Estrutura familiar e dinâmica educacional entre gerações / Family structure and educational dynamics between generations / Estructura familiar y dinámica educativa entre generaciones

O presente estudo busca identificar o impacto da estrutura familiar (biparentais e uniparentais) sobre a dinâmica educacional intergeracional e a acumulação de capital humano. Foram utilizados os microdados da Pesquisa Nacional por Amostra de Domicílio (PNAD) de 2014. A dinâmica educacional intergeracional foi analisada a partir de matrizes de transição e de processos de Markov. As diferenças de acumulação de capital humano entre as categorias de estruturas familiares foram investigadas a partir da decomposição de Blinder-Oaxaca. Os resultados indicam que ser dependente, do sexo feminino e residir na zona urbana são características associadas a uma maior mobilidade intergeracional de educação. O Nordeste se destaca como a região com menor mobilidade intergeracional educacional. A decomposição de Blinder-Oaxaca indica que, em média, as famílias uniparentais chefiadas por uma mulher possuem 0,5 ano de estudo a mais do que as uniparentais chefiadas pelo pai. Cerca de 74,2% dessa diferença é explicada pelo modelo estimado e a parte não explicada não possui significância estatística. Os resultados sugerem que a estrutura familiar afeta a dinâmica intergeracional de educação e a acumulação de capital humano dos indivíduos.

Objective. The present study seeks to identify the impact of the family structure (two-parent and one-parent) on the intergenerational educational dynamics and the accumulation of human capital. Method. The microdata from the National Household Sampling Survey (PNAD) of 2014 were used. The intergenerational educational dynamics was analyzed based on transition matrices and Markov processes. Differences in human capital accumulation between categories of family structures were investigated based on the Blinder-Oaxaca decomposition. Results. Results indicate that being dependent, female and living in the urban area are characteristics associated with greater intergenerational education mobility. The Northeast region stands out as the region with the lowest educational intergenerational mobility. The decomposition of Blinder-Oaxaca indicates that, on average, single-parent families headed by a woman have 0.5 years of study more than single-parent families headed by a father. About 74.2% of this difference is explained by the estimated model and the unexplained part has no statistical significance. Conclusion. Results suggest that the family structure affects the intergenerational dynamics of education and the accumulation of human capital of individuals.

Objetivo. El presente estudio busca identificar el impacto de la estructura familiar (biparental y monoparental) sobre la dinámica educativa intergeneracional y la acumulación de capital humano. Método. Se utilizaron los microdatos de la Encuesta Nacional de Muestreo de Hogares (PNAD) de 2014. Se analizó la dinámica educativa intergeneracional a partir de matrices de transición y procesos de Markov. Las diferencias en la acumulación de capital humano entre categorías de estructuras familiares se investigaron con base en la descomposición Blinder-Oaxaca. Resultados. Los resultados indican que ser dependiente, ser mujer y vivir en el área urbana son características asociadas a una mayor movilidad educativa intergeneracional. La nordestina se destaca como la región con menor movilidad educativa intergeneracional. La descomposición de Blinder-Oaxaca indica que, en promedio, las familias monoparentales encabezadas por una mujer tienen 0,5 años de estudio más que las familias monoparentales encabezadas por el padre. Aproximadamente el 74,2 % de esta diferencia se explica por el modelo estimado y la parte inexplicada no tiene significación estadística. Conclusión. Los resultados sugieren que la estructura familiar afecta la dinámica intergeneracional de la educación y la acumulación de capital humano de los individuos.

A Brazilian cost-utility analysis of trabecular micro-bypass with iStent inject® for the treatment of open-angle glaucoma / Análise de custo-utilidade do implante trabecular iStent inject® para o tratamento do glaucoma de ângulo aberto no Brasil

ABSTRACT Purpose To evaluate the cost-utility of the iStent inject® for the treatment of mild-to-moderate open-angle glaucoma (OAG) within the Brazilian Unified Health System (SUS). Methods A Markov model was developed, in which the effectiveness outcome measure was the incremental cost-effectiveness ratio (ICER: R$ / QALY quality-adjusted life-year). Direct medical costs were obtained from the SUS perspective. The base case comprised of a hypothetical cohort of patients with OAG using topical medication and being managed according to the Clinical Protocol and Therapeutic Guidelines (PCDT) and a real-world setting based on data from Datasus. The model's robustness through sensitivity analyses was tested. Results In the PCDT base case setting, the trabecular micro-bypass implant provided gains of 0.47 QALYs and an ICER of R$7,996.66/QALY compared to treatment with topical medication. In the real-world setting based on data from Datasus, the trabecular micro-bypass implant, provided gains of 0.47 QALYs and an ICER of R$4,485.68/QALY compared to treatment with topical medication. The results were robust to sensitivity analyses. Conclusion Incorporating iStent inject® to SUS provides an improvement in the patient's quality of life with an additional cost that warrants the benefit provided to patients. Results may be considered cost-effective compared to topical medication.

RESUMO Objetivo Avaliar a relação custo-utilidade do iStent inject® para o tratamento do glaucoma de ângulo aberto leve a moderado no Sistema Único de Saúde. Métodos Foi desenvolvido um modelo de Markov, no qual a medida de resultado de efetividade foi a razão custo-efetividade incremental (razão de custo-efetividade incremental: R$/ano de vida ajustado pela qualidade). Os custos médicos diretos foram obtidos por meio da perspectiva do Sistema Único de Saúde. O caso base foi composto de uma coorte hipotética de pacientes com glaucoma de ângulo aberto em uso de medicação tópica tratados de acordo com o Protocolo Clínico e Diretrizes Terapêuticas e um cenário do mundo real baseado em dados do Departamento de Informática do Sistema Único de Saúde. Foi testada a robustez do modelo por meio de análises de sensibilidade. Resultados No cenário base do Protocolo Clínico e Diretrizes Terapêuticas, o implante trabecular micro-bypass proporcionou ganhos de 0,47 ano de vida ajustado pela qualidade e razão de custo-efetividade incremental de R$7.996,66/ano de vida ajustado pela qualidade em relação ao tratamento com medicação tópica. No cenário real baseado em dados do Departamento de Informática do Sistema Único de Saúde, o implante trabecular proporcionou ganhos de 0,47 ano de vida ajustado pela qualidade e razão de custo-efetividade incremental de R$ 4.485,68/ano de vida ajustado pela qualidade em relação ao tratamento com medicação tópica. Os resultados foram robustos para análises de sensibilidade. Conclusão A incorporação do iStent inject® ao Sistema Único de Saúde proporciona melhora na qualidade de vida do paciente com um custo adicional que garante o benefício proporcionado a eles. Os resultados podem ser considerados custo-efetivos em comparação com a medicação tópica.

