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1.
Front Public Health ; 12: 1406566, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827615

RESUMO

Background: Emerging infectious diseases pose a significant threat to global public health. Timely detection and response are crucial in mitigating the spread of such epidemics. Inferring the onset time and epidemiological characteristics is vital for accelerating early interventions, but accurately predicting these parameters in the early stages remains challenging. Methods: We introduce a Bayesian inference method to fit epidemic models to time series data based on state-space modeling, employing a stochastic Susceptible-Exposed-Infectious-Removed (SEIR) model for transmission dynamics analysis. Our approach uses the particle Markov chain Monte Carlo (PMCMC) method to estimate key epidemiological parameters, including the onset time, the transmission rate, and the recovery rate. The PMCMC algorithm integrates the advantageous aspects of both MCMC and particle filtering methodologies to yield a computationally feasible and effective means of approximating the likelihood function, especially when it is computationally intractable. Results: To validate the proposed method, we conduct case studies on COVID-19 outbreaks in Wuhan, Shanghai and Nanjing, China, respectively. Using early-stage case reports, the PMCMC algorithm accurately predicted the onset time, key epidemiological parameters, and the basic reproduction number. These findings are consistent with empirical studies and the literature. Conclusion: This study presents a robust Bayesian inference method for the timely investigation of emerging infectious diseases. By accurately estimating the onset time and essential epidemiological parameters, our approach is versatile and efficient, extending its utility beyond COVID-19.


Assuntos
Algoritmos , Teorema de Bayes , COVID-19 , Doenças Transmissíveis Emergentes , Cadeias de Markov , Humanos , Doenças Transmissíveis Emergentes/epidemiologia , COVID-19/epidemiologia , COVID-19/transmissão , China/epidemiologia , Método de Monte Carlo , SARS-CoV-2 , Surtos de Doenças/estatística & dados numéricos , Fatores de Tempo , Modelos Epidemiológicos
2.
Spat Spatiotemporal Epidemiol ; 49: 100645, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38876555

RESUMO

Bayesian inference in modelling infectious diseases using Bayesian inference using Gibbs Sampling (BUGS) is notable in the last two decades in parallel with the advancements in computing and model development. The ability of BUGS to easily implement the Markov chain Monte Carlo (MCMC) method brought Bayesian analysis to the mainstream of infectious disease modelling. However, with the existing software that runs MCMC to make Bayesian inferences, it is challenging, especially in terms of computational complexity, when infectious disease models become more complex with spatial and temporal components, in addition to the increasing number of parameters and large datasets. This study investigates two alternative subscripting strategies for creating models in Just Another Gibbs Sampler (JAGS) environment and their performance in terms of run times. Our results are useful for practitioners to ensure the efficiency and timely implementation of Bayesian spatiotemporal infectious disease modelling.


Assuntos
Teorema de Bayes , Cadeias de Markov , Análise Espaço-Temporal , Humanos , Modelos Epidemiológicos , Método de Monte Carlo , Software , Doenças Transmissíveis/epidemiologia
3.
PLoS One ; 19(6): e0303294, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38857244

RESUMO

OBJECTIVES: To examine the cost-effectiveness of using granulocyte colony-stimulating factor (G-CSF) for primary or secondary prophylaxis in patients with breast cancer from the perspective of Taiwan's National Health Insurance Administration. METHODS: A Markov model was constructed to simulate the events that may occur during and after a high-risk chemotherapy treatment. Various G-CSF prophylaxis strategies and medications were compared in the model. Effectiveness data were derived from the literature and an analysis of the National Health Insurance Research Database (NHIRD). Cost data were obtained from a published NHIRD study, and health utility values were also obtained from the literature. Sensitivity analyses were performed to assess the uncertainty of the cost-effectiveness results. RESULTS: In the base-case analysis, primary prophylaxis with pegfilgrastim had an incremental cost-effectiveness ratio (ICER) of NT$269,683 per quality-adjusted life year (QALY) gained compared to primary prophylaxis with lenograstim. The ICER for primary prophylaxis with lenograstim versus no G-CSF prophylaxis was NT$61,995 per QALY gained. The results were most sensitive to variations in relative risk of febrile neutropenia (FN) for pegfilgrastim versus no G-CSF prophylaxis. Furthermore, in the probabilistic sensitivity analysis, at a willingness-to-pay threshold of one times Taiwan's gross domestic product per capita, the probability of being cost-effective was 88.1% for primary prophylaxis with pegfilgrastim. CONCLUSIONS: Our study suggests that primary prophylaxis with either short- or long-acting G-CSF could be considered cost-effective for FN prevention in breast cancer patients receiving high-risk regimens.


