Modeling and Simulation Laboratory, Department of Mathematics, University of Southern California, 3620 S. Vermont Ave., Los Angeles, CA 90089-2532, United States.
Department of Psychiatry, University of California, San Diego, 3350 La Jolla Village Drive, San Diego, CA 92161, United States; Veterans Affairs San Diego Healthcare System, Psychology Service (116B), 3350 La Jolla Village Drive, San Diego, CA 92161, United States; Veterans Medical Research Foundation, 3350 La Jolla Village Drive, San Diego, CA 92161, United States.
Alcohol. 2019 Dec;81:117-129. doi: 10.1016/j.alcohol.2018.09.005. Epub 2018 Sep 20.
Alcohol biosensor devices have been developed to unobtrusively measure transdermal alcohol concentration (TAC), the amount of ethanol diffusing through the skin, in nearly continuous fashion in naturalistic settings. Because TAC data are affected by physiological and environmental factors that vary across individuals and drinking episodes, there is not an elementary formula to convert TAC into easily interpretable metrics such as blood and breath alcohol concentrations (BAC/BrAC). In our prior work, we addressed this conversion problem in a deterministic way by developing physics/physiological-based models to convert TAC to estimated BrAC (eBrAC), in which the model parameter values were individually determined for each person wearing a specific transdermal sensor using simultaneously collected TAC (via a biosensor) and BrAC (via a breath analyzer) during a calibration episode. We found these individualized parameter values produced relatively good eBrAC curves for subsequent drinking episodes, but our results also indicated the models were not fully capturing the dynamics of the system and variations across drinking episodes. Here, we report on a novel mathematical framework to improve our ability to model eBrAC from TAC data that uses aggregate population data instead of individualized calibration data to determine model parameter values via a random diffusion equation. We first provide the theoretical mathematical basis for our approach, and then test the efficacy of this method using datasets of contemporaneous BrAC/TAC measurements obtained by a) a single subject during multiple drinking episodes and b) multiple subjects during single drinking episodes. For each dataset, we used a set of drinking episodes to construct the population model, and then ran the model with another set of randomly selected test episodes. We compared raw TAC data to model-simulated TAC curve, breath analyzer BrAC data to model eBrAC curve with 75% credible bands, episode summary scores of peak BrAC, times of peak BrAC, and area under the drinking curve also with 75% credible intervals, and report the percent of the raw BrAC captured within the eBrAC curve credible bands. We also display results when stratifying the data based on the relationship between the raw BrAC and TAC data. Results indicate the population-based model is promising, with better fit within a single participant when stratifying episodes. This study provides initial proof-of-concept for constructing, fitting, and using a population-based model to obtain estimates and error bands for BrAC from TAC. The advancements in this study, including new applications of math, the development of a population-based model with error bars, and the production of corresponding MATLAB codes, represent a major step forward in our ability to produce quantitatively- and temporally-accurate estimates of BrAC from TAC biosensor data.
酒精生物传感器设备已被开发出来,以便在自然环境中以非侵入性的方式连续测量经皮酒精浓度(TAC),即通过皮肤扩散的乙醇量。由于 TAC 数据受到个体和饮酒事件中变化的生理和环境因素的影响,因此没有基本公式可以将 TAC 转换为易于解释的指标,例如血液和呼气酒精浓度(BAC/BrAC)。在我们之前的工作中,我们通过开发基于物理/生理的模型来解决这个转换问题,该模型用于将 TAC 转换为估计的呼气酒精浓度(eBrAC),其中模型参数值是使用同时收集的 TAC(通过生物传感器)和 BrAC(通过呼气分析仪)在校准期间为每个佩戴特定透皮传感器的人单独确定的。我们发现,这些个性化参数值为随后的饮酒事件产生了相对较好的 eBrAC 曲线,但我们的结果也表明,这些模型并未完全捕捉系统的动态和饮酒事件之间的变化。在这里,我们报告了一种新的数学框架,该框架使用汇总的人群数据来代替个性化的校准数据来通过随机扩散方程确定模型参数值,从而提高我们从 TAC 数据建模 eBrAC 的能力。我们首先提供我们方法的理论数学基础,然后使用通过 a)单个主体在多个饮酒事件中,以及 b)多个主体在单个饮酒事件中获得的同时 BrAC/TAC 测量数据集来测试该方法的功效。对于每个数据集,我们使用一组饮酒事件来构建人群模型,然后使用另一组随机选择的测试事件运行该模型。我们将原始 TAC 数据与模型模拟的 TAC 曲线进行比较,将呼气分析仪的 BrAC 数据与具有 75%置信区间的模型 eBrAC 曲线进行比较,将峰值 BrAC、峰值时间和饮酒曲线下面积的事件摘要评分也与 75%置信区间进行比较,并报告原始 BrAC 曲线的百分比在 eBrAC 曲线的置信带内。我们还显示了基于原始 BrAC 和 TAC 数据之间关系对数据进行分层时的结果。结果表明,基于人群的模型很有前景,当对事件进行分层时,单个参与者的拟合效果更好。这项研究为构建、拟合和使用基于人群的模型提供了初步的概念验证,以便从 TAC 获得 BrAC 的估计值和误差带。这项研究的进展,包括数学的新应用、具有误差条的基于人群的模型的开发以及相应的 MATLAB 代码的生成,代表着我们从 TAC 生物传感器数据中生成定量和时间准确的 BrAC 估计值的能力向前迈出了一大步。