Evidence syntheses to support decision-making related to the Covid-19 pandemic.

The COVID-19 pandemic generated a large volume of scientific productions with different quality levels. The speed with which knowledge was produced and shared worldwide imposed on health management the challenge of seeking ways to identify the best available evidence to support its decisions. In response to this challenge, the Department of Science and Technology of the Brazilian Ministry of Health started offering a service to produce and provide scientific knowledge addressing priority public health issues in the pandemic scenario. Drug treatments, non-pharmacological measures, testing, reinfection and immunological response, immunization, pathophysiology, post-COVID syndrome and adverse events are among the topics covered. In this article, we discuss the strengths and lessons learned, as well as the challenges and perspectives that present a real example of how to offer the best scientific evidence in a timely manner in order to assist the decision-making process during a public health emergency.

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.

Sínteses de evidências para apoio à tomada de decisões relacionadas à pandemia de covid-19 / Evidence syntheses to support decision-making related to the Covid-19 pandemic

A pandemia de covid-19 gerou um numeroso volume de produções científicas com diferentes níveis de qualidade. A velocidade com que o conhecimento era produzido e compartilhado a nível mundial impôs à gestão em saúde o desafio de buscar meios de identificar as melhores evidências disponíveis para subsidiar suas decisões. Em resposta a este desafio, o Departamento de Ciência e Tecnologia do Ministério da Saúde do Brasil estabeleceu um serviço para elaborar e disponibilizar conhecimento científico abordando questões prioritárias de saúde pública no cenário da pandemia. Entre os temas abordados estão tratamentos medicamentosos, medidas não farmacológicas, testagem, reinfecção e resposta imunológica, imunização, fisiopatologia, síndrome pós-covid e eventos adversos. Neste artigo, discute-se os pontos fortes e lições aprendidas, bem como os desafios e perspectivas que fornecem um exemplo real sobre como disponibilizar as melhores evidências científicas, em tempo hábil e de forma oportuna, para auxiliar o processo decisório durante uma emergência em saúde pública.

Analysis of micro-costing through the Time-Driven Activity-Based Costing (TDABC) method in viscosupplementation procedures in different application regimens / Análise do microcusteio por meio de método Time-Driven Activity-Based Costing (TDABC) nos procedimentos de viscossuplementação do joelho em diferentes regimes de aplicação

Objective: To evaluate the micro-costing of viscosupplementation procedures compared to different infiltration regimens. Methods: This study compared, through the Time-Driven ActivityBased Costing method, the micro-costing of these different application regimens using national cost averages as a basis for calculation in a medium-sized outpatient service. Results: The results demonstrated that the difference in costs with the single application is 31.47% less for three and 119.13% for five applications. Conclusions: No study showed a superiority of the five-application regimen over the three-application regimen, which leads one to believe that there is no justification for this procedure from an economic or quality-of-life point of view.

Objective: Avaliar o microcusteio dos procedimentos de viscossuplementação do joelho em diferentes regimes de aplicação. Métodos: Este estudo comparou, por meio do método Time-Driven Activity-Based Costing, o microcusteio desses diferentes regimes de aplicação, usando com base de cálculo médias nacionais de custo em um serviço ambulatorial de porte médio. Resultados: Os resultados encontrados demonstraram que a diferença nos custos com a aplicação única é 31,47% menor para três aplicações e 119,13% para cinco aplicações. Conclusão: Em nenhum estudo houve superioridade do regime de cinco aplicações ao regime de três, fato que leva a acreditar que não há nenhuma justificativa para esse procedimento do ponto de vista econômico ou de qualidade de vida do paciente.

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.

Correlation Between Parathyroid Hormone Levels with Urinary Magnesium Excretion in Patients with Non-Dialysis Dependent Chronic Kidney Disease.

BACKGROUND: Disorders of mineral metabolism occur in most patients with chronic kidney disease (CKD). The aim of this work was to correlate parathyroid hormone (PTH) levels with urinary magnesium excretion in patients with non-dialysis dependent CKD. METHODS: Cross-sectional study. Concentrations of creatinine, magnesium, calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D] and alkaline phosphatase (ALP) were determined in blood samples. The assessment of urinary magnesium levels was performed by means of total daily excretion and by the excretion fraction (FEMg). RESULTS: The study evaluated 163 patients with a mean age of 60.7 ± 11.7 years and 51.0% were male. In the highest quartile of PTH (>89.5pg/mL), the mean levels of FEMg and ALP were higher (p<0.05). In the unadjusted regression analysis, the following variables were related to serum PTH levels: FEMg (odds ratio (OR) = 1.12; 95% confidence intervals (CI): 1.02-1.23), calcium (OR = 0.45; 95% CI: 0.22-0.90), ALP (OR = 1.02; 95% CI: 1.00-1.03) and eGFR (OR = 0.92; 95% CI: 1.00-1.03). After an adjusted analysis, only one FEMg and ALP will remain correlated with PTH. CONCLUSION: In patients with non-dialysis dependent CKD, FEMg and ALP were some variables that remained associated with PTH.

