Sickle cell disease related mortality in Brazil, 2000-2018

Abstract Introduction There is a demand to update national mortality trends data related to sickle cell disease (SCD) in Brazil. This study describes causes of death and mortality issues related to SCD using the multiple-cause-of-death methodology. Methods The annual SCD mortality data was extracted from the public databases of the Mortality Information System by researching deaths in rubric D57 "sickle-cell disorders" of the International Classification of Diseases, Tenth Revision and processed by the Multiple Cause Tabulator. Results From 2000 to 2018 in Brazil, a total of 9817 deaths related to SCD occurred during the 19-year period, as the underlying cause in 6924 (70.5%) and as the associated cause of death in 2893 (29.5%). The mean and median ages at death during the entire period were significantly lower for males, 29.4 (±19.6) and 27.5 (15.5-41.5), respectively, than for females, 33.3 (±20.3) and 31.0 (19.5-46.5), respectively. The leading SCD overall associated causes of death were septicemias (32.1%), followed by pneumonias (19.4%) and respiratory failure (18.2%). On certificates with SCD as an associated cause, the underlying causes of death were circulatory system diseases (8.7%), followed, in males, by digestive system and infectious diseases and respiratory system failures, while in females, maternal deaths, included in the chapter on pregnancy, childbirth and the puerperium, accounting for 4.6% of female deaths, were succeeded by digestive system and infectious diseases. Conclusion This study revised mortality data on death rate trends, underlying and associated causes of death, age at death and regional distribution of death in Brazil.

Mortality attributed to sickle cell disease in children and adolescents in Brazil, 2000-2019 / Mortalidade atribuída à doença falciforme em crianças e adolescentes no Brasil, 2000-2019

ABSTRACT OBJECTIVE Estimate rates and describe mortality trends attributed to sickle cell disease in children and adolescents in Brazil from 2000 to 2019. METHODS This is an ecological study of the time-trend of mortality rates that used the autoregressive method, proposed by Prais-Winsten, to evaluate trends in the estimated rates of sickle cell disease deaths in children and adolescents in Brazil. Deaths with code D57 were obtained from the Mortality Information System, considering age groups (0-4, 5-9, 10-14, 15-19 years) and were used to estimate age-specific and standardized rates by gender and age. RESULTS From 2000 to 2019, Brazil had 2,422 deaths from sickle cell disease in people under 20 years of age, with higher frequency in the Northeast (40.46%), followed by the Southeast (39.02%), Midwest (9.58%), North (7.84%), and South (3.10%). The main victims were people of Black skin/race (78.73%). In Brazil, the global standardized average rate was 0.20/100,000 people-year, with an elevation trend (annual percentage change - APC = 5.44%; confidence interval - 95%CI: 2.57-8.39). The pattern was repeated in males (APC = 4.38%; 95%CI: 2.17-6.64) and females (APC = 6.96%; 95%CI: 3.05-11.01). Elaborating age-specific rates showed that the range up to four years experienced the highest rates, without distinction by region. The age group of 15 and 19 years was the second most affected in Brazil and in the Northeast, Southeast, and Midwest regions. CONCLUSION Deaths due to sickle cell disorders showed an elevation trend in children and adolescents. Considering that the magnitude of deaths was more evident in the first years (0-4) and late adolescence (15-19), the study suggests that age-specific approaches may impact the control of fatal outcomes caused by sickle cell disease in Brazil.

