28,793 results on '"Markov chains"'
Search Results
2. Methods for constructing and evaluating consensus genomic interval sets.
- Author
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Rymuza J, Sun Y, Zheng G, LeRoy NJ, Murach M, Phan N, Zhang A, and Sheffield NC
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- Humans, Algorithms, Likelihood Functions, Genomics methods, Markov Chains
- Abstract
The amount of genomic region data continues to increase. Integrating across diverse genomic region sets requires consensus regions, which enable comparing regions across experiments, but also by necessity lose precision in region definitions. We require methods to assess this loss of precision and build optimal consensus region sets. Here, we introduce the concept of flexible intervals and propose three novel methods for building consensus region sets, or universes: a coverage cutoff method, a likelihood method, and a Hidden Markov Model. We then propose three novel measures for evaluating how well a proposed universe fits a collection of region sets: a base-level overlap score, a region boundary distance score, and a likelihood score. We apply our methods and evaluation approaches to several collections of region sets and show how these methods can be used to evaluate fit of universes and build optimal universes. We describe scenarios where the common approach of merging regions to create consensus leads to undesirable outcomes and provide principled alternatives that provide interoperability of interval data while minimizing loss of resolution., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2024
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3. A Hybrid Markov-SPC Approach to Assess Cost Differences in Urgent Care Utilization Using Patient-Reported Data in Inflammatory Bowel Disease.
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Oliver BJ, Melmed GY, Siegel CA, Kennedy AM, Testaverde J, Oberai R, Alandra Weaver S, and Almario C
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- Humans, Ambulatory Care economics, Ambulatory Care statistics & numerical data, Emergency Service, Hospital statistics & numerical data, Emergency Service, Hospital economics, Hospitalization economics, Hospitalization statistics & numerical data, Health Care Costs statistics & numerical data, Markov Chains, Patient Reported Outcome Measures, Inflammatory Bowel Diseases therapy, Inflammatory Bowel Diseases economics
- Abstract
Background: Cost is a key outcome in quality and value, but it is often difficult to estimate reliably and efficiently for use in real-time improvement efforts. We describe a method using patient-reported outcomes (PROs), Markov modeling, and statistical process control (SPC) analytics in a real-time cost-estimation prototype designed to assess cost differences between usual care and improvement conditions in a national multicenter improvement collaborative-the IBD Qorus Learning Health System (LHS)., Methods: The IBD Qorus Learning Health System (LHS) collects PRO data, including emergency department utilization and hospitalizations from patients prior to their clinical visits. This data is aggregated monthly at center and collaborative levels, visualized using Statistical Process Control (SPC) analytics, and used to inform improvement efforts. A Markov model was developed by Almario et al to estimate annualized per patient cost differences between usual care (baseline) and improvement (intervention) time periods and then replicated at monthly intervals. We then applied moving average SPC analyses to visualize monthly iterative cost estimations and assess the variation and statistical reliability of these estimates over time., Results: We have developed a real-time Markov-informed SPC visualization prototype which uses PRO data to analyze and monitor monthly annualized per patient cost savings estimations over time for the IBD Qorus LHS. Validation of this prototype using claims data is currently underway., Conclusion: This new approach using PRO data and hybrid Markov-SPC analysis can analyze and visualize near real-time estimates of cost differences over time. Pending successful validation against a claims data standard, this approach could more comprehensively inform improvement, advocacy, and strategic planning efforts.
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- 2024
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4. Latent classification model for censored longitudinal binary outcome.
- Author
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Kuo JC, Chan W, Leon-Novelo L, Lairson DR, Brown A, and Fujimoto K
- Subjects
- Humans, Longitudinal Studies, Computer Simulation, Models, Statistical, Texas epidemiology, SARS-CoV-2, Female, COVID-19 epidemiology, Markov Chains, Latent Class Analysis, Algorithms
- Abstract
Latent classification model is a class of statistical methods for identifying unobserved class membership among the study samples using some observed data. In this study, we proposed a latent classification model that takes a censored longitudinal binary outcome variable and uses its changing pattern over time to predict individuals' latent class membership. Assuming the time-dependent outcome variables follow a continuous-time Markov chain, the proposed method has two primary goals: (1) estimate the distribution of the latent classes and predict individuals' class membership, and (2) estimate the class-specific transition rates and rate ratios. To assess the model's performance, we conducted a simulation study and verified that our algorithm produces accurate model estimates (ie, small bias) with reasonable confidence intervals (ie, achieving approximately 95% coverage probability). Furthermore, we compared our model to four other existing latent class models and demonstrated that our approach yields higher prediction accuracies for latent classes. We applied our proposed method to analyze the COVID-19 data in Houston, Texas, US collected between January first 2021 and December 31st 2021. Early reports on the COVID-19 pandemic showed that the severity of a SARS-CoV-2 infection tends to vary greatly by cases. We found that while demographic characteristics explain some of the differences in individuals' experience with COVID-19, some unaccounted-for latent variables were associated with the disease., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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5. A Bayesian non-stationary heteroskedastic time series model for multivariate critical care data.
- Author
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Omar Z, Stephens DA, Schmidt AM, and Buckeridge DL
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- Humans, Multivariate Analysis, Algorithms, Computer Simulation, Quebec, Bayes Theorem, Markov Chains, Monte Carlo Method, Critical Care statistics & numerical data, Critical Care methods, Models, Statistical, Intensive Care Units
- Abstract
We propose a multivariate GARCH model for non-stationary health time series by modifying the observation-level variance of the standard state space model. The proposed model provides an intuitive and novel way of dealing with heteroskedastic data using the conditional nature of state-space models. We follow the Bayesian paradigm to perform the inference procedure. In particular, we use Markov chain Monte Carlo methods to obtain samples from the resultant posterior distribution. We use the forward filtering backward sampling algorithm to efficiently obtain samples from the posterior distribution of the latent state. The proposed model also handles missing data in a fully Bayesian fashion. We validate our model on synthetic data and analyze a data set obtained from an intensive care unit in a Montreal hospital and the MIMIC dataset. We further show that our proposed models offer better performance, in terms of WAIC than standard state space models. The proposed model provides a new way to model multivariate heteroskedastic non-stationary time series data. Model comparison can then be easily performed using the WAIC., (© 2024 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd.)
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- 2024
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6. Stability of a stochastic brucellosis model with semi-Markovian switching and diffusion.
- Author
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Chen F, Hu J, Chen Y, and Zhang Q
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- Animals, Humans, Epidemiological Models, Brucella pathogenicity, Climate Change, Brucellosis transmission, Brucellosis epidemiology, Brucellosis microbiology, Stochastic Processes, Markov Chains, Models, Biological, Computer Simulation, Mathematical Concepts
- Abstract
To explore the influence of state changes on brucellosis, a stochastic brucellosis model with semi-Markovian switchings and diffusion is proposed in this paper. When there is no switching, we introduce a critical value R s and obtain the exponential stability in mean square when R s < 1 by using the stochastic Lyapunov function method. Sudden climate changes can drive changes in transmission rate of brucellosis, which can be modelled by a semi-Markov process. We study the influence of stationary distribution of semi-Markov process on extinction of brucellosis in switching environment including both stable states, during which brucellosis dies out, and unstable states, during which brucellosis persists. The results show that increasing the frequencies and average dwell times in stable states to certain extent can ensure the extinction of brucellosis. Finally, numerical simulations are given to illustrate the analytical results. We also suggest that herdsmen should reduce the densities of animal habitation to decrease the contact rate, increase slaughter rate of animals and apply disinfection measures to kill brucella., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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7. Cost-effectiveness of ace inhibitors versus ARBs in heart failure management.
- Author
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Elendu C, Amaechi DC, Elendu TC, Amaechi EC, Elendu ID, Jingwa KA, Chiegboka SF, Bhadana U, Abdelatti AMS, Ikeji IV, Atmadibrata JC, Mohamed ASF, Janibabu Sharmila U, Soltan FEAE, Abbas NK, Eldorghamy MMF, Gurbanova T, Okeme AKB, Okeke AA, and Esangbedo IJ
- Subjects
- Humans, Aged, Male, Female, Middle Aged, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Angiotensin-Converting Enzyme Inhibitors economics, Heart Failure drug therapy, Heart Failure economics, Cost-Benefit Analysis, Angiotensin Receptor Antagonists therapeutic use, Angiotensin Receptor Antagonists economics, Quality-Adjusted Life Years, Markov Chains
- Abstract
Background: Heart failure is a chronic condition that imposes a significant burden on healthcare systems worldwide. Effective management is crucial for improving patient outcomes and reducing costs. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are widely used to manage heart failure by reducing cardiac strain and preventing disease progression. Despite their common use, ACE inhibitors and ARBs differ in mechanisms, cost, and potential side effects. ACE inhibitors have long been the standard treatment, while ARBs are often prescribed to patients intolerant to ACE inhibitors, particularly due to side effects like cough. Given these differences, evaluating the cost-effectiveness of these treatments is essential. This study compares the cost-effectiveness of ACE inhibitors and ARBs from a healthcare system perspective, considering both direct medical costs and health outcomes., Methods: A cost-effectiveness analysis was conducted using a decision-analytic Markov model to simulate heart failure progression in a hypothetical cohort. Data inputs included clinical trial outcomes, real-world effectiveness data, direct medical costs (medications, hospitalizations, monitoring), and utility values for quality of life. The primary outcome measures were the cost per quality-adjusted life year gained and the incremental cost-effectiveness ratio. Sensitivity analyses tested the robustness of results, and subgroup analyses were conducted based on age and disease severity., Results: The base-case analysis showed that ACE inhibitors were associated with lower overall costs and slightly higher quality-adjusted life years than ARBs. Sensitivity analyses revealed that variations in key parameters, such as transition probabilities, mortality rates, and healthcare expenses, had limited impact on the overall cost-effectiveness conclusions. Subgroup analyses indicated that ACE inhibitors and ARBs exhibited similar cost-effectiveness profiles for patients aged <65 and ≥65 years. However, among patients with severe heart failure, ARBs demonstrated a higher incremental cost-effectiveness ratio compared with ACE inhibitors, suggesting reduced cost-effectiveness in this subgroup., Conclusion: ACE inhibitors are likely a more cost-effective option for managing heart failure than ARBs, particularly from a healthcare system perspective. The findings underscore the importance of tailoring treatment decisions to individual patient factors, preferences, and clinical conditions, providing valuable insights for healthcare policy and practice, particularly regarding cost-effectiveness across patient subgroups., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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8. Modelling the age distribution of longevity leaders.
