Prognostic Factors, Survival Analyses and the Risk of Second Primary Cancer: A Population-Based Study on Burkitt Lymphoma/Leukemia.

Burkitt lymphoma/leukemia (BL/L) is an aggressive oncohematological disease. This study evaluated the population-based prognosis and survival on BL/L as well as if BL/L behaved as a risk factor for the development of second primary cancers (SPCs) and if other first tumors behaved as risk factors for the occurrence of BL/L as an SPC. A retrospective cohort using the Surveillance, Epidemiology and End Results (SEER) Program (2008-2016) was performed. Kaplan-Meier, time-dependent covariate Cox regression and Poisson regression models were conducted. Overall, 3094 patients were included (median, 45 years; IQR, 22-62). The estimated overall survival was 65.4 months (95% CI, 63.6-67.3). Significantly more deaths occurred for older patients, black race, disease at an advanced stage, patients without chemotherapy/surgery and patients who underwent radiotherapy. Hodgkin lymphomas (nodal) (RR, 7.6 (3.9-15.0; p < 0.001)), Kaposi sarcomas (34.0 (16.8-68.9; p < 0.001)), liver tumors (3.4 (1.2-9.3; p = 0.020)) and trachea, mediastinum and other respiratory cancers (15.8 (2.2-113.9; p = 0.006)) behaved as risk factors for the occurrence of BL/L as an SPC. BL/L was a risk factor for the occurrence of SPCs as acute myeloid leukemias (4.6 (2.1-10.4; p < 0.001)), Hodgkin lymphomas (extranodal) (74.3 (10.0-549.8; p < 0.001)) and Kaposi sarcomas (35.1 (12.1-101.4; p < 0.001)). These results may assist the development of diagnostic and clinical recommendations for BL/L.

Second Primary Malignancy after Acute Promyelocytic Leukemia: A Population-Based Study.

Acute promyelocytic leukemia (APL), is now highly curable with treatment approaches that include all-trans retinoic acid (ATRA). The high incidence of APL in the Hispanics suggests an association with genetic variants in this population. Information on second primary malignancies (SPMs) in patients with APL is limited. The Surveillance, Epidemiology, and End Results (SEER) database was used to interrogate whether the rate of SPMs in patients with APL was associated with ethnicity and/or ATRA treatment. Between 2000 and 2016, 116 cases of SPM were diagnosed among 4019 patients with APL. The mean age at diagnosis of primary APL was 53.9 years (±15.7 years), and the mean age at diagnosis of SPMs was 59.0 years (±14.5 years). Comparisons with 3774 APL survivors who did not develop SPMs revealed that age ≥40 years at diagnosis of APL (p < 0.001) and non-Hispanic white ethnicity (p = 0.025) were associated with SPMs in APL survivors. Salivary gland, liver, and soft tissue malignancies were significantly more common in patients with primary APL than in individuals with non-APL malignancies. A risk analysis comparing patients who had APL with patients who had non-APL AML suggests that SPMs after APL is associated with ATRA treatment. Therefore, patient follow-up after APL should focus on early diagnosis of SPMs.

From adrenarche to aging of adrenal zona reticularis: precocious female adrenopause onset.

OBJECTIVE: Adaptive changes in DHEA and sulfated-DHEA (DHEAS) production from adrenal zona reticularis (ZR) have been observed in normal and pathological conditions. Here we used three different cohorts to assess timing differences in DHEAS blood level changes and characterize the relationship between early blood DHEAS reduction and cell number changes in women ZR. MATERIALS AND METHODS: DHEAS plasma samples (n = 463) were analyzed in 166 healthy prepubertal girls before pubarche (<9 years) and 324 serum samples from 268 adult females (31.9-83.8 years) without conditions affecting steroidogenesis. Guided by DHEAS blood levels reduction rate, we selected the age range for ZR cell counting using DHEA/DHEAS and phosphatase and tensin homolog (PTEN), tumor suppressor and cell stress marker, immunostaining, and hematoxylin stained nuclei of 14 post-mortem adrenal glands. RESULTS: We confirmed that overweight girls exhibited higher and earlier DHEAS levels and no difference was found compared with the average European and South American girls with a similar body mass index (BMI). Adrenopause onset threshold (AOT) defined as DHEAS blood levels <2040 nmol/L was identified in >35% of the females >40 years old and associated with significantly reduced ZR cell number (based on PTEN and hematoxylin signals). ZR cell loss may in part account for lower DHEA/DHEAS expression, but most cells remain alive with lower DHEA/DHEAS biosynthesis. CONCLUSION: The timely relation between significant reduction of blood DHEAS levels and decreased ZR cell number at the beginning of the 40s suggests that adrenopause is an additional burden for a significant number of middle-aged women, and may become an emergent problem associated with further sex steroids reduction during the menopausal transition.

Allogeneic Hematopoietic Stem Cell Transplantation for Children and Adolescents with Acute Myeloid Leukemia in Brazil: A Multicentric Retrospective Study.

