Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2017-06-21T13:42:52Z No. of bitstreams: 2 Tese - Sheila Elke Araújo Nunes - 2014.pdf: 4139252 bytes, checksum: 113368e043fc53148e1cd7b8b50b2632 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-07-10T13:36:29Z (GMT) No. of bitstreams: 2 Tese - Sheila Elke Araújo Nunes - 2014.pdf: 4139252 bytes, checksum: 113368e043fc53148e1cd7b8b50b2632 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-07-10T13:36:29Z (GMT). No. of bitstreams: 2 Tese - Sheila Elke Araújo Nunes - 2014.pdf: 4139252 bytes, checksum: 113368e043fc53148e1cd7b8b50b2632 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2014-12-18 / Introduction: Estimate the costs of treatment of pneumococcal diseases can aid the understanding of reduced economic burden of these after introduction of the pneumococcal conjugate vaccine (PCV), as run in Brazil, in March 2010, which introduced the PCV10 valiant in the National Program Immunization (NPI) for children between 2 and 23 months of age. Cost-effectiveness analysis (CEA) before the introduction indicated that the vaccine was cost-effective (R $ 24.930 / Daly avoided - Disability Adjusted Life Years), in the SUS perspective. Disease burden and the cost of the vaccine were identified as the main drivers of the results for sensitivity analysis. Objectives: Estimate the costs of pneumococcal disease and to evaluate the ratio of incremental cost-effectiveness (ICER) of implementing the PCV-10 brave after introduction into INP Brazil. Methods: Three steps have been performed in the SUS perspective: 1) cost of illness study: medical charts of children 28 days to 35 months of age hospitalized with clinical suspicion of bacterial pneumonia were reviewed to estimate the costs of pneumonia and to other syndromes costs were estimated by therapeutic guidelines; 2) comparison between the three methods of funding: (i) bottom-up / micro-costing by chart review; (ii) top-down / micro-costing through therapeutic guidelines; and (iii) top-down / gross-costing, through reimbursement paid by the SUS. 3) CEA: the strategy to vaccinate with PCV-10 was compared to the non-vaccination. The model used was the PneuModel. In acute otitis media from all causes, pneumococcal meningitis, pneumococcal sepsis and pneumococcal pneumonia were considered. Costs were obtained by microcusteio, epidemiological data from primary studies of population-based, dose costs and vaccination coverage in INP. The discount rate was 5%. Sensitivity analysis was conducted to test the robustness and variability of the model parameters. Results: The cost of study of hospitalized pneumonia records of 52 cases of severe pneumonia and 7 of very serious pneumonia were reviewed. Statistical analyzes of severe pneumonia data revealed that there is difference between the costing methodologies (p=0,015) and to compare the estimated costs by these methods there was no difference between the cost of compensation and the cost for therapeutic guideline (p=0,241). At ACE, annually, vaccination with PCV-10 would prevent 3,942 cases of the disease and 16,514 years of life lost in a cohort of children <1 year. The ICER was R $ 14,230 per DALY averted. In sensitivity analysis, the model was sensitive to variations in incidence and mortality of pneumonia and pneumococcal meningitis. Conclusions: The cost for therapy guideline, uncommonly used in disease cost estimates, was an alternative to funding for compensation, heavily used technique and lower accuracy. After introduction of ICER, using primary data revealed that PCV-10 is a low-cost intervention, as suggested by WHO (<1GDP / per capita - in Brazil, in 2010, US $ 10.933) and, ICER less than previous ACE. Despite uncertainties in critical parameters of the model, using secondary data, ACE can provide evidence to support decision making. After the implementation analysis can result in more accurate estimates and provide evidence to continue vaccination. / Introdução: Estimar os custos do tratamento das doenças pneumocócicas podem auxiliar no conhecimento da redução da carga econômica destas após introdução da vacina anti-pneumocócica conjugada (VPC), como corrido no Brasil, em março de 2010, que introduziu a VPC-10 valente no Programa Nacional de Imunização (PNI), para crianças entre 2 e 23 meses de idade. Análise de custo-efetividade (ACE) antes da introdução indicou que a vacina era custo-efetiva (R$ 24,930/Daly evitado – do inglês, Disability Adjusted Life Years), na perspectiva do SUS. Carga da doença e os custos da vacina foram identificados como os principais direcionadores do resultado para análise de sensibilidade. Objetivos: Estimar os custos da doença pneumocócica e avaliar a razão de custo-efetividade incremental (RCEI) da implementação da VPC-10 valente após introdução no PNI do Brasil. Métodos: Três etapas foram executadas, aplicadas