Cost-effectiveness of Drug-Eluting Stents in Percutaneous Coronary Intervention in Brazil's Unified Public Health System (SUS). / Custo-efetividade do Stent Farmacológico na Intervenção Coronariana Percutânea no SUS.

Background The use of drug-eluting stents (DESs), compared with bare-metal stents (BMSs), in percutaneous coronary intervention (PCI) has reduced the rate of restenosis, without an impact on mortality but with an increase in costs. Medical literature lacks randomized studies that economically compare these 2 stent types within the reality of the Brazilian Unified Public Health System (SUS). Objective To estimate the incremental cost-effectiveness ratio (ICER) between DES and BMS in SUS patients with single-vessel coronary artery disease. Methods Over a 3-year period, patients with symptomatic single-vessel coronary artery disease were randomized in a 1:2 ratio to receive a DES or BMS during PCI, with a 1-year clinical follow-up. The evaluation included in-stent restenosis (ISR), target lesion revascularization (TLR), major adverse events, and cost-effectiveness for each group. P-values <0.05 were considered significant. Results In the DES group, of 74 patients (96.1%) who completed the follow-up, 1 developed ISR (1.4%), 1 had TLR (1.4%), and 1 died (1.4%), with no cases of thrombosis. In the BMS group, of 141 patients (91.5%), ISR occurred in 14 (10.1%), TLR in 10 (7.3%), death in 3 (2.1%), and thrombosis in 1 (0.74%). In the economic analysis, the cost of the procedure was R$ 5,722.21 in the DES group and R$ 4,085.21 in the BMS group. The effectiveness by ISR and TLR was 8.7% for DES and 5.9% for BMS, with an ICER of R$ 18,816.09 and R$ 27,745.76, respectively. Conclusions In the SUS, DESs were cost-effective in accordance with the cost-effectiveness threshold recommended by the World Health Organization (Arq Bras Cardiol. 2020; 115(1):80-89).

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.

Custo-efetividade do Stent Farmacológico na Intervenção Coronariana Percutânea no SUS / Cost-effectiveness of Drug-Eluting Stents in Percutaneous Coronary Intervention in Brazils Unified Public Health System (SUS)

Resumo Fundamento O uso do stent farmacológico (SF) comparado ao stent não farmacológico (SNF) na intervenção coronariana percutânea (ICP) reduziu o percentual de reestenose, porém sem impacto na mortalidade, com aumento no custo. A literatura carece de estudos randomizados que comparem economicamente esses dois grupos de stents na realidade do Sistema Único de Saúde (SUS). Objetivo Estimar a razão custo-efetividade incremental (RCEI) entre SF e SNF na coronariopatia uniarterial em pacientes do SUS Métodos Pacientes com coronariopatia uniarterial sintomática foram randomizados em 3 anos para uso de SF ou SNF durante a ICP, na proporção de 1:2, com seguimento clínico de 12 meses. Foram avaliados reestenose intrastent (RIS), revascularização da lesão-alvo (RLA), eventos adversos maiores e custo-efetividade (CE) de cada grupo. Os valores de p < 0,05 foram considerados significativos. Resultados No grupo SF, dos 74 pacientes (96,1%) que completaram o acompanhamento, ocorreu RIS em 1(1,4%), RLA em 1 (1,4%), óbito em 1 (1,4%), sem trombose. No grupo SNF, dos 141 pacientes (91,5%),ocorreu RIS em 14 (10,1%), RLA em 10 (7,3%), óbito em 3 (2,1%) e trombose em 1 (0,74%). Na análise econômica, o custo do procedimento foi de R$ 5.722,21 no grupo SF e de R$4.085,21 no grupo SNF. A diferença de efetividade a favor do grupo SF por RIS e RLA foi 8,7% e 5,9%, respectivamente, com RCEI de R$ 18.816,09 e R$ 27.745,76. Conclusões No SUS, o SF foi custo-efetivo, em concordância com o limiar de CE preconizado pela Organização Mundial da Saúde. (Arq Bras Cardiol. 2020; 115(1):80-89)