- Author
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Kiss C, Németh L, and Vető B
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- Humans, Age Distribution, Aged, 80 and over, Longevity, Markov Chains
- Abstract
Human longevity leaders with remarkably long lifespan play a crucial role in the advancement of longevity research. In this paper, we propose a stochastic model to describe the evolution of the age of the oldest person in the world by a Markov process, in which we assume that the births of the individuals follow a Poisson process with increasing intensity, lifespans of individuals are independent and can be characterized by a gamma-Gompertz distribution with time-dependent parameters. We utilize a dataset of the world's oldest person title holders since 1955, and we compute the maximum likelihood estimate for the parameters iteratively by numerical integration. Based on our preliminary estimates, the model provides a good fit to the data and shows that the age of the oldest person alive increases over time in the future. The estimated parameters enable us to describe the distribution of the age of the record holder process at a future time point., (© 2024. The Author(s).)
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- 2024
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9. learnMSA2: deep protein multiple alignments with large language and hidden Markov models.
- Author
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Becker F and Stanke M
- Subjects
- Software, Deep Learning, Algorithms, Computational Biology methods, Amino Acid Sequence, Markov Chains, Sequence Alignment methods, Proteins chemistry, Sequence Analysis, Protein methods
- Abstract
Motivation: For the alignment of large numbers of protein sequences, tools are predominant that decide to align two residues using only simple prior knowledge, e.g. amino acid substitution matrices, and using only part of the available data. The accuracy of state-of-the-art programs declines with decreasing sequence identity and when increasingly large numbers of sequences are aligned. Recently, transformer-based deep-learning models started to harness the vast amount of protein sequence data, resulting in powerful pretrained language models with the main purpose of generating high-dimensional numerical representations, embeddings, for individual sites that agglomerate evolutionary, structural, and biophysical information., Results: We extend the traditional profile hidden Markov model so that it takes as inputs unaligned protein sequences and the corresponding embeddings. We fit the model with gradient descent using our existing differentiable hidden Markov layer. All sequences and their embeddings are jointly aligned to a model of the protein family. We report that our upgraded HMM-based aligner, learnMSA2, combined with the ProtT5-XL protein language model aligns on average almost 6% points more columns correctly than the best amino acid-based competitor and scales well with sequence number. The relative advantage of learnMSA2 over other programs tends to be greater when the sequence identity is lower and when the number of sequences is larger. Our results strengthen the evidence on the rich information contained in protein language models' embeddings and their potential downstream impact on the field of bioinformatics. Availability and implementation: https://github.com/Gaius-Augustus/learnMSA, PyPI and Bioconda, evaluation: https://github.com/felbecker/snakeMSA., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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10. Understanding the Role of Eye Movement Pattern and Consistency in Isolated English Word Reading Through Hidden Markov Modeling.
- Author
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Liao W and Hsiao JH
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- Humans, Young Adult, Female, Male, Fixation, Ocular physiology, Adult, Reaction Time physiology, Language, Reading, Eye Movements physiology, Markov Chains
- Abstract
In isolated English word reading, readers have the optimal performance when their initial eye fixation is directed to the area between the beginning and word center, that is, the optimal viewing position (OVP). Thus, how well readers voluntarily direct eye gaze to this OVP during isolated word reading may be associated with reading performance. Using Eye Movement analysis with Hidden Markov Models, we discovered two representative eye movement patterns during lexical decisions through clustering, which focused at the OVP and the word center, respectively. Higher eye movement similarity to the OVP-focusing pattern predicted faster lexical decision time in addition to cognitive abilities and lexical knowledge. However, the OVP-focusing pattern was associated with longer isolated single letter naming time, suggesting conflicting visual abilities required for identifying isolated letters and multi-letter words. In contrast, in both word and pseudoword naming, although clustering did not reveal an OVP-focused pattern, higher consistency of the first fixation as measured in entropy predicted faster naming time in addition to cognitive abilities and lexical knowledge. Thus, developing a consistent eye movement pattern focusing on the OVP is essential for word orthographic processing and reading fluency. This finding has important implications for interventions for reading difficulties., (© 2024 The Author(s). Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society (CSS).)
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- 2024
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11. US cost-utility model of lenacapavir plus optimized background regimen (OBR) vs fostemsavir plus OBR and ibalizumab plus OBR for people with HIV with multidrug resistance.
- Author
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Vardanega V, New E, Mezzio D, and Eddowes LA
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- Humans, United States, Adult, Drug Therapy, Combination, Male, HIV-1 drug effects, Drug Resistance, Multiple, Viral, Models, Economic, Female, Middle Aged, Antibodies, Monoclonal economics, Antibodies, Monoclonal therapeutic use, Viral Load drug effects, Organophosphates, Piperazines, Cost-Benefit Analysis, HIV Infections drug therapy, HIV Infections economics, Quality-Adjusted Life Years, Markov Chains, Anti-HIV Agents economics, Anti-HIV Agents therapeutic use, Anti-HIV Agents administration & dosage
- Abstract
Background: Heavily treatment-experienced (HTE) people with HIV (PWH) have limited treatment options owing to multidrug resistance (MDR). Lenacapavir (LEN) is indicated, in combination with other antiretrovirals, for the treatment of adults with MDR HIV-1 experiencing failure of their current antiretroviral regimen because of resistance, intolerance, or safety considerations., Objective: To evaluate the cost-utility of LEN in combination with an optimized background regimen (OBR) vs alternative recently approved treatments for HTE PWH, fostemsavir (FTR)+OBR and ibalizumab (IBA)+OBR, for the treatment of PWH with MDR, from a mixed US health care payer perspective., Methods: A Markov state-transition model with a lifetime time horizon was developed. Transition probabilities between viral load categories were based on individual participant data from the CAPELLA trial for LEN+OBR and on relative efficacy parameters obtained from indirect treatment comparisons for comparators. Health state utilities were sourced from the literature. Costs included drug acquisition costs, drug administration costs, disease management costs, adverse event costs, AIDS-related event costs, and treatment switching costs and were sourced from red book costs, Medicare and Medicaid fees, and the literature. Costs and outcomes were discounted at 3% annually. The model was used to estimate total and incremental costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. A deterministic and a probabilistic sensitivity analysis, as well as scenario analyses, were performed to address elements of uncertainty in the model and to explore the robustness of the results., Results: Over a lifetime time horizon, LEN+OBR was associated with the highest absolute QALYs (9.41) and the greatest number of LYs (12.09) compared with FTR+OBR (QALYs: 8.75; LYs: 11.26) and IBA+OBR (QALYs: 8.36; LYs: 10.78). LEN+OBR was also associated with the lowest total lifetime costs of the 3 interventions (LEN+OBR: $1,441,122 [US dollars]; FTR+OBR: $1,504,986; IBA+OBR: $1,524,396) and therefore was dominant over both comparators in the base case. LEN+OBR remained dominant vs FTR+OBR and IBA+OBR across the range of scenarios tested and LEN+OBR had a 99% probability of being cost-effective compared with FTR+OBR and IBA+OBR in the probabilistic sensitivity analysis at a willingness-to-pay threshold of $50,000/QALY., Conclusions: This economic evaluation demonstrated that LEN+OBR provides meaningful increases in QALYs and LYs, and is dominant over a lifetime time horizon, compared with FTR+OBR and IBA+OBR for the treatment of PWH with MDR in the United States.
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- 2024
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12. Unsupervised EEG-Based Seizure Anomaly Detection with Denoising Diffusion Probabilistic Models.
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Wang J, Sun M, and Huang W
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- Humans, Unsupervised Machine Learning, Algorithms, Signal Processing, Computer-Assisted, Seizures diagnosis, Seizures physiopathology, Electroencephalography methods, Markov Chains, Models, Statistical
- Abstract
While many seizure detection methods have demonstrated great accuracy, their training necessitates a substantial volume of labeled data. To address this issue, we propose a novel method for unsupervised seizure anomaly detection called SAnoDDPM, which uses denoising diffusion probabilistic models (DDPM). We designed a novel pipeline that uses a variable lower bound on Markov chains to identify potential values that are unlikely to occur in anomalous data. The model is first trained on normal data, then anomalous data is input to the trained model. The model resamples the anomalous data and converts it to normal data. Finally, the presence of seizures can be determined by comparing the before and after data. Moreover, the input 2D spectrograms are encoded into vector-quantized representations, which enables powerful and efficient DDPM while maintaining its quality. Experimental comparisons on the publicly available datasets, CHB-MIT and TUH, show that our method delivers better results, significantly reduces inference time, and is suitable for deployment in a clinical environments. As far as we are aware, this is the first DDPM-based method for seizure anomaly detection. This novel approach significantly contributes to the progression of seizure detection algorithms, thereby augmenting their practicality in clinical settings.
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- 2024
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13. A collaborative study on the precision of the Markov chain Monte Carlo algorithms used for DNA profile interpretation.
- Author
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Riman S, Bright JA, Huffman K, Moreno LI, Liu S, Sathya A, and Vallone PM
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- Humans, Likelihood Functions, Reproducibility of Results, Software, Genotype, Monte Carlo Method, Markov Chains, Algorithms, DNA Fingerprinting
- Abstract
Several fully continuous probabilistic genotyping software (PGS) use Markov chain Monte Carlo algorithms (MCMC) to assign weights to different proposed genotype combinations at a locus. Replicate interpretations of the same profile in these software are expected not to produce identical weights and likelihood ratio (LR) values due to the Monte Carlo aspect. This paper reports a detailed precision study under reproducibility conditions conducted as a collaborative exercise across the National Institute of Standards and Technology (NIST), Federal Bureau of Investigation (FBI), and Institute of Environmental Science and Research (ESR). Replicate interpretations generated across the three laboratories used the same input files, software version, and settings but different random number seed and different computers. This work demonstrates that using different computers to analyze replicate interpretations does not contribute to any variations in LR values. The study quantifies the magnitude of differences in the assigned LRs that is only due to run-to-run MCMC variability and addresses the potential explanations for the observed differences., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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14. Cost-effectiveness of tisotumab vedotin as a second- or third-line therapy for cervical cancer.
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Huo G, Liu W, and Chen P
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- Humans, Female, Progression-Free Survival, Antibodies, Monoclonal economics, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal administration & dosage, Antineoplastic Agents, Immunological economics, Antineoplastic Agents, Immunological therapeutic use, United States, Uterine Cervical Neoplasms drug therapy, Uterine Cervical Neoplasms economics, Cost-Benefit Analysis, Markov Chains, Quality-Adjusted Life Years, Neoplasm Recurrence, Local drug therapy
- Abstract
Objective: To evaluate the cost-effectiveness of tisotumab vedotin to treat recurrent or metastatic cervical cancer in second- or third-line from the U.S. payer perspective., Methods: A Markov model with three-state was employed to simulate recurrent or metastatic cervical cancer patients who were administered either tisotumab vedotin or investigator's choice of chemotherapy based on the phase III, open-labeled innovaTV 301 randomized clinical trial. The data on cost and health preferences were collected from the literature., Results: Tisotumab vedotin generated an additional 0.25 quality-adjusted life-years (QALYs) compared to chemotherapy, but at an additional cost of $206,779. This results in incremental cost-effectiveness ratios of $839,107.88 per QALY. The results of the univariate sensitivity analysis indicated that cost of tisotumab vedotin, utility of progressive disease and progression-free survival had the greatest impacts on the outcomes. Probability sensitivity analysis showed that tisotumab vedotin had a 0% chance of being considered cost-effective., Conclusion: Tisotumab vedotin was unlikely cost-effective compared to chemotherapy for recurrent or metastatic cervical cancer patients at a willingness-to-pay threshold of $150,000/QALY from the perspective of a U.S. payer. Lowering the prices of tisotumab vedotin could potentially enhance its cost-effectiveness., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)
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- 2024
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15. Cost-Utility Analysis of Maintenance Pemetrexed Plus Best Supportive Care Compared With Best Supportive Care Alone in Treating Patients With Non-Small Cell Lung Cancer in Jordan.