The survival rates of children with high-risk acute myeloid leukemia (AML) treated with hematopoietic stem cell transplant (HSCT) range from 60% to 70% in high-income countries. The corresponding rate for Brazilian children with AML who undergo HSCT is unknown. We conducted a retrospective analysis of 114 children with AML who underwent HSCT between 2008 and 2012 at institutions participating in the Brazilian Pediatric Bone Marrow Transplant Working Group. At transplant, 38% of the children were in first complete remission (CR1), 37% were in CR2, and 25% were in CR3+ or had persistent disease. The donors included 49 matched-related, 59 matched-unrelated, and six haploidentical donors. The most frequent source of cells was bone marrow (69%), followed by the umbilical cord (19%) and peripheral blood (12%). The 4-year overall survival was 47% (95% confidence interval [CI] 30%-57%), and the 4-year progression-free survival was 40% (95% CI 30%-49%). Relapse occurred in 49 patients, at a median of 122 days after HSCT. There were 65 deaths: 40 related to AML, 19 to infection, and six to graft versus host disease. In conclusion, our study suggests that HSCT outcomes for children with AML in CR1 or CR2 are acceptable and that this should be considered in the overall treatment planning for children with AML in Brazil. Therapeutic standardization through the adoption of multicentric protocols and appropriate supportive care treatment will have a significant impact on the results of HSCT for AML in Brazil and possibly in other countries with limited resources.

Local references for ultrasound-estimated fetal weight based on 2, 211 singleton pregnancies in the City of Curitiba, south of Brazil / Referências locais para o peso fetal estimado por ultrassom baseado em 2. 211 gestações únicas na cidade de Curitiba, Sul do Brasil

Abstract Objective To develop reference curves of estimated fetal weight for a local population in Curitiba, South of Brazil, and compare them with the curves established for other populations. Methods An observational, cross-sectional, retrospective study was conducted. A reference model for estimated fetal weight was developed using a local sample of 2,211 singleton pregnancies with low risk of growth disorders and well-defined gestational age. This model was compared graphically with the Hadlock and Intergrowth 21st curves. Results Reference curves for estimated fetal weight were developed for a local population. The coefficient of determination was R2 = 99.11%, indicating that 99.11% of the fetal weight variations were explained by the model. Compared with Hadlock curves, the 50th, 90th, and 97th percentiles in this model were lower, whereas the 10th percentile nearly overlapped, and the 3rd percentile was slightly higher in the proposed model. The percentiles were higher in the proposed model compared with the Intergrowth 21st curves, particularly for the 3rd, 10th, and 50th percentiles. Conclusion We provide a local reference curve for estimated fetal weight. The proposed model was different from other models, and these differences might be due to the use of different populations for model construction.

Resumo Objetivo Desenvolver curvas de referência para o peso fetal estimado em uma população de Curitiba, Sul do Brasil, e compará-las com curvas estabelecidas para outras populações. Métodos Foi realizado um estudo observacional, transversal e retrospectivo. Um modelo de referência para o peso fetal estimado foi desenvolvido usando uma amostra local de 2.211 gestações únicas de baixo risco de distúrbios do crescimento e idade gestacional bem definida. Este modelo foi comparado graficamente com as curvas de Hadlock e Intergrowth 21st. Resultados As curvas de referência para o peso fetal estimado foram desenvolvidas para uma população local. O coeficiente de determinação foi de R2 = 99,11%, indicando que 99,11% das variações do peso fetal foram explicadas pelo modelo. Em comparação com as curvas de Hadlock, os percentis 50, 90, e 97 neste modelo foram inferiores, enquanto o percentil 10 quase se sobrepôs, e o percentil 3 foi ligeiramente superior no modelo proposto. Os percentis foram maiores no modelo proposto em comparação com as curvas do Intergrowth 21st, particularmente para os percentis 3, 10, e 50. Conclusão Fornecemos uma curva de referência local para o peso fetal estimado. O modelo proposto foi diferente de outros modelos, e essas diferenças podem ser devido ao uso de diferentes populações para a construção do modelo.

The Impact of Flt3 Gene Mutations in Acute Promyelocytic Leukemia: A Meta-Analysis.

The association of FLT3 mutations with white blood cell (WBC) counts at diagnosis and early death was studied in patients with acute promyelocytic leukemia (APL). Publications indexed in databases of biomedical literature were analyzed. Potential publication bias was evaluated by analyzing the standard error in funnel plots using the estimated relative risk (RR). Mixed-effect models were used to obtain the consolidated RR. All analyses were conducted using the R statistical software package. We used 24 publications in the final meta-analysis. Of 1005 males and 1376 females included in these 24 publications, 645 had FLT3-ITD (internal tandem duplication) mutations. Information on FLT3-D835 mutations was available in 10 publications for 175 patients. Concurrent occurrence of the two mutations was rare. WBC count at diagnosis was ≥10 × 109/L in 351 patients. For patients with the FLT3-ITD mutation, RR was 0.59 for overall survival (OS) and 1.62 for death during induction. For those with FLT3-D835 mutations, the RR was 0.50 for OS and 1.77 for death during induction. RR for WBC count ≥10 × 109/L was 3.29 and 1.48 for patients with FLT3-ITD and FLT3-D835, respectively. APL patients with FLT3-ITD or FLT3-D835 are more likely to present with elevated WBC counts and poorer prognosis than those without these mutations.

