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BACKGROUND: Refractory cardiogenic shock (CS) is associated with high mortality rates, and the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a therapeutic option has generated discussions. Therefore, its cost-effectiveness, especially in low- and middle-income countries like Brazil, remains uncertain.Objectives: To conduct a cost-utility analysis from the Brazilian Unified Health System perspective to assess the cost-effectiveness of VA-ECMO combined with standard care compared to standard care alone in adult refractory CS patients. METHODS: We followed a cohort of refractory CS patients treated with VA-ECMO in tertiary care centers located in Southern Brazilian. We collected data on hospital outcomes and costs. We conducted a systematic review to supplement our data and utilized a Markov model to estimate incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY) and per life-year gained. RESULTS: In the base-case analysis, VA-ECMO yielded an ICER of Int$ 37,491 per QALY. Sensitivity analyses identified hospitalization cost, relative risk of survival, and VA-ECMO group survival as key drivers of results. Probabilistic sensitivity analysis favored VA-ECMO, with a 78% probability of cost-effectiveness at the recommended willingness-to-pay threshold. CONCLUSIONS: Our study suggests that, within the Brazilian Health System framework, VA-ECMO may be a cost-effective therapy for refractory CS. However, limited efficacy data and recent trials questioning its benefit in specific patient subsets highlight the need for further research. Rigorous clinical trials, encompassing diverse patient profiles, are essential to confirm cost-effectiveness and ensure equitable access to advanced medical interventions within healthcare systems, particularly in socio-economically diverse countries like Brazil.

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FUNDAMENTO: O choque cardiogênico (CC) refratário está associado com altas taxas de mortalidade, e o uso de oxigenação por membrana extracorpórea venoarterial (VA-ECMO, do inglês venoarterial extracorporeal membrane oxygenation) como uma opção terapêutica tem gerado discussões. Nesse sentido, sua custo-efetividade, principalmente em países de baixa e média renda como o Brasil, continua incerto.Objetivos: Conduzir uma análise de custo-efetividade na perspectiva do Sistema Único de Saúde (SUS) para avaliar a custo-efetividade de VA-ECMO combinado com o tratamento padrão em comparação ao tratamento padrão isolado em pacientes adultos com CC refratário. MÉTODOS: Acompanhamos uma coorte de pacientes com CC refratário tratados com VA-ECMO em centros de assistência terciária do sul brasileiro. Coletamos dados de desfechos e custos hospitalares. Realizamos uma revisão sistemática para complementar nossos dados e usamos o modelo de Markov para estimar a razão de custo-efetividade incremental (RCEI) por ano de vida ajustado pela qualidade (QALY) e por ano de vida ganho. RESULTADOS: Na análise do caso-base, a VA-ECMO gerou uma RCEI de Int$ 37 491 por QALY. Análises de sensibilidade identificaram o custo de internação, o risco relativo de sobrevida, e a sobrevida do grupo submetido à VA-ECMO como principais variáveis influenciando os resultados. A análise de sensibilidade probabilística mostrou um benefício do uso de VA-ECMO, com uma probabilidade de 78% de custo-efetividade no limiar recomendado de disposição a pagar. CONCLUSÕES: Nosso estudo sugere que, dentro do SUS, VA-ECMO pode ser uma terapia custo-efetiva para o CC refratário. Contudo, a escassez de dados sobre a eficácia e de ensaios clínicos recentes que abordem seus benefícios em subgrupos específicos de pacientes destaca a necessidade de mais pesquisas. Ensaios clínicos rigorosos, incluindo perfis diversos de pacientes, são essenciais para confirmar a custo-efetividade com uso de VA-ECMO e assegurar acesso igualitário a intervenções médicas avançadas dentro dos sistemas de saúde, especialmente em países com desigualdades socioeconômicas como o Brasil.

Asunto(s)

Análisis Costo-Beneficio , Oxigenación por Membrana Extracorpórea , Años de Vida Ajustados por Calidad de Vida , Choque Cardiogénico , Humanos , Brasil , Oxigenación por Membrana Extracorpórea/economía , Cadenas de Markov , Choque Cardiogénico/terapia , Choque Cardiogénico/economía , Choque Cardiogénico/mortalidad , Resultado del Tratamiento