- Author
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Al Rabayah A, Al Froukh R, Sawalha R, Al Shnekat M, Jahn B, Siebert U, and Jaddoua SM
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- Humans, Jordan, Female, Male, Antineoplastic Agents therapeutic use, Antineoplastic Agents economics, Middle Aged, Pemetrexed therapeutic use, Pemetrexed economics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung economics, Cost-Benefit Analysis methods, Quality-Adjusted Life Years, Lung Neoplasms drug therapy, Lung Neoplasms economics, Markov Chains
- Abstract
Objectives: To assess the cost-effectiveness of maintenance pemetrexed plus best supportive care (BSC) in non-small cell lung cancer patients from a Jordanian healthcare system perspective., Methods: A Markov model with 4 health states was developed to estimate life years, quality-adjusted life-years (QALY), costs, and the incremental cost-utility ratio of pemetrexed plus BSC versus BSC. A lifelong time horizon was used in the base-case analysis. The transition probabilities were estimated from the PARAMOUNT trial, the utility weights were taken from published literature, and costs were based on data and unit costs at King Hussein Cancer Center and the Jordan Food and Drug Administration. Both costs and outcomes were discounted using a 3%. The parameter uncertainty was tested using deterministic and probabilistic sensitivity analyses., Results: The base-case analysis showed that pemetrexed plus BSC increased QALYs and cost compared with BSC. Pemetrexed plus BSC leads to incremental 0.255 QALYs and incremental costs of US $30 826, resulting in an incremental cost-utility ratio of US $120 886/QALY. The results were sensitive to changes in the utility estimates during the progression-free health state, the progression health state, and the cost of postprogression medications The probabilistic sensitivity analysis showed that the probability of pemetrexed plus BSC being a cost-effective option compared with BSC is 0 at a threshold of $56 000., Conclusions: Maintenance pemetrexed for non-small cell lung cancer is not a cost-effective option compared with BSC from a healthcare system perspective based on the listed price at a threshold of $56 000/QALY., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. The study has been approved by the Institutional Review Board at King Hussein Cancer Center. Proposal No. 20 KHCC 05., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)
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- 2024
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16. Lifecycle model-based evaluation of infant 4CMenB vaccination in the UK.
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Sevilla JP, Tortorice D, Kantor D, Regan J, Meszaros KH, Beck EC, Begum N, and Bloom DE
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- Humans, United Kingdom, Infant, Retrospective Studies, Vaccination economics, Vaccination statistics & numerical data, Male, Female, Cost-Benefit Analysis, Meningococcal Infections prevention & control, Meningococcal Infections economics, Meningococcal Vaccines economics, Meningococcal Vaccines administration & dosage, Markov Chains, Quality-Adjusted Life Years
- Abstract
Objectives: Invasive meningococcal disease, an uncommon but severe disease, imposes catastrophic health and economic burdens. Cost-utility analysis (CUA) assumes separability in lifetime health and economic variables and cannot capture the full value of preventing such burdens. We overcome these limitations with a retrospective societal perspective cost-benefit analysis (CBA) of meningococcal serogroup B vaccination (4CMenB) of one infant cohort in the United Kingdom using a health-augmented lifecycle model (HALM) incorporating health's interactions with consumption, earnings, non-market time and financial risk., Methods: We used a static Markov model of vaccination's health impact and an HALM to estimate the private willingness to pay (PWTP) for the intrinsic and instrumental value of health under perfect capital markets, financial risk protection in the absence of insurance against permanent disability, parental spillovers, and acute phase disability. We estimated social WTP (SWTP) incorporating social severity preferences. We estimated rates of return that inform health payer reimbursement decisions, finance ministry budgeting decisions, and legislature taxation decisions. An expert Advisory Board investigated the validity of applying the HALM to infant 4CMenB., Results: The PWTP for a 2 + 1 vaccination schedule is £395, comprising £166 of disability insurance value, £79 of positive parental spillover value, £28 in the value of averting acute phase disability, and £122 in residual intrinsic and instrumental value of health. SWTP is £969., Conclusions: HALM-based CBA provides an empirically richer, more utility-theoretically grounded approach to vaccine evaluation than CUA, demonstrating good value for money for legislatures (based on private values) and for all decision-makers (based on social values)., (© 2024. The Author(s).)
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- 2024
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17. RevGraphVAMP: A protein molecular simulation analysis model combining graph convolutional neural networks and physical constraints.
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Huang Y, Zhang H, Lin Z, Wei Y, and Xi W
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- Humans, Deep Learning, Neural Networks, Computer, Molecular Dynamics Simulation, Markov Chains, Proteins chemistry
- Abstract
Molecular dynamics simulation is a crucial research domain within the life sciences, focusing on comprehending the mechanisms of biomolecular interactions at atomic scales. Protein simulation, as a critical subfield, often utilizes MD for implementation, with trajectory data play a pivotal role in drug discovery. The advancement of high-performance computing and deep learning technology becomes popular and critical to predict protein properties from vast trajectory data, posing challenges regarding data features extraction from the complicated simulation data and dimensionality reduction. Simultaneously, it is essential to provide a meaningful explanation of the biological mechanism behind dimensionality. To tackle this challenge, we propose a new unsupervised model named RevGraphVAMP to intelligently analyze the simulation trajectory. This model is based on the variational approach for Markov processes (VAMP) and integrates graph convolutional neural networks and physical constraint optimization to enhance the learning performance. Additionally, we introduce attention mechanism to assess the importance of key interaction region, facilitating the interpretation of molecular mechanism. In comparison to other VAMPNets models, our model showcases competitive performance, improved accuracy in state transition prediction, as demonstrated through its application to two public datasets and the Shank3-Rap1 complex, which is associated with autism spectrum disorder. Moreover, it enhanced dimensionality reduction discrimination across different substates and provides interpretable results for protein structural characterization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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18. Lifetime economic potential of mobile stroke units in acute stroke care: A model-based analysis of the drivers of cost-effectiveness.
- Author
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Rink JS, Froelich MF, Nour M, Saver JL, Szabo K, Hoyer C, Fassbender KC, Schoenberg SO, and Tollens F
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- Humans, United States, Germany, Telemedicine economics, Models, Economic, Cost-Benefit Analysis, Stroke economics, Stroke therapy, Markov Chains, Mobile Health Units economics, Quality-Adjusted Life Years
- Abstract
Background and Purpose: To simulate patient-level costs, analyze the economic potential of telemedicine-based mobile stroke units for acute prehospital stroke care, and identify major determinants of cost-effectiveness, based on two recent prospective trials from the United States and Germany., Methods: A Markov decision model was developed to simulate lifetime costs and outcomes of mobile stroke unit. The model compares diagnostic and therapeutic pathways of ischemic stroke, hemorrhagic stroke, and stroke mimic patients by conventional care or by mobile stroke units. The treatment outcomes were derived from the B_PROUD and the BEST-mobile stroke unit trials and further input parameters were derived from recent literature. Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. A lifetime horizon based on the US healthcare system was adopted to evaluate different cost thresholds for mobile stroke unit and the resulting cost-effectiveness. Willingness-to-pay thresholds were set at 1x and 3x gross domestic product per capita, as recommended by the World Health Organization., Results: In the base case scenario, mobile stroke unit care yielded an incremental gain of 0.591 quality-adjusted life years per dispatch. Mobile stroke unit was highly cost-effective up to a maximum average cost of 43,067 US dollars per patient. Sensitivity analyses revealed that MSU cost-effectiveness is mainly affected by reduction of long-term disability costs. Also, among other parameters, the rate of stroke mimics patients diagnosed by MSU plays an important role., Conclusion: This study demonstrated that mobile stroke unit can possibly be operated on an excellent level of cost-effectiveness in urban areas in North America with number of stroke mimic patients and long-term stroke survivor costs as major determinants of lifetime cost-effectiveness., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JSR, MFF, SOS, and FT: The Department of Radiology and Nuclear Medicine has research agreements with Siemens Healthineers. KS, CH, MN, and KCF: The authors declare that there is no conflict of interest.JLS: Contracted hourly payments from Medtronic, Cerenovus, Phillips, Neurovasc, Boehringer Ingelheim (prevention only), and Rapid Medical for service on Trial Steering Committee/DSMBs advising on rigorous study design and conduct.
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- 2024
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19. Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention.
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Dioun SM, Perez LR, Prabhu M, Brewer JT, Ahsan MD, Hou JY, Sharaf RN, Wright JD, and Frey MK
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- Humans, Female, Pregnancy, Quality-Adjusted Life Years, Adult, Decision Support Techniques, Ovarian Neoplasms prevention & control, Ovarian Neoplasms genetics, Ovarian Neoplasms diagnosis, Genes, BRCA1, Prenatal Diagnosis economics, Prenatal Diagnosis methods, Middle Aged, BRCA1 Protein genetics, Early Detection of Cancer economics, Early Detection of Cancer methods, Cost-Benefit Analysis, Genetic Carrier Screening methods, Breast Neoplasms genetics, Breast Neoplasms prevention & control, Breast Neoplasms diagnosis, Genetic Testing economics, Genetic Testing methods, Markov Chains
- Abstract
Background: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial., Objective: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective., Study Design: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening., Results: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness., Conclusion: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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20. Cost-effectiveness of atezolizumab plus chemotherapy for advanced/recurrent endometrial cancer.