Custo da Doença em Pacientes com Carcinoma Mamário Tratados com Tamoxifeno / Cost of the Disease in Patients with Breast Cancer Treated with Tamoxifen / Costo de la Enfermedad en Pacientes com Carcinoma Mamário Tratados com Tamoxifeno

Introdução: A estimativa do Instituto Nacional de Câncer José Alencar Gomes da Silva para o Brasil, para cada ano do biênio 2018-2019, foi de 59.700 novos casos de câncer de mama, com um risco estimado de 56,33 casos a cada 100 mil mulheres. Em 2014, os gastos públicos com atenção oncológica foram de aproximadamente R$ 2,5 bilhões. Objetivo: Avaliar o impacto dos custos diretos médicos em pacientes com carcinoma mamário tratados com tamoxifeno pelo Sistema Único de Saúde. Método: Estudo exploratório de custo da doença, quantitativo, retrospectivo, com caráter de prevalência e de abordagem bottom-up. A coleta dos dados foi realizada no ambulatório de Oncologia do Hospital São Vicente em Curitiba, Paraná. Resultados: A média do custo do tratamento dos pacientes foi R$ 14.497,70 em tratamento neoadjuvante ou adjuvante e de R$ 9.108,60 em tratamento paliativo. Em relação a essas variáveis, o custo do tamoxifeno foi o que mais impactou em relação ao custo total do tratamento, representando mais de 80% deste valor. A média do custo anual gasto com tamoxifeno por paciente foi de R$ 1.947,60. Conclusão: O custo médio do tratamento demonstrou ser alto em relação à média salarial dos brasileiros de R$ 2.110.00 (IBGE-2017). Os custos levantados neste estudo podem auxiliar os gestores de saúde pública em estratégias para racionalização dos gastos, otimização do capital e manutenção do atendimento à população.

Introduction: The estimate of the National Cancer Institute José Alencar Gomes da Silva, for each year of the 2018-2019 biennium in Brazil, was 59,700 new cases of breast cancer, with an estimated risk of 56.33 cases per 100,000 women. In 2014, public expenditures on cancer care were approximately R$ 2.5 billion. Objective: To evaluate the impact of direct medical costs on breast cancer patients treated with tamoxifen using the Unified Health System. Method: Prospective, quantitative, retrospective, cost-of-disease study with prevalence and bottom-up approach. Data collection was performed at the Oncology Outpatient Clinic of the Hospital São Vicente in Curitiba, Paraná. Results: The mean cost of the treatment was R$ 14,497.70 for neoadjuvant or adjuvant treatment and R$ 9,108.60 for palliative treatment. In relation to these variables, the cost of tamoxifen was the one that most impacted, in relation to the total cost of the treatment, representing more than 80% of this value. The mean annual cost of tamoxifen per patient was R$ 1,947.60. Conclusion: The average cost of treatment was high in relation to the Brazilian average salary of R$ 2,110.00 (IBGE-2017). The costs investigated in this study can help public health managers in strategies to rationalize expenditures, optimize capital and maintain patient care.

Introducción: La estimación del Instituto Nacional del Cáncer José Alencar Gomes da Silva para Brasil, para cada año del bienio 2018-2019, fue de 59,700 casos nuevos de cáncer de mama, con un riesgo estimado de 56.33 casos por 100,000 mujeres. En 2014, los gastos públicos con atención oncológica fueron de aproximadamente R $ 2,5 mil millones. Objetivo: Evaluar el impacto de los costos directos médicos en pacientes con carcinoma mamario tratados con tamoxifeno por el Sistema Único de Salud. Método: Estudio exploratorio de costo de la enfermedad, cuantitativo, retrospectivo, con carácter de prevalencia y de enfoque bottom-up. La recolección de los datos fue realizada en el Ambulatorio de Oncología del Hospital São Vicente en Curitiba, Paraná. Resultados: El promedio del costo del tratamiento de los pacientes fue R$ 14.497,70 en tratamiento neoadyuvante o adyuvante y de R$ 9.108,60 en tratamiento paliativo. En relación a estas variables el costo del tamoxifeno fue el que más impactó en relación al costo total del tratamiento, representando más del 80% de este valor. El promedio del costo anual gastado con tamoxifeno por paciente fue de R$ 1.947,60. Conclusión:El costo promedio del tratamiento demostró ser alto en relación al promedio salarial de los brasileños de R $ 2.110.00 (IBGE-2017). Los costos levantados en este estudio pueden auxiliar a los gestores de salud pública en estrategias para racionalización de los gastos, optimización del capital y mantenimiento de la atención a la población.

Comparative efficacy and safety of tyrosine kinase inhibitors for chronic myeloid leukaemia: A systematic review and network meta-analysis.

BACKGROUND: The pharmacotherapy of chronic myeloid leukaemia (CML) is mainly based on tyrosine kinase inhibitors (TKIs). The aim of this study was to compare the efficacy and safety of all TKIs in CML patients. METHODS: We conducted a systematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs), including imatinib, nilotinib, dasatinib, bosutinib, radotinib and ponatinib. Searches were performed in PubMed, Scopus, Web of Science and SciELo (March 2018). The NMAs were built for six outcomes at 12 months: complete cytogenetic response (CCyR), major cytogenetic response (MCyR), deep molecular response, major molecular response (MMR), complete haematologic response and incidence of serious adverse events. We conducted rank order and surface under the cumulative ranking curve (SUCRA) analyses. RESULTS: Thirteen RCTs were included (n = 5079 patients). Statistical differences were observed for some comparisons in all outcomes. Imatinib 400 mg was considered the safest drug (SUCRA values of 10.3%) but presented low efficacy. Overall, nilotinib 600 mg was superior to the other TKI in efficacy (SUCRA values of 61.1% for CCyR, 81.0% for MMR, 90.0% for MCyR); however, no data on its safety profile at 12 months were reported. INTERPRETATION: Our results suggest that nilotinib should be upgraded to first-line therapy for CML, although further cost-effectiveness analyses, including the new TKI (i.e., ponatinib, radotinib), are needed.

