Browsing by Author "Gonçalves, R."
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- Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic EscalationPublication . Magro, F.; Afonso, J.; Lopes, S.; Coelho, R.; Gonçalves, R.; Caldeira, P.; Lago, P.; Sousa, H.; Ramos, J.; Gonçalves, A.; Ministro, P.; Rosa, I.; Vieira, A.; Andrade, P.; Soares, J.; Carvalho, D.; Sousa, P.; Meira, T.; Lopes, J.; Moleiro, J.; Dias, C.; Falcão, A.; Geboes, K.; Carneiro, F.Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62μg/mL vs. 1.15μg/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3μg/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250μg/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.
- Clinical performance of an infliximab rapid quantification assayPublication . Magro, F.; Afonso, J.; Lopes, S.; Coelho, R.; Gonçalves, R.; Caldeira, P.; Lago, P.; Sousa, H.; Ramos, J.; Gonçalves, A.; Ministro, P.; Rosa, I.; Meira, T.; Andrade, P.; Soares, J.; Carvalho, D.; Sousa, P.; Vieira, A.; Lopes, J.; Dias, C.; Geboes, K.; Carneiro, F.BACKGROUND: Therapeutic drug monitoring (TDM)-based algorithms can be used to guide infliximab (IFX) adjustments in inflammatory bowel disease (IBD) patients. This study aimed to explore a rapid IFX-quantification test from a clinical perspective. METHODS: This manuscript describes a prospective cohort study involving 110 ulcerative colitis (UC) patients on the maintenance phase of IFX. IFX trough levels were quantified using a rapid quantification assay and a commonly-used reference kit. RESULTS: Irrespective of the assay used to measure IFX, its through levels were statistically different between patients with and without endoscopic remission (Mayo endoscopic score = 0), as well as between patients stratified by their faecal calprotectin (FC) levels. Despite the fact that the two methods correlated well with each other [Spearman's rank correlation coefficient = 0.843, p < 0.001; intraclass correlation coefficients = 0.857, 95% confidence interval (CI): 0.791-0.903], there was a discernible systematic variation; values obtained with the reference kit were on average 2.62 units higher than those obtained with the rapid assay. Notwithstanding, 3 µg/ml was shown to be an acceptable cut-off to assess endoscopic status and inflammatory burden levels using both assays. The percentage of patients that had a positive outcome when the IFX concentration measured by the rapid assay ranked above 3 µg/ml was 88% both for a Mayo endoscopic score ⩽ 1 and for an FC concentration <250 µg/g. CONCLUSIONS: Based on this study, we concluded that using the rapid IFX assessment system with a 3 µg/ml threshold is a reliable alternative to the time-consuming enzyme-linked immunosorbent assays in patients on the maintenance phase of IFX.
- Co-selection of the H63D mutation and the HLA-A29 allele: a new paradigm of linkage disequilibrium?Publication . Cardoso, C.; Alves, H.; Mascaranhas, M.; Gonçalves, R.; Oliveira, P.; Rodrigues, P.; Cruz, E.; Sousa, M.; Porto, G.The major histocompatibility complex (MHC) shows a remarkable conservation of particular HLA antigens and haplotypes in linkage disequilibrium in most human populations, suggesting the existence of a convergent evolution. A recent example of such conservation is the association of particular HLA haplotypes with the HFE mutations. With the objective of exploring the significance of that association, the present paper offers an analysis of the linkage disequilibrium between HLA alleles or haplotypes and the HFE mutations in a Portuguese population. Allele and haplotype associations between HLA and HFE mutations were first reviewed in a population of 43 hemochromatosis families. The results confirmed the linkage disequilibrium of the HLA haplotype HLA-A3-B7 and the HLA-A29 allele, respectively, with the HFE mutations C282Y and H63D. In order to extend the study of the linkage disequilibrium between H63D and the HLA-A29-containing haplotypes in a normal, random population, an additional sample of 398 haplotypes was analyzed. The results reveal significant linkage disequilibrium between the H63D mutation and all HLA-A29-containing haplotypes, favoring the hypothesis of a co-selection of H63D and the HLA-A29 allele itself. An insight into the biological significance of this association is given by the finding of significantly higher CD8+ T-lymphocyte counts in subjects simultaneously carrying the H63D mutation and the HLA-A29 allele.
- Organization of rehabilitation care in Portuguese intensive care unitsPublication . Mendes, R.; Nunes, M.; Pinho, J.; Gonçalves, R.Objective: To describe the different rehabilitation care models in practice in Portuguese adult intensive care units. Methods: A simple observational (cross-sectional) study was conducted through an online survey sent to the head nurses or individuals responsible for the 58 adult intensive care units that are part of the database of the Sociedade Portuguesa de Cuidados Intensivos. Results: We identified three models of organization of rehabilitation care: care provided by the staff of the intensive care unit (22.9%), care provided by specialized external teams (25.0%), and a mixture of the previous models, combining the two situations (52.1%). In the first model, the care was provided mainly by nurses with specialization in rehabilitation and, in the second model, the care was provided by physiotherapists. No significant differences were found between the models regarding the availability of care, in hours/day or days/week (p = 0.268 and 0.994, respectively), or results such as length of hospital stay in intensive care, ventilation time, or mortality rate in the unit (p = 0.418, 0.923, and 0.240, respectively). Conclusion: The organization of rehabilitation care in Portuguese intensive care units is unique and heterogeneous. Despite different care organization models, the availability of hours of care is similar, as are the overall results observed in patients.
- Sentimento de mulheres atendidas por graduandos de Medicina na realização do exame ginecológico em ambulatório de Ginecologia e Obstetrícia da Fundação Santa Casa de Misericórdia do ParáPublication . Silva, J.; Botelho, N.; Melo, N.; Gonçalves, R.; Brito, N.Introdução: As aulas práticas são fundamentais para a formação médica. Entretanto, matérias como Ginecologia e Obstetrícia, o exame físico é profundamente íntimo, lidando com áreas do corpo humano, na qual imperam preconceitos e tabus. Objetivo: Avaliar o sentimento das mulheres atendidas por graduandos de medicina em um hospital de ensino de referência no estado do Pará. Método: O estudo foi realizado nos meses de março a abril de 2013, com uma casuística de 110 mulheres atendidas por graduandos de medicina em ambulatório de ginecologia e obstetrícia de um hospital de ensino. Resultados: A maioria das mulheres deste estudo obtiveram esclarecimentos acerca do exame ginecológico a ser executado (79%) e alegam que foi solicitado consentimento para realização do exame (58%), que ocorreu sem dor ou desconforto (55%), sendo que a 66% dos graduandos prosseguiu na realização do exame na presença da dor ou desconforto. Após a realização do mesmo 41% das mulheres referiu sentir vergonha e as que não receberam esclarecimento revelaram que se sentiriam melhor (48%) ou indiferente (48%) caso recebessem. 62% referiram não ser solicitada a participação do graduando durante exame, porem sua conduta foi considerada adequada (64%), sendo o ambiente serio durante a realização do exame (65%). 55% das mulheres referem ter conhecimento do caráter acadêmico do hospital de ensino. Conclusão: A maioria das mulheres obteve esclarecimento acerca do exame ginecológico, principalmente pelo médico preceptor, alegam que foi requerido consentimento para realização do exame, e não foi questionada a participação do graduando durante o mesmo.