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Browsing by Author "Fonseca, J."

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  • Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies
    Publication . Jorge, P.; Garcia, E.; Gonçalves, A.; Marques, I.; Maia, N.; Rodrigues, B.; Santos, H.; Fonseca, J.; Soares, G.; Correia, C.; Reis-Lima, M.; Cirigliano, V.; Santos, R.
    BACKGROUND: We describe a female infant with Fragile-X syndrome, with a fully expanded FMR1 allele and preferential inactivation of the homologous X-chromosome carrying a de novo deletion. This unusual and rare case demonstrates the importance of a detailed genomic approach, the absence of which could be misguiding, and calls for reflection on the current clinical and diagnostic workup for developmental disabilities. CASE PRESENTATION: We present a female infant, referred for genetic testing due to psychomotor developmental delay without specific dysmorphic features or relevant family history. FMR1 mutation screening revealed a methylated full mutation and a normal but inactive FMR1 allele, which led to further investigation. Complete skewing of X-chromosome inactivation towards the paternally-inherited normal-sized FMR1 allele was found. No pathogenic variants were identified in the XIST promoter. Microarray analysis revealed a 439 kb deletion at Xq28, in a region known to be associated with extreme skewing of X-chromosome inactivation. CONCLUSIONS: Overall results enable us to conclude that the developmental delay is the cumulative result of a methylated FMR1 full mutation on the active X-chromosome and the inactivation of the other homologue carrying the de novo 439 kb deletion. Our findings should be taken into consideration in future guidelines for the diagnostic workup on the diagnosis of intellectual disabilities, particularly in female infant cases.
    2018-05-10Journal article Open access Show more
  • Patient-physician discordance in assessment of adherence to inhaled controller medication: a cross-sectional analysis of two cohorts
    Publication . Jácome, C.; Pereira, A.; Almeida, R.; Ferreira-Magalhães, Manuel; Couto, M.; Araujo, L.; Pereira, M.; Correia, M.; Loureiro, C.; Catarata, M.; Maia Santos, L.; Pereira, J.; Ramos, B.; Lopes, C.; Mendes, A.; Cidrais Rodrigues, J.; Oliveira, G.; Aguiar, A.; Afonso, I.; Carvalho, J.; Arrobas, A.; Coutinho Costa, J.; Dias, J.; Todo Bom, A.; Azevedo, J.; Ribeiro, C.; Alves, M.; Leiria Pinto, P.; Neuparth, N.; Palhinha, A.; Gaspar Marques, J.; Pinto, N.; Martins, P.; Todo Bom, F.; Alvarenga Santos, M.; Gomes Costa, A.; Silva Neto, A.; Santalha, M.; Lozoya, C.; Santos, N.; Silva, D.; Vasconcelos, M.; Taborda-Barata, L.; Carvalhal, C.; Teixeira, M.; Alves, R.; Moreira, A.; Sofia Pinto, C.; Morais Silva, P.; Alves, C.; Câmara, R.; Coelho, D.; Bordalo, D.; Fernandes, R.; Ferreira, R.; Menezes, F.; Gomes, R.; Calix, M.; Marques, A.; Cardoso, J.; Emiliano, M.; Gerardo, R.; Nunes, C.; Câmara, R.; Ferreira, J.; Carvalho, A.; Freitas, P.; Correia, R.; Fonseca, J.
    Objective: We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance. Design: Baseline data from two prospective multicentre observational studies. Setting: 29 allergy, pulmonology and paediatric secondary care outpatient clinics in Portugal. Participants: 395 patients (≥13 years old) with persistent asthma. Measures: Data on demographics, patient-physician relationship, upper airway control, asthma control, asthma treatment, forced expiratory volume in one second (FEV1) and healthcare use were collected. Patients and physicians independently assessed adherence to inhaled controller medication during the previous week using a 100 mm Visual Analogue Scale (VAS). Discordance was defined as classification in distinct VAS categories (low 0-50; medium 51-80; high 81-100) or as an absolute difference in VAS scores ≥10 mm. Correlation between patients' and physicians' VAS scores/categories was explored. A multinomial logistic regression identified the predictors of physician overestimation and underestimation. Results: High inhaler adherence was reported both by patients (median (percentile 25 to percentile 75) 85 (65-95) mm; 53% VAS>80) and by physicians (84 (68-95) mm; 53% VAS>80). Correlation between patient and physician VAS scores was moderate (rs=0.580; p<0.001). Discordance occurred in 56% of cases: in 28% physicians overestimated adherence and in 27% underestimated. Low adherence as assessed by the physician (OR=27.35 (9.85 to 75.95)), FEV1 ≥80% (OR=2.59 (1.08 to 6.20)) and a first appointment (OR=5.63 (1.24 to 25.56)) were predictors of underestimation. An uncontrolled asthma (OR=2.33 (1.25 to 4.34)), uncontrolled upper airway disease (OR=2.86 (1.35 to 6.04)) and prescription of short-acting beta-agonists alone (OR=3.05 (1.15 to 8.08)) were associated with overestimation. Medium adherence as assessed by the physician was significantly associated with higher risk of discordance, both for overestimation and underestimation of adherence (OR=14.50 (6.04 to 34.81); OR=2.21 (1.07 to 4.58)), while having a written action plan decreased the likelihood of discordance (OR=0.25 (0.12 to 0.52); OR=0.41 (0.22 to 0.78)) (R2=44%). Conclusion: Although both patients and physicians report high inhaler adherence, discordance occurred in half of cases. Implementation of objective adherence measures and effective communication are needed to improve patient-physician agreement.
    2019-11-07Journal article Open access Show more
  • The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing Policies
    Publication . Sá-Sousa, A.; Fonseca, J.; Pereira, A.; Ferreira, A.; Arrobas, A.; Mendes, A.; Drummond, M.; Videira, W.; Costa, T.; Farinha, P.; Soares, J.; Rocha, P.; Todo-Bom, A.; Sokolova, A.; Costa, A.; Fernandes, B.; Chaves Loureiro, C.; Longo, C.; Pardal, C.; Costa, C.; Cruz, C.; Loureiro, C.; Lopes, C.; Mesquita, D.; Faria, E.; Magalhães, E.; Menezes, F.; Todo-Bom, F.; Carvalho, F.; Regateiro, F.; Falcao, H.; Fernandes, I.; Gaspar-Marques, J.; Viana, J.; Ferreira, J.; Silva, J.; Simão, L.; Almeida, L.; Fernandes, L.; Ferreira, L.; van Zeller, M.; Quaresma, M.; Castanho, M.; André, N.; Cortesão, N.; Leiria-Pinto, P.; Pinto, P.; Rosa, P.; Carreiro-Martins, P.; Gerardo, R.; Silva, R.; Lucas, S.; Almeida, T.; Calvo, T.
    The Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.
    2018-11-21Journal article Open access Show more