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Huo G, Song Y, and Chen P
- Subjects
- Humans, Female, DNA Mismatch Repair, Cost-Benefit Analysis, Antibodies, Monoclonal, Humanized economics, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Endometrial Neoplasms drug therapy, Endometrial Neoplasms economics, Antineoplastic Combined Chemotherapy Protocols economics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Quality-Adjusted Life Years, Neoplasm Recurrence, Local drug therapy, Markov Chains
- Abstract
Objective: This study assessed the cost-effectiveness of atezolizumab in combination with chemotherapy for patients with advanced or recurrent endometrial cancer (EC) from the U.S. payer's perspective., Methods: A cost-effectiveness study was conducted using a Markov model based on ENGOT-en7/MaNGO/AtTEnd clinical trials. The population consisted of patients with EC, stratified by mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) subgroups. The model simulated patients receiving either atezolizumab plus chemotherapy or chemotherapy alone. Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated using a Willingness-to-Pay (WTP) threshold of $150,000/QALY. Sensitivity analyses were performed., Results: Adding atezolizumab to chemotherapy in dMMR EC resulted in an incremental gain of 3.31 QALYs but at an additional cost of $855,042, leading to an ICER of $258,391.07/QALY compared to chemotherapy alone. In pMMR EC, there was a gain of 0.50 QALYs with an additional cost of $140,502, resulting in an ICER of $279,239.72/QALY. The overall ICER for EC was $216,459.34/QALY. Scenario analysis indicated that administering atezolizumab for a maximum of 2 years improved cost-effectiveness in dMMR EC, with an ICER of $70,695.96/QALY falling within the predetermined WTP threshold., Conclusion: For patients with advanced or recurrent EC, the combination of atezolizumab and chemotherapy may not prove cost-effective. However, administering atezolizumab for a limited period of maximum 2 years could improve cost-effectiveness in dMMR EC., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)
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- 2024
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21. Cost-effectiveness and health impact of screening and treatment of Mycobacterium tuberculosis infection among formerly incarcerated individuals in Brazil: a Markov modelling study.
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van Lieshout Titan A, Klaassen F, Pelissari DM, de Barros Silva JN Júnior, Alves K, Alves LC, Sanchez M, Bartholomay P, Johansen FDC, Croda J, Andrews JR, Castro MC, Cohen T, Vuik C, and Menzies NA
- Subjects
- Humans, Brazil epidemiology, Adult, Male, Female, Antitubercular Agents therapeutic use, Antitubercular Agents economics, Middle Aged, Rifampin therapeutic use, Rifampin economics, Mycobacterium tuberculosis isolation & purification, Young Adult, Cost-Benefit Analysis, Markov Chains, Prisoners statistics & numerical data, Tuberculosis diagnosis, Tuberculosis economics, Tuberculosis drug therapy, Tuberculosis epidemiology, Mass Screening economics, Mass Screening methods
- Abstract
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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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22. Cost-Utility Analysis of Prophylactic Laser Peripheral Iridotomy for Primary Angle Closure Suspects.
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Rothman AL and Gibbons A
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- Humans, Aged, Female, Male, Middle Aged, Prophylactic Surgical Procedures economics, Health Care Costs, Lasers, Solid-State therapeutic use, Visual Field Tests, Gonioscopy, Glaucoma, Angle-Closure surgery, Glaucoma, Angle-Closure physiopathology, Cost-Benefit Analysis, Iridectomy methods, Quality-Adjusted Life Years, Intraocular Pressure physiology, Laser Therapy economics, Laser Therapy methods, Iris surgery, Markov Chains
- Abstract
Purpose: To assess the cost-utility of prophylactic laser peripheral iridotomy (LPI) for primary angle closure (PAC) suspects (PACS)., Design: Economic evaluation., Methods: Our Markov model randomized PACS eyes to LPI or observation for 40 one-year cycles (100,000 iterations per strategy). Each cycle, an eye remained in its current health state, advanced linearly through PAC, mild, moderate, severe, and end-stage PAC glaucoma (PACG), or died. Transition rates were derived from the literature including the Zhongshan Angle Closure Prevention (ZAP) trial and the Singapore Asymptomatic Narrow Angles Laser Iridotomy Study (ANA-LIS). Eyes with acute-angle closure advanced to either PAC or directly to various PACG severities. A tracker monitored accumulated perimetric decibel reduction to progress PACG through increasing severities, with an annual probability of either stable or severity-dependent perimetry loss. We set a willingness to pay of an incremental cost-effectiveness ratio (ICER) <$50,000/quality-adjusted life-years., Results: At age 50 years, LPI was cost-saving using ZAP data and cost-effective using ANA-LIS data. The ZAP iterations became cost-effective from the societal perspective when the model started at age 55 years and third-party perspective at age 70 years. LPI was no longer cost-effective from the societal perspective using ANA-LIS data at age 80 years or from the societal perspective using ZAP data or third-party perspective with ANA-LIS data at age 85. Probabilistic sensitivity analyses favored LPI until starting age 85., Conclusions: Prophylactic LPI for PACS is cost-effective across a spectrum of ages and should be considered from a public health perspective., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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23. 3M: Measuring Vital Signs With Markov-Gauss Model.
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Tang C, Jin T, Dai Y, and Li Z
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- Humans, Respiratory Rate physiology, Monitoring, Physiologic methods, Radar, Markov Chains, Signal Processing, Computer-Assisted, Heart Rate physiology, Algorithms, Vital Signs physiology
- Abstract
Measuring vital signs (VS) contained in the echoes is crucial to the analyses of breathing and heartbeat signals using medical radar. Although many advanced signal processing algorithms have been developed for radar-based VS measurement and make some improved progress, existing schemes cannot achieve a good estimation of echo phases modulated by the respiratory and cardiac activities with high accuracy or low computation, and thus resulting in serious performance degradation on the subsequent separation of breathing and heartbeat patterns as well as the assessment of breathing rate (BR), heart rate (HR), and heart rate variability (HRV). In this paper, we propose a simple yet effective method to measure VS for medical radar, named 3M method. Specifically, our method firstly introduces the Markov-Gauss model to obtain the recursive expression of the echo phases carrying VS, and secondly derive a simple observation equation (SOE) to reflect the relationship between the observed signal and VS of radar measurement. Thirdly, the aforementioned Markov-Gauss model and SOE are fused by Kalman filter to measure VS with accurate estimation. The 3M method demonstrates an elegant structure, low complexity and excellent features introduced by Kalman filter. Simulation results show the superiority of 3M over other methods. Then, we conduct extensive experiments with insightful visualizations to validate the effectiveness of the 3M method. Comparative results on different scenarios illustrate that the 3M method not only achieves state-of-the-art VS measurement performance but also expresses robust properties to HRV analysis.
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- 2024
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24. Cost-effectiveness Analysis of COMT-inhibitors as Adjuvant Treatments to Levodopa in Patients with Advanced Parkinson's Disease.
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Kwak N, Lee MJ, Kang HY, and Lee H
- Subjects
- Humans, Quality-Adjusted Life Years, Decision Trees, Drug Therapy, Combination, Catechol O-Methyltransferase, Cost-Effectiveness Analysis, Oxadiazoles, Cost-Benefit Analysis, Parkinson Disease drug therapy, Parkinson Disease economics, Levodopa therapeutic use, Levodopa economics, Levodopa administration & dosage, Catechol O-Methyltransferase Inhibitors therapeutic use, Nitriles therapeutic use, Nitriles economics, Markov Chains, Antiparkinson Agents economics, Antiparkinson Agents therapeutic use, Catechols economics, Catechols therapeutic use
- Abstract
Purpose: We aimed to elicit scientific evidence on the cost-effectiveness of two catechol-O-methyltransferase inhibitors (COMT-i) versus no COMT-i in patients with advanced Parkinson's disease., Methods: A mixed model of the decision tree and a Markov model with three health states by OFF-time level (<25%, ≥25%, and death) was constructed to compare opicapone (OPC), entacapone (ENT), and no COMT-i over a lifetime. A hypothetical cohort of 10,000 patients was created and simulated based on the characteristics of the BIPARK trial subjects., Findings: Two COMT-i (OPC and ENT) were identified as a cost-effective option compared to no COMT-i. Probabilistic sensitivity analysis showed that over 90% of the simulations proved the robust cost-effectiveness of COMT-i. When the time horizon as the most influential factor decreases to a 5- and 10-year period, COMT-i can be a cost-saving option. Although ENT may be the preferred option over OPC economically because of its lower price, OPC can be acceptable if the drug price is reduced by 17%., Implications: Add-on treatment with COMT-i in patients with PD receiving levodopa/carbidopa appears to be cost-saving compared with not using COMT-i. In the future, it is necessary to evaluate the economic evaluation of COMT-i based on long-term real-world evidence., Competing Interests: Declaration of competing interest The authors have no conflict of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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25. Cost-Effectiveness Analysis Comparing Biopsy in Advance of Ablation with Concurrent Biopsy and Ablation for Small Renal Masses Measuring 1-3 cm.
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Florea A, Zaric GS, Kang Z, and Cool DW
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- Humans, Male, Aged, Biopsy economics, Treatment Outcome, Tumor Burden, Ablation Techniques economics, Time Factors, Incidental Findings, Decision Trees, Predictive Value of Tests, Cost-Effectiveness Analysis, Cost-Benefit Analysis, Kidney Neoplasms pathology, Kidney Neoplasms surgery, Kidney Neoplasms economics, Quality-Adjusted Life Years, Markov Chains, Models, Economic, Health Care Costs, Decision Support Techniques
- Abstract
Purpose: To analyze the cost effectiveness of performing a renal mass biopsy in advance of ablation or concurrently with a percutaneous ablation procedure for the management of small renal masses (SRMs)., Materials and Methods: A decision-analytic model was developed with a cohort of 65-year-old male patients with an incidental, unilateral 1-3 cm SRM. A decision tree modeled the first year of clinical intervention, after which patients entered a Markov model with a lifetime horizon. Patients were assumed to be treated in accordance with established clinical practice guidelines, including surveillance, repeat ablation for recurrence, and systemic therapy for metastasis. Healthcare cost and utility values were determined from published literature or local hospital estimates, discounted at 1.5%. Total lifetime costs were calculated from the perspective of a Canadian healthcare payer and converted to 2022 Canadian dollars (C$). The primary outcome was incremental cost-effectiveness ratio (ICER) at a willingness-to-pay threshold of C$50,000 per quality-adjusted life year (QALY) gained. The secondary outcome was ICER at a willingness-to-pay threshold of C$50,000 per life year (LY) gained., Results: Concurrent biopsy and ablation resulted in a gain of 16.4 quality-adjusted days, at an incremental cost of $386, with an ICER of C$8,494/QALY. The concurrent strategy was the dominant strategy for a prevalence of benign mass of <5%. Sequential biopsy and ablation was only cost-effective when LYs were not quality-adjusted and ablation cost was >C$4,300 or benign mass prevalence was >28%., Conclusions: Concurrent biopsy and ablation is cost-effective relative to pretreatment diagnostic biopsy for management of incidental SRMs., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)
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- 2024
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26. Screening strategy to advance HCV elimination in Italy: a cost-consequence analysis.