Assuntos
Neoplasias da Mama , Neutropenia Febril Induzida por Quimioterapia , Análise Custo-Benefício , Fator Estimulador de Colônias de Granulócitos , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Neoplasias da Mama/tratamento farmacológico , Feminino , Taiwan/epidemiologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/economia , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Neutropenia Febril Induzida por Quimioterapia/economia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Cadeias de Markov , Filgrastim/uso terapêutico , Filgrastim/economia , Antineoplásicos/efeitos adversos , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Análise de Custo-Efetividade , Polietilenoglicóis
4.
Open Biol ; 14(6): 230449, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38862018

RESUMO

Nanopore sequencing platforms combined with supervised machine learning (ML) have been effective at detecting base modifications in DNA such as 5-methylcytosine (5mC) and N6-methyladenine (6mA). These ML-based nanopore callers have typically been trained on data that span all modifications on all possible DNA [Formula: see text]-mer backgrounds-a complete training dataset. However, as nanopore technology is pushed to more and more epigenetic modifications, such complete training data will not be feasible to obtain. Nanopore calling has historically been performed with hidden Markov models (HMMs) that cannot make successful calls for [Formula: see text]-mer contexts not seen during training because of their independent emission distributions. However, deep neural networks (DNNs), which share parameters across contexts, are increasingly being used as callers, often outperforming their HMM cousins. It stands to reason that a DNN approach should be able to better generalize to unseen [Formula: see text]-mer contexts. Indeed, herein we demonstrate that a common DNN approach (DeepSignal) outperforms a common HMM approach (Nanopolish) in the incomplete data setting. Furthermore, we propose a novel hybrid HMM-DNN approach, amortized-HMM, that outperforms both the pure HMM and DNN approaches on 5mC calling when the training data are incomplete. This type of approach is expected to be useful for calling other base modifications such as 5-hydroxymethylcytosine and for the simultaneous calling of different modifications, settings in which complete training data are not likely to be available.


Assuntos
5-Metilcitosina , Metilação de DNA , Epigênese Genética , Redes Neurais de Computação , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/química , 5-Metilcitosina/metabolismo , Sequenciamento por Nanoporos/métodos , Nanoporos , Humanos , Cadeias de Markov , DNA/química , DNA/genética
5.
Front Public Health ; 12: 1308867, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832225

RESUMO

Background: Perinatal depression affects the physical and mental health of pregnant women. It also has a negative effect on children, families, and society, and the incidence is high. We constructed a cost-utility analysis model for perinatal depression screening in China and evaluated the model from the perspective of health economics. Methods: We constructed a Markov model that was consistent with the screening strategy for perinatal depression in China, and two screening strategies (screening and non-screening) were constructed. Each strategy was set as a cycle of 3 months, corresponding to the first trimester, second trimester, third trimester, and postpartum. The state outcome parameters required for the model were obtained based on data from the National Prospective Cohort Study on the Mental Health of Chinese Pregnant Women from August 2015 to October 2016. The cost parameters were obtained from a field investigation on costs and screening effects conducted in maternal and child health care institutions in 2020. The cost-utility ratio and incremental cost-utility ratio of different screening strategies were obtained by multiplicative analysis to evaluate the health economic value of the two screening strategies. Finally, deterministic and probabilistic sensitivity analyses were conducted on the uncertain parameters in the model to explore the sensitivity factors that affected the selection of screening strategies. Results: The cost-utility analysis showed that the per capita cost of the screening strategy was 129.54 yuan, 0.85 quality-adjusted life years (QALYs) could be obtained, and the average cost per QALY gained was 152.17 yuan. In the non-screening (routine health care) group, the average cost was 171.80 CNY per person, 0.84 QALYs could be obtained, and the average cost per QALY gained was 205.05 CNY. Using one gross domestic product per capita in 2021 as the willingness to pay threshold, the incremental cost-utility ratio of screening versus no screening (routine health care) was about -3,126.77 yuan, which was lower than one gross domestic product per capita. Therefore, the screening strategy was more cost-effective than no screening (routine health care). Sensitivity analysis was performed by adjusting the parameters in the model, and the results were stable and consistent, which did not affect the choice of the optimal strategy. Conclusion: Compared with no screening (routine health care), the recommended perinatal depression screening strategy in China is cost-effective. In the future, it is necessary to continue to standardize screening and explore different screening modalities and tools suitable for specific regions.


