Challenges and opportunities for access to Advanced Therapy Medicinal Products in Brazil.

BACKGROUND AIMS: The marketing authorization of Advanced Therapy Medicinal Products (ATMPs) in Brazil is recent. The features of these therapies impose specialized regulatory action and are consequently challenging for developers. The goal of this study was to identify the industry's experience in clinical development, marketing authorization and access to ATMPs through the Unified Health System (SUS, acronym in Portuguese), from a regulatory perspective. METHODS: A survey containing structured questions was conducted among research participants who work at companies that commercialize ATMPs. A descriptive analysis was performed. RESULTS: We invited 15 foreign pharmaceutical companies, of which 10 agreed to participate. Overall, participants assessed that Brazil has a well-established regulatory system, especially the sanitary registration by the National Health Surveillance Agency (Anvisa), which ensures the quality, safety, and efficacy of the products. The Agency's good interaction with the regulated sector, the harmonization of sanitary and ethical assessment systems with other countries, and the analysis time in the biosafety assessment of Genetically Modified Organisms (GMOs) stand out as positive in industry's evaluation. On the other hand, it is important to advance the pricing regulation for these products since Brazilian regulations do not establish specific criteria for ATMP. One of the biggest challenges is the difficulty for the SUS in reimbursing these very high-cost therapies, especially using current Health Technology Assessment (HTA) methods. CONCLUSIONS: Considering the increasing number of approvals of cell and gene therapies in Brazil in the coming years, a close dialogue between the industry and the public sector is recommended to advance regulatory improvements (pricing and HTA). Additionally, the construction of policies to promote the national Health Economic-Industrial Complex, based on a mission-oriented vision that encourages innovative models of financing, especially those that consider risk-sharing and co-financing technologies, will help provide the population with universal, equitable and sustainable access to ATMP in the SUS.

Cost-effectiveness of mechanical thrombectomy for acute ischemic stroke in Brazil: Results from the RESILIENT trial.

BACKGROUND: The RESILIENT trial demonstrated the clinical benefit of mechanical thrombectomy in patients presenting acute ischemic stroke secondary to anterior circulation large vessel occlusion in Brazil. AIMS: This economic evaluation aims to assess the cost-utility of mechanical thrombectomy in the RESILIENT trial from a public healthcare perspective. METHODS: A cost-utility analysis was applied to compare mechanical thrombectomy plus standard medical care (n = 78) vs. standard medical care alone (n = 73), from a subset sample of the RESILIENT trial (151 of 221 patients). Real-world direct costs were considered, and utilities were imputed according to the Utility-Weighted modified Rankin Score. A Markov model was structured, and probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of results. RESULTS: The incremental costs and quality-adjusted life years gained with mechanical thrombectomy plus standard medical care were estimated at Int$ 7440 and 1.04, respectively, compared to standard medical care alone, yielding an incremental cost-effectiveness ratio of Int$ 7153 per quality-adjusted life year. The deterministic sensitivity analysis demonstrated that mRS-6 costs of the first year most affected the incremental cost-effectiveness ratio. After 1000 simulations, most of results were below the cost-effective threshold. CONCLUSIONS: The intervention's clear long-term benefits offset the initially higher costs of mechanical thrombectomy in the Brazilian public healthcare system. Such therapy is likely to be cost-effective and these results were crucial to incorporate mechanical thrombectomy in the Brazilian public stroke centers.

Fighting Against Stroke in Latin America: A Joint Effort of Medical Professional Societies and Governments.

Introduction: Stroke is one of the leading causes of death in Latin America, a region with countless gaps to be addressed to decrease its burden. In 2018, at the first Latin American Stroke Ministerial Meeting, stroke physician and healthcare manager representatives from 13 countries signed the Declaration of Gramado with the priorities to improve the region, with the commitment to implement all evidence-based strategies for stroke care. The second meeting in March 2020 reviewed the achievements in 2 years and discussed new objectives. This paper will review the 2-year advances and future plans of the Latin American alliance for stroke. Method: In March 2020, a survey based on the Declaration of Gramado items was sent to the neurologists participants of the Stroke Ministerial Meetings. The results were confirmed with representatives of the Ministries of Health and leaders from the countries at the second Latin American Stroke Ministerial Meeting. Results: In 2 years, public stroke awareness initiatives increased from 25 to 75% of countries. All countries have started programs to encourage physical activity, and there has been an increase in the number of countries that implement, at least partially, strategies to identify and treat hypertension, diabetes, and lifestyle risk factors. Programs to identify and treat dyslipidemia and atrial fibrillation still remained poor. The number of stroke centers increased from 322 to 448, all of them providing intravenous thrombolysis, with an increase in countries with stroke units. All countries have mechanical thrombectomy, but mostly restricted to a few private hospitals. Pre-hospital organization remains limited. The utilization of telemedicine has increased but is restricted to a few hospitals and is not widely available throughout the country. Patients have late, if any, access to rehabilitation after hospital discharge. Conclusion: The initiative to collaborate, exchange experiences, and unite societies and governments to improve stroke care in Latin America has yielded good results. Important advances have been made in the region in terms of increasing the number of acute stroke care services, implementing reperfusion treatments and creating programs for the detection and treatment of risk factors. We hope that this approach can reduce inequalities in stroke care in Latin America and serves as a model for other under-resourced environments.

Costs of cancer attributable to excess body weight in the Brazilian public health system in 2018.