A Gaussian mixture-hidden Markov model of human visual behavior / 生物医学工程学杂志

Vision is an important way for human beings to interact with the outside world and obtain information. In order to research human visual behavior under different conditions, this paper uses a Gaussian mixture-hidden Markov model (GMM-HMM) to model the scanpath, and proposes a new model optimization method, time-shifting segmentation (TSS). The TSS method can highlight the characteristics of the time dimension in the scanpath, improve the pattern recognition results, and enhance the stability of the model. In this paper, a linear discriminant analysis (LDA) method is used for multi-dimensional feature pattern recognition to evaluates the rationality and the accuracy of the proposed model. Four sets of comparative trials were carried out for the model evaluation. The first group applied the GMM-HMM to model the scanpath, and the average accuracy of the classification could reach 0.507, which is greater than the opportunity probability of three classification (0.333). The second set of trial applied TSS method, and the mean accuracy of classification was raised to 0.610. The third group combined GMM-HMM with TSS method, and the mean accuracy of classification reached 0.602, which was more stable than the second model. Finally, comparing the model analysis results with the saccade amplitude (SA) characteristics analysis results, the modeling analysis method is much better than the basic information analysis method. Via analyzing the characteristics of three types of tasks, the results show that the free viewing task have higher specificity value and a higher sensitivity to the cued object search task. In summary, the application of GMM-HMM model has a good performance in scanpath pattern recognition, and the introduction of TSS method can enhance the difference of scanpath characteristics. Especially for the recognition of the scanpath of search-type tasks, the model has better advantages. And it also provides a new solution for a single state eye movement sequence.

Evaluación económica en salud: costo-utilidad de la incorporación del reemplazo total de rodilla en la cobertura del régimen de Garantías Explícitas en Salud en Chile / Economic evaluation in health: Cost-utility of the incorporation of total knee replacement to the Chilean Explicit Health-Guarantees regime

Antecedentes La osteoartritis destaca por su alta prevalencia y deterioro funcional, siendo la causa más común de incapacidad en mayores de 65 años. El régimen de Garantías Explícitas en Salud chileno otorga cobertura a tratamiento médico a las presentaciones leves y moderadas, excluyendo el manejo quirúrgico en la presentación severa. Objetivos Evaluar el costo-utilidad de incorporar el reemplazo total de rodilla al régimen de Garantías Explícitas en Salud para asegurados del seguro público sobre 65 años en Chile, versus la mantención con manejo farmacológico. Métodos Revisión sistemática explortaria para identificar los parámetros del modelo y evaluaciones económicas basadas en un modelo de Markov de seis estados de salud, desde la perspectiva del pagador público y horizonte lifetime. Se calculó la razón de costo-utilidad incremental que condujo al análisis de incertidumbre determinístico y probabilístico. Resultados Se seleccionaron 22 artículos como fuentes de referencia. Incorporar el procedimiento al alero del régimen, implicaría beneficiarse de 9,8 años de vida ajustados por calidad versus 2,4 en el escenario sin acceso a cirugía. La razón de costo-utilidad incremental es menos $445 689 pesos chilenos por años de vida ajustados por calidad (menos 633,8 dólares americanos por años de vida ajustados por calidad), siendo la incorporación de cirugía de reemplazo al régimen una alternativa dominante, versus el escenario de acceso insuficiente en otros regímenes de cobertura. Cada año de vida ajustado por calidad gracias a la cirugía ahorrará $445 689 pesos chilenos. A una voluntad de pago de $502 596 pesos chilenos por años de vida ajustados por calidad (714,7 dólares americanos por años de vida ajustados por calidad), la alternativa de acceso a reemplazo es costo-útil con 99,9% de certeza. Conclusión El reemplazo total de rodilla en mayores de 65 años es una alternativa dominante. El acceso a cirugía en el régimen de Garantías Explícitas en Salud para el sistema público es costo-útil a un umbral de un producto interno bruto per cápita.

Background Osteoarthritis is an important health condition due to its prevalence and functional deterioration, being the most common cause of disability in people over 65 years of age. The Chilean Explicit Health-Guarantees regime provides coverage for medical treatment in mild and moderate presentations, excluding surgical treatment in end-stage knee osteoarthritis. Objectives To evaluate the cost-utility of incorporating total knee replacement to the Explicit Health-Guarantees regime for over-65-years beneficiaries of the public insurance system, versus maintenance with medical treatment. Methods A Scoping review was coducted to identify model parameters and economic evaluation based in a 6 health states Markov Model, from the perspective of the public payer and lifetime horizon. The Incremental Cost-Utility Ratio (ICUR) was calculated, and deterministic and probabilistic uncertainty analysis were performed. Results Twenty-two articles were selected as reference sources. If the regime were to adopt the procedure, the implication would be a benefit of 9.8 Years of Life Adjusted by Quality (QALY) versus 2.4 QALY in the scenario without access to total knee replacement. The ICUR was $ -445 689 CLP/QALY (U$D -633.8/QALY), wherein the inclusion of total knee replacement to the regime becomes a dominant alternative versus the current scenario. Each quality-adjusted life-year gained by the surgery will save CLP 445 689. At a willingness to pay of CLP 502,596/QALY (U$D 714.7/QALY), access to surgery is cost-useful with a 99.9% certainty. Conclusion Total knee replacement in patients older than 65 years is a dominant alternative. Access to this procedure in the Chilean Explicit Health-Guarantees regime in the public system is cost-useful at a threshold of 1 GDP per capita.

