scholarly journals 63. PK-RNN-V: A Deep Learning Model for Vancomycin Therapeutic Drug Monitoring using Electronic Health Record Data

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S42-S43
Author(s):  
Nigo Masayuki ◽  
Hong Thoai Nga Tran ◽  
Ziqian Xie ◽  
Han Feng ◽  
Laila Bekhet ◽  
...  

Abstract Background Therapeutic drug monitoring (TDM) for vancomycin (VAN) with Bayesian models is recommended by national guidelines. However, limited data incorporating the models may hurt the performance. Our aim is to develop a novel deep learning-based pharmacokinetic model for vancomycin (PK-RNN-V) using electronic medical records (EHRs) data to achieve more accurate and personalized predictions for VAN levels. Methods EHR data were retrospectively retrieved from Memorial Hermann Hospital System, comprising 14 hospitals in the greater Houston area. All patients who received VAN and had any VAN levels were eligible. Patients receiving hemodialysis and extracorporeal membrane oxygenation were excluded. Demographic data, vital signs, diagnostic codes, concomitant medications, VAN administration, and laboratory data were preprocessed as longitudinal data. VAN infusion, VAN level measurement, or each hospital day were the time steps for the models. The dataset was splited 70:15:15 for training, validation, and test sets. Our PK-RNN-V model predicted individual patient volume distribution (v) and VAN elimination (k) at each time step using an irregular timesteps GRU model. To compare, Bayesian models were developed from publicly available models, and tuned to feedback the first VAN level to update the v and k. (VTDM) Results A total of 12,258 patients with 195,140 encounters were identified from Aug, 2019 and March, 2020. After exclusion of 6,775 patients, 5,483 patients with 8,689 encounters were included. Table 1 summarized the characteristics of patients included in our study. 55,336 doses of VAN were administered with a median dosage of 1.0 gm. VAN levels were measured 18,588 times at various timings. The median VAN level was 14.7 mcg/mL Table 2 described the performance of our models and VTDM models. Our model exhibited better performance compared to VTDM model (RMSE: 5.64 vs. 6.57, respectively). Figure 1 shows example prediction curves of VAN levels from each model. Conclusion PK-RNN-V model is a novel approach to predict patient PK and VAN levels. Our results revealed promising performance of this model. Our model can take a wide range of real-world patient data into the model. Further studies are warranted for external validations and model optimizations. Disclosures All Authors: No reported disclosures

2013 ◽  
Vol 57 (4) ◽  
pp. 1888-1894 ◽  
Author(s):  
William W. Hope ◽  
Michael VanGuilder ◽  
J. Peter Donnelly ◽  
Nicole M. A. Blijlevens ◽  
Roger J. M. Brüggemann ◽  
...  

ABSTRACTThe efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice.


2019 ◽  
Vol 57 (6) ◽  
pp. 856-863 ◽  
Author(s):  
Dorien Van den Bossche ◽  
Dieter De Smet ◽  
Johan Debrabandere ◽  
Hilde Vanpoucke

Abstract Background Infliximab (IFX) is an effective therapy in patients with inflammatory bowel disease. Serum IFX trough concentrations correlate well with clinical, biological and endoscopic outcomes. Therefore, therapeutic drug monitoring (TDM) of infliximab is useful for dose optimization and prevention of secondary treatment failure. In the present study, analytical and clinical performance of two point-of-care (POC) tests, RIDA®QUICK IFX Monitoring assay (R-biopharm) and Quantum Blue® Infliximab assay (Bühlmann), have been evaluated and compared to our established enzyme-linked immunosorbent assay (ELISA) (apDia IFX ELISA). Methods Analytical performance was assessed according to the CLSI EP5-A2 protocol using the manufacturer’s kit controls and different serial dilution series. Method comparison with our established ELISA was done using a wide range of consecutive patient samples (n=180). Clinical concordance was evaluated by categorization based on well-known therapeutic cut-off points (3–7 μg/mL). Results The analytical performance of both POC tests was inferior to the established ELISA, but acceptable based on the manufacturer’s quality claims. Eight-point serial dilution confirmed the analytical performance data in the low-level measuring range. Eleven-point serial dilution demonstrated linearity for both POC tests over the studied concentration range. Method comparison with the ELISA showed significant negative proportional bias for the RIDA®QUICK IFX Monitoring assay. However, good correlation and clinical concordance were shown. Quantum Blue® Infliximab assay showed a significant positive proportional and a negative systematic bias in comparison with the ELISA, resulting in overestimation of IFX levels with impact on clinical concordance data. Conclusions Both POC tests have their own specific benefits and drawbacks but are suitable for therapeutic drug monitoring of IFX. However, long-term monitoring of IFX trough levels requires measurement of IFX concentrations with the same assay.


1989 ◽  
Vol 35 (1) ◽  
pp. 120-124 ◽  
Author(s):  
B A Wolf ◽  
M C Daft ◽  
J W Koenig ◽  
M W Flye ◽  
J W Turk ◽  
...  