OBJECTIVES: The prevalence of excess body weight (EBW) has increased over the last decades in Brazil, where 55.4% of the adult population was overweight in 2019. EBW is a well-known risk factor for several types of cancer. We estimated the federal cost of EBW-related cancers in adults, considering the medical expenditures in the Brazilian Public Health System. METHODS: We calculated the costs related to 11 types of cancer considering the procedures performed in 2018 by all organizations that provide cancer care in the public health system. We obtained data from the Hospital and Ambulatory Information Systems of the Brazilian Public Health System. We calculated the fractions of cancer attributable to EBW using the relative risks from the literature and prevalence from a nationally representative survey. We converted the monetary values in Reais (R$) to international dollars (Int$), considering the purchasing power parity (PPP) of 2018. RESULTS: In Brazil, the 2018 federal cost for all types of cancers combined was Int$ 1.73 billion, of which nearly Int$ 710 million was spent on EBW-related cancer care and Int$ 30 million was attributable to EBW. Outpatient and inpatient expenditures reached Int$ 20.41 million (of which 80% was for chemotherapy) and Int$ 10.06 million (of which 82% was for surgery), respectively. Approximately 80% of EBW-attributable costs were due to breast, endometrial and colorectal cancers. CONCLUSION: A total of 1.76% of all federal cancer-related costs could be associated with EBW, representing a substantial economic burden for the public health system. We highlight the need for integrated policies for excess body weight control and cancer prevention.

Integrative Review of Managed Entry Agreements: Chances and Limitations.

BACKGROUND AND OBJECTIVE: Managed entry agreements (MEAs) consist of a set of instruments to reduce the uncertainty and the budget impact of new high-priced medicines; however, there are concerns. There is a need to critically appraise MEAs with their planned introduction in Brazil. Accordingly, the objective of this article is to identify and appraise key attributes and concerns with MEAs among payers and their advisers, with the findings providing critical considerations for Brazil and other high- and middle-income countries. METHODS: An integrative review approach was adopted. This involved a review of MEAs across countries. The review question was 'What are the health technology MEAs that have been applied around the world?' This review was supplemented with studies not retrieved in the search known to the senior-level co-authors including key South American markets. It also involved senior-level decision makers and advisers providing guidance on the potential advantages and disadvantages of MEAs and ways forward. RESULTS: Twenty-five studies were included in the review. Most MEAs included medicines (96.8%), focused on financial arrangements (43%) and included mostly antineoplastic medicines. Most countries kept key information confidential including discounts or had not published such data. Few details were found in the literature regarding South America. Our findings and inputs resulted in both advantages including reimbursement and disadvantages including concerns with data collection for outcome-based schemes. CONCLUSIONS: We are likely to see a growth in MEAs with the continual launch of new high-priced and often complex treatments, coupled with increasing demands on resources. Whilst outcome-based MEAs could be an important tool to improve access to new innovative medicines, there are critical issues to address. Comparing knowledge, experiences, and practices across countries is crucial to guide high- and middle-income countries when designing their future MEAs.

Economic burden of diabetes in Brazil in 2014.

BACKGROUND: Diabetes and its complications produce significant clinical, economic and social impact. The knowledge of the costs of diabetes generates subsidies to maintain the financial sustainability of public health and social security systems, guiding research and health care priorities. AIMS: The aim of this study was to estimate the economic burden of diabetes in Brazilian adults in 2014, considering the perspectives of the public health care system and the society. METHODS: A prevalence-based approach was used to estimate the annual health resource utilization and costs attributable to diabetes and related conditions. The healthcare system perspective considered direct medical costs related to outpatient and hospitalization costs. The societal perspective considered non-medical (transportation and dietary products) and indirect costs (productivity loss, disability, and premature retirement). Outpatient costs included medicines, health professional visits, exams, home glucose monitoring, ophthalmic procedures, and costs related to end stage renal disease. The costs of hospitalization attributed to diabetes related conditions were estimated using attributable risk methodology. Costs were estimated in Brazilian currency, and then converted to international dollars (2014). RESULTS: Based on a national self-reported prevalence of 6.2%, the total cost of diabetes in 2014 was Int$ 15.67 billion, including Int$ 6.89 billion in direct medical costs (44%), Int$ 3.69 billion in non-medical costs (23.6%) and Int$ 5.07 billion in indirect costs (32.4%). Outpatient costs summed Int$ 6.62 billion and the costs of 314,334 hospitalizations attributed to diabetes and related conditions was Int$ 264.9 million. Most hospitalizations were due to cardiovascular diseases (47.9%), followed by diabetes itself (18%), and renal diseases (13.6%). Diet and transportation costs were estimated at Int$ 3.2 billion and Int$ 462.3 million, respectively. CONCLUSIONS: Our results showed a substantial economic burden of diabetes in Brazil, and most likely are underrated as they are based on an underestimated prevalence of diabetes. Healthcare policies aiming at diabetes prevention and control are urgently sought.

Refractory secondary hyperparathyroidism in waiting list for parathyroidectomy: who we should operate first in a quaternary hospital in Brazil regarding survival.