Safety of Biologics Approved for the Treatment of Rheumatoid Arthritis and Other Autoimmune Diseases: A Disproportionality Analysis from the FDA Adverse Event Reporting System (FAERS).

INTRODUCTION: The molecular and pharmacological complexity of biologic disease-modifying antirheumatic drugs used for the management of rheumatoid arthritis (RA) favors the occurrence of adverse drug reactions (ADRs), which should be constantly monitored in post-marketing safety studies. OBJECTIVE: The aim of this study was to identify signals of disproportionate reporting (SDR) of clinical relevance related to the use of biologic drugs approved for RA and other autoimmune diseases. METHODS: All suspected ADRs registered in the FDA Adverse Event Reporting System between January 2003 and June 2016 were collected. The reporting odds ratio was used as a measure of disproportionality to identify possible SDRs related to biologics. Those involving important medical events and designated medical events (DME) were prioritized. RESULTS: In total, 2602 SDRs were prioritized. The most commonly reported were 'Infections and infestations' (32.2%) and 'Neoplasms benign, malignant, and unspecified' (20.4%), and were mainly related to use of infliximab (25.3%, p < 0.001, and 28.8%, p = 0.002, respectively). Sixty-three signals involving DMEs were identified, most of which were related to rituximab (n = 27), and were mainly due to 'blood disorders'. Amongst the DMEs detected for more than one biologic, 'intestinal perforation' and 'pulmonary fibrosis' were related to most of them. CONCLUSIONS: The results of this study highlight possible safety issues associated with biologics, whose relationship should be more thoroughly investigated. Our results contribute to future research on the identification of clinically relevant risks associated with these drugs, and may help contribute to their rational and safe use.

Suporte Social e HIV: Relações Entre Características Clínicas, Sociodemográficas e Adesão ao Tratamento / Social support and HIV: Relationship between Clinical and Sociodemographic Characteristics and Treatment Adherence

RESUMO Este estudo investigou a relação entre suporte social, características sociodemográficas, clínicas e adesão ao Tratamento Antirretroviral (TARV) utilizando o questionário Social Support Inventory for People who are HIV Positive or Have AIDS. Para isso, foram avaliados 119 usuários HIV-positivos - dos quais 53,8% eram homens. Em relação à disponibilidade e satisfação, os valores médios foram de 3,37 (DP=1,00) para o suporte instrumental e 3,48 (DP=1,06) para o suporte emocional. Observaram-se diferenças significativas na disponibilidade e satisfação do suporte social com variáveis sociodemográficas e clínicas. Verificou-se que, quanto maior a disponibilidade e a satisfação com o suporte social, maior o OR para a adesão ao tratamento. O desenvolvimento de estratégias de apoio social pode contribuir positivamente para o controle da doença e melhor qualidade de vida dos usuários.

ABSTRACT This study aimed to assess the relationship between social support, sociodemographic and clinical characteristics and treatment adherence using the Social Support Inventory for People who are HIV Positive or Have AIDS. Thus, it were evaluated 119 HIV-positive patients, of which 53.8% were men. Regarding the availability and satisfaction mean values were 3.37 (DP=1.00) for the instrumental support and 3.48 (DP=1.06) for emotional support. Significant differences were found in the availability and satisfaction of social support with clinical and sociodemographic variables. It was found that the greater the availability and satisfaction with social support, the greater the OR for adherence to treatment. The development of social support strategies can positively contribute to disease control and better quality of life of HIV-positive patients.

The frequency of ßS-globin haplotypes in the state of Paraná, Brazil, and clinical manifestations of sickle cell anemia / Frequência dos haplótipos da globina ßS no estado do Paraná, Brasil, e manifestações clínicas em pacientes com anemia falciforme

ABSTRACT Introduction: Haplotypes in the β S-globin cluster are named according to their geographical origin as Central African Republic (CAR), Benin (BEN), Senegal (SEN), Cameroon (CAM) and Arab-Indian. They are considered to have influence on the diversity of clinical manifestations in sickle cell anemia (HbSS). Objective: To identify β S haplotypes and genotypes, their frequencies and their probable association with clinical presentation in patients with sickle cell anemia in the state of Paraná. Method: Longitudinal and descriptive study for the definition of haplotypes, and associative study for analysis of their influence on clinical severity. By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), polymorphic regions of 100 HbSS patients were identified. The association of haplotypes with clinical manifestations was analyzed in a subset of 52 pediatric patients. Results: In the state of Paraná, haplotype frequencies were: CAR: 76% BEN: 17.5% SEN: 0.5%, CAM: 0.5% and Atypical (Atp): 5.5%. Genotype frequencies were: CAR/CAR: 62%; CAR/BEN: 20%; CAR/Atp: 6%; CAR/ SEN: 1%; CAR/CAM: 1%; BEN/BEN: 6%; BEN/Atp: 3%, Atp/Atp: 1%. The average percentage of fetal hemoglobin (HbF) in CAR/CAR and CAR/BEN patients was higher than in other studies. Clinical manifestations were not influenced by β S haplotypes. Dactylitis and splenic sequestration occurred more frequently in children below 3 years of age. Conclusion: In this study, no association was found between haplotypes and clinical manifestations, probably given the almost absolute predominance of CAR and BEN haplotypes. However, this fact alerts to the possible influence of other polymorphisms and miscegenation in the Brazilian population.