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Marcellusi A, Mennini FS, Andreoni M, and Kondili LA
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- Humans, Italy epidemiology, Female, Male, Middle Aged, Hepatitis C diagnosis, Liver Cirrhosis economics, Adult, Disease Eradication economics, Hepatitis C, Chronic diagnosis, Hepatitis C, Chronic economics, Aged, Mass Screening economics, Mass Screening methods, Markov Chains, Cost-Benefit Analysis
- Abstract
Background and Aims: Italy has the greatest burden of hepatitis C virus (HCV) infection in Western Europe. The screening strategy represents a crucial prevention tool to achieve HCV elimination in Italy. We evaluated the cost-consequences of different screening strategies for the diagnosis of HCV active infection in the birth cohort 1948-1968 to achieve the HCV elimination goal., Methods: We designed a probabilistic model to estimate the clinical, and economic outcomes of different screening coverage uptakes, considering the direct costs of HCV management according to each liver fibrosis stage, in the Italian context. A decision probabilistic tree simulates 4 years of HCV testing of the 1948-1968 general population birth cohort, (15,485,565 individuals to be tested) considering different coverage rates. A No-screening scenario was compared with two alternative screening scenarios that represented different coverage rates each year: (1) Incremental approach (coverage rates equal to 5%, 10%, 30%, and 50% at years 1, 2, 3, and 4, respectively) and (2) Fast approach (50% coverage rate at years 1, 2, 3 and 4). Overall 106,200 cases were previously estimated to have an HCV active infection. A liver disease progression Markov model was considered for an additional 6 years (horizon-time 10 years)., Results: The highest increased number of deaths and clinical events are reported for the No-screening scenario (21,719 cumulative deaths at the end of ten years; 10,148 cases with HCC and/or 7618 cases with Decompensated Cirrhosis). Following the Fast-screening scenario, the reductions in clinical outcomes and deaths were higher compared with No-screening and Incremental-screening. At ten years time horizon, less than 5696 liver deaths (PSA CI95%: - 3873 to 7519), 3,549 HCC (PSA CI95%: - 2413 to 4684) and less than 3005 liver decompensations (PSA CI 95%: - 2104 to 3907) were estimated compared with the Incremental-scenario. The overall costs of the Fast-screening, including the costs of the DAA and liver disease management of the infected patients for 10 years, are estimated to be € 43,107,543 more than no-investment in screening and € 62,289,549 less compared with the overall costs estimated by the Incremental-scenario., Conclusion: It is necessary to guarantee dedicated funds and efficiency of the system for the cost-efficacious screening of the 1948-1968 birth cohort in Italy. A delay in HCV diagnosis and treatment in the general population, yet not addressed for the HCV free-of-charge screening, will have important clinical and economic consequences in Italy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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27. Cost-effectiveness of mepolizumab for severe eosinophilic asthma in China.
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Chaogang X, Mengna A, Zhen W, Ying L, Xin G, Xin Z, Shengjie Z, Yuan Z, Qian L, Wenbin M, and Weiyi F
- Subjects
- Humans, China, Middle Aged, Male, Female, Adult, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized economics, Asthma drug therapy, Asthma economics, Cost-Benefit Analysis, Quality-Adjusted Life Years, Anti-Asthmatic Agents economics, Anti-Asthmatic Agents therapeutic use, Markov Chains
- Abstract
Objective: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China., Methods: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab., Results: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold., Conclusion: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing.
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- 2024
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28. Cost-effectiveness of adjuvant endocrine treatment with tamoxifen for male breast cancer.
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Huang Y, Ke C, Cai J, Wei X, Chen M, and Sun H
- Subjects
- Humans, Male, Chemotherapy, Adjuvant economics, Chemotherapy, Adjuvant methods, Middle Aged, Aged, Receptors, Estrogen metabolism, Medication Adherence statistics & numerical data, United States, Tamoxifen therapeutic use, Tamoxifen economics, Cost-Benefit Analysis, Antineoplastic Agents, Hormonal therapeutic use, Antineoplastic Agents, Hormonal economics, Breast Neoplasms, Male drug therapy, Breast Neoplasms, Male economics, Quality-Adjusted Life Years, Markov Chains
- Abstract
Background: Tamoxifen (TAM) is recommended as the first-line strategy for men with estrogen receptor (ER)-positive early breast cancer who are candidates for adjuvant endocrine therapy in ASCO guideline. Our study aims to analyze the cost-effectiveness of receiving adjuvant endocrine therapy with TAM compared to no TAM, and to assess the cost-effectiveness of using TAM with high adherence over low adherence for ER-positive early male breast cancer in the USA., Methods: Two Markov models comprising three mutually exclusive health states were constructed: (1) the first Markov model compared the cost-effectiveness of adding TAM with not using TAM (TAM versus Not-TAM); (2) the second model compared the cost-effectiveness of receiving TAM with high adherence and low adherence (High-adherence-TAM versus Low-adherence-TAM). The simulation time horizon for both models was the lifetime of patients. The efficacy and safety data of two models were elicited from the real-world studies. Model inputs were derived from the US website and published literature. The main outcomes of two models both included the total cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs)., Results: In the first model, TAM yielded an ICER of $5707.29 per QALY compared to Not-TAM, which was substantially below the WTP threshold of $50,000.00 per QALY in the USA. Probabilistic sensitivity analysis results demonstrated a 100.00% probability of cost-effectiveness for this strategy. In the second model, High-adherence-TAM was dominated absolutely compared to Low-adherence-TAM. The High-adherence-TAM was cost-effective with a 99.70% probability over Low-adherence-TAM when WTP was set as $50,000.00/QALY. All of these parameters within their plausible ranges did not reversely change the results of our models., Conclusions: Our study will offer valuable guidance for physicians or patients when making treatment decisions and provide an effective reference for decision-making to consider the appropriate allocation of funds to this special group., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)
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- 2024
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29. Cost-utility analysis of prenatal supplementation with long-chain n-3 fatty acids to reduce the incidence of wheezing and asthma in neonates.
- Author
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Buendia JA, Guerrero-Patino D, and Zuluaga A
- Subjects
- Humans, Female, Pregnancy, Colombia, Infant, Newborn, Incidence, Prenatal Care economics, Prenatal Care methods, Asthma prevention & control, Asthma economics, Asthma epidemiology, Cost-Benefit Analysis, Dietary Supplements economics, Fatty Acids, Omega-3 administration & dosage, Fatty Acids, Omega-3 economics, Respiratory Sounds, Quality-Adjusted Life Years, Markov Chains
- Abstract
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.
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- 2024
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30. Molecular Dynamics Simulation Combined with Neural Relationship Inference and Markov Model to Reveal the Relationship between Conformational Regulation and Bioluminescence Properties of Gaussia Luciferase.
- Author
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Yang X, Zhang R, Han W, and Han L
- Subjects
- Protein Conformation, Mutation, Animals, Copepoda enzymology, Copepoda genetics, Imidazoles chemistry, Imidazoles metabolism, Protein Binding, Luminescent Measurements, Pyrazines, Molecular Dynamics Simulation, Luciferases metabolism, Luciferases genetics, Luciferases chemistry, Markov Chains
- Abstract
Gaussia luciferase (Gluc) is currently known as the smallest naturally secreted luciferase. Due to its small molecular size, high sensitivity, short half-life, and high secretion efficiency, it has become an ideal reporter gene and is widely used in monitoring promoter activity, studying protein-protein interactions, protein localization, high-throughput drug screening, and real-time monitoring of tumor occurrence and development. Although studies have shown that different Gluc mutations exhibit different bioluminescent properties, their mechanisms have not been further investigated. The purpose of this study is to reveal the relationship between the conformational changes of Gluc mutants and their bioluminescent properties through molecular dynamics simulation combined with neural relationship inference (NRI) and Markov models. Our results indicate that, after binding to the luciferin coelenterazine (CTZ), the α-helices of the 109-119 residues of the Gluc Mutant2 (GlucM2, the flash-type mutant) are partially unraveled, while the α-helices of the same part of the Gluc Mutant1 (GlucM1, the glow-type mutant) are clearly formed. The results of Markov flux analysis indicate that the conformational differences between glow-type and flash-type mutants when combined with luciferin substrate CTZ mainly involve the helicity change of α7. The most representative conformation and active pocket distance analysis indicate that compared to the flash-type mutant GlucM2, the glow-type mutant GlucM1 has a higher degree of active site closure and tighter binding. In summary, we provide a theoretical basis for exploring the relationship between the conformational changes of Gluc mutants and their bioluminescent properties, which can serve as a reference for the modification and evolution of luciferases.
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- 2024
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31. Spatial Markov matrices for measuring the spatial dependencies of an epidemiological spread : case Covid'19 Madagascar.
- Author
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Tabera Tsilefa S and Raherinirina A
- Subjects
- Madagascar epidemiology, Humans, SARS-CoV-2, COVID-19 epidemiology, Markov Chains, Spatial Analysis
- Abstract
Background: This article applies a variant of the Markov chain that explicitly incorporates spatial effects. It is an extension of the Markov class allowing a more complete analysis of the spatial dimensions of transition dynamics. The aim is to provide a methodology for applying the explicit model to spatial dependency analysis., Methods: Here, the question is to study and quantify whether neighborhood context affects transitional dynamics. Rather than estimating a homogeneous law, the model requires the estimation of k transition laws each dependent on spatial neighbor state. This article used published data on confirmed cases of Covid'19 in the 22 regions of Madagascar. These data were discretized to obtain a discrete state of propagation intensity., Results: The analysis gave us the transition probabilities between Covid'19 intensity states knowing the context of neighboring regions, and the propagation time laws knowing the spatial contexts. The results showed that neighboring regions had an effect on the propagation of Covid'19 in Madagascar., Conclusion: After analysis, we can say that there is spatial dependency according to these spatial transition matrices., (© 2024. The Author(s).)
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- 2024
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32. What Is the Economic Benefit of Annual COVID-19 Vaccination From the Adult Individual Perspective?
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Bartsch SM, O'Shea KJ, Weatherwax C, Strych U, Velmurugan K, John DC, Bottazzi ME, Hussein M, Martinez MF, Chin KL, Ciciriello A, Heneghan J, Dibbs A, Scannell SA, Hotez PJ, and Lee BY
- Subjects
- Humans, Middle Aged, Adult, Adolescent, Young Adult, United States epidemiology, Male, Female, COVID-19 prevention & control, COVID-19 economics, COVID-19 epidemiology, COVID-19 Vaccines economics, COVID-19 Vaccines administration & dosage, SARS-CoV-2 immunology, Vaccination economics, Cost-Benefit Analysis, Markov Chains
- Abstract
Background: With coronavirus disease 2019 (COVID-19) vaccination no longer mandated by many businesses/organizations, it is now up to individuals to decide whether to get any new boosters/updated vaccines going forward., Methods: We developed a Markov model representing the potential clinical/economic outcomes from an individual perspective in the United States of getting versus not getting an annual COVID-19 vaccine., Results: For an 18-49 year old, getting vaccinated at its current price ($60) can save the individual on average $30-$603 if the individual is uninsured and $4-$437 if the individual has private insurance, as long as the starting vaccine efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is ≥50% and the weekly risk of getting infected is ≥0.2%, corresponding to an individual interacting with 9 other people in a day under Winter 2023-2024 Omicron SARS-CoV-2 variant conditions with an average infection prevalence of 10%. For a 50-64 year old, these cost-savings increase to $111-$1278 and $119-$1706 for someone without and with insurance, respectively. The risk threshold increases to ≥0.4% (interacting with 19 people/day), when the individual has 13.4% preexisting protection against infection (eg, vaccinated 9 months earlier)., Conclusions: There is both clinical and economic incentive for the individual to continue to get vaccinated against COVID-19 each year., Competing Interests: Potential conflicts of interest . P. J. H., M. E. B., and U. S. are coinventors of a COVID-19 recombinant protein vaccine technology owned by Baylor College of Medicine (BCM) that was recently licensed by BCM nonexclusively and with no patent restrictions to several companies committed to advance vaccines for low- and middle-income countries. The coinventors have no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries that result in a commercial license, a share of any royalty income, according to BCM policy. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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33. Dynamic functional connectivity and gene expression correlates in temporal lobe epilepsy: insights from hidden markov models.