BACKGROUND: Few centers in Brazil perform parathyroidectomy (PTX) for recalcitrant secondary hyperparathyroidism (SHPT) generating a long queue. There is little data regarding prioritize criteria besides chronological order and survival. OBJECTIVES: To determine the difference of clinical and laboratory factors between PTX patients and those who remained in the line despite the need for surgery and their survival. METHODS: A retrospective cohort study was conducted in a quaternary hospital in Brazil, where 43 patients with PTX indication due to severe SHPT were followed from 2009 to 2016. While 31 patients underwent PTX, 12 remained in the queue. Data on clinical and laboratory factors were collected for comparison and Kaplan-Meier and Cox regression survival analysis were used. RESULTS: PTX group was younger (40.9 vs. 49.3 years, p = .03), had higher PTH levels (2578 vs. 1937 pg/ml, p = .01) and higher CaxP product (62 vs. 47.5, p = .02). There were no percentage differences between groups of fractures, calciphylaxis and other complications due to SHPT. Patients who were not operated had a worst overall survival (5 y 62.2% vs. 96.7%, p = .04) with a HR for death of 8.08 (p = .07, PTX as a TVC). Other variables associated with decreased survival included a history of previous myocardial infarction (HR: 10.4, p = .01) and age per additional year (HR: 1.09, p = .02). CONCLUSIONS: Patients with severe SHPT are at increased risk of death while waiting for PTX. Clinical events like fracture were not used to prioritize patients beyond consecutive order. Therefore, optimizing priority criteria for PTX may result in improved survival in this population.

Estudos de Microcusteio aplicados a avaliações econômicas em saúde: uma proposta metodológica para o Brasil / Microcosting methods applied to health economic assessment: a Brazilian methods guideline

Objetivo: No cenário da avaliação de tecnologias em saúde (ATS), as estimativas de custos são um fator crítico no desenvolvimento das avaliações econômicas completas, especialmente pelo uso de diferentes metodologias de custeio. A fim de contribuir com a acurácia dos dados de custos usados nessas análises, este artigo sugere recomendações para apuração de custos em saúde no Brasil. Métodos: Reuniram-se pesquisadores de ATS de diferentes expertises e centros de pesquisa do Brasil, e ao longo de dois anos foram conduzidas revisões da literatura nacional e internacional e discussões sobre as formas de abordar a temática. Três simpósios foram realizados reunindo os pesquisadores com o propósito de alcançar o consenso entre os autores sobre as melhores recomendações para a realização de estudos de Microcusteio. Resultados: Consolidou-se em forma de uma recomendação este artigo que representa uma versão compacta da diretriz completa a ser publicada pela Rede Brasileira de Avaliação de Tecnologias em Saúde. A metodologia de Microcusteio é considerada como padrão-ouro para a identificação dos custos em saúde. Os métodos de definição do estudo, coleta e análise de dados apresentados são descritos de modo a permitir uma valoração dos custos validada e homogênea, principalmente para o uso dessa informação em avaliações econômicas de saúde. Conclusão: Essa recomendação tem o propósito de aumentar a acurácia das estimativas dos custos de saúde no nosso meio e homogeneizar a comunicação entre estudos conduzidos por diferentes grupos de pesquisa. Por fim, é esperado que a utilização dessas recomendações contribua para que as decisões baseadas em dados econômicos sejam mais acuradas e equânimes quando da incorporação de tecnologias no país.

Objective: In the context of health technology assessment (HTA), cost estimates are a critical factor in the development of economic evaluations, especially through the use of different costing methodologies. In order to contribute to the accuracy of the cost data used in these analyzes, this article suggests recommendations to develop health cost analysis in Brazil. Methods: HTA researchers with heterogeneous background and from different Brazilian research centers were engaged on the development of this health cost analysis recommendation over two years. Reviews of national and international literature and discussions on how to approach the theme were conducted. Three symposia were held bringing together the researchers with the purpose of reaching consensus among the authors on the best recommendations for micro-accounting studies. Results: This article was consolidated as a recommendation, which represents a compact version of the complete guideline that will be published by the Brazilian Health Technology Assessment Network (REBRATS). The Microcosting methodology is considered as a gold standard for the analysis of health costs. Methods to define the study, to perform data collection and analysis are described in order to allow a validated and homogeneous cost evaluation, mainly for the use of this information in economic health assessments. Conclusion: This recommendation is intended to increase the health cost estimated accuracy in our country and to homogenize the communication between studies conducted by different research groups. Finally, it is expected that the use of these recommendations will contribute to make decisions based on economic data more accurate and equitable when incorporating health technologies in the country.

Role of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Systematic Review and Updated Meta-Analysis of Risk Markers for Sudden Death.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated with sudden death (SD). Myocardial fibrosis is reportedly correlated with SD. OBJECTIVE: We performed a systematic review with meta-analysis, updating the risk markers (RMs) in HCM emphasizing myocardial fibrosis. METHODS: We reviewed HCM studies that addressed severe arrhythmic outcomes and the certain RMs: SD family history, severe ventricular hypertrophy, unexplained syncope, non-sustained ventricular tachycardia (NSVT) on 24-hour Holter monitoring, abnormal blood pressure response to exercise (ABPRE), myocardial fibrosis and left ventricular outflow tract obstruction (LVOTO) in the MEDLINE, LILACS, and SciELO databases. We used relative risks (RRs) as an effect measure and random models for the analysis. The level of significance was set at p < 0.05. RESULTS: Twenty-one studies were selected (14,901 patients aged 45 ± 16 years; men, 62.8%). Myocardial fibrosis was the major RISK MARKER (RR, 3.43; 95% CI, 1.95-6.03). The other RMs, except for LVOTO, were also predictors: SD family history (RR, 1.75; 95% CI, 1.39-2.20), severe ventricular hypertrophy (RR, 1.86; 95% CI, 1.26-2.74), unexplained syncope (RR, 2.27; 95% CI, 1.69-3.07), NSVT (RR, 2.79; 95% CI, 2.29-3.41), and ABPRE (RR, 1.53; 95% CI, 1.12-2.08). CONCLUSIONS: We confirmed the association of myocardial fibrosis and other RMs with severe arrhythmic outcomes in HCM and emphasize the need for new prediction models in managing these patients.

