High Incidence of Diseases Endemic to the Amazon Region of Brazil, 2001–2006

Vector-borne and mycobacterial diseases are a major public health problem in this region

Impact on tuberculosis incidence rates of removal of repeat notification records

OBJETIVO: Avaliar o impacto nas taxas de incidência de tuberculose com a exclusão de registros indevidamente repetidos no sistema de notificação. MÉTODOS: Foram analisados dados do Sistema de Informação de Agravos de Notificação do Ministério da Saúde, referentes ao período de 2000 a 2004. Os registros repetidos foram identificados por pareamento probabilístico e classificados em seis categorias excludentes que determinaram suas remoções, vinculações ou permanências na base. RESULTADOS: Verificou-se que 73,7% das notificações eram únicas, 18,9% formavam duplas, 4,7% triplas e 2,7% grupos de quatro ou mais registros. Dentre os registros repetidos, 47,3% foram classificados como transferência entre unidades de saúde, 23,6% reingresso, 16,4% duplicidade verdadeira, 10% recidiva, 2,5% foram inconclusivos e 0,2% tinham dados incompletos. Essas percentagens variaram entre estados. A exclusão de registros indevidamente repetidos resultou em redução na taxa de incidência por 100.000 habitantes de 6,1% em 2000 (de 44 para 41,3), 8,3% em 2001 (de 44,5 para 40,8), 9,4% em 2002 (de 45,8 para 41,5), 9,2% em 2003 (de 46,9 para 42,6) e 8,4% em 2004 (de 45,4 para 41,6). CONCLUSÕES: Os resultados sugerem que as taxas observadas de incidência de tuberculose representem estimativas mais próximas do que seriam os valores reais do que as obtidas com a base em seu estado bruto, tanto em nível nacional como estadual. A prática de pareamento de registros de notificação de tuberculose deve ser estimulada e mantida para melhoria da qualidade dos dados de notificação.OBJECTIVE: To evaluate the impact on tuberculosis (TB) incidence rates of removal of improper duplicate records from the notification system. METHODS: Data from the Sistema de Informação de Agravos de Notificação (Brazilian Information System for Tuberculosis Notification) from 2000 to 2004 were analyzed. Repeat records were identified through probabilistic record linkage and classified into six mutually exclusive categories and then kept, combined or removed from database. RESULTS: Of all TB records, 73.7% had no duplicate, 18.9% were duplicate, 4.7% were triplicate, and 2.7% were quadruplicate or more. Of all repeat records, 47.3% were classified as transfer in/out; 23.6% return after default, 16.4% true duplicates, 10% relapse, 2.5% inconclusive and 0.2% had missing data. These proportions were different in Brazilian states. Removal of improper duplicate records reduced TB incidence rate per 100.000 inhabitants by 6.1% in the year 2000 (from 44 to 41.3), 8.3% in 2001 (from 44.5 to 40.8), 9.4% in 2002 (from 45.8 to 41.5), 9.2% in 2003 (from 46.9 to 42.6) and 8.4% in 2004 (from 45.4 to 41.6). CONCLUSIONS: The study results indicate that the observed tuberculosis incidence rates represent estimates that would be closer to the actual rates than those obtained from the raw database at state and country level. The use of record linkage approach should be promoted for better quality of notification system data

Efeito da remoção de notificações repetidas sobre a incidência da tuberculose no Brasil