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BACKGROUND: Individuals who were formerly incarcerated have high tuberculosis incidence, but are generally not considered among the risk groups eligible for tuberculosis prevention. We investigated the potential health impact and cost-effectiveness of Mycobacterium tuberculosis infection screening and tuberculosis preventive treatment (TPT) for individuals who were formerly incarcerated in Brazil. METHODS: Using published evidence for Brazil, we constructed a Markov state transition model estimating tuberculosis-related health outcomes and costs among individuals who were formerly incarcerated, by simulating transitions between health states over time. The analysis compared tuberculosis infection screening and TPT, to no screening, considering a combination of M tuberculosis infection tests and TPT regimens. We quantified health effects as reductions in tuberculosis cases, tuberculosis deaths, and disability-adjusted life-years (DALYs). We assessed costs from a tuberculosis programme perspective. We report intervention cost-effectiveness as the incremental costs per DALY averted, and tested how results changed across subgroups of the target population. FINDINGS: Compared with no intervention, an intervention incorporating tuberculin skin testing and treatment with 3 months of isoniazid and rifapentine would avert 31 (95% uncertainty interval 14-56) lifetime tuberculosis cases and 4·1 (1·4-5·8) lifetime tuberculosis deaths per 1000 individuals, and cost US$242 per DALY averted. All test and regimen combinations were cost-effective compared with no screening. Younger age, longer incarceration, and more recent prison release were each associated with significantly greater health benefits and more favourable cost-effectiveness ratios, although the intervention was cost-effective for all subgroups examined. INTERPRETATION: M tuberculosis infection screening and TPT for individuals who were formerly incarcerated appears cost-effective, and would provide valuable health gains. FUNDING: National Institutes of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Asunto(s)

Análisis Costo-Beneficio , Cadenas de Markov , Tamizaje Masivo , Prisioneros , Tuberculosis , Humanos , Brasil/epidemiología , Prisioneros/estadística & datos numéricos , Tuberculosis/diagnóstico , Tuberculosis/economía , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Adulto , Masculino , Femenino , Antituberculosos/uso terapéutico , Antituberculosos/economía , Persona de Mediana Edad , Rifampin/uso terapéutico , Rifampin/economía , Mycobacterium tuberculosis/aislamiento & purificación , Adulto Joven

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OBJECTIVES: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina's national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina's pediatric NIP. METHODS: A decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty. RESULTS: Compared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments. CONCLUSION: Over a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options.

Asunto(s)

Análisis Costo-Beneficio , Infecciones Neumocócicas , Vacunas Neumococicas , Vacunas Conjugadas , Vacunas Neumococicas/economía , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Humanos , Argentina/epidemiología , Infecciones Neumocócicas/prevención & control , Infecciones Neumocócicas/economía , Infecciones Neumocócicas/epidemiología , Lactante , Vacunas Conjugadas/economía , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunología , Preescolar , Programas de Inmunización/economía , Cadenas de Markov , Años de Vida Ajustados por Calidad de Vida , Niño , Femenino , Masculino , Análisis de Costo-Efectividad

RESUMEN

In the present work, both direct and inverse problems are considered for a Fisher-type fractional diffusion equation, which is proposed to describe the phenomenon of cell migration. For the direct problem, a solution is given via the Fourier method and the Laplace transform. On the other hand, we solved the inverse problem from a Bayesian statistical framework using a set of data that are the result of a cell migration experiment on a wound closure assay. We estimated the parameters of the mathematical model via Markov Chain Monte Carlo methods.

Asunto(s)

Teorema de Bayes , Movimiento Celular , Cadenas de Markov , Modelos Biológicos , Método de Montecarlo , Humanos , Simulación por Computador , Algoritmos , Difusión , Análisis de Fourier , Animales

RESUMEN

We introduce a model that can be used for the description of the distribution of species when there is scarcity of data, based on our previous work (Ballesteros et al. J Math Biol 85(4):31, 2022). We address challenges in modeling species that are seldom observed in nature, for example species included in The International Union for Conservation of Nature's Red List of Threatened Species (IUCN 2023). We introduce a general method and test it using a case study of a near threatened species of amphibians called Plectrohyla Guatemalensis (see IUCN 2023) in a region of the UNESCO natural reserve "Tacaná Volcano", in the border between Mexico and Guatemala. Since threatened species are difficult to find in nature, collected data can be extremely reduced. This produces a mathematical problem in the sense that the usual modeling in terms of Markov random fields representing individuals associated to locations in a grid generates artificial clusters around the observations, which are unreasonable. We propose a different approach in which our random variables describe yearly averages of expectation values of the number of individuals instead of individuals (and they take values on a compact interval). Our approach takes advantage of intuitive insights from environmental properties: in nature individuals are attracted or repulsed by specific features (Ballesteros et al. J Math Biol 85(4):31, 2022). Drawing inspiration from quantum mechanics, we incorporate quantum Hamiltonians into classical statistical mechanics (i.e. Gibbs measures or Markov random fields). The equilibrium between spreading and attractive/repulsive forces governs the behavior of the species, expressed through a global control problem involving an energy operator.