Role of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Systematic Review and Updated Meta-Analysis of Risk Markers for Sudden Death / Papel da Fibrose Miocárdica na Cardiomiopatia Hipertrófica: Revisão Sistemática e Metanálise Atualizada de Marcadores de Risco para Morte Súbita

Abstract Background: Hypertrophic cardiomyopathy (HCM) is associated with sudden death (SD). Myocardial fibrosis is reportedly correlated with SD. Objective: We performed a systematic review with meta-analysis, updating the risk markers (RMs) in HCM emphasizing myocardial fibrosis. Methods: We reviewed HCM studies that addressed severe arrhythmic outcomes and the certain RMs: SD family history, severe ventricular hypertrophy, unexplained syncope, non-sustained ventricular tachycardia (NSVT) on 24-hour Holter monitoring, abnormal blood pressure response to exercise (ABPRE), myocardial fibrosis and left ventricular outflow tract obstruction (LVOTO) in the MEDLINE, LILACS, and SciELO databases. We used relative risks (RRs) as an effect measure and random models for the analysis. The level of significance was set at p < 0.05. Results: Twenty-one studies were selected (14,901 patients aged 45 ± 16 years; men, 62.8%). Myocardial fibrosis was the major RISK MARKER (RR, 3.43; 95% CI, 1.95-6.03). The other RMs, except for LVOTO, were also predictors: SD family history (RR, 1.75; 95% CI, 1.39-2.20), severe ventricular hypertrophy (RR, 1.86; 95% CI, 1.26-2.74), unexplained syncope (RR, 2.27; 95% CI, 1.69-3.07), NSVT (RR, 2.79; 95% CI, 2.29-3.41), and ABPRE (RR, 1.53; 95% CI, 1.12-2.08). Conclusions: We confirmed the association of myocardial fibrosis and other RMs with severe arrhythmic outcomes in HCM and emphasize the need for new prediction models in managing these patients.

Resumo Fundamento: A cardiomiopatia hipertrófica (CMH) está associada à morte súbita (MS). A fibrose miocárdica está supostamente correlacionada à MS. Objetivo: Realizamos uma revisão sistemática com metanálise, atualizando os marcadores de risco (MR) em CMH enfatizando a fibrose miocárdica. Métodos: Revisamos estudos de CMH que abordaram desfechos arrítmicos graves e certos MR: história familiar de MS, hipertrofia ventricular grave, síncope inexplicada, taquicardia ventricular não sustentada (TVNS) na monitorização com Holter de 24 horas, resposta anormal da pressão arterial ao exercício (ABPRE), fibrose miocárdica e obstrução da via de saída do ventrículo esquerdo (VSVE) nas bases de dados MEDLINE, LILACS e SciELO. Utilizamos os riscos relativos (RRs) como uma medida de efeito e modelos aleatórios para a análise. O nível de significância foi estabelecido em p < 0,05. Resultados: Vinte e um estudos foram selecionados (14.901 pacientes com idade de 45 ± 16 anos; homens, 62,8%). A fibrose miocárdica foi o principal MARCADOR DE RISCO (RR, 3,43; IC95%, 1,95-6,03). Os outros MR, exceto obstrução da VSVE, também foram preditores: história familiar de MS (RR, 1,75; IC95%, 1,39-2,20), hipertrofia ventricular grave (RR, 1,86; IC95%, 1,26-2,74), síncope inexplicada (RR, 2,27; IC95%, 1,69-3,07), TVNS (RR, 2,79; IC95%, 2,29-3,41) e ABPRE (RR, 1,53; IC95%, 1,12-2,08). Conclusões: Confirmamos a associação de fibrose miocárdica e outros MR com desfechos arrítmicos graves na CMH e enfatizamos a necessidade de novos modelos de previsão no manejo desses pacientes.

Student Evaluation of Distance Learning for Health Care Professionals.

Background:To meet the population's health needs, it is necessary to have health professionals highly trained and updated with the latest skills. The Brazilian government, through the Open University of Brazilian National Health System (UNA-SUS), offers continuing education with free access, in distance learning (DL) modality.Objective:This study aimed to analyze students' perceptions regarding didactic and pedagogical aspects related to the content and activities, educational resources, and tutoring in a module offered by UNA-SUS/Federal University of Maranhão (UFMA).Methods:The authors analyzed a sample of 319 students, enrolled in four postgraduate classes, who had completed the communicable diseases module, from 2013 to 2014, and responded to evaluation questions through the Integrated Management System (SIGU) questionnaire, an auxiliary system for processing and interpreting assessments of DL modules offered by UNA-SUS/UFMA. For statistical analysis, evaluation variables were dichotomized into either a positive outcome ("great" and "good") or a negative outcome ("bad" and "insufficient"). Data were analyzed using Statistical Package for the Social Sciences (SPSS®; version 18); the significance level was set at 5% (p < 0.05).Results:The authors observed that 99% of the students evaluated the module positively. Regarding the evaluation of the content and activities, 53% (169), 43.6% (139), and 3.4% (11) of students evaluated the item unit workload as great, good, and bad, respectively. The highest rated item was tutor performance, rated as great by 229 (71.8%) students.Conclusions:The results contributed to the improvement of DL courses offered by UNA-SUS/UFMA from the perspectives of controlling dropout rates and the development of public health services offered in Brazil.