Radioterapia intraoperatória com elétrons no tratamento do câncer colorretal localmente avançado submetido a ressecção incompleta: análise econômica sob a perspectiva do Sistema de Saúde Suplementar brasileiro / Intraoperative electron-beam radiotherapy in locally advanced rectal cancer, in patients submitted to suboptimal surgery: economic analysis on the Brazilian Private Health Care system perspective

Objetivo: Este estudo objetivou avaliar o custo-efetividade da aplicação da radioterapia intraoperatória com elétrons (RIOe) no paciente com câncer retal localmente avançado (CRLA) submetido a radio/quimioterapia neoadjuvante seguida de ressecção incompleta (margem comprometida ou doença grosseira residual). Métodos: Para tanto, foi elaborado um modelo de Markov. Os dados de eficácia, efeitos secundários, controle local e sobrevida global foram extraídos da literatura. A perspectiva considerada foi a do sistema de saúde privado brasileiro. Considerou-se, para o custo e para a efetividade, uma taxa de desconto anual de 5%. Resultados: A estratégia que continha a RIOe mostrou-se, nesse cenário, dominante em comparação à estratégia que não envolvia essa abordagem. Os resultados mostraram-se robustos após análises de sensibilidade uni e multivariadas. Conclusão: Concluiu-se que pode ser vantajosa, tanto para os pacientes com CRLA quanto para as operadoras de saúde do mercado privado brasileiro, a aplicação de RIOe na ocorrência de cirurgia subótima, ainda que se sugira que esses dados devem ser confirmados posteriormente, por meio da coleta de dados de mundo real, devido à ausência de níveis robustos de evidência, na literatura, para esse cenário clínico específico.

Objective: This study aimed to evaluate the cost-effectiveness of intraoperative electron radiotherapy (IOeRT) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant radio-chemotherapy, followed by incomplete resection (compromised margin or gross residual disease). Methods: A Markov model was constructed. Data on efficacy, side effects, local control and overall survival were extracted from the literature. The perspective was that of the Brazilian private health system. For the cost and effectiveness, an annual discount rate of 5% was considered. Results: The strategy that contained IOeRT was, in this scenario, dominant, in comparison to standard of care. Results were considered robust, after univariate and multivariate sensitivity analyzes. Conclusions: We concluded that it can be advantageous, both for patients with LARC submitted to suboptimal surgery, as well as for Brazilian health insurance companies, the application of IOeRT. Although it is suggested that these results should be confirmed later, through the collection of real-world data, due to the absence of randomized controlled trials, in this specific clinical scenario.

Segmentation of heart sound signals based on duration hidden Markov model / 生物医学工程学杂志

Heart sound segmentation is a key step before heart sound classification. It refers to the processing of the acquired heart sound signal that separates the cardiac cycle into systolic and diastolic, etc. To solve the accuracy limitation of heart sound segmentation without relying on electrocardiogram, an algorithm based on the duration hidden Markov model (DHMM) was proposed. Firstly, the heart sound samples were positionally labeled. Then autocorrelation estimation method was used to estimate cardiac cycle duration, and Gaussian mixture distribution was used to model the duration of sample-state. Next, the hidden Markov model (HMM) was optimized in the training set and the DHMM was established. Finally, the Viterbi algorithm was used to track back the state of heart sounds to obtain S

Network meta-analysis: application and practice using R software / 한국역학회지

The objective of this study is to describe the general approaches to network meta-analysis that are available for quantitative data synthesis using R software. We conducted a network meta-analysis using two approaches: Bayesian and frequentist methods. The corresponding R packages were “gemtc” for the Bayesian approach and “netmeta” for the frequentist approach. In estimating a network meta-analysis model using a Bayesian framework, the “rjags” package is a common tool. “rjags” implements Markov chain Monte Carlo simulation with a graphical output. The estimated overall effect sizes, test for heterogeneity, moderator effects, and publication bias were reported using R software. The authors focus on two flexible models, Bayesian and frequentist, to determine overall effect sizes in network meta-analysis. This study focused on the practical methods of network meta-analysis rather than theoretical concepts, making the material easy to understand for Korean researchers who did not major in statistics. The authors hope that this study will help many Korean researchers to perform network meta-analyses and conduct related research more easily with R software.

Cost-Effectiveness of Rate- and Rhythm-Control Drugs for Treating Atrial Fibrillation in Korea

PURPOSE: Although the economic and mortality burden of atrial fibrillation (AF) is substantial, it remains unclear which treatment strategies for rate and rhythm control are most cost-effective. Consequently, economic factors can play an adjunctive role in guiding treatment selection. MATERIALS AND METHODS: We built a Markov chain Monte Carlo model using the Korean Health Insurance Review & Assessment Service database. Drugs for rate control and rhythm control in AF were analyzed. Cost-effective therapies were selected using a cost-effectiveness ratio, calculated by net cost and quality-adjusted life years (QALY). RESULTS: In the National Health Insurance Service data, 268149 patients with prevalent AF (age ≥18 years) were identified between January 1, 2013 and December 31, 2015. Among them, 212459 and 55690 patients were taking drugs for rate and rhythm control, respectively. Atenolol cost $714/QALY. Among the rate-control medications, the cost of propranolol was lowest at $487/QALY, while that of carvedilol was highest at $1363/QALY. Among the rhythm-control medications, the cost of pilsicainide was lowest at $638/QALY, while that of amiodarone was highest at $986/QALY. Flecainide and propafenone cost $834 and $830/QALY, respectively. The cost-effectiveness threshold of all drugs was lower than $30000/QALY. Compared with atenolol, the rate-control drugs propranolol, betaxolol, bevantolol, bisoprolol, diltiazem, and verapamil, as well as the rhythm-control drugs sotalol, pilsicainide, flecainide, propafenone, and dronedarone, showed better incremental cost-effectiveness ratios. CONCLUSION: Propranolol and pilsicainide appear to be cost-effective in patients with AF in Korea assuming that drug usage or compliance is the same.