RESUMO OBJETIVO Estimar taxas e descrever tendências de mortalidade atribuídas à doença falciforme em crianças e adolescentes no Brasil, de 2000 a 2019. MÉTODOS Este é um estudo ecológico do tipo séries temporais de taxas de mortalidade que usou o método autorregressivo, proposto por Prais-Winsten, para avaliar tendências das taxas estimadas de mortes por doença falciforme em crianças e adolescentes no Brasil. Os óbitos com código D57 foram obtidos no Sistema de Informações sobre Mortalidade, considerando as faixas etárias (0-4, 5-9, 10-14, 15-19 anos) e usados para estimar taxas específicas por idade e taxas padronizadas por sexo e idade. RESULTADOS De 2000 a 2019, houve 2.422 óbitos por doença falciforme em menores de 20 anos no Brasil, com maior frequência na região Nordeste (40,46%), seguida de Sudeste (39,02%), Centro-Oeste (9,58%), Norte (7,84%) e Sul (3,10%). As principais vítimas foram pessoas de raça/cor da pele negra (78,73%). No Brasil, a taxa média padronizada global foi de 0,20/100 mil pessoa-ano, com tendência de elevação (mudança percentual anual - APC = 5,44%; intervalo de confiança - IC95% 2,57-8,39). O padrão se repetiu no sexo masculino (APC = 4,38%; IC95% 2,17-6,64) e no sexo feminino (APC = 6,96%; IC95% 3,05-11,01). A elaboração de taxas específicas por idade mostrou que a faixa até quatro anos experimentou as maiores taxas, sem distinção por região. A faixa etária de 15 e 19 anos foi a segunda mais afetada no Brasil e nas regiões Nordeste, Sudeste e Centro-Oeste. CONCLUSÃO Houve tendência de aumento dos óbitos por transtornos falciformes em crianças e adolescentes. Considerando que a magnitude dos óbitos foi mais evidente nos primeiros anos (0-4) e no final da adolescência (15-19), o estudo sugere que abordagens específicas por faixa etária podem impactar no controle dos desfechos fatais causados pela doença falciforme no Brasil.

Fatores de risco para mortalidade em pacientes com doença falciforme: uma revisão integrativa / Factores de riesgo para la mortalidad en pacientes con enfermedad falciforme: una revisión integradora / Risk factors for mortality in patients with sickle cell disease: an integrative review

RESUMO Objetivo Sumarizar fatores de risco e indicadores de mortalidade em pacientes com doença falciforme. Método Revisão integrativa em periódicos indexados nas bases de dados CINAHL, PubMed/MEDLINE, Science Direct/SCOPUS, SciELO e Web of Science. A questão norteadora foi elaborada por meio da estratégia Population, variable, outcome (PVO). A busca ocorreu no portal de periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior entre outubro e novembro de 2018. Resultados Dos 19 artigos, 18 eram coorte e um ensaio clínico randomizado. A amostra foi constituída, em sua maioria, pelo sexo feminino e genótipo HbSS. Se repetiram mais a taxa de mortalidade cumulativa e a curva de mortalidade global. Sete estudos identificaram fatores de risco com associação estatisticamente significativa para morte. Os mais frequentes foram o baixo nível de hemoglobina, variáveis hepáticas (enzimas fosfatase alcalina e transaminase glutâmico oxalacética) e cardiovasculares (velocidade de regurgitação da válvula tricúspide ≥ 2,5m/s). Conclusão e implicações para a prática Indicadores de mortalidade constituem ferramentas de manejo de pacientes com doença falciforme e prevenção de riscos e complicações. Há necessidade de estudos sobre os fatores relacionados à mortalidade desses pacientes. A prevenção do óbito, certamente, promoverá uma melhoria na qualidade de vida e na sobrevida dessa população.

RESUMEN Objetivo Resumir los factores de riesgo y los indicadores de mortalidad en pacientes con enfermedad de células falciformes. Método revisión integradora de publicaciones en las bases de datos CINAHL, PubMed/MEDLINE, Science Direct/SCOPUS, SciELO y Web of Science. La pregunta guía basada en Population, variable, outcome (PVO) conduciu la búsqueda en el Portal de revistas de la Coordinación de Mejoramiento de Personal de Nivel Superior, entre octubre-noviembre de 2018, con los descriptores anemia, sickle cell "and" mortality "and" survival y sus sinónimos. Resultados De 18/19 artículos son cohortes y un ensayo controlado aleatorio. La muestra consistió en mujeres y genotipo HbSS. La tasa de mortalidad acumulada y la curva de mortalidad general fueron más repetidas. Siete estudios identificaron factores de riesgo con asociación estadísticamente significativa con la muerte. Los más frecuentes fueron el bajo nivel de hemoglobina, variables hepáticas (fosfatasa alcalina y enzimas glutámicas transaminasas oxalacéticas) y variables cardiovasculares (velocidad de regurgitación de la válvula tricúspide ≥ 2.5m/s). Conclusión e implicaciones para la práctica Los indicadores de mortalidad son herramientas de manejo de los pacientes con esta enfermedad, la prevención de factores de riesgo y complicaciones. Hace necesidad de estudios sobre los factores relacionados con la mortalidad. La prevención de las muertes mejorará la calidad de vida y la supervivencia.