O uso de recursos digitais no ensino de Radiologia Odontológica: uma revisão integrativa de literatura / The use of digital resources in the teaching of Dental Radiology: an integrative literature review

Na Odontologia, diversos recursos vêm sendo adotados como estratégias de auxílio ao processo de ensino-aprendizagem na perspectiva de integrar a teoria com a prática. Este estudo objetivou levantar os principais recursos educacionais digitais na área de Radiologia Odontológica e discorrer sobre as características de aprendizagem destes recursos, de acordo com o modelo de Kirkpatrick. Realizouse revisão integrativa de trabalhos publicados no período de 2007 a 2017, nas bases de dados PubMed, Biblioteca Virtual em Saúde e Biblioteca Digital Brasileira de Teses e Dissertações, considerando os descritores: "computer-assisted instruction"; "dental education"; "educational technology"; "radiology". A amostra final foi composta por 13 artigos que atenderam aos critérios de inclusão e exclusão, em que foram identificados os seguintes recursos educacionais digitais: 3 módulos interativos baseado na Web; 3 objetos de aprendizagem digital; 2 cursos em plataforma virtual; 2 ferramentas digitais interativas; 1 software de visualização 3D; 1 simulador em radiologia oral e 1 sistema tecnológico de resposta ao aluno. A partir modelo de aprendizagem adotado, foram identificados os seguintes níveis nos trabalhos: satisfação dos participantes e/ou ganho de conhecimento dos participantes antes ou depois de uma intervenção ou ambos. A presente revisão de literatura identificou 7 tipos de recursos educacionais digitais utilizados em radiologia oral, que apresentaram atitudes positivas dos alunos em relação ao e-learning em todos os estudos, além de ganho significativo do conhecimento na maioria dos estudos (AU).

In dentistry, several resources have been adopted as strategies to aid the teaching-learning process in order to integrate theory and practice. This study aims to raise the main digital educational resources in the area of Dental Radiology and discuss the learning characteristics of these resources, according to the Kirkpatrick model. An integrative review of papers published between 2007 and 2017 was carried out in the databases PubMed, Virtual Health Library and Brazilian Digital Library of Theses and Dissertations, considering the descriptors: "computer-assisted instruction"; dental education"; "educational technology"; "radiology". The final sample consisted of 13 articles that met the inclusion and exclusion criteria, in which the following digital educational resources were identified: 03 interactive module based on the Web; 03 digital learning objects; 02 virtual platform courses; 02 interactive digital tools; 01 3D visualization software; 01 simulator in oral radiology and 01 technological system of response to the student. From the adopted learning model, the following levels were identified in the study: participants' satisfaction and / or gain of knowledge of the participants before or after an intervention or both. The present literature review identified 7 types of digital educational resources used in oral radiology, which presented positive attitudes of students in relation to e-learning in all studies, in addition to a significant gain in knowledge in most of the studies (AU).

Estimated cost of asthma in outpatient treatment: a real-world study.

OBJECTIVE: To estimate the cost of diagnosis and treatment of asthma. METHODS: We used the perspective of society. We sequentially included for 12 months, in 2011-2012, 117 individuals over five years of age who were treated for asthma in the Pneumology and Allergy-Immunology Services of the Piquet Carneiro Polyclinic, Universidade do Estado do Rio de Janeiro. All of them were interviewed twice with a six-month interval for data collection, covering 12 months. The cost units were identified and valued according to defined methods. We carried out a sensitivity analysis and applied statistical methods with a significance level of 5% for cost comparisons between subgroups. RESULTS: The study consisted of 108 patients, and 73.8% of them were women. Median age was 49.5 years. Rhinitis was present in 83.3% of the individuals, and more than half were overweight or obese. Mean family income was U$915.90/month (SD = 879.12). Most workers and students had absenteeism related to asthma. Total annual mean cost was U$1,291.20/patient (SD = 1,298.57). The cost related to isolated asthma was U$1,155.43/patient-year (SD = 1,305.58). Obese, severe, and uncontrolled asthmatic patients had higher costs than non-obese, non-severe, and controlled asthmatics, respectively. Severity and control level were independently associated with higher cost (p = 0.001 and 0.000, respectively). The direct cost accounted for 82.3% of the estimated total cost. The cost of medications for asthma accounted for 62.2% of the direct costs of asthma. CONCLUSIONS: Asthma medications, environmental control measures, and long-term health leaves had the greatest potential impact on total cost variation. The results are an estimate of the cost of treating asthma at a secondary level in the Brazilian Unified Health System, assuming that the treatment used represents the ideal approach to the disease.

Prevalence of chronic kidney disease and comorbidities in isolated African descent communities (PREVRENAL): methodological design of a cohort study.