Network meta-analysis: application and practice using R software / 한국역학회지

The objective of this study is to describe the general approaches to network meta-analysis that are available for quantitative data synthesis using R software. We conducted a network meta-analysis using two approaches: Bayesian and frequentist methods. The corresponding R packages were “gemtc” for the Bayesian approach and “netmeta” for the frequentist approach. In estimating a network meta-analysis model using a Bayesian framework, the “rjags” package is a common tool. “rjags” implements Markov chain Monte Carlo simulation with a graphical output. The estimated overall effect sizes, test for heterogeneity, moderator effects, and publication bias were reported using R software. The authors focus on two flexible models, Bayesian and frequentist, to determine overall effect sizes in network meta-analysis. This study focused on the practical methods of network meta-analysis rather than theoretical concepts, making the material easy to understand for Korean researchers who did not major in statistics. The authors hope that this study will help many Korean researchers to perform network meta-analyses and conduct related research more easily with R software.

Análise de custo-efetividade da abiraterona para câncer de próstata metastático resistente à castração em pacientes com uso prévio de quimioterapia / Cost-effectiveness analysis of abiraterone for metastatic, castrateresistant prostate cancer following previous chemotherapy

Objetivo: Avaliar a custo-utilidade e o impacto orçamentário (IO) da abiraterona para o tratamento de câncer de próstata resistente à castração, em pacientes previamente tratados com docetaxel. Métodos: Foi construído um modelo de Markov com ciclos mensais sob a perspectiva do Sistema Único de Saúde (SUS), em um horizonte temporal de cinco anos e taxa de desconto de 5%. A estimativa de efetividade foi oriunda do principal ensaio clínico dessa condição de saúde. Para dados de utilidade, aplicaram-se estimativas internacionais, enquanto para custos se utilizaram tabelas de remuneração do SUS. Para o IO, a população-alvo foi estimada com base em dados do Departamento de Informática do SUS (DATASUS). Resultados: A abiraterona ocasionou ganho de 1,045 ano de vida ajustado para qualidade (QALY) e 1,609 ano de vida ganho (AVG), enquanto para o placebo esses valores foram de 0,763 e 1,299, respectivamente. O custo total na estratégia abiraterona foi de R$ 83.295 e para o placebo, de R$ 2.895. A relação de custo-efetividade incremental (RCEI) foi de R$ 284.416 por QALY ganho. Em nenhuma das análises de sensibilidade os valores ficaram abaixo de R$ 100.000 por QALY. Mesmo quando variados simultaneamente seis parâmetros, todos no seu limite mais favorável à abiraterona, os resultados seguiram elevados, com RCEI de R$ 98.330 por QALY. O IO foi de R$ 270 milhões em cinco anos no cenário mais conservador (tempo médio de tratamento de 7,4 meses e 10% de novos casos/ano). Conclusão: A abiraterona se mostrou pouco custo-efetiva nesta situação clínica, com RCEI superior a nove vezes o PIB per capita por QALY, sendo os resultados robustos em análise de sensibilidade.

Objective: To evaluate the cost-utility and the budget impact (BI) of abiraterone in patients with castration-resistant prostate cancer previously treated with docetaxel. Methods: A Markov model was constructed, with monthly cycles, under the perspective of the Brazilian Public Healthcare System (SUS), in a 5-year time horizon, and with a 5% discount rate. The effectiveness estimate was obtained from the pivotal clinical trial for abiraterone in this health condition. For utility data, international estimates were applied; while for costs, SUS reimbursement information were used. In the BI analysis, the target population was estimated with claims data from DATASUS. Results: Abiraterone resulted in a gain of 1.045 quality-adjusted life years (QALY) and 1.609 life years gained (LYG), while for placebo these values were 0.763 and 1.299, respectively. The total cost for the abiraterone strategy was BRL 83,295, and for placebo, BRL 2,895. The incremental cost-effectiveness ratio (ICER) was BRL 284,416 per QALY gained. None of the estimates from the sensitivity analysis was below BRL 100,000 per QALY. Even when six parameters were variated simultaneously in the range more favorable to abiraterone, the results were still elevated, with an ICER of BRL 98,330 per QALY. The BI was BRL 270 million in 5 years in the most conservative scenario (average time of the treatment of 7.4 months and 10% of the new cases/year). Conclusion: Abiraterone shows unfavorable cost-effective results for this clinical condition in Brazil, with an ICER above 9 times the per capita per QALY. Results were robust in sensitivity analysis.

Costo efectividad de la cirugía reductora de riesgo en trompas y ovarios en casos con mutación del gen BRCAI en Colombia / Cost-effectiveness of risk-reducing salpingo-oophorectomy in cases of BRCA1 gene mutation in Colombia

RESUMEN Objetivo Evaluar la utilidad de la cirugía reductora de riesgo en trompas y ovarios en casos con mutación del gen BRCA1 en Colombia Material y Métodos Análisis de costo-efectividad en el que se incorporan tres procesos: a. Pacientes con pruebas de tamización para cáncer de mama y ovario. b. cirugía reductora de riesgo en trompas y ovarios c. cirugía reductora de riesgo en trompas y ovarios con mastectomía bilateral. Se evalúa como desenlace la ganancia en años de supervivencia. Resultados La cohorte con cirugía reductora de riesgo en trompas y ovarios y mastectomía bilateral es la de mayor ganancia con 13 años mientras que la cirugía reductora de riesgo en trompas y ovarios gana 4,95 años con respecto al grupo de seguimiento. Conclusiones Las tres opciones evaluadas son aceptables, pero de ellas la de mayor ganancia en la supervivencia es la combinación de cirugía reductora de riesgo en trompas y ovarios con mastectomía bilateral.(AU)

