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1.
J Adv Res ; 32: 27-36, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34484823

RESUMO

Introduction: In long-term induced general anesthesia cases such as those uniquely defined by the ongoing Covid-19 pandemic context, the clearance of hypnotic and analgesic drugs from the body follows anomalous diffusion with afferent drug trapping and escape rates in heterogeneous tissues. Evidence exists that drug molecules have a preference to accumulate in slow acting compartments such as muscle and fat mass volumes. Currently used patient dependent pharmacokinetic models do not take into account anomalous diffusion resulted from heterogeneous drug distribution in the body with time varying clearance rates. Objectives: This paper proposes a mathematical framework for drug trapping estimation in PK models for estimating optimal drug infusion rates to maintain long-term anesthesia in Covid-19 patients. We also propose a protocol for measuring and calibrating PK models, along with a methodology to minimize blood sample collection. Methods: We propose a framework enabling calibration of the models during the follow up of Covid-19 patients undergoing anesthesia during their treatment and recovery period in ICU. The proposed model can be easily updated with incoming information from clinical protocols on blood plasma drug concentration profiles. Already available pharmacokinetic and pharmacodynamic models can be then calibrated based on blood plasma concentration measurements. Results: The proposed calibration methodology allow to minimize risk for potential over-dosing as clearance rates are updated based on direct measurements from the patient. Conclusions: The proposed methodology will reduce the adverse effects related to over-dosing, which allow further increase of the success rate during the recovery period.


Assuntos
Anestesia , COVID-19 , Hipnóticos e Sedativos , Modelos Biológicos , SARS-CoV-2 , Idoso , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacocinética , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Pandemias
2.
Sensors (Basel) ; 21(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34502811

RESUMO

The present manuscript aims at raising awareness of the endless possibilities of fractional calculus applied not only to system identification and control engineering, but also into sensing and filtering domains. The creation of the fractance device has enabled the physical realization of a new array of sensors capable of gathering more information. The same fractional-order electronic component has led to the possibility of exploring analog filtering techniques from a practical perspective, enlarging the horizon to a wider frequency range, with increased robustness to component variation, stability and noise reduction. Furthermore, fractional-order digital filters have developed to provide an alternative solution to higher-order integer-order filters, with increased design flexibility and better performance. The present study is a comprehensive review of the latest advances in fractional-order sensors and filters, with a focus on design methodologies and their real-life applicability reported in the last decade. The potential enhancements brought by the use of fractional calculus have been exploited as well in sensing and filtering techniques. Several extensions of the classical sensing and filtering methods have been proposed to date. The basics of fractional-order filters are reviewed, with a focus on the popular fractional-order Kalman filter, as well as those related to sensing. A detailed presentation of fractional-order filters is included in applications such as data transmission and networking, electrical and chemical engineering, biomedicine and various industrial fields.

3.
J Adv Res ; 32: 61-71, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34484826

RESUMO

Introduction: As pulmonary dysfunctions are prospective factors for developing cancer, efforts are needed to solve the limitations regarding applications in lung cancer. Fractional order respiratory impedance models can be indicative of lung cancer dynamics and tissue heterogeneity. Objective: The purpose of this study is to investigate how the existence of a tumorous tissue in the lung modifies the parameters of the proposed models. The first use of a prototype forced oscillations technique (FOT) device in a mimicked lung tumor setup is investigated by comparing and interpreting the experimental findings. Methods: The fractional order model parameters are determined for the mechanical properties of the healthy and tumorous lung. Two protocols have been performed for a mimicked lung tumor setup in a laboratory environment. A low frequency evaluation of respiratory impedance model and nonlinearity index were assessed using the forced oscillations technique. Results: The viscoelastic properties of the lung tissue change, results being mirrored in the respiratory impedance assessment via FOT. The results demonstrate significant differences among the mimicked healthy and tumor measurements, (p-values < 0.05) for impedance values and also for heterogeneity index. However, there was no significant difference in lung function before and after immersing the mimicked lung in water or saline solution, denoting no structural changes. Conclusion: Simulation tests comparing the changes in impedance support the research hypothesis. The impedance frequency response is effective in non-invasive identification of respiratory tissue abnormalities in tumorous lung, analyzed with appropriate fractional models.