Asunto(s)

Conservación de los Recursos Naturales , Especies en Peligro de Extinción , Cadenas de Markov , Conceptos Matemáticos , Modelos Biológicos , Densidad de Población , Animales , Especies en Peligro de Extinción/estadística & datos numéricos , México , Conservación de los Recursos Naturales/estadística & datos numéricos , Guatemala , Anuros/fisiología , Ecosistema , Distribución Animal , Dinámica Poblacional/estadística & datos numéricos

RESUMEN

Zika, a viral disease transmitted to humans by Aedes mosquitoes, emerged in the Americas in 2015, causing large-scale epidemics. Colombia alone reported over 72,000 Zika cases between 2015 and 2016. Using national surveillance data from 1121 municipalities over 70 weeks, we identified sociodemographic and environmental factors associated with Zika's emergence, re-emergence, persistence, and transmission intensity in Colombia. We fitted a zero-state Markov-switching model under the Bayesian framework, assuming Zika switched between periods of presence and absence according to spatially and temporally varying probabilities of emergence/re-emergence (from absence to presence) and persistence (from presence to presence). These probabilities were assumed to follow a series of mixed multiple logistic regressions. When Zika was present, assuming that the cases follow a negative binomial distribution, we estimated the transmission intensity rate. Our results indicate that Zika emerged/re-emerged sooner and that transmission was intensified in municipalities that were more densely populated, at lower altitudes and/or with less vegetation cover. Warmer temperatures and less weekly-accumulated rain were also associated with Zika emergence. Zika cases persisted for longer in more densely populated areas with more cases reported in the previous week. Overall, population density, elevation, and temperature were identified as the main contributors to the first Zika epidemic in Colombia. We also estimated the probability of Zika presence by municipality and week, and the results suggest that the disease circulated undetected by the surveillance system on many occasions. Our results offer insights into priority areas for public health interventions against emerging and re-emerging Aedes-borne diseases.

Asunto(s)

Aedes , Cadenas de Markov , Infección por el Virus Zika , Virus Zika , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/epidemiología , Colombia/epidemiología , Humanos , Animales , Aedes/virología , Teorema de Bayes , Mosquitos Vectores/virología , Brotes de Enfermedades

RESUMEN

Aims: We adopted a modeling approach to predict the likely future prevalence of type 2 diabetes, taking into account demographic changes and trends in obesity and smoking in Brazil. We then used the model to estimate the likely future impact of different policy scenarios, such as policies to reduce obesity. Methods: The IMPACT TYPE 2 DIABETES model uses a Markov approach to integrate population, obesity, and smoking trends to estimate future type 2 diabetes prevalence. We developed a model for the Brazilian population from 2006 to 2036. Data on the Brazilian population in relation to sex and age were collected from the Brazilian Institute of Geography and Statistics, and data on the prevalence of type 2 diabetes, obesity, and smoking were collected from the Surveillance of Risk and Protection Factors for Chronic Diseases by Telephone Survey (VIGITEL). Results: The observed prevalence of type 2 diabetes among Brazilians aged over 25 years was 10.8% (5.2-14.3%) in 2006, increasing to 13.7% (6.9-18.4%) in 2020. Between 2006 and 2020, the observed prevalence in men increased from 11.0 to 19.1% and women from 10.6 to 21.3%. The model forecasts a dramatic rise in prevalence by 2036 (27.0% overall, 17.1% in men and 35.9% in women). However, if obesity prevalence declines by 1% per year from 2020 to 2036 (Scenario 1), the prevalence of diabetes decreases from 26.3 to 23.7, which represents approximately a 10.0% drop in 16 years. If obesity declined by 5% per year in 16 years as an optimistic target (Scenario 2), the prevalence of diabetes decreased from 26.3 to 21.2, representing a 19.4% drop in diabetes prevalence. Conclusion: The model predicts an increase in the prevalence of type 2 diabetes in Brazil. Even with ambitious targets to reduce obesity prevalence, type 2 diabetes in Brazil will continue to have a large impact on Brazilian public health.

Asunto(s)

Diabetes Mellitus Tipo 2 , Obesidad , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Brasil/epidemiología , Masculino , Femenino , Prevalencia , Adulto , Persona de Mediana Edad , Obesidad/epidemiología , Anciano , Fumar/epidemiología , Predicción , Cadenas de Markov , Factores de Riesgo