Abstract Background The use of drug-eluting stents (DESs), compared with bare-metal stents (BMSs), in percutaneous coronary intervention (PCI) has reduced the rate of restenosis, without an impact on mortality but with an increase in costs. Medical literature lacks randomized studies that economically compare these 2 stent types within the reality of the Brazilian Unified Public Health System (SUS). Objective To estimate the incremental cost-effectiveness ratio (ICER) between DES and BMS in SUS patients with single-vessel coronary artery disease. Methods Over a 3-year period, patients with symptomatic single-vessel coronary artery disease were randomized in a 1:2 ratio to receive a DES or BMS during PCI, with a 1-year clinical follow-up. The evaluation included in-stent restenosis (ISR), target lesion revascularization (TLR), major adverse events, and cost-effectiveness for each group. P-values <0.05 were considered significant. Results In the DES group, of 74 patients (96.1%) who completed the follow-up, 1 developed ISR (1.4%), 1 had TLR (1.4%), and 1 died (1.4%), with no cases of thrombosis. In the BMS group, of 141 patients (91.5%), ISR occurred in 14 (10.1%), TLR in 10 (7.3%), death in 3 (2.1%), and thrombosis in 1 (0.74%). In the economic analysis, the cost of the procedure was R$ 5,722.21 in the DES group and R$ 4,085.21 in the BMS group. The effectiveness by ISR and TLR was 8.7% for DES and 5.9% for BMS, with an ICER of R$ 18,816.09 and R$ 27,745.76, respectively. Conclusions In the SUS, DESs were cost-effective in accordance with the cost-effectiveness threshold recommended by the World Health Organization (Arq Bras Cardiol. 2020; 115(1):80-89)

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.

Clinical Outcomes and Cost-Effectiveness Analysis of FFR Compared with Angiography in Multivessel Disease Patient / Impacto Clínico e Custo-Efetividade da FFR em Comparação à Angiografia em Pacientes com Doenças Multiarteriais Submetidos à ICP

Abstract Background: In multivessel disease patients with moderate stenosis, fractional flow reserve (FFR) allows the analysis of the lesions and guides treatment, and could contribute to the cost-effectiveness (CE) of non-pharmacological stents (NPS). Objectives: To evaluate CE and clinical impact of FFR-guided versus angiography-guided angioplasty (ANGIO) in multivessel patients using NPS. Methods: Multivessel disease patients were prospectively randomized to FFR or ANGIO groups during a 5 year-period and followed for < 12 months. Outcomes measures were major adverse cardiac events (MACE), restenosis and CE. Results: We studied 69 patients, 47 (68.1%) men, aged 62.0 ± 9.0 years, 34 (49.2%) in FFR group and 53 (50.7%) in ANGIO group, with stable angina or acute coronary syndrome. In FFR, there were 26 patients with biarterial disease (76.5%) and 8 (23.5%) with triarterial disease, and in ANGIO, 24 (68.6%) with biarterial and 11 (31.4%) with triarterial disease. Twelve MACEs were observed - 3 deaths: 2 (5.8%) in FFR and 1 (2.8%) in ANGIO, 9 (13.0%) angina: 4(11.7%) in FFR and 5(14.2%) in ANGIO, 6 restenosis: 2(5.8%) in FFR and 4 (11.4%) in ANGIO. Angiography detected 87(53.0%) lesions in FFR, 39(23.7%) with PCI and 48(29.3%) with medical treatment; and 77 (47.0%) lesions in ANGIO, all treated with angioplasty. Thirty-nine (33.3%) stents were registered in FFR (0.45 ± 0.50 stents/lesion) and 78 (1.05 ± 0.22 stents/lesion) in ANGIO (p = 0.0001), 51.4% greater in ANGIO than FFR. CE analysis revealed a cost of BRL 5,045.97 BRL 5,430.60 in ANGIO and FFR, respectively. The difference of effectiveness was of 1.82%. Conclusion: FFR reduced the number of lesions treated and stents, and the need for target-lesion revascularization, with a CE comparable with that of angiography.