4.
Sensors (Basel) ; 20(23)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33256120

RESUMO

The paper aims to revive the interest in bioimpedance analysis for pain studies in communicating and non-communicating (anesthetized) individuals for monitoring purpose. The plea for exploitation of full potential offered by the complex (bio)impedance measurement is emphasized through theoretical and experimental analysis. A non-invasive, low-cost reliable sensor to measure skin impedance is designed with off-the-shelf components. This is a second generation prototype for pain detection, quantification, and modeling, with the objective to be used in fully anesthetized patients undergoing surgery. The 2D and 3D time-frequency, multi-frequency evaluation of impedance data is based on broadly available signal processing tools. Furthermore, fractional-order impedance models are implied to provide an indication of change in tissue dynamics correlated with absence/presence of nociceptor stimulation. The unique features of the proposed sensor enhancements are described and illustrated here based on mechanical and thermal tests and further reinforced with previous studies from our first generation prototype.


Assuntos
Dor Aguda , Processamento de Sinais Assistido por Computador , Dor Aguda/diagnóstico , Impedância Elétrica , Humanos
5.
J Clin Med ; 9(6)2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32545464

RESUMO

This paper introduces a mathematical compartmental formulation of dose-effect synergy modelling for multiple therapies in non small cell lung cancer (NSCLC): antiangiogenic, immuno- and radiotherapy. The model formulates the dose-effect relationship in a unified context, with tumor proliferating rates and necrotic tissue volume progression as a function of therapy management profiles. The model accounts for inter- and intra-response variability by using surface model response terms. Slow acting peripheral compartments such as fat and muscle for drug distribution are not modelled. This minimal pharmacokinetic-pharmacodynamic (PKPD) model is evaluated with reported data in mice from literature. A systematic analysis is performed by varying only radiotherapy profiles, while antiangiogenesis and immunotherapy are fixed to their initial profiles. Three radiotherapy protocols are selected from literature: (1) a single dose 5 Gy once weekly; (2) a dose of 5 Gy × 3 days followed by a 2 Gy × 3 days after two weeks and (3) a dose of 5 Gy + 2 × 0.075 Gy followed after two weeks by a 2 Gy + 2 × 0.075 Gy dose. A reduction of 28% in tumor end-volume after 30 days was observed in Protocol 2 when compared to Protocol 1. No changes in end-volume were observed between Protocol 2 and Protocol 3, this in agreement with other literature studies. Additional analysis on drug interaction suggested that higher synergy among drugs affects up to three-fold the tumor volume (increased synergy leads to significantly lower growth ratio and lower total tumor volume). Similarly, changes in patient response indicated that increased drug resistance leads to lower reduction rates of tumor volumes, with end-volume increased up to 25-30%. In conclusion, the proposed minimal PKPD model has physiological value and can be used to study therapy management protocols and is an aiding tool in the clinical decision making process. Although developed with data from mice studies, the model is scalable to NSCLC patients.

6.
J Clin Med ; 9(3)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143327

RESUMO

Although the measurement of dielectric properties of the skin is a long-known tool for assessing the changes caused by nociception, the frequency modulated response has not been considered yet. However, for a rigorous characterization of the biological tissue during noxious stimulation, the bioimpedance needs to be analyzed over time as well as over frequency. The 3-dimensional analysis of nociception, including bioimpedance, time, and frequency changes, is provided by ANSPEC-PRO device. The objective of this observational trial is the validation of the new pain monitor, named as ANSPEC-PRO. After ethics committee approval and informed consent, 26 patients were monitored during the postoperative recovery period: 13 patients with the in-house developed prototype ANSPEC-PRO and 13 with the commercial device MEDSTORM. At every 7 min, the pain intensity was measured using the index of Anspec-pro or Medstorm and the 0-10 numeric rating scale (NRS), pre-surgery for 14 min and post-anesthesia for 140 min. Non-significant differences were reported for specificity-sensitivity analysis between ANSPEC-PRO (AUC = 0.49) and MEDSTORM (AUC = 0.52) measured indexes. A statistically significant positive linear relationship was observed between Anspec-pro index and NRS (r2 = 0.15, p < 0.01). Hence, we have obtained a validation of the prototype Anspec-pro which performs equally well as the commercial device under similar conditions.