ABSTRACT Objective To assess the usefulness of risk reduction salpingo-oophorectomy in cases with mutation of the BRCA1 gene in Colombia. Material and Methods Cost-effectiveness analysis in which three processes are incorporated: a. Patients with screening tests for breast and ovarian cancer. b. Risk reduction surgery in the fallopian tubes and ovaries c. Reductive surgery in the fallopian tubes and ovaries with bilateral mastectomy. The outcome is evaluated as the gain in years of survival. Results The cohort with risk reduction surgery in the fallopian tubes and ovaries and bilateral mastectomy is the one with the highest gain with 13 years, while the risk reduction surgery in the fallopian tubes and ovaries gain 4.95 years with respect to the follow-up group. Conclusions The three options evaluated are acceptable, but of them the one with the greatest gain in survival is the combination of risk-reducing surgery in the fallopian tubes and ovaries with bilateral mastectomy.(AU)

Intensity-modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) for head and neck cancer: cost-effectiveness analysis

SUMMARY BACKGROUND: A cost-effectiveness analysis of IMRT compared to 3D-CRT for head and neck cancer patients (HNCPs) was conducted in the Brazilian Public Health System. METHODS: A Markov model was used to simulate radiation therapy-induced dysphagia and xerostomia in HNCPs. Data from the PARSPORT trial and the quality-of-life study were used as parameters. The incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained were calculated. RESULTS: At 2 years, IMRT was associated with an incremental benefit of 0.16 QALYs gained per person, resulting in an ICER of BRL 31,579 per QALY gained. IMRT was considered cost-effective when using the guideline proposed by the World Health Organization (WHO) of three times the national gross domestic product (GDP) per capita (BRL 72,195). Regarding life expectancy (15 years), the incremental benefit of IMRT was 1.16 QALYs gained per person, with an ICER of BRL 4,341. IMRT was also cost-effective using the WHO definition, which states that the maximum cost is equal to the GDP per capita (BRL 24,065). CONCLUSIONS: IMRT was considered cost-effective from the perspective of the Brazilian public health system.

RESUMO INTRODUÇÃO: Foi realizada uma análise de custo-efetividade da radioterapia com intensidade modulada de feixe (IMRT) comparada com a radioterapia conformada para pacientes com câncer de cabeça e pescoço (CCP) no contexto do Sistema Único de Saúde (SUS). MÉTODOS: Foi elaborado um modelo de Markov para comparar os custos médicos diretos e os desfechos de saúde relacionados à qualidade de vida do paciente pós-intervenção radioterápica sofrendo de xerostomia e disfagia. Com essa finalidade, foram usados os dados do estudo PARSPORT e parâmetros de qualidade de vida. Os resultados comparativos das estratégias alternativas de tratamento foram medidos pela razão de custo-efetividade incremental (RCEI). O desfecho analisado foi o de anos de vida ajustados à qualidade (QALY). RESULTADOS: Em um horizonte de tempo de dois anos, a IMRT foi associada com um benefício incremental de ganho de 0,16 QALYs por indivíduo, resultando em um RCEI de R$ 31.579 por QALY ganhado. A IMRT foi custo-efetivo, adotando-se o limite máximo de disposição a pagar, proposto pela OMS, de três vezes o PIB per capita nacional, equivalente a R$ 72.195. No horizonte de tempo de 15 anos, o benefício incremental de ganho foi de 1,16 QALYs por indivíduo, com um RCEI de R$ 4.341. A IMRT foi custo-efetivo, adotando-se o limite de disposição a pagar, proposto pela OMS, de uma vez o PIB per capita nacional, equivalente a R$ 24.065. CONCLUSÃO: A IMRT foi considerada um tratamento custo-efetivo na perspectiva do SUS.

Neurocognitive Graphs of First-Episode Schizophrenia and Major Depression Based on Cognitive Features / 神经科学通报·英文版

Neurocognitive deficits are frequently observed in patients with schizophrenia and major depressive disorder (MDD). The relations between cognitive features may be represented by neurocognitive graphs based on cognitive features, modeled as Gaussian Markov random fields. However, it is unclear whether it is possible to differentiate between phenotypic patterns associated with the differential diagnosis of schizophrenia and depression using this neurocognitive graph approach. In this study, we enrolled 215 first-episode patients with schizophrenia (FES), 125 with MDD, and 237 demographically-matched healthy controls (HCs). The cognitive performance of all participants was evaluated using a battery of neurocognitive tests. The graphical LASSO model was trained with a one-vs-one scenario to learn the conditional independent structure of neurocognitive features of each group. Participants in the holdout dataset were classified into different groups with the highest likelihood. A partial correlation matrix was transformed from the graphical model to further explore the neurocognitive graph for each group. The classification approach identified the diagnostic class for individuals with an average accuracy of 73.41% for FES vs HC, 67.07% for MDD vs HC, and 59.48% for FES vs MDD. Both of the neurocognitive graphs for FES and MDD had more connections and higher node centrality than those for HC. The neurocognitive graph for FES was less sparse and had more connections than that for MDD. Thus, neurocognitive graphs based on cognitive features are promising for describing endophenotypes that may discriminate schizophrenia from depression.

Simple but not simpler: a systematic review of Markov models for economic evaluation of cervical cancer screening

The aim of this study was to critically evaluate the quality of the models used in economic evaluations of screening strategies for cervical cancer prevention. We systematically searched multiple databases, selecting model-based full economic evaluations (cost-effectiveness analyses, cost-utility analyses, and cost-benefit analyses) of cervical cancer screening strategies. Two independent reviewers screened articles for relevance and performed data extraction. Methodological assessment of the quality of the models utilized formal checklists, and a qualitative narrative synthesis was performed. Thirty-eight articles were reviewed. The majority of the studies were conducted in high-income countries (82%, n=31). The Pap test was the most used screening strategy investigated, which was present in 86% (n=33) of the studies. Half of the studies (n=19) used a previously published Markov model. The deterministic sensitivity analysis was performed in 92% (n=35) of the studies. The mean number of properly reported checklist items was 9 out of the maximum possible 18. Items that were better reported included the statement of decision problem, the description of the strategies/comparators, the statement of time horizon, and information regarding the disease states. Compliance with some items of the checklist was poor. The Markov models for economic evaluation of screening strategies for cervical cancer varied in quality. The following points require improvement: 1) assessment of methodological, structural, heterogeneity, and parameter uncertainties; 2) model type and cycle length justification; 3) methods to account for heterogeneity; and 4) report of consistency evaluation (through calibration and validation methods).

Análisis costo-efectividad de lenalidomida en combinación con dexametasona frente a bortezomib combinado con dexametasona en el tratamiento en segunda línea del mieloma múltiple en Chile / Cost-effectiveness of lenalidomide in combination with dexamethasone compared to bortezomib in combination with dexamethasone for the second-line treatment of multiple myeloma in Chile

CONTEXTO: El mieloma múltiple es una neoplasia de las células plasmáticas de la medula ósea. Las terapias disponibles no son curativas y la mayoría de los pacientes se vuelve refractario al tratamiento. Agentes como lenalidomida y bortezomib han demostrado su eficacia en el tratamien-to en segunda línea de estos pacientes. OBJETIVO: Evaluar el costo-efectividad de la combinación lenalidomida/dexametasona frente a bortezomib/dexametasona en pacientes con mieloma múltiple, no candidatos a trasplante, previamente tratados con bortezomib, desde la perspectiva del sistema nacional de salud chileno. METODOLOGÍA: Se empleó un modelo de Markov que simula la evolución de una cohorte de pacientes a través de cuatro estados de salud (preprogresión en tratamiento, preprogresión sin tratamiento, progresión o muerte) en un horizonte temporal de 25 años. Los datos de eficacia, uso de recursos y frecuencia de efectos adversos fueron extraídos de los ensayos sobre mieloma múltiple MM-009 y MM-010 y de un estudio retrospectivo de retratamiento con bortezomib. Todos los parámetros fueron validados por expertos. Se aplicó una tasa de descuento en costos y beneficios de 3%. La robustez de los resultados fue evaluada mediante un análisis de sensibilidad univariante y probabilístico. RESULTADOS: El tratamiento con lenalidomida/dexametasona proporciona 1,41 años de vida y 0,83 años de vida ajustados por calidad incrementales respecto a bortezomib/dexametasona, con un costo incremental de 11 864 597,86 pesos chilenos (19 589,86 dólares). La ratio de cos-to-efectividad y costo-utilidad incremental se cifró en 8 410 266,92 pesos chilenos (13 886,35 dólares) por año de vida ganado y 14 271 896,16 pesos chilenos (23 564,59 dólares) por año de vida ajustado por calidad respectivamente. CONCLUSIÓN: La lenalidomida/dexametasona representa una alternativa potencialmente costo-efectiva, desde la perspectiva del sistema nacional de salud chileno, para el tratamiento en segunda línea de pacientes con mieloma múltiple no candidatos a trasplante.

BACKGROUND: Multiple myeloma is a hematologic malignancy affecting bone marrow derived plasma cells. Current therapies are not able to eradicate the disease and most patients become refractory to the treatment. Lenalidomide and bortezomib have proved effective in the second-line treatment of these patients. OBJECTIVE: To evaluate the cost-effectiveness of lenalidomide in combination with dexamethasone compared to bortezomib in combination with dexamethasone in patients with multiple myeloma previously treated with bortezomib, from the perspective of the Chilean National Health Service. METHODOLOGY: A four-state Markov model (preprogression on treatment; preprogression off treatment, progression and death) was used to simulate the evolution of a cohort of multiple myeloma patients over a 25-year time horizon. Efficacy data, resource use and frequency of adverse events were extracted from MM009/010 studies and a retrospective analysis of retreatment with bortezomib. All inputs were validated by experts. A 3% annual discount rate was used for costs and health outcomes. The robustness of the results was evaluated through univariate and probabilistic sensitivity analyses. RESULTS: Lenalidomide in combination with dexamethasone treatment provided 1.41 incremental life years and 0.83 incremental quality-adjusted life years in comparison with bortezomib in combination with dexamethasone, with an incremental cost of 11 864 597.86 CLP (19 589.86 US$). The incremental cost-effectiveness and cost-utility ratio were estimated at 8 410 266.92 CLP (13 886,35 US$) / incremental life year and 14 271 896.16 CLP (23 564,59 US$)/incremental quality-adjusted life years, respectively. CONCLUSIONS: Lenalidomide in combination with dexamethasone represents a potentially cost-effective alternative for the second-line treatment of patients with multiple myeloma who are not eligible for transplantation, from the perspective of the Chilean National Health Service.

Cost effectiveness of the cancer prevention program for carriers of the BRCA1/2 mutation

ABSTRACT OBJECTIVE: To analyze the cost effectiveness of the diagnostic program for the germline mutation in BRCA1/2 genes and of preventative strategies for the relatives of patients diagnosed with ovarian cancer associated with this mutation. METHODS: The study analyzed the cost effectiveness by developing an analysis of the Markov decision process from the perspective of the National Health System. The strategies compared reflect upon the adoption of genetic testing and preventative strategies for relatives or the usual care currently proposed. The incremental cost-effectiveness ratio was expressed in terms of cost per case avoided. The sensitivity analysis was performed in a univariate and deterministic manner. RESULTS: The study showed increments for effectiveness and for costs when performing genetic testing and adopting prophylactic measures for family members. The incremental cost-effectiveness ratio was estimated at R$908.58 per case of cancer avoided, a figure considered lower than the study's cost-effectiveness threshold (R$7,543.50). CONCLUSIONS: The program analyzed should be considered a cost-effective strategy for the national situation. Studies in various other countries have reached similar conclusions. One possible ramification of this research might the need to perform a budgetary-impact analysis of making the program one of the country's health policies.

