Therapeutic Drug Monitoring最新文献

{"title":"Serum Lenvatinib Concentration Monitoring in a Patient With Thyroid Cancer Exhibiting Hand-Foot Syndrome: A Case Report.","authors":"Yusuke Watanabe, Kosuke Doki, Ikuo Sekine, Hisato Hara, Masato Homma","doi":"10.1097/FTD.0000000000001312","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001312","url":null,"abstract":"<p><strong>Background: </strong>Hand-foot syndrome (HFS) is a common adverse event associated with lenvatinib treatment. Lenvatinib dose adjustment using therapeutic drug monitoring may be beneficial in the management of HFS, as symptoms improve with dose reduction or treatment interruption. The serum lenvatinib levels were monitored in a patient with lenvatinib-induced HFS.</p><p><strong>Case presentation: </strong>A 74-year-old woman was administered lenvatinib (24 mg/d) for papillary thyroid cancer. Although lenvatinib was withheld several times owing to the occurrence of HFS, the severity of the HFS was controlled to within grade 1 by reducing the dose to 4 mg/d. The lenvatinib dose was subsequently increased to 8 mg/d owing to the progression of lung metastases, resulting in increased HFS severity. The association between serum lenvatinib levels and the severity of HFS was examined in this case: serum lenvatinib levels were higher in grade 2 HFS than in grade 1 HFS (median 42.1 vs. 22.5 ng/mL; P < 0.05).</p><p><strong>Conclusions: </strong>This case's findings suggest that serum lenvatinib concentrations are associated with the severity of lenvatinib-induced HFS and that there may be an overlap between drug concentrations, metastatic suppression, and the grade of HFS.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Validation of a Nomogram for Determining the Optimal Dose of Lamotrigine for Augmentation Therapy in Patients With Treatment-Resistant Depression.","authors":"Takeshi Suzuki, Goyo Nagai, Kazuo Mihara, Yoko Tomori, Shoko Kagawa, Akifumi Nakamura, Kenji Nemoto, Tsuyoshi Kondo","doi":"10.1097/FTD.0000000000001316","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001316","url":null,"abstract":"<p><strong>Background: </strong>Previous research has shown that a plasma lamotrigine concentration of 12.7 µmol/L may be a threshold for a good therapeutic response to lamotrigine augmentation therapy in Japanese patients with treatment-resistant depression. The optimal dose of lamotrigine can be predicted using a previously established nomogram based on the plasma lamotrigine concentration at week 2. The aim of the present study was to prospectively evaluate the validity of this nomogram.</p><p><strong>Methods: </strong>Participants included 59 patients with depression who showed insufficient therapeutic responses to psychotropics, including antidepressants, antipsychotics, and mood stabilizers. The patients were diagnosed with major depressive disorder (n = 26), bipolar II disorder (n = 25), or bipolar I disorder (n = 8). Lamotrigine was administered to all the patients. The initial dose of lamotrigine was 25 mg/d for 32 patients not taking valproate and 25 mg/d every other day for 27 patients taking valproate. Blood samples were collected at week 2 and at least 2 weeks after the final daily dose, which was estimated by a nomogram based on the plasma lamotrigine concentration at week 2. The plasma concentrations of lamotrigine were measured by liquid chromatography-mass spectrometry.</p><p><strong>Results: </strong>In 30 of the 32 patients (93.8%) who were not taking valproate and 23 of the 27 patients (85.2%) who were taking valproate, a plasma lamotrigine concentration of 12.7 mcg/mL or higher was achieved at the final daily administration of lamotrigine.</p><p><strong>Conclusions: </strong>The results of the present study suggest that the previously established nomogram is valid for determining the optimal dose of lamotrigine for Japanese patients with treatment-resistant depression in clinical settings.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Application of Volumetric Absorptive Microsampling for Therapeutic Drug Monitoring of Oral Targeted Anticancer Drugs.","authors":"Marinda Meertens, Nikki Kerssemakers, Niels de Vries, Hilde Rosing, Neeltje Steeghs, Jos H Beijnen, Alwin D R Huitema","doi":"10.1097/FTD.0000000000001315","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001315","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic Drug Monitoring optimizes oral anticancer drug treatment by measuring plasma levels. Volumetric absorptive microsampling (VAMS) allows home sampling with a minimal blood sample. However, methods for converting whole blood into plasma are required to interpret these results. This study aimed to establish conversion methods for abiraterone, alectinib, cabozantinib, imatinib, olaparib, sunitinib, and their metabolites, while assessing the differences between venous and capillary blood. The feasibility of home sampling was also evaluated.</p><p><strong>Methods: </strong>Plasma and VAMS samples, both from venipuncture-collected whole blood tubes and from a finger prick, were collected from each patient. The VAMS samples were deemed comparable if their concentrations were within ±20% of each other for ≥2/3rd of the patients. The Passing-Bablok regression and conversion factor methods were tested for the plasma and VAMS finger prick samples. The estimated plasma concentrations using both methods were required to be within ±20% of the measured plasma concentrations for ≥2/3rd of the pairs.</p><p><strong>Results: </strong>Overall, 153 patients were enrolled in this study. Conversion methods were applied to the VAMS samples, and the acceptance criteria were met for alectinib-M4, cabozantinib, imatinib, N-desmethyl imatinib, olaparib, sunitinib, and N-desethyl sunitinib but not for abiraterone, D4A, or alectinib. The capillary and venous VAMS concentrations were similar, except for that of D4A. