and/or c) the scoring key.
This instrument is very difficult to construct, apply and correct. These difficulties may make application of an SCT as an assessment method unfeasible in units with limited resources.
CONTEXT AND OBJECTIVE The cognitive processes relating to the development of clinical reasoning are only partially understood, which explains the difficulties in teaching this skill in medical ...courses. This study aimed to understand how clinical reasoning develops among undergraduate medical students. DESIGN AND SETTING Quantitative and qualitative exploratory descriptive study conducted at the medical school of Universidade Federal de Goiás. METHODS The focus group technique was used among 40 students who participated in five focus groups, with eight students from each year, from the first to fifth year of the medical school program. The material was subjected to content analysis in categories, and was subsequently quantified and subjected to descriptive statistical analysis and chi-square test for inferential statistics. RESULTS The content of the students' statements was divided into two categories: clinical reasoning - in the preclinical phase, clinical reasoning was based on knowledge of basic medical science and in the clinical phase, there was a change to pattern recognition; knowledge of basic medical science - 80.6% of the students recognized its use, but they stated that they only used it in difficult cases. CONCLUSION In the preclinical phase, in a medical school with a traditional curriculum, clinical reasoning depends on the knowledge acquired from basic medical science, while in the clinical phase, it becomes based on pattern recognition.
Resumo: Introdução: A Faculdade de Medicina da Universidade Federal de Goiás (FM-UFG) iniciou um novo processo de mudança curricular em 2014. As disciplinas de Semiologia I e II passaram a adotar ...metodologias ativas de ensino para adequação às necessidades da reforma curricular. O objetivo deste artigo foi avaliar a percepção dos discentes do primeiro ano da FM-UFG sobre o ambiente educacional das disciplinas de Semiologia I e II. Método: Trata-se de um estudo descritivo, do tipo corte transversal, envolvendo 86 alunos. O instrumento de coleta de dados foi o questionário Dundee Ready Education Environment Measure (Dreem), versão em português. Os resultados foram considerados em três níveis: questões individuais, cinco dimensões e Dreem global. Calcularam-se a média, o desvio padrão e os respectivos intervalos de confiança de 95%. Obteve-se a confiabilidade interna do Dreem pelo cálculo do alfa de Cronbach, avaliou-se a distribuição dos dados da amostra pelo teste de Shapiro-Wilk e realizou-se a comparação entre os percentuais da média dos escores dos domínios e do DRREM global pela ANOVA, seguida do teste de Tukey. Resultados: A média do Dreem global foi de 134,83/200 ± 17,42, uma percepção mais positiva que negativa. As cinco dimensões tiveram os seguintes resultados: percepção da aprendizagem (32,74 / 48 ± 5,59 / uma visão mais positiva); percepção dos docentes (32,71 / 44 ± 6,23 / na direção certa); percepção dos resultados acadêmicos (20,22 / 32 ± 4,09 / sentimento positivo); percepção do ambiente geral (31,74 / 48 ± 5,69 / atitude positiva); percepção das relações sociais (17,42 / 28 ± 3,83 / não é tão ruim). Foram encontrados alguns pontos problemáticos em relação a fatos memorizáveis, metodologia de ensino prévio e cansaço para cursarem a disciplina. A dimensão com mais áreas fortes foi a percepção dos docentes. Houve significância estatística quando os percentuais da média dos escores dos domínios e do Dreem global foram comparados. Conclusão: O ambiente educacional das disciplinas de Semiologia I e II da Faculdade de Medicina da UFG criado pelas inovações metodológicas foi avaliado positivamente pelos discentes participantes, com destaque para o domínio percepção dos docentes.
Abstract: Introduction: In 2014, the Medical School of the Federal University of Goias (FM-UFG) started its curricular changing process. The disciplines of Semiology I and II started to use active teaching methodologies to fit the curricular reform needs. The objective of this article was to evaluate the FM-UFG students’ perception of the Educational Environment in the disciplines of Semiology I and II. Method: This is a descriptive, cross-sectional study encompassing 86 students. The data collection tool was the Dundee Ready Education Environment Measure (DREEM) questionnaire, in its Portuguese version. Results were considered at three levels: individual questions, five domains and global DREEM. Mean values, standard deviation and respective 95% confidence intervals were calculated. The internal reliability of the DREEM was determined using Cronbach’s alpha; the sample normality was determined using the Shapiro-Wilk test; and the comparison between the mean score percentages of the domains and of the global DREEM was performed by ANOVA ,followed by Tukey’s test. Results: The global DREEM mean was 134.83 / 200 ± 17.42, a more positive than negative perception. The five domains showed the following results: Students’ Perception of Learning - SPL (32.74 / 48 ± 5.59 / a more positive approach); Students’ Perception of Teachers - SPT (32.71 / 44 ± 6.23 / going in the right direction); Students’ Academic Self-Perception - SASP: (20.22 / 32 ± 4.09 / feeling more on the positive side); Students’ Perception of the Atmosphere - SPA (31.74 / 48 ± 5.69 / a more positive attitude); Students’ Social Self-Perception - SSSP: (17.42 / 28 ± 3.83 / not too bad). Some issues were found in relation to: memorizable facts; previous teaching methodology; and, fatigue to attend the discipline. The SPT was the domain with the largest number of strong areas. Statistical significance was found when comparing the mean score percentages of the domains and the global DREEM. Conclusion: Students positively evaluated the educational environment in the subjects Semiology I and II created by the new active teaching methodologies adopted by the institution, with the SPT domain being highlighted.