ABSTRACT Objective To summarize the risk factors and mortality indicators in sickle cell disease patients. Method Integrative review searched publications in journals in CINAHL, PubMed/MEDLINE, Science Direct/SCOPUS, SciELO, and Web of Science databases. The guiding question was elaborated through the Population, Variable, Outcome (PVO) strategy and the search was from October-to-November 2018, at the Coordination of Higher Level Personnel Improvement Periodicals' Gate. The keywords anemia, sickle cell "and" mortality "and" survival and their synonyms were used. Results From 18/19 articles were cohort and one randomized controlled trial. The sample consisted mostly of females and HbSS genotype. The cumulative mortality rate and the overall mortality curve were the most repeated. Seven studies identified risk factors with a statistically significant association with death. The most frequent were low hemoglobin level, liver variables (alkaline phosphatase and oxalacetic glutamic transaminase enzymes) and cardiovascular variables (tricuspid valve regurgitation speed ≥ 2.5m/s). Conclusion and implications for practice Mortality indicators are tools for better management of sickle cell disease's patient, prevention of risks and complications. There is a need for further studies on the factors related to mortality of these patients. Preventing the causes that lead to death will certainly improve the quality of life and survival of this population.

Mortality by sickle cell disease in Brazil

Abstract This work aimed to characterize mortality by sickle cell disease in Brazil. The MEDLINE electronic database was searched using the terms ‘mortality' and ‘sickle cell disease' and ‘Brazil' for articles published in the last five years aiming to provide a current analysis of the subject in question. Eight studies on mortality by sickle cell disease were carried out in the Brazilian states of Maranhão, Bahia, Minas Gerais, Rio de Janeiro and Mato Grosso do Sul. The majority of the deaths occurred in patients with sickle cell anemia, which is the most common genotype and causes the most severe clinical manifestation of the disease. In summary, there are few published studies on mortality related to sickle cell disease in Brazil, and most are from the state of Minas Gerais. This study emphasizes the importance of developing more studies on sickle cell disease mortality, so that it may be possible to profile gene carriers and give health professionals more data to strategize the delivery of more effective assistance to these individuals. Despite the early diagnosis of sickle cell disease by the Neonatal Screening Program and the use of preventive and therapeutic measures (penicillin, immunization and hydroxyurea), mortality by sickle cell disease on the world stage is still significant.

Characterization of mortality in children with sickle cell disease diagnosed through the Newborn Screening Program / Caracterização do óbito de crianças com doença falciforme diagnosticadas por Programa de Triagem Neonatal