OBJECTIVE: To evaluate the impact on tuberculosis (TB) incidence rates of removal of improper duplicate records from the notification system. METHODS: Data from the Sistema de Informação de Agravos de Notificação (Brazilian Information System for Tuberculosis Notification) from 2000 to 2004 were analyzed. Repeat records were identified through probabilistic record linkage and classified into six mutually exclusive categories and then kept, combined or removed from database. RESULTS: Of all TB records, 73.7% had no duplicate, 18.9% were duplicate, 4.7% were triplicate, and 2.7% were quadruplicate or more. Of all repeat records, 47.3% were classified as transfer in/out; 23.6% return after default, 16.4% true duplicates, 10% relapse, 2.5% inconclusive and 0.2% had missing data. These proportions were different in Brazilian states. Removal of improper duplicate records reduced TB incidence rate per 100.000 inhabitants by 6.1% in the year 2000 (from 44 to 41.3), 8.3% in 2001 (from 44.5 to 40.8), 9.4% in 2002 (from 45.8 to 41.5), 9.2% in 2003 (from 46.9 to 42.6) and 8.4% in 2004 (from 45.4 to 41.6). CONCLUSIONS: The study results indicate that the observed tuberculosis incidence rates represent estimates that would be closer to the actual rates than those obtained from the raw database at state and country level. The use of record linkage approach should be promoted for better quality of notification system data.OBJETIVO: Avaliar o impacto nas taxas de incidência de tuberculose com a exclusão de registros indevidamente repetidos no sistema de notificação. MÉTODOS: Foram analisados dados do Sistema de Informação de Agravos de Notificação do Ministério da Saúde, referentes ao período de 2000 a 2004. Os registros repetidos foram identificados por pareamento probabilístico e classificados em seis categorias excludentes que determinaram suas remoções, vinculações ou permanências na base. RESULTADOS: Verificou-se que 73,7% das notificações eram únicas, 18,9% formavam duplas, 4,7% triplas e 2,7% grupos de quatro ou mais registros. Dentre os registros repetidos, 47,3% foram classificados como transferência entre unidades de saúde, 23,6% reingresso, 16,4% duplicidade verdadeira, 10% recidiva, 2,5% foram inconclusivos e 0,2% tinham dados incompletos. Essas percentagens variaram entre estados. A exclusão de registros indevidamente repetidos resultou em redução na taxa de incidência por 100.000 habitantes de 6,1% em 2000 (de 44 para 41,3), 8,3% em 2001 (de 44,5 para 40,8), 9,4% em 2002 (de 45,8 para 41,5), 9,2% em 2003 (de 46,9 para 42,6) e 8,4% em 2004 (de 45,4 para 41,6). CONCLUSÕES: Os resultados sugerem que as taxas observadas de incidência de tuberculose representem estimativas mais próximas do que seriam os valores reais do que as obtidas com a base em seu estado bruto, tanto em nível nacional como estadual. A prática de pareamento de registros de notificação de tuberculose deve ser estimulada e mantida para melhoria da qualidade dos dados de notificação

Analysis of protein-coding genetic variation in 60,706 humans

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes

Analysis of protein-coding genetic variation in 60,706 humans

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.Peer reviewe

Quality analysis of the AIDS daase in the notification information systems (SINAN)