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Qin L, Zhou Q, Sun Y, Pang X, Chen Z, and Zheng J
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- Humans, Male, Female, Adult, Brain diagnostic imaging, Brain physiopathology, Gene Expression Regulation, Case-Control Studies, Young Adult, Middle Aged, Rest physiology, Nerve Net physiopathology, Nerve Net diagnostic imaging, Epilepsy, Temporal Lobe genetics, Epilepsy, Temporal Lobe physiopathology, Epilepsy, Temporal Lobe diagnostic imaging, Magnetic Resonance Imaging, Markov Chains
- Abstract
Backgroud: Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE., Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database., Results: Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients (p < 0.05). The temporal reconfiguration of states in TLE and TLE-CI patients was associated with several brain networks (including the high-order default mode network (DMN), subcortical network (SCN), and cerebellum network (CN). Furthermore, a total of 1580 genes were revealed to be significantly associated with dynamic brain states of TLE, mainly enriched in neuronal signaling and synaptic function., Conclusions: This study provides new insights into characterizing dynamic neural activity in TLE. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, indicating a linkage between neural configuration and gene expression in TLE., (© 2024. The Author(s).)
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- 2024
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34. Influenza vaccination for heart failure patients: a cost-effectiveness analysis from the perspective of Chinese healthcare system.
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Zhao M, Liu F, Wang L, and Chen D
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- Humans, China, Male, Female, Aged, Middle Aged, Vaccination economics, Vaccination statistics & numerical data, Hospitalization economics, Hospitalization statistics & numerical data, Cost-Effectiveness Analysis, Heart Failure, Cost-Benefit Analysis, Influenza Vaccines economics, Influenza Vaccines administration & dosage, Influenza, Human prevention & control, Influenza, Human economics, Markov Chains, Quality-Adjusted Life Years
- Abstract
Purpose: Influenza infection induces cardiovascular events in heart failure (HF) patients, with potential risk reduction through vaccination. This study aims to evaluate the cost-effectiveness of influenza vaccination for HF patients in China., Methods: We developed a Markov model with a 3-month cycle to simulate the cost-effectiveness of administering the influenza vaccine to patients with HF over a 3-year period. Patients in the model received either the influenza vaccine or a placebo, in addition to standard HF treatment. Cost data, sourced from the China Healthcare Statistic Yearbook and other public records, and effectiveness data from the IVVE (Influenza Vaccine to Prevent Adverse Vascular Events in HF) trial, were incorporated. Specifically, the cost of the influenza vaccine was 75 Chinese Yuan (CNY) (11 USD), the cost of hospitalization for heart failure (HHF) was 9,326 CNY (1,386 USD), and the cost of treatment for pneumonia was 5,984 CNY (889 USD). The study's primary outcome, the incremental cost-effectiveness ratio (ICER), quantifies the incremental cost (CNY and USD) per incremental quality-adjusted life year (QALY). Additional outcomes included total cost, total effectiveness, incremental cost, and incremental effectiveness. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess certainty and uncertainty, respectively. Scenario analysis, considering various situations, was performed to evaluate the robustness of the results., Results: In the base case analysis, influenza vaccine, compared to placebo, among Chinese HF patients, resulted in a cost increase from 21,004 CNY (3,121 USD) to 21,062 CNY (3,130 USD) and in QALYs from 1.89 to 1.92 (2.55 life years vs. 2.57 life years) per patient. The resulting ICER was 2,331 CNY (346 USD) per QALY [2,080 CNY (309 USD) per life year], falling below the willingness-to-pay threshold based on per capita GDP. One-way sensitivity analysis revealed that disparities in HHF and cardiovascular death rates between groups had the most significant impact on the ICER, while the cost of vaccines had a marginal impact. PSA and scenario analysis collectively affirmed the robustness of our findings., Conclusion: This study suggests that adding the influenza vaccine to standard treatment regimens for Chinese patients with HF may represent a highly cost-effective option. Further real-world data studies are essential to validate these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Liu, Wang and Chen.)
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- 2024
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35. A Markovian dynamics for Caenorhabditis elegans behavior across scales.
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Costa AC, Ahamed T, Jordan D, and Stephens GJ
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- Animals, Models, Biological, Movement physiology, Caenorhabditis elegans physiology, Markov Chains, Behavior, Animal physiology
- Abstract
How do we capture the breadth of behavior in animal movement, from rapid body twitches to aging? Using high-resolution videos of the nematode worm Caenorhabditis elegans , we show that a single dynamics connects posture-scale fluctuations with trajectory diffusion and longer-lived behavioral states. We take short posture sequences as an instantaneous behavioral measure, fixing the sequence length for maximal prediction. Within the space of posture sequences, we construct a fine-scale, maximum entropy partition so that transitions among microstates define a high-fidelity Markov model, which we also use as a means of principled coarse-graining. We translate these dynamics into movement using resistive force theory, capturing the statistical properties of foraging trajectories. Predictive across scales, we leverage the longest-lived eigenvectors of the inferred Markov chain to perform a top-down subdivision of the worm's foraging behavior, revealing both "runs-and-pirouettes" as well as previously uncharacterized finer-scale behaviors. We use our model to investigate the relevance of these fine-scale behaviors for foraging success, recovering a trade-off between local and global search strategies., Competing Interests: Competing interests statement:The authors declare no competing interest.
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- 2024
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36. The economics of a national anterior cruciate ligament injury prevention program for amateur football players: a Markov model analysis.
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Ross A, Kim J, McKay M, Pappas E, Hardaker N, Whalan M, and Peek K
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- Humans, Australia epidemiology, Male, Adolescent, Adult, Female, Young Adult, Cost-Benefit Analysis, Child, Knee Injuries prevention & control, Knee Injuries economics, Osteoarthritis, Knee prevention & control, Osteoarthritis, Knee economics, Anterior Cruciate Ligament Injuries prevention & control, Markov Chains, Soccer injuries, Quality-Adjusted Life Years
- Abstract
Objectives: To estimate the long term cost savings, return on investment, and gain in quality-adjusted life years (QALYs) that could be achieved by a national anterior cruciate ligament (ACL) injury prevention program for amateur football (soccer) players in Australia., Study Design: Markov model decision analysis., Setting, Participants: Two hypothetical scenarios including all amateur football players in Australia (340 253 players): no intervention, and a national ACL injury prevention program. Transitions between health states, including ACL rupture, meniscal injury, knee osteoarthritis, and total knee replacement were made in one-year cycles over 35 years from a societal perspective., Main Outcome Measures: Cost savings, return on investment, and QALY gain achieved in the prevention program scenario relative to control scenario, by age group (10-17, 18-34, 35 years or older) and gender., Secondary Outcomes: incidence of ACL rupture, knee osteoarthritis, total knee replacement, and total knee replacement revision., Results: The total mean cost of an ACL injury was estimated to be $30 665. The national injury prevention program was projected to save $52 539 751 in medical and societal costs caused by ACL ruptures in amateur footballers over 35 years; the estimated return on each dollar invested in the program was $3.51. Over this period, the number of players with ruptured ACLs could be reduced by 4385 (9%), the number of knee osteoarthritis cases by 780 (8.1%), and the number of total knee replacements by 121 (8.1%); 445 QALYs were gained., Conclusion: Our findings support investing in a national, evidence-based program for the primary prevention of ACL injuries in amateur football players., (© 2024 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)
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- 2024
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37. Variational Supertrees for Bayesian Phylogenetics.
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Karcher MD, Zhang C, and Matsen FA 4th
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- Computer Simulation, Probability, Bayes Theorem, Phylogeny, Algorithms, Markov Chains, Mathematical Concepts, Models, Genetic
- Abstract
Bayesian phylogenetic inference is powerful but computationally intensive. Researchers may find themselves with two phylogenetic posteriors on overlapping data sets and may wish to approximate a combined result without having to re-run potentially expensive Markov chains on the combined data set. This raises the question: given overlapping subsets of a set of taxa (e.g. species or virus samples), and given posterior distributions on phylogenetic tree topologies for each of these taxon sets, how can we optimize a probability distribution on phylogenetic tree topologies for the entire taxon set? In this paper we develop a variational approach to this problem and demonstrate its effectiveness. Specifically, we develop an algorithm to find a suitable support of the variational tree topology distribution on the entire taxon set, as well as a gradient-descent algorithm to minimize the divergence from the restrictions of the variational distribution to each of the given per-subset probability distributions, in an effort to approximate the posterior distribution on the entire taxon set., (© 2024. The Author(s).)
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- 2024
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38. Individual-level models of disease transmission incorporating piecewise spatial risk functions.
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Rahul CR and Deardon R
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- Humans, United Kingdom epidemiology, Spatial Analysis, Epidemiological Models, Computer Simulation, Models, Statistical, Bayes Theorem, Foot-and-Mouth Disease epidemiology, Foot-and-Mouth Disease transmission, Markov Chains, Monte Carlo Method
- Abstract
Modelling epidemics is crucial for understanding the emergence, transmission, impact and control of diseases. Spatial individual-level models (ILMs) that account for population heterogeneity are a useful tool, accounting for factors such as location, vaccination status and genetic information. Parametric forms for spatial risk functions, or kernels, are often used, but rely on strong assumptions about underlying transmission mechanisms. Here, we propose a class of non-parametric spatial disease transmission model, fitted within a Bayesian Markov chain Monte Carlo (MCMC) framework, allowing for more flexible assumptions when estimating the effect on spatial distance and infection risk. We focus upon two specific forms of non-parametric spatial infection kernel: piecewise constant and piecewise linear. Although these are relatively simple forms, we find them to produce results in line with, or superior to, parametric spatial ILMs. The performance of these models is examined using simulated data, including under circumstances of model misspecification, and then applied to data from the UK 2001 foot-and-mouth disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rob Deardon reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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39. Stochastic viability in an island model with partial dispersal: Approximation by a diffusion process in the limit of a large number of islands.