Evaluación de la costo-efectividad de un modelo integral de tratamiento ambulatorio en pacientes con síndrome coronario agudo: aplicación de un modelo de Markov probabilístico / Evaluation of the cost-effectiveness of an integral model of ambulatory treatment in patients with acute coronary syndrome: application of a probabilistic Markov model / Avaliação da relação custo-eficácia de um modelo integral de tratamento ambulatorial em pacientes com síndrome coronariana aguda: aplicação de um modelo probabilístico de Markov

RESUMEN Objetivo Evaluar la costo-efectividad de un modelo integral de tratamiento ambulatorio en pacientes que presentaron un síndrome coronario agudo. Métodos Se realizó una evaluación económica a partir de un estudio de intervención cuasi-experimental, que incluyó 442 pacientes con edades entre 30 y 70 años, quienes presentaron un síndrome coronario agudo. El grupo de intervención (n = 165) recibió un modelo integral de tratamiento ambulatorio fundamentado en el cuidado gestionado (disease management), mientras que el grupo control (n = 277) recibió rehabilitación cardiovascular convencional. Durante un año de seguimiento, se evaluó la presentación de reeventos cardiovasculares y hospitalizaciones. Se desarrolló un modelo de Markov probabilístico. La perspectiva de estudio se aplicó dentro del Sistema General de Seguridad Social en Salud Colombiano, incluidos los costos sanitarios directos; el horizonte temporal fue de 50 años con descuentos de 3,42% para costos y efectividades; y la medida de efectividad fue los años de vida ganados ajustados por calidad. Se realizó un análisis de sensibilidad probabilístico y multivariante mediante de la simulación de Montecarlo. Resultados Durante el año de seguimiento, los costos directos relacionados con el valor pagado fueron en promedio de USD 2 577 para el grupo control y USD 2 245 para el grupo de intervención. En el análisis de sensibilidad probabilístico, 91,3% de las simulaciones se ubicaron en el cuadrante correspondiente a costos incrementales negativos y efectividades incrementales positivas (intervención evaluada de menor costo, más efectiva). En las simulaciones, se observó un ahorro promedio anual por paciente de USD 1 215 por cada año de vida ganado ajustado por calidad. Conclusiones El modelo integral de tratamiento ambulatorio implementado en pacientes que sufrieron un síndrome coronario agudo mostró ser menos costoso y más efectivo en comparación con el cuidado convencional. Por ser una alternativa dominante, se recomienda como modelo de cuidado en esta población.

ABSTRACT Objective To evaluate the cost-effectiveness of an integral model of ambulatory treatment in patients who presented an acute coronary syndrome. Methods An economic evaluation was made from a quasi-experimental intervention study, which included 442 patients aged 30 to 70 years who presented an acute coronary syndrome. The intervention group (n = 165) received an integral model of ambulatory treatment based on managed care (disease management), while the control group (n = 277) received conventional cardiovascular rehabilitation. During one year of follow-up, the presentation of cardiovascular events and hospitalizations was evaluated. A probabilistic Markov model was developed. The study perspective was applied within the General System of Health Social Security in Colombia, including the direct health costs; the time horizon was 50 years with discounts of 3.42% for costs and effectiveness; and the measure of effectiveness was quality-adjusted life years (QALYs). A probabilistic and multivariate sensitivity analysis was performed using the Montecarlo simulation. Results During the year of follow-up, the direct costs related to the value paid were, on average, USD 2 577 for the control group and USD 2 245 for the intervention group. In the probabilistic sensitivity analysis, 91.3% of the simulations were located in the quadrant corresponding to incremental negative costs and positive incremental effectiveness (evaluated intervention at a lower cost, more effective). In the simulations, an average annual savings per patient of USD 1 215 per QALY was observed. Conclusions The integral model of ambulatory treatment implemented in patients who suffered an acute coronary syndrome was found to be less expensive and more effective compared to conventional care. Considering it is a dominant alternative, it is recommended as a model of care in this population.

RESUMO Objetivo Avaliar a relação custo-eficácia de um modelo integral de tratamento ambulatorial em pacientes que apresentaram síndrome coronariana aguda. Métodos Uma avaliação econômica foi feita a partir de um estudo de intervenção quase experimental, que incluiu 442 pacientes com idade entre 30 a 70 anos que apresentaram síndrome coronariana aguda. O grupo de intervenção (n = 165) recebeu um modelo integral de tratamento ambulatorial com base em cuidados gerenciados (gerenciamento de doenças), enquanto o grupo controle (n = 277) recebeu reabilitação cardiovascular convencional. Durante um ano de acompanhamento, foi avaliada a apresentação de eventos cardiovasculares e hospitalizações. Um modelo probabilístico de Markov foi desenvolvido. A perspectiva do estudo foi aplicada no Sistema Geral de Segurança Social na Saúde da Colômbia, incluindo os custos diretos de saúde; o horizonte temporal foi de 50 anos com descontos de 3,42% em custos e efetividade; e a medida de eficácia foi os anos de vida ajustados pela qualidade (QALY). Uma análise de sensibilidade probabilística e multivariada foi realizada utilizando a simulação de Montecarlo. Resultados Durante o ano de acompanhamento, os custos diretos relacionados ao valor pago foram, em média, USD 2 577 para o grupo controle e USD 2 245 para o grupo de intervenção. Na análise de sensibilidade probabilística, foram localizadas 91,3% das simulações no quadrante correspondente a custos negativos incrementais e eficácia incremental positiva (intervenção avaliada a menor custo, mais efetiva). Nas simulações, observou-se uma economia anual média por paciente de US $ 1 215 por QALY. Conclusões O modelo integral de tratamento ambulatorial implementado em pacientes que sofreram síndrome coronariana aguda foi considerado menos caro e mais eficaz em comparação com os cuidados convencionais. Por ser uma alternativa dominante, é recomendado como modelo de cuidados nesta população.