RESUMO Introdução: A variabilidade nas manifestações clínicas da anemia falciforme (HbSS) pode ser influenciada pelos haplótipos no grupamento da globina β S, nomeados de acordo com a origem geográfica: República Centro-Africana (CAR), Benin (BEN), Senegal (SEN) Camarões (CAM) e árabe-indiano. Objetivo: Identificar haplótipos e genótipos da globina β S, suas frequências e as possíveis associações com manifestações clínicas em pacientes com anemia falciforme no estado do Paraná. Método: Estudo longitudinal e descritivo na distribuição dos haplótipos e associativo na análise da influência destes sobre as manifestações clínicas. Identificaram-se as regiões polimórficas da globina β S de 100 pacientes HbSS pela técnica da polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A associação dos haplótipos com as manifestações clínicas foi analisada em um subgrupo de 52 pacientes pediátricos. Resultados: As frequências dos haplótipos foram CAR: 76%; BEN: 17,5%; SEN: 0,5%; CAM: 0,5% e Atípico (Atp): 5,5%. Os genótipos foram CAR/CAR: 62%; CAR/BEN: 20%; CAR/Atp: 6%; CAR/SEN: 1%; CAR/CAM: 1%; BEN/BEN: 6%; BEN/Atp: 3% e Atp/Atp: 1%. A porcentagem média de hemoglobina fetal (HbF) dos pacientes CAR/CAR e CAR/BEN foi maior que em outros estudos. Os haplótipos da globina β S não tiveram influência nas manifestações clínicas. A dactilite e o sequestro esplênico ocorreram com mais frequência nas crianças abaixo de 3 anos de idade. Conclusão: Na população estudada, não foi possível identificar associação dos haplótipos com as manifestações clínicas. Esse fato pode ser decorrente do predomínio quase absoluto dos haplótipos CAR e BEN, de diferentes polimorfismos e da miscigenação da população brasileira.

Quality of life perception of type 1 diabetic patients treated with insulin analogs and receiving medication review with follow-up in a public health care service from Ponta Grossa-PR, Brazil

ABSTRACT Glycemic control in patients with diabetes mellitus type 1 (DM1) reduces the risk of complications but requires a rigorous health care routine. Thus, diabetes education is central to increasing treatment compliance and self-care practices. This study aimed to evaluate the quality of life (QoL) and glycemic control of DM1 patients being treated with insulin analogs and receiving medication review with follow-up. This was a transversal study that included 110 patients registered at the 3rd Health Regional of Ponta Grossa-PR, aged ≥ 18 years, and receiving pharmaceutical care for at least 1 year. The Diabetes Quality of Life Measure (DQOL)-Brazil was used to evaluate QoL. The data were statistically analyzed using SPSS version 17.0 with 95% confidence levels. Of the 110 patients, 58.2% were women. The average age was 33.7 years (±10.5), and the average glycated hemoglobin (HbA1c) value was 8% (±1.4). The mean total DQOL-Brazil score was 2.11 (95% confidence interval, 2.02 - 2.21). All DQOL-Brazil scores were lower in patients with HbA1c ≤ 8%, indicating a better QoL. Good glycemic control, thus, appears to have a positive influence on the QoL, and pharmaceutical interventions are able to contribute to the achievement of therapeutic targets.

Fatores relacionados ao óbito pela Influenza Pandêmica A (H1N1) 2009 em pacientes tratados com Oseltamivir / Factors related to death by the Pandemic Influenza A (H1N1) 2009 in patients treated with Oseltamivir / Factores relacionados con la muerte por la Influenza Pandémica A (H1N1) 2009 en pacientes tratados con Oseltamivir

Este estudo pretende identificar os fatores relacionados ao óbito na Influenza Pandêmica A(H1N1) 2009 em pacientes tratados com Oseltamivir. Trata-se de um estudo observacional e retrospectivo, realizado com dados de pacientes que apresentaram diagnóstico laboratorial da doença. Os dados foram coletados dos formulários de notificação da doença, pertencentes a uma base de dados do Ministério da Saúde. As análises estatísticas foram realizadas pelos testes de qui-quadrado, t de Student e por regressão logística, considerando significativos os valores de p<0,05. A maior ocorrência de óbitos foi observada nos pacientes com idade entre 20 e 59 anos, de baixa escolaridade, com a presença de comorbidades, não vacinados, tratados tardiamente e que apresentavam sintomas mais severos da infecção. A identificação de fatores de risco para o óbito reforça a necessidade de prevenção e assistência precoce, principalmente na presença de fatores que aumentam a gravidade clínica da doença.

This study aimed to identify factors related to death in Pandemic Influenza A(H1N1)2009 in patients treated with Oseltamivir. It is an observational and retrospective study, carried out with data of patients who had presented laboratorial diagnosis of the illness. Data were collected from the notification forms of the disease, belonging to a database of the Ministry of Health. Statistical analysis was performed by chi-square, Student t test and logistic regression, considering significant p values <0,05. The highest mortality was observed in patients aged between 20 and 59 years, low schooling, with the presence of comorbidities, not vaccinated, treated late and had more severe symptoms of infection. The identification of risk factors for death reinforces the need for prevention and early care, especially in the presence of factors that increase the clinical severity of disease.

