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Noninvasive assessment of dofetilide plasma concentration using a deep learning (neural network) analysis of the surface electrocardiogram: A proof of concept study.

ABSTRACT: BACKGROUND:Dofetilide is an effective antiarrhythmic medication for rhythm control in atrial fibrillation, but carries a significant risk of pro-arrhythmia and requires meticulous dosing and monitoring. The cornerstone of this monitoring, measurement of the QT/QTc interval, is an imperfect surrogate for plasma concentration, efficacy, and risk of pro-arrhythmic potential. OBJECTIVE:The aim of our study was to test the application of a deep learning approach (using a convolutional neural network) to assess morphological changes on the surface ECG (beyond the QT interval) in relation to dofetilide plasma concentrations. METHODS:We obtained publically available serial ECGs and plasma drug concentrations from 42 healthy subjects who received dofetilide or placebo in a placebo-controlled cross-over randomized controlled clinical trial. Three replicate 10-s ECGs were extracted at predefined time-points with simultaneous measurement of dofetilide plasma concentration We developed a deep learning algorithm to predict dofetilide plasma concentration in 30 subjects and then tested the model in the remaining 12 subjects. We compared the deep leaning approach to a linear model based only on QTc. RESULTS:Fourty two healthy subjects (21 females, 21 males) were studied with a mean age of 26.9 ± 5.5 years. A linear model of the QTc correlated reasonably well with dofetilide drug levels (r = 0.64). The best correlation to dofetilide level was achieved with the deep learning model (r = 0.85). CONCLUSION:This proof of concept study suggests that artificial intelligence (deep learning/neural network) applied to the surface ECG is superior to analysis of the QT interval alone in predicting plasma dofetilide concentration.

SUBMITTER: Attia ZI

PROVIDER: S-EPMC6104915 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlthough total plasma lipoproteome consists of proteins that have shown promises as biomarkers that can identify Alzheimer's disease (AD), effect sizes are modest. The objective of this study is to provide initial proof-of-concept that the plasma lipoproteome more likely differ between AD cases and controls when measured in individual plasma lipoprotein fractions than when measured as total in immunodepleted plasma.MethodsWe first developed a targeted proteomics method based on selected reaction monitoring (SRM) and liquid chromatography and tandem mass spectrometry for measurement of 120 tryptic peptides from 79 proteins that are commonly present in plasma lipoproteins. Then in a proof-of concept case-control study of 5 AD cases and 5 sex- and age-matched controls, we applied the targeted proteomic method and performed relatively quantification of 120 tryptic peptides in plasma lipoprotein fractions (fractionated by sequential gradient ultracentrifugation) and in immunodepleted plasma (of albumin and IgG). Unadjusted p values from two-sample t-tests and overall fold change was used to evaluate a peptide relative difference between AD cases and controls, with lower p values (<?0.05) or greater fold differences (>?1.05 or?<?0.95) suggestive of greater peptide/protein differences.ResultsWithin-day and between-days technical precisions (mean %CV [SD] of all SRM transitions) of the targeted proteomic method were 3.95% (2.65) and 9.31% (5.59), respectively. Between-days technical precisions (mean % CV [SD]) of the entire plasma lipoproteomic workflow including plasma lipoprotein fractionation was 27.90% (14.61). Ten tryptic peptides that belonged to 5 proteins in plasma lipoproteins had unadjusted p values?<?0.05, compared to no peptides in immunodepleted plasma. Furthermore, 27, 32, 17, and 20 tryptic peptides in VLDL, IDL, LDL and HDL, demonstrated overall peptide fold differences?>?1.05 or?<?0.95, compared to only 6 tryptic peptides in immunodepleted plasma. The overall comparisons, therefore, suggested greater peptide/protein differences in plasma lipoproteome when measured in individual plasma lipoproteins than as total in immunodepleted plasma. Specifically, protein complement C3's peptide IHWESASLLR, had unadjusted p values of 0.00007, 0.00012, and 0.0006 and overall 1.25, 1.17, 1.14-fold changes in VLDL, IDL, and LDL, respectively. After positive False Discovery Rate (pFDR) adjustment, the complement C3 peptide IHWESASLLR in VLDL remained statistically different (adjusted p value?<?0.05).DiscussionThe findings may warrant future studies to investigate plasma lipoproteome when measured in individual plasma lipoprotein fractions for AD diagnosis.

Project description:BACKGROUND:High numbers of consumable medical materials (eg, sterile needles and swabs) are used during the daily routine of intensive care units (ICUs) worldwide. Although medical consumables largely contribute to total ICU hospital expenditure, many hospitals do not track the individual use of materials. Current tracking solutions meeting the specific requirements of the medical environment, like barcodes or radio frequency identification, require specialized material preparation and high infrastructure investment. This impedes the accurate prediction of consumption, leads to high storage maintenance costs caused by large inventories, and hinders scientific work due to inaccurate documentation. Thus, new cost-effective and contactless methods for object detection are urgently needed. OBJECTIVE:The goal of this work was to develop and evaluate a contactless visual recognition system for tracking medical consumable materials in ICUs using a deep learning approach on a distributed client-server architecture. METHODS:We developed Consumabot, a novel client-server optical recognition system for medical consumables, based on the convolutional neural network model MobileNet implemented in Tensorflow. The software was designed to run on single-board computer platforms as a detection unit. The system was trained to recognize 20 different materials in the ICU, while 100 sample images of each consumable material were provided. We assessed the top-1 recognition rates in the context of different real-world ICU settings: materials presented to the system without visual obstruction, 50% covered materials, and scenarios of multiple items. We further performed an analysis of variance with repeated measures to quantify the effect of adverse real-world circumstances. RESULTS:Consumabot reached a >99% reliability of recognition after about 60 steps of training and 150 steps of validation. A desirable low cross entropy of <0.03 was reached for the training set after about 100 iteration steps and after 170 steps for the validation set. The system showed a high top-1 mean recognition accuracy in a real-world scenario of 0.85 (SD 0.11) for objects presented to the system without visual obstruction. Recognition accuracy was lower, but still acceptable, in scenarios where the objects were 50% covered (P<.001; mean recognition accuracy 0.71; SD 0.13) or multiple objects of the target group were present (P=.01; mean recognition accuracy 0.78; SD 0.11), compared to a nonobstructed view. The approach met the criteria of absence of explicit labeling (eg, barcodes, radio frequency labeling) while maintaining a high standard for quality and hygiene with minimal consumption of resources (eg, cost, time, training, and computational power). CONCLUSIONS:Using a convolutional neural network architecture, Consumabot consistently achieved good results in the classification of consumables and thus is a feasible way to recognize and register medical consumables directly to a hospital's electronic health record. The system shows limitations when the materials are partially covered, therefore identifying characteristics of the consumables are not presented to the system. Further development of the assessment in different medical circumstances is needed.

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Noninvasive assessment of dofetilide plasma concentration using a deep learning (neural network) analysis of the surface electrocardiogram: A proof of concept study.

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