Assuntos
Análise Custo-Benefício , Árvores de Decisões , Depressão , Cadeias de Markov , Programas de Rastreamento , Humanos , Feminino , Gravidez , China , Programas de Rastreamento/economia , Depressão/diagnóstico , Depressão/economia , Estudos Prospectivos , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/economia , Adulto , Anos de Vida Ajustados por Qualidade de Vida
6.
J Manag Care Spec Pharm ; 30(6): 517-527, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38824625

RESUMO

BACKGROUND: Eculizumab and efgartigimod were approved to treat anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (anti-AChR Ab-positive gMG). These relatively new biological treatments provide a more rapid onset of action and improved efficacy compared with conventional immunosuppressive treatments, but at a higher cost. OBJECTIVE: To assess the cost-effectiveness of eculizumab and, separately, efgartigimod, each added to conventional therapy vs conventional therapy alone, among patients with refractory anti-AChR Ab-positive gMG and those with anti-AChR Ab-positive gMG, respectively. METHODS: A Markov model with 4 health states was developed, evaluating costs and utility with a 4-week cycle length and lifetime time horizon from a health care system perspective and a modified societal perspective including productivity losses from patients and caregiver burden. Model inputs were informed by key clinical trials and relevant publications identified from targeted literature reviews, and drug costs were identified from Micromedex Red Book. Costs and outcomes were discounted at 3% per year. Incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted life-year [QALY] gained) were calculated for each comparison. RESULTS: Among the corresponding populations, lifetime costs and QALYs, respectively, for eculizumab were $5,515,000 and 11.85, and for conventional therapy, $308,000 and 10.29, resulting in an ICER of $3,338,000/QALY gained. For efgartigimod, lifetime costs and QALYs, respectively, were $6,773,000 and 13.22, and for conventional therapy, $322,000 and 9.98, yielding an ICER of $1,987,000/QALY gained. After applying indirect costs in a modified societal perspective, the ICERs were reduced to $3,310,000/QALY gained for eculizumab and $1,959,000/QALY gained for efgartigimod. CONCLUSIONS: Eculizumab and efgartigimod are rapidly acting and effective treatments for myasthenia gravis. However, at their current price, both therapies greatly exceeded common cost-effectiveness thresholds, likely limiting patient access to these therapies.


Assuntos
Anticorpos Monoclonais Humanizados , Análise Custo-Benefício , Cadeias de Markov , Miastenia Gravis , Anos de Vida Ajustados por Qualidade de Vida , Receptores Colinérgicos , Humanos , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/economia , Miastenia Gravis/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Receptores Colinérgicos/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Custos de Medicamentos , Adulto , Autoanticorpos
7.
Bull Math Biol ; 86(8): 90, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886260

RESUMO

Phylogenetic networks represent evolutionary histories of sets of taxa where horizontal evolution or hybridization has occurred. Placing a Markov model of evolution on a phylogenetic network gives a model that is particularly amenable to algebraic study by representing it as an algebraic variety. In this paper, we give a formula for the dimension of the variety corresponding to a triangle-free level-1 phylogenetic network under a group-based evolutionary model. On our way to this, we give a dimension formula for codimension zero toric fiber products. We conclude by illustrating applications to identifiability.