BACKGROUND: Chronic kidney disease (CKD) is considered a serious public health problem, both in Brazil and worldwide, with an increasing number of cases observed inrecent years. Especially, CKD has been reported to be highly prevalent in those of African descent. However, Brazil lacks data from early-stage CKD population studies, and the prevalence of CKD is unknown for both the overall and African descent populations. Hence, the present study aimsto estimate the prevalence of early-stage CKD and its associated risk factors in African-Brazilians from isolated African-descent communities. Herein, the detailed methodology design of the study is described. METHODS: This population-based, prospective, longitudinal, cohort study (PREVRENAL) is performed in three stages: first, clinical, nutritional, and anthropometric evaluations; measurements of serum and urinary markers; and examinations of comorbiditieswere performed. Second, repeated examinations of individuals with CKD, systemic arterial hypertension, and/or diabetes mellitus; image screening; and cardiac risk assessment were performed. Third, long-term monitoring of all selected individuals will be conducted (ongoing). Using probability sampling, 1539 individuals from 32 communities were selected. CKD was defined asaglomerular filtration rate (GFR) ≤60 mL/min/1.73m2 and albuminuria > 30 mg/day. DISCUSSION: This study proposes to identify and monitor individuals with and without reduced GFR and high albuminuria in isolated populations of African descendants in Brazil. As there are currently no specific recommendations for detecting CKD in African descendants, four equations for estimating the GFR based on serum creatinine and cystatin C were used and will be retrospectively compared. The present report describes the characteristics of the target population, selection of individuals, and detection of a population at risk, along with the imaging, clinical, and laboratory methodologies used. The first and second stages have been concluded and the results will be published in the near future. The subsequent (third) stage is the long-term, continuous monitoring of individuals diagnosed with renal abnormalities or with CKD risk factors. The entire study population will be re-evaluated five years after the study initiation. The expectation is to obtain information about CKD evolution among this population, including the progression rate, complication development, and cardiovascular events.

Estimated cost of asthma in outpatient treatment: a real-world study / Estimativa de custo da asma em tratamento ambulatorial: estudo com dados de mundo real

ABSTRACT OBJECTIVE To estimate the cost of diagnosis and treatment of asthma. METHODS We used the perspective of society. We sequentially included for 12 months, in 2011-2012, 117 individuals over five years of age who were treated for asthma in the Pneumology and Allergy-Immunology Services of the Piquet Carneiro Polyclinic, Universidade do Estado do Rio de Janeiro. All of them were interviewed twice with a six-month interval for data collection, covering 12 months. The cost units were identified and valued according to defined methods. We carried out a sensitivity analysis and applied statistical methods with a significance level of 5% for cost comparisons between subgroups. RESULTS The study consisted of 108 patients, and 73.8% of them were women. Median age was 49.5 years. Rhinitis was present in 83.3% of the individuals, and more than half were overweight or obese. Mean family income was U$915.90/month (SD = 879.12). Most workers and students had absenteeism related to asthma. Total annual mean cost was U$1,291.20/patient (SD = 1,298.57). The cost related to isolated asthma was U$1,155.43/patient-year (SD = 1,305.58). Obese, severe, and uncontrolled asthmatic patients had higher costs than non-obese, non-severe, and controlled asthmatics, respectively. Severity and control level were independently associated with higher cost (p = 0.001 and 0.000, respectively). The direct cost accounted for 82.3% of the estimated total cost. The cost of medications for asthma accounted for 62.2% of the direct costs of asthma. CONCLUSIONS Asthma medications, environmental control measures, and long-term health leaves had the greatest potential impact on total cost variation. The results are an estimate of the cost of treating asthma at a secondary level in the Brazilian Unified Health System, assuming that the treatment used represents the ideal approach to the disease.

RESUMO OBJETIVO Estimar o custo do diagnóstico e tratamento da asma. MÉTODOS Foi utilizada a perspectiva da sociedade. Foram incluídos por 12 meses em 2011-2012, sequencialmente, 117 indivíduos maiores de cinco anos de idade, em tratamento por asma nos Serviços de Pneumologia e Alergia-Imunologia da Policlínica Piquet Carneiro, Universidade do Estado do Rio de Janeiro. Todos realizaram duas entrevistas com seis meses de intervalo para coleta de dados, cobrindo 12 meses. As unidades de custos foram identificadas e valoradas de acordo com métodos definidos. Foi feita análise de sensibilidade e foram aplicados métodos estatísticos com nível de significância de 5% para comparações de custos entre subgrupos. RESULTADOS Cento e oito pacientes completaram o estudo, 73,8% eram mulheres. Mediana de idade foi de 49,5 anos. Rinite esteve presente em 83,3%, e mais da metade tinha sobrepeso ou obesidade. A renda familiar média foi de R$1.566,19/mês (DP = 1.503,30). A maioria dos trabalhadores e dos estudantes teve absenteísmo relacionado à asma. O custo médio anual total foi de R$2.207,99/paciente (DP = 2.220,55). O custo relacionado à asma isolada foi de R$1.984,17/paciente-ano (DP = 2.232,55). Asmáticos obesos, graves ou não controlados tiveram maiores custos em comparação aos não obesos (p = 0,001), não graves e controlados (p = 0,000). O custo direto correspondeu a 82,3% do custo total estimado. O custo com medicamentos para asma correspondeu a 62,2% dos custos diretos da asma. CONCLUSÕES Medicamentos para asma, medidas de controle ambiental e licenças de saúde prolongadas tiveram maior impacto potencial na variação do custo total. Os resultados são uma estimativa do custo do tratamento da asma em nível secundário no Sistema Único de Saúde, assumindo-se que o tratamento utilizado represente a abordagem ideal da doença.