OBJECTIVE: To characterize the deaths of 193 children with sickle cell disease screened by a neonatal program from 1998 to 2012 and contrast the initial years with the final years. METHODS: Deaths were identified by active surveillance of children absent to scheduled appointments in Blood Bank Clinical Centers (Hemominas). Clinical and epidemiological data came from death certificates, neonatal screening database, medical records, and family interviews. RESULTS: Between 1998 and 2012, 3,617,919 children were screened and 2,591 had sickle cell disease (1:1,400). There were 193 deaths (7.4%): 153 with SS/Sß0-talassemia, 34 SC and 6 Sß+thalassemia; 76.7% were younger than five years; 78% died in the hospital and 21% at home or in transit. The main causes of death were infection (45%), indeterminate (28%), and acute splenic sequestration (14%). In 46% of death certificates, the term "sickle cell" was not recorded. Seven-year death rate for children born between 1998 and 2005 was 5.43% versus 5.12% for those born between 2005 and 2012 (p = 0.72). Medical care was provided to 75% of children; 24% were unassisted. Medical care was provided within 6 hours of symptom onset in only half of the interviewed cases. In 40.5% of cases, death occurred within the first 24 hours. Low family income was recorded in 90% of cases, and illiteracy in 5%. CONCLUSIONS: Although comprehensive and effective, neonatal screening for sickle cell disease was not sufficient to significantly reduce mortality in a newborn screening program. Economic and social development and increase of the knowledge on sickle cell disease among health professionals and family are needed to overcome excessive mortality. .

OBJETIVO: Caracterizar os 193 óbitos de crianças com doença falciforme diagnosticadas por programa de triagem neonatal entre 1998-2012 e comparar os primeiros com os últimos anos. MÉTODOS: Os óbitos foram identificados pela busca ativa das crianças ausentes nas consultas agendadas nos hemocentros. Dados clínicos e epidemiológicos provieram dos documentos de óbito, banco de dados da triagem neonatal, prontuários médicos e das entrevistas com parentes. RESULTADOS: Entre 1998-2012 foram triadas 3.617.919 crianças, 2.591 com doença falciforme (1:1.400). Ocorreram 193 óbitos (7,4%): 153 com SS/Sß0-talassemia, 34 SC e 6 Sß+-talassemia; 76,7% em crianças com menos de cinco anos; 78% faleceram em hospitais e 21% em domicílio ou trânsito. Causas principais do óbito: 45% infecção, 28% indeterminada, 14% sequestro esplênico agudo. Em 46% dos documentos de óbito, não houve registro do termo "falciforme". A taxa de mortalidade até sete anos das crianças nascidas entre 1998-2005 foi 5,43% versus 5,12%, entre 2005-2012 (p = 0,72). Receberam assistência médica 75% das crianças; 24% ficaram desassistidas. Pelas entrevistas, atendimento médico teria ocorrido nas primeiras seis horas do início dos sintomas em metade dos casos. O óbito ocorreu em 40,5% dos casos, nas primeiras 24 horas. Baixa renda familiar foi registrada em 90% dos casos e analfabetismo em 5%. CONCLUSÕES: A triagem para doença falciforme, mesmo abrangente e eficaz, não foi suficiente para reduzir significativamente a mortalidade no Programa de Triagem Neonatal. Necessita-se de desenvolvimento econômico e social do Estado e ampliação, pela educação continuada, do conhecimento sobre a doença falciforme entre os profissionais de saúde e parentes. .

Mortalidade de crianças com doença falciforme: um estudo de base populacional / Mortality of children with sickle cell disease: a population study

OBJETIVO: Caracterizar os óbitos das crianças com doença falciforme (DF) triadas no estado de Minas Gerais e acompanhadas na Fundação Hemominas. MÉTODOS: Coorte de crianças diagnosticadas pelo Programa de Triagem Neonatal de Minas Gerais (março/1998 - fevereiro/2005). Os óbitos foram identificados pela busca ativa das crianças ausentes nas consultas agendadas nos hemocentros. Dados clínicos e epidemiológicos foram coletados dos documentos de óbito, banco de dados da triagem neonatal, prontuários médicos e em entrevistas com as famílias. RESULTADOS: Foram triadas 1.833.030 crianças no período, sendo 1.396 com DF (1:1.300). Ocorreram 78 óbitos: 63 em crianças com genótipo SS, 12 em crianças com genótipo SC e três em crianças com genótipo S/β+ talassemia. Cinquenta e seis crianças (71,8 por cento) morreram antes dos 2 anos de idade; 59 morreram em hospitais e 18 no domicílio ou trânsito. Causas de óbito pelo atestado (n = 78): 38,5 por cento infecção; 16,6 por cento sequestro esplênico agudo; 9 por cento outras causas; 15,4 por cento sem assistência médica; e 20,5 por cento indeterminada. Segundo as entrevistas (n = 52), o sequestro esplênico foi responsável por quase 1/3 dos óbitos, contrastando com a porcentagem de apenas 14 por cento registrada nos atestados de óbito. As probabilidades de sobrevida aos 5 anos (erro padrão da média) para crianças SS, SC e Sβ+ talassemia foram: 89,4 (1,4), 97,7 (0,7) e 94,7 por cento (3,0), respectivamente (SS versus SC, p < 0,0001). CONCLUSÕES: Mesmo em um programa de triagem neonatal com rigoroso controle do tratamento, a probabilidade de óbito em crianças com genótipo SS ainda é elevada. Os óbitos com causa indeterminada indicam dificuldades no reconhecimento da DF e das suas complicações. Esforços educativos dirigidos a profissionais da saúde e familiares devem ser incrementados para diminuir a mortalidade pela DF.

