Extensive CFTR sequencing through NGS in Brazilian individuals with cystic fibrosis: unravelling regional discrepancies in the country.

BACKGROUND: The Brazilian population has a tri-hybrid composition with a high degree of ethnic admixture. We hypothesized that Brazilian individuals with CF from different Brazilian regions have a specific distribution of CFTR variants. METHODS: Individuals with CF with data available in the Patient Registry and without an established genotype were submitted to CFTR sequencing by Next Generation Sequencing (NGS) methodology, and results were anonymously incorporated to the Registry Database. Genotyping results were expressed as 'positive', 'inconclusive' or 'negative'. Logistic regression models were performed to investigate the association between demographic/clinical variables and genotyping results. Mediation analysis was conducted to estimate direct and indirect effects of Brazilian region on a binary positive genotyping response. RESULTS: In October 2017, data from 4,654 individuals with CF were available, and 3,104(66.7%) of them had a genotyping result. A total of 236 variants (114 new variants) were identified, with F508del identified in 46% of the alleles tested. Genotyping revealed 2,002(64.5%) individuals positive, 757(24.4%) inconclusive and 345(11.1%) negative. Distribution of genotype categories was markedly different across Brazilian Regions, with greater proportions of negative individuals in the North (45%) and Northeast (26%) regions. Newborn screening (CF-NBS) and age at diagnosis were identified as mediators of the effect of Brazilian region on a positive genotyping result. CONCLUSIONS: This large initiative of CFTR genotyping showed significant regional discrepancies in Brazil, probably related to socio-economic conditions, lack of adequate CF-NBS and poor access to reliable sweat testing. These results may be useful to indicate Regions where CF care demands more attention.

Development of a pilot telemedicine network for paediatric oncology in Brazil.

We established a pilot telemedicine network for paediatric oncology in Brazil, linking the School of Medicine at the University of Sao Paulo in Sao Paulo City to the 'Hospital de Base' in Porto Velho, Rondonia, located in the Amazon region, 3,000 km away. The videoconferencing link used ISDN transmission at 384 kbit/s. The network was used for patient screening, follow-up, treatment monitoring and other activities. Between March 2000 and 2002, 69 videoconferences were held for 33 patients, 29 with cancer. During this period, 16 patients required transfer, 18 patients died and 11 achieved cancer remission. The main cause for patient mortality (infection) was not one that could be addressed directly by telemedicine. Using the School of Medicine as a benchmark, the average mortality rate for paediatric cancer patients in the pilot was higher. However, it was lower than previous levels observed at Rondonia (62% versus 80%).

Establishment of the Brazilian telehealth network for paediatric oncology.

A telemedicine network has been established in Brazil to support distance medical practice in paediatric oncology. ONCONET comprises a national network of universities, research institutes and medical institutions. The system is Web-based and hosted on a high-performance computing infrastructure based on clusters of computers. It is based on open-source software, designed to provide high performance, fault tolerance and high availability. The ONCONET began operation in 2004. Currently, 30 hospitals affiliated to the Brazilian Society for Paediatric Oncology are users of the ONCONET. Six hospitals are connected by broadband access through the National Education and Research Network and 24 by conventional Internet access. The Multimedia Patients Registry also became operational in 2004, and its database contains information on 3,200 patients from the 30 hospitals. The technological platform was notable for its low production cost. It thus appears to be a sustainable solution to the problem of delivering continuing medical education in a large country with widely dispersed health professionals.

Web-based patient records and treatment guidelines in paediatric oncology.

We have established a Web-based system in Brazil offering health information in childhood cancer and services such as electronic patient records and treatment protocols. The system was based on open-source software. The database has records for about 3,200 patients from 30 Brazilian hospitals. An evaluation by doctors from the six hospitals comprising the Neuroblastoma Cooperative Group was positive, mainly because the system allows easy online access, but also because the electronic register performs data validation when information is inserted. Our experience shows that it is possible to use a Web-based system to provide paediatric cancer services at a distance.