Made available in DSpace on 2012-09-06T01:11:58Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 751.pdf: 2440085 bytes, checksum: 55667cbaf3feab1ea5eac6f6cd588845 (MD5) Previous issue date: 2005Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.A notificação de casos tem sido a principal estratégia de vigilância da aids no Brasil. O presente estudo analisa a qualidade das notificações registradas no Sinan, no nível nacional, no que se refere à duplicidade de registros, completitude dos campos e consistência dos dados. Descreve-se o histórico do Sinan e principais características da versão Windows. Foram analisados os bancos com casos de aids notificados, adultos e crianças, de 1980 a 2003, disponibilizados pelo Programa Nacional de DST e Aids do Ministério da Saúde. Calculou-se a completitude de cada campo e a proporção de notificações com cada inconsistência selecionada. Completitudes de variáveis essenciais ≤ 90% ou inconsistências > 5% foram analisadas quanto à sua evolução temporal e distribuição segundo unidade federada notificante. Construíram-se três medidas-resumo da completitude e ou consistência das notificações (e não de cada campo) e classificaram-se os estados segundo seus resultados. As duplicidades identificadas e confirmadas por critérios específicos foram analisadas segundo distribuição por unidade federada notificante. Analisaram-se os fatores determinantes das duplicidades no âmbito de cada estado. Os resultados indicam que a consistência dos dados é superior à completitude dos campos. Houve, ao longo dos anos, aumento da completitude da maioria dos campos das notificações de aids - crianças e adultos. A falta de padronização nas categorias, na obrigatoriedade e na rotina de preenchimento automático dos campos pelo sistema determinou diferenças na completitude de campos comuns das notificações de crianças e adultos. Deficiências no programa de crítica de entrada de dados no sistema e na normalização da vigilância e sua divulgação causaram inconsistências entre campos/datas. A classificação dos estados segundo resultados dos indicadores-síntese da completitude e consistência deve ser interpretada com cautela, considerando características da vigilância da aids em cada estado. A duplicidade de registros foi um aspecto relevante da qualidade dos bancos analisados, decorrente dos atendimentos ao paciente em unidades de saúde diferentes, como de fatores relacionados ao gerenciamento e operacionalização do Sinan. A distribuição desses fatores variou entre as unidades federadas, indicando soluções distintas para o problema. São recomendadas medidas visando à melhoria da qualidade dos dados. Os procedimentos utilizados foram sistematizados em programas estruturados do SPSS, para aplicação em análises futuras.Case reports have been the main strategy of AIDS surveillance in Brazil. This study analyzes the quality of national data related to AIDS notifications in Sinan, considering duplications of reports, the completeness and consistency of data. It describes the chronology of Sinan and the main characteristics of the Windows version. AIDS case reports of children and adults, from 1980 to 2003, disclosed by The National Program of STD/AIDS in the Health Ministry, were analyzed. Data completeness and proportion of case reports with each chosen inconsistency were calculated. For key variables, completeness ≤90% or inconsistency >5% were analyzed in relation to time of report, and distribution by State. Three measures to evaluate the completeness of reporting and/or inconsistency level were created, and States were classified according to these results. Duplications of case reports were identified and confirmed based on specific criteria and analyzed by state. The situations which implicated them were verified within each state. The results demonstrate that data consistency is superior to data completeness. Over time, there has been an increase in the completeness of most data fields in case reports of AIDS in children and adults. The lack of standardization of some field categories, of requirement to fill out fields or of the system’s automatic procedure of filling out, resulted in differences in common data completeness of case reports of children and adults. Deficiencies in computer program to identify data inconsistencies in data-entry and in surveillance normalization and dissemination produced inconsistencies between data fields. Classification of States according report completeness and consistency should be interpreted carefully, considering each State’s AIDS surveillance characteristics. The duplication of case reports was a relevant aspect in relation to the quality of databases analyzed, and was due not only to patient care at different health centers, but also to aspects related to Sinan management and operation. The distribution of these aspects varies by State, suggesting distinct solutions to the problem. Several recommendations were made to improve data quality. The procedures used were systematized in structured programs using SPSS software for use in future analyses

Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: Evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation

Objective Interleukin (IL)-17A has emerged as pivotal in driving tissue pathology in immune-mediated inflammatory diseases. The role of IL-17F, sharing 50% sequence homology and overlapping biological function, remains less clear. We hypothesised that IL-17F, together with IL-17A, contributes to chronic tissue inflammation, and that dual neutralisation may lead to more profound suppression of inflammation than inhibition of IL-17A alone. Methods Preclinical experiments assessed the role of IL-17A and IL-17F in tissue inflammation using disease-relevant human cells. A placebo-controlled proof-of-concept (PoC) clinical trial randomised patients with psoriatic arthritis (PsA) to bimekizumab (n=39) or placebo (n=14). Safety, pharmacokinetics and clinical efficacy of multiple doses (weeks 0, 3, 6 (240 mg/160 mg/160 mg; 80 mg/40 mg/40 mg; 160 mg/80 mg/80 mg and 560 mg/320 mg/320 mg)) of bimekizumab, a humanised monoclonal IgG1 antibody neutralising both IL-17A and IL-17F, were investigated. Results IL-17F induced qualitatively similar inflammatory responses to IL-17A in skin and joint cells. Neutralisation of IL-17A and IL-17F with bimekizumab more effectively suppressed in vitro cytokine responses and neutrophil chemotaxis than inhibition of IL-17A or IL-17F alone. The PoC trial met both prespecified efficacy success criteria and showed rapid, profound responses in both joint and skin (pooled top three doses vs placebo at week 8: American College of Rheumatology 20% response criteria 80.0% vs 16.7% (posterior probability >99%); Psoriasis Area and Severity Index 100% response criteria 86.7% vs 0%), sustained to week 20, without unexpected safety signals. Conclusions These data support IL-17F as a key driver of human chronic tissue inflammation and the rationale for dual neutralisation of IL-17A and IL-17F in PsA and related conditions. Trial registration number NCT02141763; Results