RESUMEN

Importance: Standard of care for unresectable locally advanced non-small cell lung cancer (NSCLC) involves definitive chemoradiotherapy followed by maintenance therapy with durvalumab. However, the cost of durvalumab has been cited as a barrier to its use in various health systems. Objective: To evaluate the cost-effectiveness of durvalumab vs placebo as maintenance therapy in patients with unresectable stage III NSCLC from 4 international payer perspectives (US, Brazil, Singapore, and Spain). Design, Setting, and Participants: In this economic evaluation, a Markov model was designed to compare the lifetime cost-effectiveness of maintenance durvalumab for unresectable stage III NSCLC with that of placebo, using 5-year outcomes data from the PACIFIC randomized placebo-controlled trial. Individual patient data were extracted from the PACIFIC, KEYNOTE-189, ADAURA, ALEX, and REVEL randomized clinical trials to develop a decision-analytic model to determine the cost-effectiveness of durvalumab compared with placebo maintenance therapy over a 10-year time horizon. Direct costs, adverse events, and patient characteristics were based on country-specific payer perspectives and demographic characteristics. The study was conducted from June 1, 2022, through December 27, 2023. Main Outcomes and Measures: Life-years, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs) were estimated at country-specific willingness-to-pay thresholds ([data reported in US$] US: $150 000 per QALY; Brazil: $22 251 per QALY; Singapore: $55 288 per QALY, and Spain: $107 069 per QALY). One-way and probabilistic sensitivity analyses were performed to account for parameters of uncertainty. A cost-threshold analysis was also performed. Results: The US base-case model found that treatment with durvalumab was associated with an increased cost of $114 394 and improved effectiveness of 0.50 QALYs compared with placebo, leading to an ICER of $228 788 per QALY. Incremental cost-effectiveness ratios, according to base-case models, were $141 146 for Brazil, $153 461 for Singapore, and $125 193 for Spain. Durvalumab price adjustments to the PACIFIC data improved cost-effectiveness in Singapore, with an ICER of $45 164. The model was most sensitive to the utility of durvalumab. Conclusions and Relevance: In this cost-effectiveness analysis of durvalumab as maintenance therapy for unresectable stage III NSCLC, the therapy was found to be cost-prohibitive from the perspective of various international payers according to country-specific willingness-to-pay thresholds per QALY. The findings of the study suggest that discounted durvalumab acquisition costs, as possible in Singapore, might improve cost-effectiveness globally.

Asunto(s)

Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas , Análisis Costo-Beneficio , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/economía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/economía , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/economía , Brasil , España , Años de Vida Ajustados por Calidad de Vida , Masculino , Singapur , Femenino , Estados Unidos , Persona de Mediana Edad , Estadificación de Neoplasias , Anciano , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/economía , Cadenas de Markov , Análisis de Costo-Efectividad

RESUMEN

OBJECTIVES: To undertake a cost-effectiveness analysis of restorative treatments for a first permanent molar with severe molar incisor hypomineralization from the perspective of the Brazilian public system. MATERIALS AND METHODS: Two models were constructed: a one-year decision tree and a ten-year Markov model, each based on a hypothetical cohort of one thousand individuals through Monte Carlo simulation. Eight restorative strategies were evaluated: high viscosity glass ionomer cement (HVGIC); encapsulated GIC; etch and rinse adhesive + composite; self-etch adhesive + composite; preformed stainless steel crown; HVGIC + etch and rinse adhesive + composite; HVGIC + self-etch adhesive + composite, and encapsulated GIC + etch and rinse adhesive + composite. Effectiveness data were sourced from the literature. Micro-costing was applied using 2022 USD market averages with a 5% variation. Incremental cost-effectiveness ratio (ICER), net monetary benefit (%NMB), and the budgetary impact were obtained. RESULTS: Cost-effective treatments included HVGIC (%NMB = 0%/ 0%), encapsulated GIC (%NMB = 19.4%/ 19.7%), and encapsulated GIC + etch and rinse adhesive + composite (%NMB = 23.4%/ 24.5%) at 1 year and 10 years, respectively. The benefit gain of encapsulated GIC + etch and rinse adhesive + composite in relation to encapsulated GIC was small when compared to the cost increase at 1 year (gain of 3.28% and increase of USD 24.26) and 10 years (gain of 4% and increase of USD 15.54). CONCLUSION: Within the horizon and perspective analyzed, the most cost-effective treatment was encapsulated GIC restoration. CLINICAL RELEVANCE: This study can provide information for decision-making.

Asunto(s)

Hipoplasia del Esmalte Dental , Restauración Dental Permanente , Cementos de Ionómero Vítreo , Humanos , Brasil , Árboles de Decisión , Hipoplasia del Esmalte Dental/terapia , Restauración Dental Permanente/métodos , Restauración Dental Permanente/economía , Cementos de Ionómero Vítreo/uso terapéutico , Cadenas de Markov , Diente Molar , Hipomineralización Molar , Método de Montecarlo