Resumo Fundamentos: Em pacientes multiarteriais e lesões moderadas, a reserva de fluxo fracionada (FFR) avalia cada lesão e direciona o tratamento, podendo ser útil no custo-efetividade (CE) de implante de stents não farmacológicos (SNF). Objetivos: Avaliar CE e impacto clínico da angioplastia + FFR versus angioplastia + angiografia (ANGIO), em multiarteriais, utilizando SNF. Métodos: pacientes com doença multiarteriais foram randomizados prospectivamente durante ±5 anos para FFR ou ANGIO, e acompanhados por até 12 meses. Foram avaliados eventos cardíacos maiores (ECAM), reestenose e CE. Resultados: foram incluídos 69 pacientes, 47(68,1%) homens, 34(49,2%) no FFR e 35(50,7%) no ANGIO, idade 62,0 ± 9,0 anos, com angina estável e Síndrome Coronariana Aguda estabilizada. No FFR, havia 26 com doença (76,5%) biarterial e 8 (23,5%) triarterial, e no grupo ANGIO, 24(68,6%) biarteriais e 11(31,4%) triarteriais. Ocorreram 12(17,3%) ECAM - 3(4,3%) óbitos: 2(5,8%) no FFR e 1(2,8%) no ANGIO, 9(13,0%) anginas, 4(11,7%) no FFR e 5(14,2%) no ANGIO, 6 reestenoses: 2(5,8%) no FFR e 4 (11,4%) no ANGIO. Angiografia detectou 87(53,0%) lesões no FFR, 39(23,7%) com ICP e 48(29,3%) com tratamento clínico; e 77(47,0%) lesões no ANGIO, todas submetidas à angioplastia. Quanto aos stents, registrou-se 39(33,3%) (0,45 ± 0,50 stents/lesão) no FFR e 78(66,6%) (1,05 ± 0,22 stents/lesão) no ANGIO (p = 0,0001); ANGIO utilizou 51,4% a mais que o FFR. Análise de CE revelou um custo de R$5045,97 e R$5.430,60 nos grupos ANGIO e FFR, respectivamente. A diferença de efetividade foi 1,82%. Conclusões: FFR diminuiu o número de lesões tratadas e de stents e necessidade de revascularização do vaso-alvo, com CE comparável ao da angiografia.

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.

Clinical Outcomes and Cost-Effectiveness Analysis of FFR Compared with Angiography in Multivessel Disease Patient.

BACKGROUND: In multivessel disease patients with moderate stenosis, fractional flow reserve (FFR) allows the analysis of the lesions and guides treatment, and could contribute to the cost-effectiveness (CE) of non-pharmacological stents (NPS). OBJECTIVES: To evaluate CE and clinical impact of FFR-guided versus angiography-guided angioplasty (ANGIO) in multivessel patients using NPS. METHODS: Multivessel disease patients were prospectively randomized to FFR or ANGIO groups during a 5 year-period and followed for < 12 months. Outcomes measures were major adverse cardiac events (MACE), restenosis and CE. RESULTS: We studied 69 patients, 47 (68.1%) men, aged 62.0 ± 9.0 years, 34 (49.2%) in FFR group and 53 (50.7%) in ANGIO group, with stable angina or acute coronary syndrome. In FFR, there were 26 patients with biarterial disease (76.5%) and 8 (23.5%) with triarterial disease, and in ANGIO, 24 (68.6%) with biarterial and 11 (31.4%) with triarterial disease. Twelve MACEs were observed - 3 deaths: 2 (5.8%) in FFR and 1 (2.8%) in ANGIO, 9 (13.0%) angina: 4(11.7%) in FFR and 5(14.2%) in ANGIO, 6 restenosis: 2(5.8%) in FFR and 4 (11.4%) in ANGIO. Angiography detected 87(53.0%) lesions in FFR, 39(23.7%) with PCI and 48(29.3%) with medical treatment; and 77 (47.0%) lesions in ANGIO, all treated with angioplasty. Thirty-nine (33.3%) stents were registered in FFR (0.45 ± 0.50 stents/lesion) and 78 (1.05 ± 0.22 stents/lesion) in ANGIO (p = 0.0001), 51.4% greater in ANGIO than FFR. CE analysis revealed a cost of BRL 5,045.97 BRL 5,430.60 in ANGIO and FFR, respectively. The difference of effectiveness was of 1.82%. CONCLUSION: FFR reduced the number of lesions treated and stents, and the need for target-lesion revascularization, with a CE comparable with that of angiography.

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).