Abstract We compared cyclosporine concentrations in whole blood as measured by HPLC and by RIA with a monoclonal antibody specific for cyclosporine with 3H- or 125I-labeled cyclosporine ligand. The 3H-RIA kit slightly underestimated cyclosporine concentrations (greater than 600 micrograms/L) in comparison with HPLC. Over a wide range of concentrations, cyclosporine measured with the 125I-RIA kit correlated well with HPLC (slope = 0.99, n = 301, r = 0.98), observed for samples from recipients of kidney, heart, or liver allografts (respective slopes: 1.01, 0.93, and 1.00). The 125I-RIA standard curve was linear to 1000 micrograms of cyclosporine per liter. Inter- and intra-assay CVs for 125I-RIA measurements of cyclosporine were less than or equal to 7%. Evidently, the 125I-RIA kit involving a monoclonal antibody specific for cyclosporine is equivalent to the HPLC assay and can replace it for therapeutic drug monitoring of cyclosporine therapy.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Oliver Chung ◽  
Klaus BONAVENTURA ◽  
Christian Sohns ◽  
Wilhelm Haverkamp ◽  
Wilhelm Haverkamp ◽  
...  

Background: Non-adherence to anti-hypertensive medications poses a significant problem in the treatment of patients with presumed resistant hypertension (RH). Our recent study has shown that therapeutic drug monitoring (TDM) is a useful tool not only for detecting medication non-adherence but also exploring the barrier to antihypertensive drug therapy, resulting effective BP control. However, the cost effectiveness of TDM in the management of resistant hypertension has not been investigated. Method: A Markov model was used to evaluate life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios in RH patients receiving either TDM optimized therapy or standard best medical therapy (BMT). The model ran from the age of 30 to 100 years or death, using a cycle length of 1 year. Efficacy of TDM was modeled by reducing risk of hypertension-related morbidity and mortality. Results: In the age group of 60-year olds, TDM gained 1.07 QALYs in men and 0.97 QALYs in women at additional costs of є3,854 and є3,922, respectively. Given a willingness-to-pay threshold of є35,000 per QALY gained, the probability of TDM being cost-effective compared to BMT was ≥95% in all age groups from 30 to 90 years. Incremental cost-effectiveness ratios were influenced mostly by the annual frequency of TDM testing, the rate of non-responders to TDM, and the magnitude of effect of TDM on systolic blood pressure (Figure). Conclusion: Therapeutic drug monitoring presents a potential cost-effective health care intervention in patients diagnosed with RH. Importantly, this finding is valid for a wide range of patients, independent of gender and age.


2018 ◽  
Vol 75 (5) ◽  
pp. 316-328
Author(s):  
Christian Ansprenger ◽  
Emanuel Burri

Zusammenfassung. Die Diagnose und auch die Überwachung von chronisch entzündlichen Darmerkrankungen ruht auf mehreren Säulen: Anamnese, körperliche Untersuchung, Laborwerte (im Blut und Stuhl), Endoskopie, Histologie und Bildgebung. Die Diagnose kann nicht anhand eines einzelnen Befundes gestellt werden. In den letzten Jahren hat sich das Therapieziel weg von klinischen Endpunkten hin zu endoskopischen und sogar histologischen Endpunkten entwickelt. Für einige dieser neuen Therapieziele existiert allerdings noch keine allgemein gültige Definition. Regelmässige Endoskopien werden von Patienten schlecht toleriert, weshalb Surrogat-Marker wie Calprotectin untersucht wurden und eine gute Korrelation mit der mukosalen Entzündungsaktivität nachgewiesen werden konnte. Entsprechend zeigte sich bei Morbus Crohn eine Algorithmus-basierte Therapiesteuerung – unter anderem basierend auf Calprotectin – einer konventionellen Therapiesteuerung überlegen. Die Überwachung der medikamentösen Therapie («Therapeutic Drug Monitoring» [TDM]) ist ein zweites Standbein des Monitoring von chronisch entzündlichen Darmerkrankungen. Mit zunehmendem Einsatz vor allem der Biologika-Therapien wurden sowohl reaktives TDM (in Patienten mit klinischem Rezidiv) als auch proaktives TDM (in Patienten in Remission / stabiler Erkrankung) untersucht und haben (teilweise) Eingang in aktuelle Richtlinien gefunden. Zukünftige Studien werden die vorgeschlagenen Therapieziele besser definieren und den Nutzen der medikamentösen Therapieüberwachung auf den Krankheitsverlauf weiter untersuchen müssen.


2011 ◽  
Vol 44 (06) ◽  
Author(s):  
L Mercolini ◽  
G Fulgenzi ◽  
M Melis ◽  
G Boncompagni ◽  
LJ Albers ◽  
...  

2011 ◽  
Vol 44 (06) ◽  
Author(s):  
R Mandrioli ◽  
L Mercolini ◽  
N Ghedini ◽  
M Amore ◽  
E Kenndler ◽  
...  

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