RESUMEN

In this paper, we presented a mathematical model for tuberculosis with treatment for latent tuberculosis cases and incorporated social implementations based on the impact they will have on tuberculosis incidence, cure, and recovery. We incorporated two variables containing the accumulated deaths and active cases into the model in order to study the incidence and mortality rate per year with the data reported by the model. Our objective is to study the impact of social program implementations and therapies on latent tuberculosis in particular the use of once-weekly isoniazid-rifapentine for 12 weeks (3HP). The computational experimentation was performed with data from Brazil and for model calibration, we used the Markov Chain Monte Carlo method (MCMC) with a Bayesian approach. We studied the effect of increasing the coverage of social programs, the Bolsa Familia Programme (BFP) and the Family Health Strategy (FHS) and the implementation of the 3HP as a substitution therapy for two rates of diagnosis and treatment of latent at 1% and 5%. Based of the data obtained by the model in the period 2023-2035, the FHS reported better results than BFP in the case of social implementations and 3HP with a higher rate of diagnosis and treatment of latent in the reduction of incidence and mortality rate and in cases and deaths avoided. With the objective of linking the social and biomedical implementations, we constructed two different scenarios with the rate of diagnosis and treatment. We verified with results reported by the model that with the social implementations studied and the 3HP with the highest rate of diagnosis and treatment of latent, the best results were obtained in comparison with the other independent and joint implementations. A reduction of the incidence by 36.54% with respect to the model with the current strategies and coverage was achieved, and a greater number of cases and deaths from tuberculosis was avoided.

Asunto(s)

Antituberculosos , Teorema de Bayes , Isoniazida , Tuberculosis Latente , Cadenas de Markov , Conceptos Matemáticos , Método de Montecarlo , Rifampin , Humanos , Brasil/epidemiología , Incidencia , Isoniazida/administración & dosificación , Antituberculosos/administración & dosificación , Rifampin/administración & dosificación , Rifampin/análogos & derivados , Rifampin/uso terapéutico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/mortalidad , Modelos Biológicos , Tuberculosis/mortalidad , Tuberculosis/epidemiología , Tuberculosis/tratamiento farmacológico , Simulación por Computador

RESUMEN

OBJECTIVES: To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system. METHODS: A decision tree model for the induction phase and a Markov model for the maintenance phase were built. A review of the clinical literature was conducted to extract probabilities, and the life-years were used as the outcome. Costs were calculated using the administrative databases. The evaluating treatment schemes are organized by groups of evidence with direct comparisons. RESULTS: In the induction phase, anti-thymocyte immunoglobulin+ methylprednisolone is dominant, more effective, and less expensive, compared with basiliximab+methylprednisolone. In the maintenance phase, azathioprine (AZA) is dominant in contrast to mycophenolate mofetil (MFM) both with cyclosporine (CIC)+ corticosteroids (CE); CIC is dominant relative to sirolimus (SIR) and tacrolimus (TAC) (both with MFM+CE or AZA+CE), and TAC is dominant compared with SIR (in addition with MFM+CE or mycophenolate sodium [MFS]+CE); MFM is dominant in relation to MFS and everolimus, and SIR is more effective MFM but it does not exceed the threshold (in sum with TAC+CE); MFS and MFM are dominant relative to everolimus, and SIR is more effective than MFM, but it does not exceed the threshold (in addiction with CIC+CE); MFM is dominant in relation to TAC (in sum with SIR+CE), and CIC+AZA+CE is dominant in relation to TAC+MFM+CE. CONCLUSIONS: The base-case results for all evidence groups are consistent with the different sensitivity analyses.

Asunto(s)

Inmunosupresores , Trasplante de Riñón , Adulto , Humanos , Corticoesteroides/uso terapéutico , Corticoesteroides/economía , Azatioprina/uso terapéutico , Azatioprina/economía , Colombia , Análisis de Costo-Efectividad , Ciclosporina/uso terapéutico , Ciclosporina/economía , Árboles de Decisión , Rechazo de Injerto/prevención & control , Rechazo de Injerto/economía , Inmunosupresores/economía , Inmunosupresores/uso terapéutico , Trasplante de Riñón/economía , Cadenas de Markov , Ácido Micofenólico/uso terapéutico , Ácido Micofenólico/economía , Sirolimus/uso terapéutico , Sirolimus/economía , Tacrolimus/economía , Tacrolimus/uso terapéutico , Receptores de Trasplantes/estadística & datos numéricos

RESUMEN

INTRODUCTION: Recent evidence indicates that Maternal Supplementation with Long-Chain n-3 Fatty Acids During Pregnancy Substantially Mitigates Offspring's Asthma. Adding information regarding its cost-utility will undoubtedly allow its adoption, or not, in clinical practice guidelines. This research aimed to determine the cost-utility of LCPUFA supplementation in the third trimester of pregnancy to reduce the risk of wheezing and asthma in infants in Colombia. METHODS: A Markov model was formulated to estimate the cost and quality-adjusted life-years (QALYs) attributed to individuals with severe asthma in Colombia, with a time horizon of five years and a cycle length of two weeks. Probabilistic sensitivity analysis and a value of information (VOI) analysis were conducted to evaluate the uncertainties in the case base. Cost-utility was assessed at a willingness-to-pay (WTP) value of US$5180. All costs were adjusted to 2021 with a 5% annual discounting rate for cost and QALYs. RESULTS: The mean incremental cost of LCPUFA supplementation versus no supplementation was US-43.65. The mean incremental benefit of LCPUFA supplementation versus no supplementation was 0.074 QALY. The incremental cost-utility ratio was estimated at US$590.68 per QALY. The outcomes derived from our primary analysis remained robust when subjected to variations in all underlying assumptions and parameter values. CONCLUSION: Supplementation strategy supplementation with long-chain n-3 fatty acids during pregnancy is cost-effective in reducing the risk of developing asthma during childhood in Colombia.