7.
Front Physiol ; 10: 1390, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803060

RESUMO

This paper introduces the use of low frequencies forced oscillation technique (FOT) in the presence of breathing signal. The hypothesis tested is to evaluate the sensitivity of FOT to various degrees of obstruction in COPD patients. The measurements were performed in the frequency range 0-2 Hz. The use of FOT to evaluate respiratory impedance has been broadly recognized and its complementary use next to standardized method as spirometry and body plethysmography has been well-documented. Typical use of FOT uses frequencies between 4-32 Hz and above. However, interesting information at frequencies below 4 Hz is related to viscoelastic properties of parenchyma. Structural changes in COPD affect viscoelastic properties and we propose to investigate the use of FOT at low frequencies with a fourth generation fan-based FOT device. The generator non-linearity introduced by the device is separated from the linear approximation of the impedance before evaluating the results on patients. Three groups of COPD obstruction, GOLD II, III, and IV are evaluated. We found significant differences in mechanical parameters (tissue damping, tissue elasticity, hysteresivity) and increased degrees of non-linear dynamic contributions in the impedance data with increasing degree of obstruction (p < 0.01). The results obtained suggest that the non-linear index correlates better with degrees of heterogeneity linked to COPD GOLD stages, than the currently used hysteresivity index. The protocol and method may prove useful to improve current diagnosis percentages for various COPD phenotypes.

8.
IEEE Trans Biomed Eng ; 66(3): 718-726, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30010543

RESUMO

OBJECTIVE: This paper introduces a primer in the health care practice, namely a mathematical model and methodology for detecting and analysing nociceptor stimulation followed by related tissue memory effects. METHODS: Noninvasive nociceptor stimulus protocol and prototype device for measuring bioimpedance is provided. Various time instants, sensor location, and stimulus train have been analysed. RESULTS: The method and model indicate that nociceptor stimulation perceived as pain in awake healthy volunteers is noninvasively detected. The existence of a memory effect is proven from data. Sensor location had minimal effect on detection level, while day-to-day variability was observed without being significant. CONCLUSION: Following the experimental study, the model enables a comprehensive management of chronic pain patients, and possibly other analgesia, or pain related regulatory loops. SIGNIFICANCE: A device and methodology for noninvasive for detecting nociception stimulation have been developed. The proposed method and models have been validated on healthy volunteers.


Assuntos
Impedância Elétrica , Nociceptividade/fisiologia , Dor , Processamento de Sinais Assistido por Computador , Vigília/fisiologia , Adulto , Analgesia , Dor Crônica , Feminino , Mãos/fisiologia , Humanos , Masculino , Dor/diagnóstico , Dor/fisiopatologia
9.
PLoS One ; 12(5): e0177969, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28542377

RESUMO

This paper proposes a mathematical framework for understanding how the structural changes in the COPD lung reflect in model parameters. The core of the analysis is a correlation between the heterogeneity in the lung as COPD degree changes (GOLD II, III and IV) and the nonlinearity index evaluated using the forced oscillation technique. A low frequency evaluation of respiratory impedance models and nonlinearity degree is performed since changes in tissue mechanics are related to viscoelastic properties. Simulation analysis of our model indicates a good correlation to expected changes in heterogeneity and nonlinear effects. A total of 43 COPD diagnosed patients are evaluated, distributed as GOLD II (18), GOLD III (15) and GOLD IV (10). Experimental data supports the claims and indicate that the proposed model and index for nonlinearity is well-suited to capture COPD structural changes.


Assuntos
Pulmão/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Idoso , Impedância Elétrica , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Modelos Teóricos , Índice de Gravidade de Doença
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