a perspectiva do SUS: 1º) estudo de custo de doenças: prontuários de crianças com 28 dias a 35 meses de idade internadas por suspeita clínica de pneumonia bacteriana foram revisados para estimar os custos da pneumonia e para demais síndromes os custos foram estimados por diretrizes terapêuticas; 2º) comparação entre as três metodologias de custeio: (i) bottom-up/micro-costing através da revisão de prontuários; (ii) top-down/micro-costing através de diretriz terapêutica; e (iii) top-down/gross-costing através de ressarcimento pago pelo SUS. 3º) ACE: a estratégia de vacinar com a VPC-10 foi comparada com a não vacinação. O modelo empregado foi o PneuModel. Neste, otite média aguda por todas as causas, meningite pneumocócica, sepse pneumocócica e pneumonia pneumocócica foram consideradas. Os custos foram obtidos por microcusteio, dados epidemiológicos a partir de estudos primários de base populacional, custos da dose e de cobertura vacinal no PNI. A taxa de desconto aplicada foi de 5%. Análise de sensibilidade foi conduzida para testar a robustez e variabilidade de parâmetros do modelo. Resultados: No estudo de custo da pneumonia hospitalizada prontuários de 52 casos de pneumonias graves e 7 de pneumonias muito graves foram revisados. Análises estatísticas dos dados de pneumonias graves revelaram que há diferença entre as metodologias de custeio (p=0,015) e ao comparar os custos estimados por estas metodologias não houve diferença entre o custeio por ressarcimento e o custeio por diretriz terapêutica (p=0,241). Na ACE, anualmente, a vacinação com VPC-10 evitaria 3.942 casos da doença e 16.514 anos de vida perdidos em uma coorte de crianças <1 ano. A RCEI foi de R$ 14.230 por DALY evitado. Na análise de sensibilidade, o modelo foi sensível às variações de incidência e letalidade de pneumonia e meningite pneumocócica. Conclusões: O custeio por diretriz terapêutica, pouco empregado nas estimativas de custo de doença, se mostrou uma alternativa ao custeio por ressarcimento, técnica muito utilizada e de menor acurácia. A RCEI pós introdução, com dados primários, revelou que a VPC-10 é uma intervenção de baixo custo, como sugerido pela OMS (<1PIB/per capita – no Brasil, em 2010, R$ 10,933) e, com menor RCEI que ACE anterior. Mesmo com incertezas em parâmetros críticos do modelo, usando dados secundários, ACE podem fornecer evidências para apoiar tomadas de decisões. Analise pós-introdução pode resultar em estimativas mais precisas e fornecer evidências para continuar a vacinação.

The overall aim of this thesis is to improve knowledge about the prevention of infectious and bleeding complications in patients with hematological malignancies, primarily in those with chronic lymphocytic leukemia (CLL) and myelodysplatic syndrome (MDS). Hypogammaglobulinemia, impaired production of immunoglobulins (Ig), is an established risk factor for infection, but the impact of IgG pure subclass deficiency (IgG subclass deficiency with adequate production of IgG, IgA, and IgM) has been debated. In a retrospective single institution study, we concluded that pure IgG subclass deficiency in CLL patients is rare and is not associated with an increased risk of infection. Hence, routine analysis of IgG subclasses in patients with CLL is not warranted. There is no consensus on recommending vaccination against Streptococcus pneumoniae to CLL patients mainly because comparative studies are lacking. In our randomized trial, the efficacy of a conjugated pneumococcal vaccine on immune response was superior or equal to a polysaccharide vaccine for all pneumococcal serotypes common for the two vaccines. A conjugate pneumococcal vaccine should therefore be included in vaccination programs for patients with CLL. Bronchoalveolar lavage (BAL) is a well-established invasive method to identify the cause of pulmonary infiltrates in immunocompromised patients. In a retrospective trial, we have studied the diagnostic yield of BAL in patients with hematological malignancies. We concluded that BAL is highly useful in either verifying or excluding some of the important respiratory tract infections affecting these patients, particularly invasive pulmonary aspergillosis (IPA) and Pneumocystis jirovecii pneumonia (PJP). However, standardized procedures for BAL sampling should be continually revised to avoid unnecessary microbiological tests. Thrombocytopenia, an adverse prognostic factor in patients with MDS, can be aggravated by azacitidine, first-line treatment for high-risk MDS. Eltrombopag, a thrombopoietin-receptor agonist (TPO-R), alleviates thrombocytopenia in patients with immune thrombocytopenic purpura (ITP). In a phase I clinical trial, we concluded that the combination of eltrombopag and azacitidine in high-risk MDS patients with thrombocytopenia is feasible and well tolerated in doses up to 200 mg eltrombopag daily.