Asunto(s)

Asma , Análisis Costo-Beneficio , Suplementos Dietéticos , Ácidos Grasos Omega-3 , Cadenas de Markov , Años de Vida Ajustados por Calidad de Vida , Ruidos Respiratorios , Humanos , Asma/prevención & control , Asma/economía , Asma/epidemiología , Femenino , Embarazo , Suplementos Dietéticos/economía , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/economía , Colombia , Recién Nacido , Incidencia , Atención Prenatal/economía , Atención Prenatal/métodos

RESUMEN

The present work intends to discuss parameter estimation and statistical analysis in adsorption. The Langmuir and Tóth isotherm models are compared for a set of carbon dioxide adsorption data on 13X zeolite from literature at different temperatures: 303, 323, 373, and 423 K. Statistical analyses were performed under frequentist and Bayesian perspectives. Under the frequentist statistical view, parameters were estimated using Maximum Likelihood estimation (MLE). Statistical analyses of parameters were performed by confidence regions in terms of elliptical approximation and likelihood region, while the evaluation of models was performed by chi-square statistics. The results showed that, for these nonlinear models, the elliptical region offers a poor approximation of the parameter estimates' confidence region, especially for the most correlated parameter pairs. Additionally, the four-parameter Tóth's equation yields less correlated parameters than the three-parameter Langmuir model. From a Bayesian perspective, the Markov chain Monte Carlo (MCMC) technique facilitated the reconstruction of the probability density functions of parameters as well as enabled the propagation of parametric uncertainties in the model responses. Finally, the accurate assessment of experimental uncertainty significantly influences the evaluation of models and their respective parameters.

Asunto(s)

Teorema de Bayes , Adsorción , Método de Montecarlo , Zeolitas/química , Dióxido de Carbono/química , Cadenas de Markov , Modelos Estadísticos , Temperatura

RESUMEN

Evolutionary tempo and mode summarize ancient and controversial subjects of theoretical biology such as gradualism, convergence, contingence, trends, and entrenchment. We employed an integrative methodological approach to explore the evolutionary tempo and mode of Lepidosaurian phalangeal formulae (PFs). This approach involves quantifying the frequencies of morphological changes along an evolutionary trajectory. The five meristic characters encoded by PFs are particularly valuable in revealing evolutionary patterns, owing to their discrete nature and extensive documentation in the literature. Based on a pre-existing dataset of PFs from 649 taxa (35 Lepidosauria families, including fossils), from which there exists a unique repertoire of 53 formulations, our approach simultaneously considers phenetic and phylogenetic data. This culminates in a diagram accounting for the phylogenetic dynamic of evolution traversing across different regions of morphospace. The method involves enumerating phenotypical options, reconstructing phenotypes across the phylogeny, projecting phenotypes onto a morphospace, and constructing a flow network from the frequency of evolutionary transitions between unique phenotypic conditions. This approach links Markovian chains and evolutionary trajectories to formally define parameters that describe the underlying transitions of morphological change. Among other results, we found that (a) PF evolution exhibits a clear trend towards reduction in the phalangeal count and that (b) evolutionary change tends to occur significantly between morphologically similar PFs. Notwithstanding, although minor but not trivial, transitions between distant formulas -jumps- occur. Our results support a pluralistic view including stasis, gradualism, and saltationism discriminating their prevalence in a target character evolution.

Asunto(s)

Evolución Biológica , Fósiles , Humanos , Filogenia , Cadenas de Markov , Fenotipo

RESUMEN

In this work, we propose a methodology based on Monte Carlo Markov chains to explore the parameter space of kinetic models for ion channels. The methodology allows the detection of potential parameter sets of a model that are compatible with experimentally obtained whole-cell currents, which could remain hidden when methods focus on obtaining the parameters that provide the best fit. To show its implementation and utility, we considered a four-state kinetic model proposed in the literature to describe the activation of the voltage-gated proton channel (Hv1), Biophysical Journal, 2014, 107, 1564. In that work, a set of values for the rate transitions that describe the channel kinetics at different intracellular H+ concentration (pHi) were obtained by the Simplex method. With our approach, we find that, in fact, there is more than one parameter set for each pHi, which renders the same open probability temporal course within the experimental error margin for all of the considered voltages. The large differences that we obtained for the values of some rate constants among the different solutions show that there is more than one possible interpretation of this channel behavior as a function of pHi. We also simulated a proposed new experimental condition where it is possible to observe that different sets of parameters yield different results. Our study highlights the importance of a comprehensive analysis of parameter space in kinetic models and the utility of the proposed methodology for finding potential solutions.