OBJECTIVE: To describe the deaths of children with sickle cell disease (SCD) in Minas Gerais, Brazil, and followed up at the Fundação Hemominas. METHODS: Cohort of children diagnosed by the Neonatal Screening Program in Minas Gerais (March/1998 - February/2005). Deaths were identified by searching for children who did not attend scheduled consultations at hemocenters. Clinical and epidemiological data were abstracted from death certificates, the newborn screening database, individual medical records, and from interviews with families. RESULTS: During the period, 1,833,030 newborns were screened; 1,396 had SCD (1:1,300). There were 78 deaths: 63 with SS genotype, 12 with SC genotype, and three with Sβ+thalassemia genotype. Fifty-six children (71.8 percent) died before 2 years of age; 59 died in hospitals and 18 at home or during transportation. Causes of death according to certificates (n = 78): infections, 38.5 percent; acute splenic sequestration, 16.6 percent; other causes, 9 percent; did not receive medical care, 15.4 percent; and not identified on certificates, 20.5 percent. According to interviews (n = 52), acute splenic sequestration was responsible for one third of deaths, in contrast with 14 percent recorded on death certificates. Survival probabilities at 5y (SEM) for children with SS, SC, and Sβ+thalassemia were 89.4 (1.4), 97.7 (0.7), and 94.7 percent (3.0), respectively (SS vs. SC, p < 0.0001). CONCLUSIONS: Even with a carefully controlled newborn screening program, the probability of SS children dying was still found to be high. Causes not identified on death certificates may indicate difficulties recognizing SCD and its complications. Educational campaigns directed at health professionals and SCD patients' families should be boosted in order to decrease SCD mortality.

Maternal mortality in Bahrain 1987-2004: an audit of causes of avoidable death

The aim of this report was to establish the national maternal mortality rate in Bahrain over the period 1987-2004, to identify preventable factors in maternal deaths and to make recommendations for safe motherhood. There were 60 maternal deaths out of 243 232 deliveries giving an average maternal mortality rate of 24.7 per 100 000 total births. The main causes of death were sickle-cell disease [25.0%], hypertension [18.3%], embolism [13.3%], haemorrhage [13.3%], heart disease [11.7%], infection [8.3%] and other [10.0%]. In an audit of care, 17 [28.3%] out of 60 deaths were judged to be avoidable, nearly half of which were due to a shortage of intensive care beds. We recommend that a confidential enquiry of maternal deaths be conducted at the national level every 3 to 5 years

Estudo da mortalidade por anemia falciforme / Study ofanemia sickle cell mortality

Organiza dados sobre mortalidade por anemia falciforme, trabalhando com a totalidade dos óbitos registrados pelo Sistema de Informaçöes de Mortalidade, no período de 1979 a 1995. Apresenta descriçäo da doença, estima prevalência e incidência e conclui com a mensuraçäo do sub-registro dos óbitos alternativos de soluçäo dos problemas levantados