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Kroumi D and Lessard S
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- Stochastic Processes, Islands, Mutation, Models, Theoretical, Biological Evolution, Markov Chains, Population Dynamics
- Abstract
In this paper, we investigate a finite population undergoing evolution through an island model with partial dispersal and without mutation, where generations are discrete and non-overlapping. The population is structured into D demes, each containing N individuals of two possible types, A and B, whose viability coefficients, s
A and sB , respectively, vary randomly from one generation to the next. We assume that the means, variances and covariance of the viability coefficients are inversely proportional to the number of demes D, while higher-order moments are negligible in comparison to 1/D. We use a discrete-time Markov chain with two timescales to model the evolutionary process, and we demonstrate that as the number of demes D approaches infinity, the accelerated Markov chain converges to a diffusion process for any deme size N≥2. This diffusion process allows us to evaluate the fixation probability of type A following its introduction as a single mutant in a population that was fixed for type B. We explore the impact of increasing the variability in the viability coefficients on this fixation probability. At least when N is large enough, it is shown that increasing this variability for type B or decreasing it for type A leads to an increase in the fixation probability of a single A. The effect of the population-scaled variances, σA 2 and σB 2 , can even cancel the effects of the population-scaled means, μA and μB . We also show that the fixation probability of a single A increases as the deme-scaled migration rate increases. Moreover, this probability is higher for type A than for type B if the population-scaled geometric mean viability coefficient is higher for type A than for type B, which means that μA -σA 2 /2>μB -σB 2 /2., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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40. The grapheme-valued Wright-Fisher diffusion with mutation.
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Greven A, den Hollander F, Klimovsky A, and Winter A
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- Models, Genetic, Stochastic Processes, Humans, Markov Chains, Mutation, Genetics, Population
- Abstract
In Athreya et al. (2021), models from population genetics were used to define stochastic dynamics in the space of graphons arising as continuum limits of dense graphs. In the present paper we exhibit an example of a simple neutral population genetics model for which this dynamics is a Markovian diffusion that can be characterized as the solution of a martingale problem. In particular, we consider a Markov chain in the space of finite graphs that resembles a Moran model with resampling and mutation. We encode the finite graphs as graphemes, which can be represented as a triple consisting of a vertex set (or more generally, a topological space), an adjacency matrix, and a sampling (Borel) measure. We equip the space of graphons with convergence of sample subgraph densities and show that the grapheme-valued Markov chain converges to a grapheme-valued diffusion as the number of vertices goes to infinity. We show that the grapheme-valued diffusion has a stationary distribution that is linked to the Griffiths-Engen-McCloskey (GEM) distribution. In a companion paper (Greven et al. 2023), we build up a general theory for obtaining grapheme-valued diffusions via genealogies of models in population genetics., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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41. Hysterectomy versus chemotherapy for low-risk non-metastatic gestational trophoblastic neoplasia (GTN): A cost-effectiveness analysis.
- Author
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Mitric C, Sayyid RK, Fleshner NE, Look Hong NJ, and Bouchard-Fortier G
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- Humans, Female, Pregnancy, Adult, Antineoplastic Combined Chemotherapy Protocols economics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Dactinomycin economics, Dactinomycin administration & dosage, Dactinomycin therapeutic use, Methotrexate economics, Methotrexate administration & dosage, Methotrexate therapeutic use, Decision Support Techniques, Canada, Cyclophosphamide economics, Cyclophosphamide administration & dosage, Cyclophosphamide therapeutic use, Cost-Effectiveness Analysis, Hysterectomy economics, Cost-Benefit Analysis, Gestational Trophoblastic Disease economics, Gestational Trophoblastic Disease drug therapy, Gestational Trophoblastic Disease surgery, Quality-Adjusted Life Years, Markov Chains
- Abstract
Objective: Determine the cost-effectiveness for hysterectomy versus standard of care single agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN)., Methods: A cost-effectiveness analysis was conducted comparing single agent chemotherapy with hysterectomy using decision analysis and Markov modeling from a healthcare payer perspective in Canada. The base case was a 40-year-old patient with low-risk non-metastatic GTN that completed childbearing. Outcomes were life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and adjusted 2022 costs (CAD). Discounting was 1.5% annually and the time horizon was the patient's lifetime. Model validation included face validity, deterministic sensitivity analyses, and scenario analysis., Results: Mean costs for chemotherapy and hysterectomy arms were $34,507 and $17,363, respectively, while effectiveness measure were 30.37 QALYs and 31.04 LYs versus 30.14 QALYs and 30.82 Lys, respectively. The ICER was $74,526 (USD $54,516) per QALY. Thresholds favoring hysterectomy effectiveness were 30-day hysterectomy mortality below 0.2% and recurrence risk during surveillance above 9.2% (low-risk) and 33.4% (high-risk). Scenario analyses for Dactinomycin and Methotrexate led to similar results. Sensitivity analysis using tornado analysis found the cost to be most influenced by single agent chemotherapy cost and risk of resistance, number of weeks of chemotherapy, and probability of postoperative mortality., Conclusion: Compared to hysterectomy, single agent chemotherapy as a first-line treatment costs $74,526 for each additional QALY gained. Given that this cost falls below the accepted $100,000 willingness-to-pay threshold and waitlist limitations within public healthcare systems, these results support the continued use of chemotherapy as standard of care approach for low-risk GTN., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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42. Cost-effectiveness of Accepting Kidneys From Deceased Donors With Common Cancers-A Modeling Study.
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Shah KK, Hedley JA, Robledo KP, Wyld M, Webster AC, and Morton RL
- Subjects
- Humans, Male, Female, Australia, Middle Aged, Breast Neoplasms surgery, Breast Neoplasms economics, Prostatic Neoplasms surgery, Prostatic Neoplasms economics, Colorectal Neoplasms surgery, Colorectal Neoplasms economics, Adult, Registries, Donor Selection economics, Risk Factors, Waiting Lists, Models, Economic, Time Factors, Kidney Transplantation economics, Cost-Benefit Analysis, Quality-Adjusted Life Years, Markov Chains, Tissue Donors supply & distribution
- Abstract
Background: The disparity between the demand for and supply of kidney transplants has resulted in prolonged waiting times for patients with kidney failure. A potential approach to address this shortage is to consider kidneys from donors with a history of common cancers, such as breast, prostate, and colorectal cancers., Methods: We used a patient-level Markov model to evaluate the outcomes of accepting kidneys from deceased donors with a perceived history of breast, prostate, or colorectal cancer characterized by minimal to intermediate transmission risk. Data from the Australian transplant registry were used in this analysis. The study compared the costs and quality-adjusted life years (QALYs) from the perspective of the Australian healthcare system between the proposed practice of accepting these donors and the conservative practice of declining them. The model simulated outcomes for 1500 individuals waitlisted for a deceased donor kidney transplant for a 25-y horizon., Results: Under the proposed practice, when an additional 15 donors with minimal to intermediate cancer transmission risk were accepted, QALY gains ranged from 7.32 to 20.12. This translates to an approximate increase of 7 to 20 additional years of perfect health. The shift in practice also led to substantial cost savings, ranging between $1.06 and $2.3 million., Conclusions: The proposed practice of accepting kidneys from deceased donors with a history of common cancers with minimal to intermediate transmission risk offers a promising solution to bridge the gap between demand and supply. This approach likely results in QALY gains for recipients and significant cost savings for the health system., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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43. Modeling correlated uncertainties in stochastic compartmental models.
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Mamis K and Farazmand M
- Subjects
- Humans, Uncertainty, Models, Biological, Pandemics statistics & numerical data, COVID-19 epidemiology, Stochastic Processes, Markov Chains, SARS-CoV-2
- Abstract
We consider compartmental models of communicable disease with uncertain contact rates. Stochastic fluctuations are often added to the contact rate to account for uncertainties. White noise, which is the typical choice for the fluctuations, leads to significant underestimation of the disease severity. Here, starting from reasonable assumptions on the social behavior of individuals, we model the contacts as a Markov process which takes into account the temporal correlations present in human social activities. Consequently, we show that the mean-reverting Ornstein-Uhlenbeck (OU) process is the correct model for the stochastic contact rate. We demonstrate the implication of our model on two examples: a Susceptibles-Infected-Susceptibles (SIS) model and a Susceptibles-Exposed-Infected-Removed (SEIR) model of the COVID-19 pandemic and compare the results to the available US data from the Johns Hopkins University database. In particular, we observe that both compartmental models with white noise uncertainties undergo transitions that lead to the systematic underestimation of the spread of the disease. In contrast, modeling the contact rate with the OU process significantly hinders such unrealistic noise-induced transitions. For the SIS model, we derive its stationary probability density analytically, for both white and correlated noise. This allows us to give a complete description of the model's asymptotic behavior as a function of its bifurcation parameters, i.e., the basic reproduction number, noise intensity, and correlation time. For the SEIR model, where the probability density is not available in closed form, we study the transitions using Monte Carlo simulations. Our modeling approach can be used to quantify uncertain parameters in a broad range of biological systems., Competing Interests: Declaration of competing interest The author declare that they do not have any competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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44. Evidence for mood instability in patients with bipolar disorder: Applying multilevel hidden Markov modeling to intensive longitudinal ecological momentary assessment data.
- Author
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Mildiner Moraga S, Bos FM, Doornbos B, Bruggeman R, van der Krieke L, Snippe E, and Aarts E
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Self Report, Longitudinal Studies, Depression psychology, Depression epidemiology, Mania psychology, Bipolar Disorder psychology, Bipolar Disorder diagnosis, Ecological Momentary Assessment, Markov Chains, Affect
- Abstract
Bipolar disorder (BD) is a chronic psychiatric condition characterized by large episodic changes in mood and energy. Recently, BD has been proposed to be conceptualized as chronic cyclical mood instability, as opposed to the traditional view of alternating discrete episodes with stable periods in-between. Recognizing this mood instability may improve care and call for high-frequency measures coupled with advanced statistical models. To uncover empirically derived mood states, a multilevel hidden Markov model (HMM) was applied to 4-month ecological momentary assessment data in 20 patients with BD, yielding ∼9,820 assessments in total. Ecological momentary assessment data comprised self-report questionnaires (5 × daily) measuring manic and depressive constructs. Manic and depressive symptoms were also assessed weekly using the Altman Self-Rating Mania Scale and the Quick Inventory for Depressive Symptomatology Self-Report. Alignment between HMM-uncovered momentary mood states and weekly questionnaires was assessed with a multilevel linear model. HMM uncovered four mood states: neutral, elevated, mixed, and lowered, which aligned with weekly symptom scores. On average, patients remained < 25 hr in one state. In almost half of the patients, mood instability was observed. Switching between mood states, three patterns were identified: patients switching predominantly between (a) neutral and lowered states, (b) neutral and elevated states, and (c) mixed, elevated, and lowered states. In all, elevated and lowered mood states were interspersed by mixed states. The results indicate that chronic mood instability is a key feature of BD, even in "relatively" euthymic periods. This should be considered in theoretical and clinical conceptualizations of the disorder. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
- Published
- 2024
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45. Pathways and mechanism of MRTX1133 binding to KRAS G12D elucidated by molecular dynamics simulations and Markov state models.