Assuntos
Cadeias de Markov , Conceitos Matemáticos , Modelos Genéticos , Filogenia , Evolução Molecular , Evolução Biológica
8.
Sci Rep ; 14(1): 13935, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886516

RESUMO

Breast cancer is one of the tumors with the highest prevalence rate among women in the world, and its BRCA1/2 gene is a common mutation site. Talazoparib, as a targeted PARP inhibitor, can effectively control the occurrence and development of breast cancer with BRCA1/2 gene mutation, and play a therapeutic role. Based on the findings from the Phase III EMBRACE trial (NCT01945775 clinical trial), our analysis reveals that the talazoparib group demonstrated a significant extension in progression-free survival, along with improved response markers and patient-reported outcomes when compared to conventional therapies. This study aims to assess the cost-effectiveness of talazoparib for treating advanced breast cancer with germline BRCA1/2 mutations and HER2 negativity, considering the perspectives of health services in China and the United States. The results obtained will serve as a valuable reference for promoting rational drug utilization and enhancing medical resource efficiency. To evaluate the cost-effectiveness of Talazoparib more scientifically and provide clinicians with chemotherapy options, this paper developed a Markov model based on the EMBRACA clinical trial (clinical Trails.gov No., NCT01945775) to simulate the survival events of breast cancer patients in the Talazoparib group and the standard treatment group. The state transition probability and clinical data of breast cancer patients during treatment were extracted from the phase III EMBRACA clinical trial. The cost data generated during the treatment process comes from local hospital pricing, other references, and expert consultation. This article uses US dollars to calculate the treatment cost and incremental cost-effectiveness ratio. Health outcomes are expressed in Quality Adjusted Life Years (QALYs). In addition, Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. This article establishes a Markov model for single-item sensitivity analysis. The results show that the economic benefits of using Talazoparib as a new treatment strategy in both China and the United States are higher than other drugs, and it is cost-effective. Compared to the control group, the incremental cost incurred by the Talazoparib treatment group in China was $2484.48/QALY, with an incremental QALY of 1.5. However, Talazoparib in the United States holds a dominant position, saving costs of $10,223.43 and increasing QALYs by 1.5. The clinical treatment effect of Talazoparib group in BRCA1/2 mutant advanced breast cancer patients is better than that of the standard treatment group, and the progression free survival period is significantly prolonged. From the perspective of medical and health services in China and the United States, the Talazoparib group is more economical than the standard treatment group in treating patients with BRCA1/2 mutant advanced breast cancer.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Análise Custo-Benefício , Mutação em Linhagem Germinativa , Ftalazinas , Receptor ErbB-2 , Humanos , Feminino , Ftalazinas/uso terapêutico , Ftalazinas/economia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/economia , Neoplasias da Mama/patologia , China , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Proteína BRCA2/genética , Estados Unidos , Proteína BRCA1/genética , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/economia , Anos de Vida Ajustados por Qualidade de Vida , Pessoa de Meia-Idade , Cadeias de Markov , Adulto , Intervalo Livre de Progressão
9.
BMC Health Serv Res ; 24(1): 739, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886718

RESUMO

BACKGROUND: Road traffic injuries are a major concern worldwide, with Thailand facing high accident mortality rates. Drunk driving is a key factor that requires countermeasures. Random breath testing (RBT) and mass media campaigns recommended by the World Health Organisation intend to deter such behaviour. This study aimed to evaluate the cost-effectiveness of implementing RBT in combination with mass media campaigns in Thailand. METHODS: A Markov simulation model estimated the lifetime cost and health benefits of RBT with mass media campaigns compared to mass media campaigns only. Direct medical and non-medical care costs were evaluated from a societal perspective. The health outcomes were quality-adjusted life years (QALY). Costs and outcomes were discounted by 3% per year. Subgroup analyses were conducted for both sexes, different age groups, and different drinking levels. Probabilistic sensitivity analyses were conducted over 5,000 independent iterations using a predetermined distribution for each parameter. RESULTS: This study suggested that RBT with mass media campaigns compared with mass media campaigns increases the lifetime cost by 24,486 THB per male binge drinker and 10,475 THB per female binge drinker (1 USD = 35 THB) and results in a QALY gain of 0.43 years per male binge drinker and 0.10 years per female binge drinker. The intervention yielded incremental cost-effectiveness ratios (ICERs) of 57,391 and 103,850 THB per QALY for male and female drinkers, respectively. Moreover, the intervention was cost-effective for all age groups and drinking levels. The intervention yielded the lowest ICER among male-dependent drinkers. Sensitivity analyses showed that at a willingness-to-pay (WTP) threshold of 160,000 per QALY gained, the RBT combined with mass media campaigns had a 99% probability of being optimal for male drinkers, whereas the probability for females was 91%. CONCLUSIONS: RBT and mass media campaigns in Thailand are cost-effective for all ages and drinking levels in both sexes. The intervention yielded the lowest ICER among male-dependent drinkers. Given the current Thai WTP threshold, sensitivity analyses showed that the intervention was more cost-effective for males than females.


