Handling underlying discrete variables with bivariate mixed hidden Markov models in NONMEM

AbstractNon-linear mixed effects models typically deal with stochasticity in observed processes but models accounting for only observed processes may not be the most appropriate for all data. Hidden Markov models (HMMs) characterize the relationship between observed and hidden variables where the hidden variables can represent an underlying and unmeasurable disease status for example. Adding stochasticity to HMMs results in mixed HMMs (MHMMs) which potentially allow for the characterization of variability in unobservable processes. Further, HMMs can be extended to include more than one observation source and are then multivariate HMMs. In this work MHMMs were developed and applied in a chronic obstructive pulmonary disease example. The two hidden states included in the model were remission and exacerbation and two observation sources were considered, patient reported outcomes (PROs) and forced expiratory volume (FEV1). Estimation properties in the software NONMEM of model parameters were investigated with and without random and covariate effect parameters. The influence of including random and covariate effects of varying magnitudes on the parameters in the model was quantified and a power analysis was performed to compare the power of a single bivariate MHMM with two separate univariate MHMMs. A bivariate MHMM was developed for simulating and analysing hypothetical COPD data consisting of PRO and FEV1 measurements collected every week for 60  weeks. Parameter precision ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

Related Links:

ConclusionsDepletion of miR-380 alleviated cells damage caused by CSE through targeting CHRNA4, suggesting that miR-380/CHRNA4 may serve as novel therapeutic targets for COPD treatment.
Source: Molecular and Cellular Probes - Category: Molecular Biology Source Type: research
Conditions:   COPD;   Chronic Respiratory Insufficiency Intervention:   Device: Free 02 Sponsor:   ADIR Association Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Mucosal Immunology, Published online: 09 December 2019; doi:10.1038/s41385-019-0241-6The role of miR-155 in cigarette smoke-induced pulmonary inflammation and COPD
Source: Mucosal Immunology - Category: Allergy & Immunology Authors: Source Type: research
In this study, we developed a codelivery system using core-shell type lipid-polymer nanoparticles (LPNs) composed of a poly(lactic acid) (PLA) core encapsulating a potent antioxidant Mn-porphyrin dimer (MnPD) and a cationic lipid (DOTAP) shell that binds HDAC2-encoding plasmid DNA (pHDAC2), as a new therapeutic approach toward COPD. The transfection of pHDAC2 combined with the elimination of ROS by MnPD exhibited a significant enhancement of intracellular HDAC2 expression levels, suggesting that the multi-antioxidative activity of MnPD plays a crucial role in the expression of HDAC2. Moreover, treatment with LPNs efficient...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research
Authors: Zhao Z, Chang MY, Frerichs I, Zhang JH, Chang HT, Gow CH, Möller K Abstract BACKGROUND: Since bronchial abnormalities often exhibit spatial non-uniformity which may be not correctly assessed by conventional global lung function measures, regional information may help to characterize the disease progress. We hypothesized that regional air trapping during mechanical ventilation could be characterized by regional end-expiratory flow (EEF) derived from electrical impedance tomography (EIT). METHODS: Twenty-five patients suffering from chronic obstructive pulmonary disease (COPD grade 3 or 4) or severe...
Source: Minerva Anestesiologica - Category: Anesthesiology Tags: Minerva Anestesiol Source Type: research
ConclusionThis may be achieved through adoption of stringent air pollution regulations and sustainable city planning. Increase in urban green infrastructures and improving road transportation will reduce PM2.5 levels in urban environment, thereby safeguarding human health from air pollution and improving citizens’ well-being.
Source: Clinical Epidemiology and Global Health - Category: Epidemiology Source Type: research
Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) often coexist and present clinicians with diagnostic and therapeutic challenges. Beta-blockers are a cornerstone of CHF treatment, in patients with a low ejection fraction, while beta-agonists are utilized for COPD. These 2 therapies exert opposing pharmacological effects. COPD patients are at an increased risk of mortality from cardiovascular events. In addition to CHF, beta-blockers are used in a number of cardiovascular conditions because of their cardioprotective properties as well as their mortality benefit. However, there is reluctance among...
Source: Cardiology in Review - Category: Cardiology Tags: Review Articles Source Type: research
CONCLUSIONS: Both low and high Hgb levels were associated with an increased risk of death from various causes, and some diseases showed different patterns according to sex. PMID: 31795616 [PubMed - in process]
Source: Journal of Preventive Medicine and Public Health - Category: International Medicine & Public Health Tags: J Prev Med Public Health Source Type: research
PMID: 31810375 [PubMed - as supplied by publisher]
Source: American Journal of Respiratory and Critical Care Medicine - Category: Respiratory Medicine Authors: Tags: Am J Respir Crit Care Med Source Type: research
ConclusionThe Turkish version of the Ex ‐SRES was found to have high validity and reliability and to be a precise tool that specifically measures exercise self‐efficacy in the COPD patient group.
Source: The Clinical Respiratory Journal - Category: Respiratory Medicine Authors: Tags: ORIGINAL ARTICLE Source Type: research
More News: Chronic Obstructive Pulmonary | Drugs & Pharmacology