- Author
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Tu G, Gong Y, Yao X, Liu Q, Xue W, and Zhang R
- Subjects
- Humans, Mutation, Heterocyclic Compounds, 2-Ring, Naphthalenes, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) chemistry, Proto-Oncogene Proteins p21(ras) metabolism, Molecular Dynamics Simulation, Protein Binding, Markov Chains
- Abstract
KRAS G12D is the most common oncogenic mutation identified in several types of cancer. Therefore, design of inhibitors targeting KRAS G12D represents a promising strategy for anticancer therapy. MRTX1133 is a highly potent inhibitor (approximate experiment K
d ≈ 0.0002 nM) of KRAS G12D and is currently in Phase 1/2 study, however, pathways of the compound binding to KRAS G12D has remained unknown, and the mechanism underlying the complicated dynamic process are challenging to capture experimentally, which hinder the structure-based anti-cancer drug design. Here, using MRTX1133 as a probe, unbiased molecular dynamics (MD) was used to simulate the process of MRTX1133 spontaneously binding to KRAS G12D. In six of 42 independent MD simulation (a total of 99 μs), MRTX1133 was observed to successfully associate with KRAS G12D. The kinetically metastable states refer to the potential pathways of MRTX1133 binding to KRAS G12D were revealed by Markov state models (MSM) analysis. Additionally, 8 key residues that are essential for MRTX1133 recognition and tight binding at the preferred low energy states were identified by MM/GBSA analysis. In sum, this study provides a new perspective on understanding the pathways and mechanism of MRTX1133 binding to KRAS G12D., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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- View/download PDF
46. The Cost-Effectiveness of Early High-Acuity Postoperative Care for Medium-Risk Surgical Patients.
- Author
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Leaman EE and Ludbrook GL
- Subjects
- Humans, Prospective Studies, Male, Female, Models, Economic, Recovery Room economics, Time Factors, Risk Factors, Length of Stay economics, Middle Aged, Treatment Outcome, Cost-Benefit Analysis, Markov Chains, Hospital Costs, Postoperative Care economics
- Abstract
Background: Initiatives in perioperative care warrant robust cost-effectiveness analysis in a cost-constrained era when high-value care is a priority. A model of anesthesia-led early high-acuity postoperative care, advanced recovery room care (ARRC), has shown benefit in terms of hospital and patient outcomes, but its cost-effectiveness has not yet been formally determined., Methods: Data from a previously published single-center prospective cohort study of ARRC in medium-risk patients were used to generate a Markov model, which described patient transition between care locations, each with different characteristics and costs. The incremental cost-effectiveness ratio (ICER), using days at home (DAH) and hospital costs, was calculated for ARRC compared to usual ward care using deterministic and probabilistic sensitivity analysis., Results: The Markov model accurately described patient disposition after surgery. For each patient, ARRC provided 4.3 more DAH within the first 90 days after surgery and decreased overall hospital costs by $1081 per patient. Probabilistic sensitivity analysis revealed that ARRC had a 99.3% probability of increased DAH and a 77.4% probability that ARRC was dominant from the perspective of the hospital, with improved outcomes and decreased costs., Conclusions: Early high-acuity care for approximately 24 hours after surgery in medium-risk patients provides highly cost-effective improvements in outcomes when compared to usual ward care., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)
- Published
- 2024
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47. Projected costs of informal care for older people in England.
- Author
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Hu B, Cartagena-Farias J, Brimblecombe N, Jadoolal S, and Wittenberg R
- Subjects
- Humans, England, Aged, Female, Male, Longitudinal Studies, Caregivers economics, Aged, 80 and over, Life Expectancy, Health Expenditures statistics & numerical data, Middle Aged, Long-Term Care economics, Patient Care economics, Health Care Costs statistics & numerical data, Markov Chains, Bayes Theorem
- Abstract
Background: Health economics research and economic evaluation have increasingly taken a societal perspective, accounting for the economic impacts of informal care. Projected economic costs of informal care help researchers and policymakers understand better the long-term consequences of policy reforms and health interventions. This study makes projections of the economic costs of informal care for older people in England., Methods: Data come from two national surveys: the English Longitudinal Study of Ageing (ELSA, N = 35,425) and the Health Survey for England (N = 17,292). We combine a Markov model with a macrosimulation model to make the projections. We explore a range of assumptions about future demographic and epidemiological trends to capture model uncertainty and take a Bayesian approach to capture parameter uncertainty., Results: We estimate that the economic costs of informal care were £54.2 billion in 2019, three times larger than the expenditure on formal long-term care. Those costs are projected to rise by 87% by 2039, faster than public expenditure but slower than private expenditure on formal long-term care. These results are sensitive to assumptions about future life expectancy, fertility rates, and progression of disabilities in the population., Conclusions: Prevention schemes aiming to promote healthy aging and independence will be important to alleviate the costs of informal care. The government should strengthen support for informal caregivers and care recipients to ensure the adequacy of care, protect the well-being of caregivers, and prevent the costs of informal care from spilling over to other sectors of the economy., (© 2023. The Author(s).)
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- 2024
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48. Interactions between Inhibitors and 5-Lipoxygenase: Insights from Gaussian Accelerated Molecular Dynamics and Markov State Models.
- Author
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Liu Y, Wang K, Cao F, Gao N, and Li W
- Subjects
- Humans, Catalytic Domain, Protein Binding, Masoprocol pharmacology, Masoprocol chemistry, Protein Conformation, Arachidonate 5-Lipoxygenase metabolism, Arachidonate 5-Lipoxygenase chemistry, Molecular Dynamics Simulation, Lipoxygenase Inhibitors pharmacology, Lipoxygenase Inhibitors chemistry, Markov Chains
- Abstract
Inflammation is a protective stress response triggered by external stimuli, with 5-lipoxygenase (5LOX) playing a pivotal role as a potent mediator of the leukotriene (Lts) inflammatory pathway. Nordihydroguaiaretic acid (NDGA) functions as a natural orthosteric inhibitor of 5LOX, while 3-acetyl-11-keto-β-boswellic acid (AKBA) acts as a natural allosteric inhibitor targeting 5LOX. However, the precise mechanisms of inhibition have remained unclear. In this study, Gaussian accelerated molecular dynamics (GaMD) simulation was employed to elucidate the inhibitory mechanisms of NDGA and AKBA on 5LOX. It was found that the orthosteric inhibitor NDGA was tightly bound in the protein's active pocket, occupying the active site and inhibiting the catalytic activity of the 5LOX enzyme through competitive inhibition. The binding of the allosteric inhibitor AKBA induced significant changes at the distal active site, leading to a conformational shift of residues 168-173 from a loop to an α-helix and significant negative correlated motions between residues 285-290 and 375-400, reducing the distance between these segments. In the simulation, the volume of the active cavity in the stable conformation of the protein was reduced, hindering the substrate's entry into the active cavity and, thereby, inhibiting protein activity through allosteric effects. Ultimately, Markov state models (MSM) were used to identify and classify the metastable states of proteins, revealing the transition times between different conformational states. In summary, this study provides theoretical insights into the inhibition mechanisms of 5LOX by AKBA and NDGA, offering new perspectives for the development of novel inhibitors specifically targeting 5LOX, with potential implications for anti-inflammatory drug development.
- Published
- 2024
- Full Text
- View/download PDF
49. An FPGA-based hardware accelerator supporting sensitive sequence homology filtering with profile hidden Markov models.
- Author
-
Anderson T and Wheeler TJ
- Subjects
- Computational Biology methods, Sequence Homology, Algorithms, Software, Markov Chains, Sequence Alignment methods
- Abstract
Background: Sequence alignment lies at the heart of genome sequence annotation. While the BLAST suite of alignment tools has long held an important role in alignment-based sequence database search, greater sensitivity is achieved through the use of profile hidden Markov models (pHMMs). Here, we describe an FPGA hardware accelerator, called HAVAC, that targets a key bottleneck step (SSV) in the analysis pipeline of the popular pHMM alignment tool, HMMER., Results: The HAVAC kernel calculates the SSV matrix at 1739 GCUPS on a ∼ $3000 Xilinx Alveo U50 FPGA accelerator card, ∼ 227× faster than the optimized SSV implementation in nhmmer. Accounting for PCI-e data transfer data processing, HAVAC is 65× faster than nhmmer's SSV with one thread and 35× faster than nhmmer with four threads, and uses ∼ 31% the energy of a traditional high end Intel CPU., Conclusions: HAVAC demonstrates the potential offered by FPGA hardware accelerators to produce dramatic speed gains in sequence annotation and related bioinformatics applications. Because these computations are performed on a co-processor, the host CPU remains free to simultaneously compute other aspects of the analysis pipeline., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
50. Unveiling Allosteric Regulation and Binding Mechanism of BRD9 through Molecular Dynamics Simulations and Markov Modeling.
- Author
-
Wang B, Wang J, Yang W, Zhao L, Wei B, and Chen J
- Subjects
- Allosteric Regulation, Humans, Binding Sites, Principal Component Analysis, Thermodynamics, Bromodomain Containing Proteins, Molecular Dynamics Simulation, Markov Chains, Transcription Factors metabolism, Transcription Factors chemistry, Transcription Factors antagonists & inhibitors, Protein Binding
- Abstract
Bromodomain-containing protein 9 (BRD9) is a key player in chromatin remodeling and gene expression regulation, and it is closely associated with the development of various diseases, including cancers. Recent studies have indicated that inhibition of BRD9 may have potential value in the treatment of certain cancers. Molecular dynamics (MD) simulations, Markov modeling and principal component analysis were performed to investigate the binding mechanisms of allosteric inhibitor POJ and orthosteric inhibitor 82I to BRD9 and its allosteric regulation. Our results indicate that binding of these two types of inhibitors induces significant structural changes in the protein, particularly in the formation and dissolution of α-helical regions. Markov flux analysis reveals notable changes occurring in the α-helicity near the ZA loop during the inhibitor binding process. Calculations of binding free energies reveal that the cooperation of orthosteric and allosteric inhibitors affects binding ability of inhibitors to BRD9 and modifies the active sites of orthosteric and allosteric positions. This research is expected to provide new insights into the inhibitory mechanism of 82I and POJ on BRD9 and offers a theoretical foundation for development of cancer treatment strategies targeting BRD9.
- Published
- 2024
- Full Text
- View/download PDF
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