Este estudio se propone identificar los factores relacionados con la muerte dela influenza pandémica A(H1N1)2009 en pacientes tratados con Oseltamivir. Es un estudio observacional y retrospectivo, realizado con datos de los pacientes que presentan diagnóstico de laboratorio. Los datos fueron recogidos de los formularios de notificación de la enfermedad, pertenecientes a una base de datos del Ministerio de Salud. Los análisis estadísticos se realizó mediante las pruebas del qui-cuadrado, t de Student y regresión logística, en vista de significativo los valores de p<0,05. La mayor mortalidad se observó en pacientes con edades entre 20 y 59 años, baja escolaridad, con la presencia de comorbilidades, no vacunados, tratados tardíamente y que habían síntomas más graves de la infección. La identificación de factores de riesgo para la muerte refuerza la necesidad de la prevención y atención temprana, especialmente en la presencia de factores que aumentan la gravedad de la enfermedad.

Economic evaluation of treatments for chronic hepatitis B

The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.

The characteristics, clinical manifestations and outcomes of pandemic influenza A (H1N1) 2009 in the elderly

Introduction The objetctive of this study was to evaluate the 2009 Pandemic Influenza A (H1N1) in the elderly and identify the clinical characteristics, mortality and prognostic factors of the infection in these patients. Methods This was an observational, retrospective study. Data were collected from the National Notifiable Diseases (SINAN), from the Brazilian Ministry of Health. Only patients 60 years old or more that had laboratory confirmed infections were included. The socio-demographic and clinical variables and outcomes were evaluated to compare mortality rates in the presence or absence of these factors. Results We included 93 patients in the study, 16.1% of whom died. The symptoms of cough and dyspnea, the use of the antiviral oseltamivir, influenza vaccine and comorbidities influenced the outcomes of cure or death. Chest radiography can aid in diagnosis. Conclusions Although relatively few elderly people were infected, this population presented high lethality that can be justified by the sum of clinical, physical and immunological factors in this population. Treatment with oseltamivir and vaccination against seasonal influenza have significantly reduced rates of hospitalization and mortality. .

Manifestações clínicas, desfechos e fatores prognósticos da influenza pandêmica A (H1N1) de 2009 em crianças / Clinical manifestations, outcomes and prognostic factors of the 2009 pandemic influenza A (H1N1) in children / Manifestaciones clínicas, desenlaces y factores pronósticos de la influenza pandémica A (H1N1) 2009 en niños

OBJETIVO: Descrever as características clínicas e a letalidade, além de analisar os fatores prognósticos da infecção pela influenza pandêmica A (H1N1), em crianças do estado do Paraná. MÉTODOS: Estudo observacional e retrospectivo. Os dados foram coletados a partir do Sistema Nacional de Agravos de Notificação (Sinan), do Ministério da Saúde, entre março e dezembro de 2010. Foram incluídas as crianças com idade entre zero e 12 anos, com confirmação laboratorial da infecção. As variáveis referentes às características demográficas e clínicas e aos desfechos foram avaliadas estatisticamente a fim de comparar as taxas de letalidade na presença e na ausência desses fatores. Os fatores prognósticos foram identificados por regressão logística. Consideraram-se como significativos os valores de p<0,05. RESULTADOS: Foram incluídas 1.307 crianças, das quais 19 foram a óbito. Os fatores de risco para o óbito foram cardiopatias (OR 7,1; IC95% 1,5 - 32,7), imunodepressão (OR 14,9; IC95% 3,9 - 56,2), dispneia (OR 9,5; IC95% 2,8 - 32,9), pneumonia (OR 23,8; IC95% 2,4 - 239,8), presença de sibilos (OR 11,9; IC95% 1,4 - 103,7) e tempo para o início do tratamento a partir do início dos sintomas (OR 1,3; IC95% 1,2 - 1,5). O tratamento precoce com o antiviral oseltamivir foi um fator de proteção ao óbito (OR 0,012; IC95% 0,003 - 0,05). CONCLUSÕES: Os fatores de risco subjacentes apresentaram papel fundamental na determinação dos desfechos. O diagnóstico e o tratamento precoce foram importantes para a diminuição dos óbitos pela influenza A (H1N1) 2009 em crianças.

OBJECTIVE: To analyze the pandemic influenza A (H1N1) 2009 in children of the state of Paraná, Southern Brazil, in order to identify clinical features, lethality, and prognostic factors for the infection. METHODS: This was a retrospective observational study. Data were collected from the National Notifiable Disease System (Sinan) from the Brazilian Ministry of Health, from March to December, 2010. Children aged between zero and 12 years-old, with laboratorial confirmation of the infection, were included. Variables related to demographic and clinical characteristics and outcomes were evaluated statistically in order to compare the lethality rates in the presence and absence of these factors. The prognostic factors were identified by logistic regression, being significant p<0.05. RESULTS: 1,307 children were included and 19 of them died. Risk factors for death were heart diseases (OR 7.1; 95%CI 1.5 - 32.7), immunosuppression (OR 14.9; 95%CI 3.9 - 56.2), dyspnea (OR 9.5; 95%CI 2.8 - 32.9), pneumonia (OR 23.8; 95%CI 2.4 - 239.8), presence of wheezing (OR 11,9; 95%CI 1.4 - 103.7), and time to start treatment since the onset of symptoms (OR 1.3; 95%CI 1.2 - 1.5). Early treatment with the antiviral drug oseltamivir was a protective factor for death (OR 0.012; 95%CI 0.003 - 0.05). CONCLUSIONS: Underlying risk factors had a major role in determining outcomes. Early diagnosis and treatment were important for the reduction of deaths from influenza A (H1N1) 2009 in children.