Assuntos
Testes Respiratórios , Análise Custo-Benefício , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Tailândia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Meios de Comunicação de Massa , Adulto Jovem , Política de Saúde , Adolescente , Consumo de Bebidas Alcoólicas/prevenção & controle , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/economia , Promoção da Saúde/economia , Promoção da Saúde/métodos
10.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(3): 441-447, 2024 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-38864129

RESUMO

OBJECTIVE: To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A decision-analytic Markov model was used to simulate and compare different antihypertensive initiation strategies, including: Strategy 1, initiation of antihypertensive therapy for Chinese adults with systolic blood pressure (SBP) ≥140 mmHg (2020 Chinese guideline on the primary prevention of cardiovascular diseases); Strategy 2, initiation of antihypertensive therapy for Chinese adults with SBP ≥130 mmHg; Strategy 3, initiation of antihypertensive therapy for Chinese adults with SBP≥140 mmHg, or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases (2017 American College of Cardiology/American Heart Association guideline for the prevention, detection, evaluation, and management of high blood pressure in adults); Strategy 4, initiation of antihypertensive therapy for Chinese adults with SBP≥160 mmHg, or with SBP between 140 and 160 mmHg and at high risk of cardiovascular diseases (2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults: Diagnosis and management). The high 10-year cardiovascular risk was defined as the predicted risk over 10% based on the 2019 World Health Organization cardiovascular disease risk charts. Different strategies were simulated by the Markov model for ten years (cycles), with parameters mainly from the CHERRY study or published literature. After ten cycles of simulation, the numbers of quality-adjusted life years (QALY), cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy, and the numbers needed to treat (NNT) for each cardiovascular event or all-cause death could be prevented were calculated to assess the intervention efficiency. One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: A total of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included. Compared with strategy 1, the number of cardiovascular events that could be prevented in strategy 2 increased by 666 (95% UI: 334-975), while the NNT per cardiovascular event prevented increased by 10 (95% UI: 7-20). In contrast to strategy 1, the number of cardiovascular events that could be prevented in strategy 3 increased by 388 (95% UI: 194-569), and the NNT per cardiovascular event prevented decreased by 6 (95% UI: 4-12), suggesting that strategy 3 had better health benefits and intervention efficiency. Compared to strategy 1, although the number of cardiovascular events that could be prevented decreased by 193 (95% UI: 98-281) in strategy 4, the NNT per cardiovascular event prevented decreased by 18 (95% UI: 13-37) with better efficiency. The results were consistent in the sensitivity analyses. CONCLUSION: When initiating antihypertensive therapy in an economically developed area of China, the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold. The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.


Assuntos
Anti-Hipertensivos , Doenças Cardiovasculares , Hipertensão , Cadeias de Markov , Prevenção Primária , Humanos , Doenças Cardiovasculares/prevenção & controle , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , China/epidemiologia , Pressão Sanguínea/efeitos dos fármacos , Feminino , Masculino , Pessoa de Meia-Idade , Técnicas de Apoio para a Decisão , Adulto , Anos de Vida Ajustados por Qualidade de Vida , Idoso
11.
BMC Public Health ; 24(1): 1540, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849785