Priorização de tecnologias em saúde: o caso brasileiro / Health technologies prioritization: the Brazilian case

Hoje em dia, os governos enfrentam brechas cada vez maiores entre as necessidades de saúde da população e os recursos disponíveis para financiar a saúde. Isso acontece por diversos motivos, incluindo a transição demográfica e epidemiológica, os avanços tecnológicos, a oferta contínua e crescente de novos tratamentos médicos, o aumento da expectativa da população em relação aos seus direitos e, em países como o Brasil ­ em que o direito universal à saúde é garantido constitucionalmente ­ a judicialização da saúde. Nesse contexto, os mecanismos de priorização explícita em saúde ganham cada vez mais força. Segundo Michael Rawlins, nenhum país do mundo possui os recursos necessários para financiar todas as tecnologias disponíveis para todos os cidadãos com os máximos padrões de qualidade (2010); por esse motivo, os países precisam definir critérios técnicos, regras e processos sistemáticos, explícitos e transparentes para apoiar os processos de decisão de cobertura. Esse conjunto de critérios, regras e processos recebe o nome de priorização de tecnologias em saúde. Esta nota técnica analisa o sistema de priorização de tecnologias em saúde no Brasil, com o objetivo de avaliar seu desempenho e identificar oportunidades de melhora nos processos de decisão de cobertura e alocação de recursos públicos em saúde. Essa análise está baseada em um marco conceitual desenvolvido pela rede de conhecimento CRITERIA: Priorização e Planos de Benefício de Saúde, do Banco Interamericano de Desenvolvimento (BID), que propõe um enfoque sistêmico para a priorização em saúde.

Cost-effectiveness of dengue vaccination in Brazil / Custo-efetividade da vacinação contra dengue no Brasil

Objective: To define the economic value of a tetravalent dengue vaccine in Brazil by estimating the cost-effectiveness vaccine price threshold per dose. Methods: A dengue dynamic transmission model was used to estimate the public health impact of dengue vaccination and related economic parameters. Two vaccination strategies were assessed: routine vaccination at 9 years old plus either a catch-up campaign of 7 cohorts (10 to 16 years old; R9&10-16) or 16 cohorts (10 to 25 years old; R9&10-25). Brazilian-specific demographic, epidemiological and economic data were used. The economic impact over 10 years was estimated from the public payer and societal perspectives. All costs were expressed in BRL2016. Results: Over 10 years, the R9&10-16 and R9&10-25 vaccination strategies would prevent 9 million and 15 million dengue cases, respectively, avoiding 269,906 (95% CI: 410,097­154,653) and 434,334 (95% CI: 547,052­304,799) disability-adjusted life years. This would result in savings of up to BRL7.4 billion (US$2.1 billion) from a societal perspective with the larger vaccination program. The cost-effective vaccine price threshold per dose for the R9&10-16 and R9&10-25 strategies would be BRL187.5 (95% CI: 109­276) (US$52.1) and BRL183.6 (95% CI: 129­230) (US$51.0), respectively, from the public payer perspective, and BRL221.5 (95% CI: 129­326) (US$61.5) and BRL216.8 (95% CI: 153­271) (US$60.2), respectively, from the societal perspective. Conclusion: The high threshold of vaccine price per dose demonstrates the significant economic value of dengue vaccination in Brazil, even for a large program with 16 catch-up cohorts.

Objetivo: Definir o valor econômico da vacina tetravalente contra dengue no Brasil por meio da estimativa do limiar de preço custo-efetivo por dose. Métodos: Um modelo dinâmico de transmissão foi utilizado para estimar o impacto em saúde pública da vacinação contra dengue e os parâmetros econômicos relacionados. A análise avaliou duas estratégias de vacinação: rotina aos 9 anos, mais campanha de vacinação com 7 coortes (10 a 16 anos; R9&10-16) ou 16 coortes (10 a 25 anos; R9&10-25). Foram utilizados dados demográficos, epidemiológicos e econômicos específicos para o Brasil. O impacto econômico foi estimado em 10 anos sob a perspectiva do pagador público e da sociedade. Todos os custos foram expressos em BRL2016. Resultados: Em 10 anos, as estratégias de vacinação R9&10-16 e R9&10-25 preveniriam 9 milhões e 15 milhões de casos de dengue, respectivamente, evitando 269,906 (95% CI: 410,097­154,653) e 434,334 (95% CI: 547,052­304,799) anos de vida ajustados por incapacidade. Isso resultaria em uma economia de até BRL7,4 bilhões (US$2,1 bilhões) sob a perspectiva da sociedade com o maior programa de vacinação. O limiar de preço custo-efetivo por dose para as estratégias R9&10-16 e R9&10-25 seria BRL187,5 (95% CI: 109­276) (US$52,1) e BRL183,6 (95% CI: 129­230) (US$51,0), respectivamente, sob a perspectiva do público pagador, e BRL221,5 (95% CI: 129­326) (US$61,5) e BRL216,8 (95% CI: 153­271) (US$60,2), respectivamente, sob a perspectiva da sociedade. Conclusão: Os altos limiares de preço custo-efetivo por dose demonstram o significativo valor econômico da vacinação contra dengue no Brasil, mesmo para um programa amplo com campanha com 16 coortes.