OBJETIVO: Describir las características clínicas y la letalidad, además de analizar los factores pronósticos de la infección por la influenza pandémica A (H1N1) en niños de la provincia de Paraná (Brasil). MÉTODOS: Se trató de un estudio observacional y retrospectivo. Los datos fueron recogidos a partir del Sistema Nacional de Agravos de Notificação (Sinan), del Ministerio de Salud, entre marzo y diciembre de 2010. Se incluyeron a los niños con edad entre cero y 12 años, con confirmación laboratorial de la infección. Las variables referentes a las características demográficas y clínicas y a los desenlaces fueron evaluadas estadísticamente, a fin de comparar las tasas de letalidad en la presencia y ausencia de esos factores. Los factores pronósticos fueron identificados por regresión logística. Se consideraron como significativos los valores de p<0,05. RESULTADOS: Se incluyeron a 1.307 niños, de los que 19 fallecieron. Los factores de riesgo para óbito fueron cardiopatías (OR 7,1; IC95% 1,5-32,7), inmunodepresión (OR 14,9; IC95% 3,9-56,2), disnea (OR 9,5; IC95% 2,8-32,9), neumonía (OR 23,8; IC95% 2,4-239,8), presencia de silbidos (OR 11,9; IC95% 1,4-103,7) y tiempo para el inicio del tratamiento a partir del inicio de los síntomas (OR 1,3; IC95% 1,2-1,5). El tratamiento temprano con el antiviral oseltamavir fue un factor de protección al óbito (OR 0,012; IC95% 0,003-0,05). CONCLUSIONES: La tasa de letalidad observada en niños fue menor que la encontrada en el grupo que contrajo la enfermedad. Los factores de riesgo subyacentes presentaron un rol fundamental en la determinación de los desenlaces. El diagnóstico y el tratamiento tempranos fueron importantes para la reducción de los óbitos por influenza A (H1N1) 2009 en niños.

Manifestações clínicas da influenza pandêmica A (H1N1) 2009 / Clinical features of pandemic influenza A (H1N1) 2009

Objetivos: Realizar uma definição mais precisa do quadro clínico da infecção pela influenza pandêmica A (H1N1) 2009, para auxiliar na realização do diagnóstico clínico-epidemiológico da doença. Métodos: Os sinais e sintomas relatados por 4.740 pacientes que apresentaram a infecção, confirmada pelo diagnóstico laboratorial (RT-PCR), foram avaliados pelos métodos estatísticos do quiquadrado, Kruskal-Wallis e teste-z, considerando significativos os valores de p < 0,05. Resultados: Os sintomas mais frequentes foram febre, tosse, mialgia, coriza, calafrio e dor de garganta, tendo sido relatados por mais de 50% dos pacientes avaliados. Os sintomas indicativos de maior gravidade clínica foram dispneia, dor torácica, hemoptise e pneumonia. Enquanto na influenza sazonal o sintoma diarreia é mais frequente em crianças, na infecção pela influenza pandêmica A (H1N1) 2009 este sintoma foi mais comum em adultos com idade entre 30 e 49 anos. Conclusões: A sintomatologia pode ser diferenciada em relação à faixa etária e ao gênero do paciente, auxiliando, assim, no diagnóstico clínico da doença. A realização da radiografia do tórax pode contribuir para a decisão do tratamento precoce dos casos graves.

Pandemic influenza A (H1N1) 2009: risk factors for hospitalization.

OBJECTIVE: To evaluate pandemic influenza A (H1N1) 2009 in hospitalized patients in order to identify risk factors for hospitalization and, consequently, for the worsening of the disease. METHODS: This retrospective observational study was conducted between March and December of 2010. The data were collected from the Brazilian Ministry of Health National Case Registry Database. We included only patients (inpatients and outpatients) in whom H1N1 infection was confirmed (via laboratory testing) during the study period. The variables regarding demographic and clinical characteristics were statistically evaluated in order to compare the hospitalization rates in the presence or absence of these factors. Risk factors were identified by logistic regression analysis. RESULTS: We included 4,740 patients with laboratory confirmation of H1N1 infection. Of these, 1,911 individuals were hospitalized, and 258 (13.5%) died. The risk factors for hospitalization were age (20-29 years), African or Indigenous ethnicity, presence of specific comorbidities (heart disease, lung disease, kidney disease, hemoglobinopathy, immunosuppression, diabetes, obesity, puerperium, and smoking), a high number of comorbidities, and specific symptoms (dyspnea, diarrhea, vomiting, chest pain, hemoptysis, pneumonia, and wheezing). Higher levels of education and early use of oseltamivir were found to be protective factors. Hospitalization contributed to an increase in survival. CONCLUSIONS: Knowledge of the epidemiological characteristics that can be associated with hospitalization, disease severity, and mortality can be helpful in the adoption of preventive measures, as well as in the early diagnosis and treatment of disease, which might contribute to the reduction in the numbers of hospitalizations and deaths.