RESUMO

OBJECTIVE: To assess the impact of self-medication on the transmission dynamics of COVID-19 across different age groups, examine the interplay of vaccination and self-medication in disease spread, and identify the age group most prone to self-medication. METHODS: We developed an age-structured compartmentalized epidemiological model to track the early dynamics of COVID-19. Age-structured data from the Government of Gauteng, encompassing the reported cumulative number of cases and daily confirmed cases, were used to calibrate the model through a Markov Chain Monte Carlo (MCMC) framework. Subsequently, uncertainty and sensitivity analyses were conducted on the model parameters. RESULTS: We found that self-medication is predominant among the age group 15-64 (74.52%), followed by the age group 0-14 (34.02%), and then the age group 65+ (11.41%). The mean values of the basic reproduction number, the size of the first epidemic peak (the highest magnitude of the disease), and the time of the first epidemic peak (when the first highest magnitude occurs) are 4.16499, 241,715 cases, and 190.376 days, respectively. Moreover, we observed that self-medication among individuals aged 15-64 results in the highest spreading rate of COVID-19 at the onset of the outbreak and has the greatest impact on the first epidemic peak and its timing. CONCLUSION: Studies aiming to understand the dynamics of diseases in areas prone to self-medication should account for this practice. There is a need for a campaign against COVID-19-related self-medication, specifically targeting the active population (ages 15-64).


Assuntos
COVID-19 , Automedicação , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Adolescente , África do Sul/epidemiologia , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Automedicação/estatística & dados numéricos , Idoso , Criança , Prevalência , Pré-Escolar , Lactente , Recém-Nascido , Modelos Epidemiológicos , SARS-CoV-2 , Fatores Etários , Masculino , Cadeias de Markov , Feminino
12.
Methods Mol Biol ; 2796: 139-156, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38856900

RESUMO

Markov models are widely used to represent ion channel protein configurations as different states in the model's topology. Such models allow for dynamic simulation of ion channel kinetics through the simulated application of voltage potentials across a cell membrane. In this chapter, we present a general method for creating Markov models of ion channel kinetics using computational optimization alongside a fully featured example model of a cardiac potassium channel. Our methods cover designing training protocols, iteratively testing potential model topologies for structure identification, creation of algorithms for model simulation, as well as methods for assessing the quality of fit for a finalized model.


Assuntos
Algoritmos , Canais Iônicos , Cadeias de Markov , Canais Iônicos/metabolismo , Canais Iônicos/química , Cinética , Simulação por Computador , Humanos , Ativação do Canal Iônico , Biologia Computacional/métodos , Simulação de Dinâmica Molecular , Software
13.
Math Biosci Eng ; 21(4): 5308-5334, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38872537

RESUMO

Tuberculosis has affected human beings for thousands of years, and until today, tuberculosis still ranks third among 29 infectious diseases in China. However, most of the existing mathematical models consider a single factor, which is not conducive to the study of tuberculosis transmission dynamics. Therefore, this study considers the combined effects of vaccination, treatment, and contaminated environments on tuberculosis, and builds a new model with seven compartments of $ SVEITRW $ based on China's tuberculosis data. The study shows that when the basic reproduction number $ R_{0} $ is less than 1, the disease will eventually disappear, but when $ R_{0} $ is greater than 1, the disease may persist. In the numerical analysis part, we use Markov-chain Monte-Carlo method to obtain the optimal parameters of the model. Through the next generation matrix theory, we calculate that the $ R_{0} $ value of tuberculosis in China is $ 2.1102 $, that is, if not controlled, tuberculosis in China will not disappear over time. At the same time, through partial rank correlation coefficients, we find the most sensitive parameter to the basic reproduction number $ R_{0} $. On this basis, we combine the actual prevalence of tuberculosis in China, apply Pontryagin's maximum principle, and perform cost-effectiveness analysis to obtain the conditions required for optimal control. The analysis shows that four control strategies could effectively reduce the prevalence of TB, and simultaneously controlling $ u_{2}, u_{3}, u_{4} $ is the most cost-effective control strategy.


Assuntos
Número Básico de Reprodução , Cadeias de Markov , Método de Monte Carlo , Tuberculose , Vacinação , Humanos , China/epidemiologia , Tuberculose/prevenção & controle , Tuberculose/epidemiologia , Vacinação/economia , Simulação por Computador , Prevalência , Modelos Teóricos , Algoritmos , Antituberculosos/uso terapêutico
14.
Math Biosci Eng ; 21(4): 5826-5837, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38872560

RESUMO

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.