Asunto(s)

Activación del Canal Iónico , Canales Iónicos , Activación del Canal Iónico/fisiología , Cadenas de Markov , Canales Iónicos/metabolismo , Concentración de Iones de Hidrógeno , Protones , Cinética , Modelos Biológicos

RESUMEN

Objetivo: Desenvolver uma análise de custo-utilidade da implementação do teste farmacogenético como uma ferramenta adicional para orientar a escolha do melhor tratamento medicamentoso para indivíduos com depressão. Métodos: Para a realização desta análise, criou-se um modelo analítico de decisão baseado em um modelo de Markov. A avaliação foi realizada sob a perspectiva do Sistema de Saúde Suplementar brasileiro, com horizonte temporal de 10 anos, incluindo custos médicos diretos e custos da tecnologia utilizada, além de ter como comparador o tratamento empírico tradicional para a depressão. As probabilidades de transição foram obtidas por meio de análise da literatura disponível. Também foram realizadas análises de sensibilidade probabilística e univariada. Adicionalmente, foi realizada uma avaliação sob a perspectiva da sociedade, incluindo os custos de tratamento medicamentoso realizados pelos pacientes. Resultados: De acordo com a análise realizada, o emprego do teste farmacogenético como guia do tratamento para depressão mostrou-se favorável, proporcionando economia de -R$ 3.439,97 por paciente e aumento de 0,39 QALY ao longo do horizonte temporal. Assim, evidencia-se uma economia significativa a favor do teste farmacogenético, correspondendo a -R$ 8.776,78 por QALY salvo. Além disso, a robustez do modelo foi comprovada por meio das análises de sensibilidade. No cenário sob perspectiva da sociedade, o resultado foi ainda mais favorável, proporcionando economia de -R$ 9.381,49 por paciente e aumento de 0,39 QALY, correspondendo a -R$ 23.936,05 por QALY salvo. Conclusão: Os resultados encontrados neste estudo demonstraram que o uso de testes farmacogenéticos no tratamento da depressão é economicamente vantajoso, com aumento no valor de QALY e redução nos custos médicos diretos, em comparação ao tratamento empírico tradicional. Essa descoberta alinha-se à tendência atual de personalização no cuidado da saúde mental, sugerindo implicações práticas na reavaliação de protocolos, com potencial incorporação dos testes farmacogenéticos como padrão de cuidado.

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Objective: To evaluate the cost-utility of pharmacogenetic testing incorporation as an additional tool in guiding the selection of optimal drug treatments for individuals with depression. Methods: A decision analytical model was created based on the Markov model for this analysis. The evaluation was conducted from the perspective of the Brazilian Supplementary Health System, with a time horizon of 10 years. The study included direct medical and technology costs and a comparison with traditional empirical treatment for depression was performed. Transition probabilities were derived from an analysis of available literature. Probabilistic and univariate sensitivity analyses were also carried out. Additionally, an evaluation was conducted from the perspective of Society, including the costs of drug treatment carried out by patients. Results: The application of pharmacogenetic testing as a guide for depression treatment demonstrated favorable outcomes, yielding savings of -R$ 3,439.97 per patient and an increase of 0.39 QALY over the specified time frame. Thus, significant savings were evident, corresponding to -R$ 8,776.78 per QALY saved. The sensitivity analyses confirmed the model's robustness. In the Society's perspective scenario, the outcome was even more favorable, resulting in savings of -R$ 9,381.49 per patient and a 0.39 increase in QALYs, equivalent to -R$ 23,936.05 per QALY saved. Conclusion: The study findings reveal that incorporating harmacogenetic tests in depression treatment offers economic benefits, evidenced by an increase in QALY value and a decrease in direct medical costs compared to conventional empirical treatment. This aligns with the ongoing trend towards personalized mental health care, implying practical considerations for protocol reassessment and the possible integration of pharmacogenetic tests as a standard of care.