Influenza pandêmica A (H1N1) 2009: fatores de risco para o internamento / Pandemic influenza A (H1N1) 2009: risk factors for hospitalization

OBJETIVO: Avaliar os aspectos da influenza pandêmica A (H1N1) 2009 em pacientes hospitalizados a fim de identificar os fatores de risco para o internamento e, consequentemente, para o agravamento da doença. MÉTODOS: Estudo observacional e retrospectivo realizado entre março e dezembro de 2010. Os dados foram coletados a partir do Sistema Nacional de Agravos de Notificação do Ministério da Saúde. Foram incluídos somente os pacientes hospitalizados e não hospitalizados com confirmação laboratorial da infecção durante o período de estudo. As variáveis referentes às características demográficas e clínicas foram avaliadas estatisticamente a fim de comparar as taxas de internamento na presença ou na ausência desses fatores. Os fatores de risco foram identificados por regressão logística. RESULTADOS: Foram incluídos no estudo 4.740 pacientes com confirmação laboratorial da infecção. Desses, 1.911 foram internados, e 258 (13,5 por cento) foram a óbito. Os fatores de risco para o internamento foram idade (faixa etária de 20 a 29 anos), etnia negra ou indígena, presença de algumas comorbidades (cardiopatias, pneumopatias, nefropatias, hemoglobinopatia, imunodepressão, diabetes, obesidade, puerpério e tabagismo), número alto de comorbidades associadas, e alguns sintomas (dispneia, diarreia, vômito, dor torácica, hemoptise, pneumonia e sibilos). Níveis maiores de escolaridade e uso precoce do oseltamivir foram relacionados a fatores de proteção. A hospitalização contribuiu para o aumento da sobrevida. CONCLUSÕES: O conhecimento das características epidemiológicas que podem estar associadas a internação, gravidade da doença e mortalidade podem ser úteis na adoção de medidas preventivas e no diagnóstico e tratamento precoce da doença, colaborando para a diminuição dos óbitos e da necessidade de hospitalização.

OBJECTIVE: To evaluate pandemic influenza A (H1N1) 2009 in hospitalized patients in order to identify risk factors for hospitalization and, consequently, for the worsening of the disease. METHODS: This retrospective observational study was conducted between March and December of 2010. The data were collected from the Brazilian Ministry of Health National Case Registry Database. We included only patients (inpatients and outpatients) in whom H1N1 infection was confirmed (via laboratory testing) during the study period. The variables regarding demographic and clinical characteristics were statistically evaluated in order to compare the hospitalization rates in the presence or absence of these factors. Risk factors were identified by logistic regression analysis. RESULTS: We included 4,740 patients with laboratory confirmation of H1N1 infection. Of these, 1,911 individuals were hospitalized, and 258 (13.5 percent) died. The risk factors for hospitalization were age (20-29 years), African or Indigenous ethnicity, presence of specific comorbidities (heart disease, lung disease, kidney disease, hemoglobinopathy, immunosuppression, diabetes, obesity, puerperium, and smoking), a high number of comorbidities, and specific symptoms (dyspnea, diarrhea, vomiting, chest pain, hemoptysis, pneumonia, and wheezing). Higher levels of education and early use of oseltamivir were found to be protective factors. Hospitalization contributed to an increase in survival. CONCLUSIONS: Knowledge of the epidemiological characteristics that can be associated with hospitalization, disease severity, and mortality can be helpful in the adoption of preventive measures, as well as in the early diagnosis and treatment of disease, which might contribute to the reduction in the numbers of hospitalizations and deaths.

Evaluation of pregnancy as a risk factor in the outcomes of influenza A (H1N1)/2009 in women of childbearing age / Avaliação da gestação como fator de risco nos desfechos da influenza A (H1N1)/2009 em mulheres em idade fértil

The aim of this study was to verify whether pregnancy was a risk factor for death in influenza A (H1N1)/2009 infection. We compared the case-fatality rates for pandemic influenza among non-pregnant women of childbearing age and pregnant women, besides investigating other factors that differentiated the groups in relation to the outcomes. The data were collected from the National Information System on Diseases of Notification (SINAN), of the Ministry of Health. The study used cases with laboratory confirmation and included 1,861 women from 10 to 49 years of age, of whom 352 were pregnant. The case-fatality rate during the 2009 pandemic was 4.5 percent for pregnant women and 6.4 percent for non-pregnant women (p = 0.197). Logistic regression did not show an association between pregnancy and death (OR = 0.7; 95 percentCI: 0.41-1.21). However, there were significant differences between the two groups in relation to mean age, treatment with oseltamivir, schooling, and presence of other risk factors.

O objetivo deste estudo foi verificar se a gestação esteve associada como fator de risco para o óbito na infecção por Influenza A (H1N1)/2009. Comparou-se a letalidade da influenza pandêmica entre mulheres em idade fértil e gestantes, realizando ainda a busca por outros fatores que diferenciem os grupos em relação aos desfechos. Os dados foram coletados no Sistema de Informação de Agravos de Notificação (SINAN), do Ministério da Saúde. Foram utilizados os casos confirmados laboratorialmente, sendo incluídas 1.861 mulheres com idades entre 10 e 49 anos, das quais 352 eram gestantes. A taxa de letalidade observada durante a pandemia de 2009 foi de 4,5 por cento para as gestantes e 6,4 por cento para as não gestantes (p = 0,197). O resultado da regressão logística não evidenciou associação entre a presença de gestação e o óbito (OR = 0,7; IC95 por cento: 0,41-1,21). No entanto, houve diferenças significativas entre os dois grupos em relação à idade média, ao tratamento com oseltamivir, à escolaridade e à presença de outros fatores de risco.