Assuntos
Teorema de Bayes , Movimento Celular , Cadeias de Markov , Modelos Biológicos , Método de Monte Carlo , Humanos , Simulação por Computador , Algoritmos , Difusão , Análise de Fourier , Animais
15.
Front Public Health ; 12: 1410355, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883194

RESUMO

Background: Progressive glioblastoma (GBM) is a malignancy with extremely poor prognosis. Chemotherapy is one of the approved systemic treatment modalities. The aim of this study is to assess the cost-effectiveness of using bevacizumab (BEV) in combination with lomustine (LOM) regimen for the treatment of progressive glioblastoma in China. Methods: The estimation results are derived from a multicenter randomized phase III trial, which demonstrated improved survival in GBM patients receiving BEV+LOM combination therapy. To calculate the incremental cost-effectiveness ratio (ICER) from the perspective of Chinese society, a Markov model was established. Univariate deterministic analysis and probabilistic sensitivity analysis were employed to address the uncertainties within the model. Results: Compared to LOM monotherapy, the total treatment cost for BEV+LOM combination therapy increased from $2,646.70 to $23,650.98. The health-adjusted life years (QALYs) for BEV+LOM combination therapy increased from 0.26 QALYs to 0.51 QALYs, representing an increment of 0.25 QALYs. The incremental cost-effectiveness ratio (ICER) was $84,071.12. The cost-effectiveness curve indicates that within the willingness-to-pay (WTP) range of $35,906 per QALY, BEV+LOM combination therapy is not a cost-effective treatment option for unresectable malignant pleural mesothelioma patients. Conclusions: Taken as a whole, the findings of this study suggest that, from the perspective of payers in China, BEV+LOM combination therapy as a first-line treatment for GBM is not a cost-effective option. However, considering the survival advantages this regimen may offer for this rare disease, it may still be one of the clinical treatment options for this patient population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Análise Custo-Benefício , Glioblastoma , Lomustina , Cadeias de Markov , Bevacizumab/economia , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Glioblastoma/tratamento farmacológico , Glioblastoma/economia , Humanos , Lomustina/uso terapêutico , Lomustina/economia , Lomustina/administração & dosagem , China , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias Encefálicas/tratamento farmacológico , Análise de Custo-Efetividade
16.
BMC Cancer ; 24(1): 654, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811891

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. METHODS: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. CONCLUSIONS AND RELEVANCE: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.


Assuntos
Análise Custo-Benefício , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidores de Checkpoint Imunológico , Metanálise em Rede , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/economia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/economia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Cadeias de Markov , Nivolumabe/uso terapêutico , Nivolumabe/economia , Análise de Custo-Efetividade
17.
United European Gastroenterol J ; 12(5): 574-584, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38717013

RESUMO

BACKGROUND: Several biologics are available for the treatment of moderate to severe Crohn's disease, but data to optimize their use are scarce. Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking monoclonal antibody that was approved in 2014 for the treatment of moderate to severe Crohn's disease. Based on real-world evidence, a model was developed to examine the effect of VDZ's position in the treatment sequence on clinical outcomes. OBJECTIVE: The aim of this study was to develop a model using real-world data to investigate how the positioning of VDZ in a sequence of biologic therapies for CD affects clinical effectiveness outcomes of quality-adjusted life-years (QALYS), patient-reported disease activity, and surgery rates. METHODS: A semi-Markov sequential model was developed to identify the optimal position of VDZ in a treatment sequence that included corticosteroids (CS), two biologics, and best supportive care (BSC). Using real-world data, three sequences were compared: VDZ as first (position), second, and last biologic (with anti-tumor necrosis factor alpha agents adalimumab (ADA) and infliximab (IFX) and the anti-interleukin-12 and -23 agent ustekinumab (UST) as alternative biologic treatments). Published real-world evidence informed model inputs. Vedolizumab sequences were compared and ranked based on QALYS, patient-reported outcomes from Crohn's disease activity index scores, or proportion of patients undergoing surgery by the 10-year time horizon for model simulation. Sensitivity analyses were used to evaluate the impact of model input uncertainty. RESULTS: Vedolizumab as the first biologic was the optimal position for this treatment according to all criteria, including yielding the highest QALYs (5.09) versus VDZ in second (4.97) and third (4.96) biologic sequence positions in sequences containing CS, anti-TNFα (aggregated data), UST, and BSC; 1780/2000 (89%) probabilistic simulations. In sequences containing ADA, VDZ, and UST biologics, ADA and VDZ in the first-line biologic position yielded QALYs of 5.09 versus 5.07, respectively. Adalimumab as the first biologic was best for clinical remission. CONCLUSIONS: This simulation model using real-world evidence indicates that positioning VDZ or ADA as the first biologic is likely to lead to improved long-term patient outcomes when compared to administering these treatments later or starting with IFX monotherapy.