A Short Report on the Markov Property of DNA Sequences on 200-bp Genomic Units of ENCODE/Broad ChromHMM Annotations: A Computational Perspective

The non-coding DNA in eukaryotic genomes encodes a language which programs chromatin accessibility, transcription factor binding, and various other activities. The objective of this short report was to determine the impact of primary DNA sequence on the epigenomic landscape across 200-base pair genomic units by integrating nine publicly available ChromHMM Browser Extensible Data files of the Encyclopedia of DNA Elements (ENCODE) project. The nucleotide frequency profiles of nine chromatin annotations with the units of 200 bp were analyzed and integrative Markov chains were built to detect the Markov properties of the DNA sequences in some of the active chromatin states of different ChromHMM regions. Our aim was to identify the possible relationship between DNA sequences and the newly built chromatin states based on the integrated ChromHMM datasets of different cells and tissue types.

Costo-efectividad de dos terapias antivirales para Hepatitis B crónica en el Perú: Entecavir y tenofovir / Cost-Fffectiveness of Two Antiviral Therapies for Chronic Hepatitis B in Peru: Entecavir and Tenofovir

RESUMEN Objetivos Comparar en términos de costo-efectividad a entecavir (ETV) y tenofovir (TDF) en el tratamiento del virus de la hepatitis B (HBV) en hospitales públicos del Perú. Materiales y métodos Estructuramos un modelo de Markov, definimos la efectividad en años de vida ajustados a calidad (AVAC). Incluimos los costos directos del tratamiento en soles desde la perspectiva del Ministerio de Salud del Perú. Calculamos la relación entre costo y efectividad incrementales (ICER). Realizamos análisis de sensibilidad determinístico y probabilístico, considerando un rango de disponibilidad de pago (WTP) desde uno hasta tres veces el producto bruto interno (PBI) per-cápita, y el beneficio monetario neto (BMN) o ICER en el caso del análisis de tornado. Resultados El tratamiento con TDF es más efectivo y menos costoso que ETV. El ETV tuvo un costo por AVAC de S/ 4482, y de S/ 1526 para TDF. El TDF mantiene un BMN progresivamente mayor conforme aumenta la WTP. La tasa de descuento fue la única variable con efecto significativo en la incertidumbre del modelo. Conclusiones El tratamiento con TDF es más costo-efectivo que ETV en hospitales públicos del Perú.

ABSTRACT Objetives To compare in terms of cost-effectiveness to entecavir (ETV) and tenofovir (TDF) in the treatment of hepatitis B virus (HBV) in public hospitals in Peru. Materials and methods We structured a Markov model. We define effectiveness adjusted life years for quality (QALY). We include the direct costs of treatment in soles from the perspective of the Ministry of Health of Peru. We estimate the relationship between cost and effectiveness ratios (ICER). We performed sensitivity analyzes considering a range of willingness to pay (WTP) from one to three times the Gross Domestic Product (GDP) per capita, and a tornado analysis regarding Monetary Net Profit (BMN) or ICER. Results Treatment with TDF is more effective and less expensive than ETV. The ETV had a cost per QALY of PEN 4482, and PEN 1526 TDF. The PTO maintains a progressively larger with increasing WTP BMN. The discount rate was the only variable with a significant effect on model uncertainty. Conclusion Treatment with TDF is more cost-effective than ETV in public hospitals in Peru.

Cadenas de markov aplicadas al análisis de la ejecución de proyectos de investigación / Markov chains applied to the analyzis of the progress of research projets

La administración moderna requiere el apoyo de herramientas de diferentes ramas de la ciencia que ayuden al proceso de toma de decisiones, como por ejemplo la Matemática Aplicada. En este contexto aparecen variables aleatorias que con el transcurso del tiempo cambian, y que pueden ser representadas a través de modelos cuantitativos. Cuando en estos modelos el estado presente de dichas variables resume toda la información anterior para describir cómo se comportarán en el futuro, se dice que se está en presencia de una cadena de Markov; una herramienta eficiente para el análisis de procesos de esta naturaleza, como por ejemplo la ejecución de proyectos de investigación, el cual reviste gran importancia en la gestión de ciencia e innovación tecnológica; área de resultados clave en cualquier universidad. En la Facultad de Tecnología de la Universidad de Ciencias Médicas de Santiago de Cuba, el análisis de la ejecución de los proyectos de investigación se consideró como una cadena de Markov, definiendo los diferentes estados por los que puede estar un proyecto, y las probabilidades de que este se encuentre en un estado determinado a partir del estado en que se encontraba. Así se determinaron elementos que permiten apoyar la toma de decisiones a corto y a largo plazo, a partir de datos históricos durante el trienio 2013 - 2015, relacionados con la cantidad promedio de inspecciones a los mismos, probabilidades de un proyecto cerrar, etc.; permitiendo pronosticar en términos de probabilidades el estado de este subsistema en el futuro(AU)

Modern management tools require support from different branches of science to help the decision-making process, such as Applied Mathematics. In this context, random variables with change over time, and that can be represented by quantitative models appear. When these models in the present state of these variables summarizes all the previous information to describe how they will behave in the future, it is said that we are in the presence of a Markov chain; an efficient tool for the analysis of processes of this nature, such as the execution of research projects, which is of great importance in the management of science and technological innovation; key result area at any university. In the Faculty of Technology, University of Medical Sciences of Santiago de Cuba, the analysis of the implementation of research projects was considered as a Markov chain, defining the different states through which can be a project and the odds of this is in a certain state from the state it was. And support elements that enable decision-making in the short and long term, from historical data in the period 2013 - 2015 were determined, related to the average number of inspections to a project, the probability of a project likely to close, etc.; allowing to predict in terms of probabilities the status of this subsystem in the future(AU)