Asunto(s)

Cadenas de Markov , Análisis Costo-Beneficio , Pruebas de Farmacogenómica , Análisis de Costo-Efectividad

RESUMEN

The main objective of this paper is to propose a novel SEIR stochastic epidemic model. A distinguishing feature of this new model is that it allows us to consider a setup under general latency and infectious period distributions. To some extent, queuing systems with infinitely many servers and a Markov chain with time-varying transition rate comprise the very technical underpinning of the paper. Although more general, the Markov chain is as tractable as previous models for exponentially distributed latency and infection periods. It is also significantly more straightforward and tractable than semi-Markov models with a similar level of generality. Based on stochastic stability, we derive a sufficient condition for a shrinking epidemic regarding the queuing system's occupation rate that drives the dynamics. Relying on this condition, we propose a class of ad-hoc stabilising mitigation strategies that seek to keep a balanced occupation rate after a prescribed mitigation-free period. We validate the approach in the light of the COVID-19 epidemic in England and in the state of Amazonas, Brazil, and assess the effect of different stabilising strategies in the latter setting. Results suggest that the proposed approach can curb the epidemic with various occupation rate levels if the mitigation is timely.

Asunto(s)

COVID-19 , Epidemias , Humanos , Procesos Estocásticos , COVID-19/epidemiología , COVID-19/prevención & control , Epidemias/prevención & control , Cadenas de Markov , Brasil , Modelos Biológicos

RESUMEN

This article proposes a new class of nonhomogeneous Poisson spatiotemporal model. In this approach, we use a state-space model-based prior distribution to handle the scale and shape parameters of the Weibull intensity function. The proposed prior distribution enables the inclusion of changes in the behavior of the intensity function over time. In defining the spatial correlation function of the model, we include anisotropy via spatial deformation. We estimate the model parameters from a Bayesian perspective, employ the Markov chain Monte Carlo approach, and validate this estimation procedure through a simulation exercise. Finally, the extreme rainfall in the southern semiarid region in northeastern Brazil is analyzed using the R10mm index. The proposed model showed better fit and prediction ability than did other nonhomogeneous Poisson spatiotemporal models available in the literature. This improvement in performance is mainly due to the flexibility of the intensity function that is achieved by allowing the incorporation, in time, of the climatic characteristics of this region.

Asunto(s)

Teorema de Bayes , Simulación por Computador , Cadenas de Markov , Método de Montecarlo , Distribución de Poisson

RESUMEN

Profile hidden Markov models (HMMs) are a powerful way of modeling biological sequence diversity and constitute a very sensitive approach to detecting divergent sequences. Here, we report the development of protocols for the rational design of profile HMMs. These methods were implemented on TABAJARA, a program that can be used to either detect all biological sequences of a group or discriminate specific groups of sequences. By calculating position-specific information scores along a multiple sequence alignment, TABAJARA automatically identifies the most informative sequence motifs and uses them to construct profile HMMs. As a proof-of-principle, we applied TABAJARA to generate profile HMMs for the detection and classification of two viral groups presenting different evolutionary rates: bacteriophages of the Microviridae family and viruses of the Flavivirus genus. We obtained conserved models for the generic detection of any Microviridae or Flavivirus sequence, and profile HMMs that can specifically discriminate Microviridae subfamilies or Flavivirus species. In another application, we constructed Cas1 endonuclease-derived profile HMMs that can discriminate CRISPRs and casposons, two evolutionarily related transposable elements. We believe that the protocols described here, and implemented on TABAJARA, constitute a generic toolbox for generating profile HMMs for the highly sensitive and specific detection of sequence classes.

Asunto(s)

Bacteriófagos , Microviridae , Bacteriófagos/genética , Biodiversidad , Evolución Biológica , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Cadenas de Markov

RESUMEN

The model selection stage has become a central theme in applying the additive main effects and multiplicative interaction (AMMI) model to determine the optimal number of bilinear components to be retained to describe the genotype-by-environment interaction (GEI). In the Bayesian context, this problem has been addressed by using information criteria and the Bayes factor. However, these procedures are computationally intensive, making their application unfeasible when the model's parametric space is large. A Bayesian analysis of the AMMI model was conducted using the Reversible Jump algorithm (RJMCMC) to determine the number of multiplicative terms needed to explain the GEI pattern. Three a priori distributions were assigned for the singular value scale parameter under different justifications, namely: i) the insufficient reason principle (uniform); ii) the invariance principle (Jeffreys' prior) and iii) the maximum entropy principle. Simulated and real data were used to exemplify the method. An evaluation of the predictive ability of models for simulated data was conducted and indicated that the AMMI analysis, in general, was robust, and models adjusted by the Reversible Jump method were superior to those in which sampling was performed only by the Gibbs sampler. In addition, the RJMCMC showed greater feasibility since the selection and estimation of parameters are carried out concurrently in the same sampling algorithm, being more attractive in terms of computational time. The use of the maximum entropy principle makes the analysis more flexible, avoiding the use of procedures for correcting prior degrees of freedom and obtaining improper posterior marginal distributions.

Asunto(s)

Ammi , Cadenas de Markov , Teorema de Bayes , Algoritmos , Método de Montecarlo