Custos do tratamento do hiperparatireoidismo secundário à doença renal crônica, com cinacalcete ou paratireoidectomia, para pacientes não controlados com a terapia clínica convencional sob a perspectiva do Sistema Único de Saúde / Secondary hyperparathyroidism treatment costs with cinacalcet or PTX, for uncontrolled patients with conventional clinical therapy under Brazilian Public Health System perspective

Objetivos: Estimar a população elegível para o tratamento de pacientes com hiperparatireoidismo secundário (HPTS), não controlados com terapia convencional, bem como avaliar a utilização de recursos para o tratamento dessa população com cinacalcete ou paratireoidectomia (PTX). Métodos: Utilização da técnica Delphi por painel de especialistas. A pesquisa foi realizada utilizando questionário estruturado, enviado por meio eletrônico aos especialistas, e seguida de encontro presencial. Os custos foram obtidos de bases de dados governamentais. Apenas custos médicos diretos foram incluídos, sob a perspectiva do Sistema Único de Saúde (SUS) (em reais no ano de 2014). Os dados foram avaliados pelo Microsoft Excel versão 2013. Resultados: A população no cenário de mundo real indicada para o tratamento com cinacalcete foi de 7.705 pacientes. Já a população real encaminhada para a PTX foi de 7.691 pacientes, sendo esse número 76,3% maior que a população ideal com indicação de PTX, que foi de 1.822 pacientes. O custo estimado do tratamento com cinacalcete foi de R$ 27.712,95 (considerando a dose recomendada em bula para cinacalcete, de 30 a 180 mg/ dia) e de R$ 16.841,85 para PTX (incluindo os períodos pré e pós-cirúrgico). A análise de sensibilidade foi baseada na dose média de cinacalcete, conforme o estudo EVOLVE (66,8 mg/dia). Nesse cenário, o custo do tratamento com cinacalcete foi de R$ 11.924,13 (57% menor que o cenário com a dose de bula). Conclusão: No cenário SUS, o número de pacientes encaminhados para PTX foi 76,3% maior que os idealmente indicados à cirurgia, o que ocorre devido à falta de opções terapêuticas.

Objectives: To estimate patient management patterns, associated medical resource utilization and use of cinacalcet for secondary hyperparathyroidism in chronic hemodialysis patients and much uncontrolled with conventional treatment, in the Unified Healthcare System (SUS) setting, in 2014. Methods: An expert panel was carried using the Delphi technique. The research was done by structured and unambiguous questionnaires that were sent by email to the entire Delphi panel, followed by a face meeting. Expense inputs were mainly obtained from government fee schedules and pharmaceutical price tables. Only medical direct costs were included under the perspective of SUS [in 2014 Brazilian Real (BRL)]. Data were analyzed using Microsoft Excel Worksheet version 2013. Results: The eligible population to cinacalcet treatment was 9,513 patients. Considering an ideal scenario, this number goes to 7,705 patients. The estimated population for parathyroidectomy was 7,691 patients in a real scenario and 1,822 in an ideal scenario (76.3% more patients than the ideally suited to the procedure). The estimated annual cost with cinacalcet treatment is 27,712.95 BRL (considering the label dose for cinacalcet) and 16,841.85 BRL for parathyroidectomy (including pre and post-operative period), respectively. A sensitivity analysis was performed considering the cost of cinacalcet treatment using the drug's dose of EVOLVE study (66.8 mg). This scenario showed a total cost of 11,924.13 BRL (57% less than label dose scenario). Conclusion: 76.3% more patients are indicated to the surgery due the absence of other therapeutic options for management of secondary hyperparathyroidism in chronic hemodialysis patients and much uncontrolled with conventional treatment, in the SUS setting.

Morte Súbita na Cardiomiopatia Hipertrófica / Sudden Death in Hypertrophic Cardiomyopathy

A cardiomiopatia hipertrófica é uma doença genética do músculo cardíaco, autossômica dominante, caracterizada por hipertrofia ventricular na ausência de qualquer outra condição clínica que leve à sobrecarga do coração. Estima-se prevalência de 1:500, sendo importante causa de morte súbita, especialmente em jovens, com incidência anual em torno de 1%. Entre os marcadores de risco para a ocorrência de arritmias ventriculares malignas e morte súbita neste cenário, enfatizam-se, além de um evento fatal já ocorrido e abortado, história familiar de morte súbita; espessura de parede maior ou igual a 30mm; síncope inexplicada; presença de taquicardia ventricular não sustentada ao Holter; resposta pressórica anormal no teste ergométrico; e presença de realce tardio na ressonância magnética do coração. A presença ou ausência destes marcadores pode definir a necessidade ou não do implante de cardiodesfibrilador implantável como forma de prevenir a morte súbita nestes pacientes. Entretanto, ainda existe muita controvérsia sobre a forma pela qual estes pacientes devam ser estratificados. Sabe-se que estes marcadores não têm o mesmo peso em predizer quem tem mais chance de sofrer um evento fatal. Este fato torna-se particularmente importante quando se constata que o procedimento de implante de cardiodesfibrilador implantável não é isento de complicações, além do impacto econômico, em termos do custo para o sistema de saúde. A proposta deste artigo é a realização de uma revisão sobre os principais aspectos envolvidos na morte súbita destes pacientes, desde a fisiopatologia, a avaliação de risco, a prevenção e as perspectivas futuras.

Cost of diseases related to alcohol consumption in the Brazilian Unified Health System.

OBJECTIVE: To estimate the direct costs associated to outpatient and hospital care of diseases related to alcohol consumption in the Brazilian Unified Health System. METHODS: Attributable populational risks were estimated for the selected diseases related to the use of 25 g/day or more of ethanol (risk consumption), considering a relative risk (RR) ≥ 1.20. The RR estimates were obtained from three meta-analysis. The risk consumption rates of the Brazilian population ≥ 18 years old were obtained by a national survey. Data from the Hospital Information System of SUS (HIS-SUS) were used to estimate the annual costs of the health system with the diseases included in the analysis. RESULTS: The total estimated costs for a year regarding diseases related to risk consumption were U$8,262,762 (US$4,413,670 and US$3,849,092, for outpatient and hospital care, respectively). CONCLUSIONS: Risk consumption of alcohol is an important economic and health problem, impacting significantly the health system and society.