Assuntos
Anticorpos Monoclonais Humanizados , Doença de Crohn , Fármacos Gastrointestinais , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Resultado do Tratamento , Infliximab/uso terapêutico , Adalimumab/uso terapêutico , Cadeias de Markov , Ustekinumab/uso terapêutico , Índice de Gravidade de Doença , Corticosteroides/uso terapêutico , Quimioterapia Combinada
18.
Proc Natl Acad Sci U S A ; 121(22): e2318329121, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38787881

RESUMO

The Hill functions, [Formula: see text], have been widely used in biology for over a century but, with the exception of [Formula: see text], they have had no justification other than as a convenient fit to empirical data. Here, we show that they are the universal limit for the sharpness of any input-output response arising from a Markov process model at thermodynamic equilibrium. Models may represent arbitrary molecular complexity, with multiple ligands, internal states, conformations, coregulators, etc, under core assumptions that are detailed in the paper. The model output may be any linear combination of steady-state probabilities, with components other than the chosen input ligand held constant. This formulation generalizes most of the responses in the literature. We use a coarse-graining method in the graph-theoretic linear framework to show that two sharpness measures for input-output responses fall within an effectively bounded region of the positive quadrant, [Formula: see text], for any equilibrium model with [Formula: see text] input binding sites. [Formula: see text] exhibits a cusp which approaches, but never exceeds, the sharpness of [Formula: see text], but the region and the cusp can be exceeded when models are taken away from thermodynamic equilibrium. Such fundamental thermodynamic limits are called Hopfield barriers, and our results provide a biophysical justification for the Hill functions as the universal Hopfield barriers for sharpness. Our results also introduce an object, [Formula: see text], whose structure may be of mathematical interest, and suggest the importance of characterizing Hopfield barriers for other forms of cellular information processing.


Assuntos
Cadeias de Markov , Termodinâmica , Modelos Biológicos , Ligantes
19.
PLoS One ; 19(5): e0301415, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38809831

RESUMO

Epidemic or pathogen emergence is the phenomenon by which a poorly transmissible pathogen finds its evolutionary pathway to become a mutant that can cause an epidemic. Many mathematical models of pathogen emergence rely on branching processes. Here, we discuss pathogen emergence using Markov chains, for a more tractable analysis, generalizing previous work by Kendall and Bartlett about disease invasion. We discuss the probability of emergence failure for early epidemics, when the number of infected individuals is small and the number of the susceptible individuals is virtually unlimited. Our formalism addresses both directly transmitted and vector-borne diseases, in the cases where the original pathogen is 1) one step-mutation away from the epidemic strain, and 2) undergoing a long chain of neutral mutations that do not change the epidemiology. We obtain analytic results for the probabilities of emergence failure and two features transcending the transmission mechanism. First, the reproduction number of the original pathogen is determinant for the probability of pathogen emergence, more important than the mutation rate or the transmissibility of the emerged pathogen. Second, the probability of mutation within infected individuals must be sufficiently high for the pathogen undergoing neutral mutations to start an epidemic, the mutation threshold depending again on the basic reproduction number of the original pathogen. Finally, we discuss the parameterization of models of pathogen emergence, using SARS-CoV1 as an example of zoonotic emergence and HIV as an example for the emergence of drug resistance. We also discuss assumptions of our models and implications for epidemiology.


Assuntos
Epidemias , Cadeias de Markov , Mutação , Humanos , Modelos Teóricos , COVID-19/epidemiologia , COVID-19/transmissão , COVID-19/virologia , Número Básico de Reprodução , Probabilidade , Animais
20.
JAMA Netw Open ; 7(5): e2413938, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38814640

RESUMO

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.


Assuntos
Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas , Análise Custo-Benefício , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/economia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/economia , Brasil , Espanha , Anos de Vida Ajustados por Qualidade de Vida , Masculino , Singapura , Feminino , Estados Unidos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/economia , Cadeias de Markov , Análise de Custo-Efetividade
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