As the Coronavirus Disease 2019 (COVID-19) pandemic unfolds around the world; answers related to the antibody response against the virus are necessary to develop treatment and prophylactic ...strategies. We attempted to understand part of the immune response of convalescent plasma donation candidates.
We carried out a cross-sectional, observational, non-intervention study, testing 102 convalescent plasma donation candidates for antibodies against the virus, relating these data to the time interval between symptom onset and sample collection, age, disease severity, and gender.
In our sample, the individuals who developed a greater antibody response were the ones who had a longer time interval between symptom onset and sample collection, the ones who had been hospitalized and the subjects above 35 years old. Moreover, 17 individuals did not present any reactive antibodies.
These results are important in that they raise questions about the role of the humoral response against the virus, as some individuals do not develop antibodies to fight it. In addition, they help develop recruitment strategies for convalescent plasma donors, who should be asymptomatic for at least 21 days and are possibly more likely to have reactive antibodies after 35 days without symptoms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Immune tolerance induction (ITI) is the treatment of choice to eradicate neutralizing anti–factor (F)VIII alloantibodies (inhibitors) in people with inherited hemophilia A. However, it is not ...successful in 10% to 40% of the cases. The biological mechanisms and biomarkers associated with ITI outcome are largely unknown.
The aim of this study was to investigate the association of plasma cytokines (interferon-γ, tumor necrosis factor, interleukin IL-2, IL-4, IL-5, IL-6, IL-10, and IL-17A), chemokines (IL-8/CXCL8, RANTES/CCL5, MIG/CXCL9, MCP-1/CCL2, and IP-10/CXCL10), and anti-FVIII immunoglobulin (Ig) G total, IgG1, and IgG4 with ITI outcome.
In this cross-sectional analysis of the Brazilian Immune Tolerance Study, we assessed plasma levels of anti-FVIII IgGs using an enzyme-linked immunosorbent assay with plasma-derived FVIII and recombinant FVIII as target antigens, immobilized in microplates.
We assayed 98 plasma samples of moderately severe and severe (FVIII activity, <2%) people with hemophilia A after completion of a first ITI course. Levels of anti–recombinant FVIII IgG total and IgG4 were higher in people with hemophilia A who failed ITI (IgG total optical density OD, 0.37; IQR, 0.15-0.73; IgG4 OD, 2.19; IQR, 0.80-2.52) than in those who had partial (IgG total OD, 0.03; IQR, 0.00-0.14; IgG4 OD, 0.39; IQR, 0.09-1.11; P < .0001 for both) or complete success (IgG total OD, 0.04; IQR, 0.00-0.07; IgG4 OD, 0.07; IQR, 0.06-0.40; P < .0001 for both). Plasma cytokines, chemokines, and anti-FVIII IgG1 were not associated with ITI outcome.
Our results show that high levels of plasma anti-FVIII IgG4 and IgG total are associated with ITI failure.
•Immune tolerance induction (ITI) eradicates factor VIII inhibitors in most people with hemophilia A.•Biological mechanisms and biomarkers associated with ITI outcome are largely unknown.•We enrolled 98 people with severe and moderately severe hemophilia A who completed a first course of ITI.•High plasma levels of anti–factor VIII immunoglobulin G4 and immunoglobulin G total were associated with ITI failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introdução: A leucemia mieloide crônica e um distúrbio mieloproliferativo clonal com uma anormalidade citogenética específica, resultante da translocação entre os cromossomos 9 e 22 com consequente ...produção de uma proteína com atividade tirosina quinase alterada. Tratamentos históricos com drogas como bussulfan, hidroxiureia e interferon passaram a ser pouco utilizados devido ao surgimento dos inibidores de tirosina quinase, cujo principal representante e o mesilato de imatinibe. Esse fármaco é a terapia de primeira linha, sendo bem tolerado pelos pacientes e com baixo risco de eventos adversos severos. Entretanto, com cerca de dez anos de uso, ainda há preocupação com efeitos colaterais em longo prazo, tais como o desenvolvimento de segunda neoplasia. Objetivo: Descrever a ocurrencia de múltiplas neoplasias em um portador de leucemia mieloide crônica. Método: Relata-se o caso de um paciente com leucemia mieloide crônica há 13 anos, tendo utilizado hidroxiureia e interferon como terapias prévias e em uso de mesilato de imatinibe há nove anos. Resultados: Há dois anos, o paciente apresentou dois nódulos em coxa esquerda que foram totalmente ressecados. Diagnosticou-se lipossarcoma mixoide e o paciente foi submetido à radioterapia. A tomografia computadorizada do abdômen de controle aos seis meses detectou nódulo espiculado na gordura mesenquimal adjacente ao jejuno/íleo. Feita laparotomia exploradora e ressecção, o anatomopatológico demonstrou fibromatose desmoide. Conclusão: O portador de tumor maligno tem risco aumentado de desenvolver uma segunda neoplasia, que pode dessa forma ocorrer nos portadores de leucemia mieloide crônica. Essa associação pode estar relacionada aos fármacos usados no tratamento da mesma.
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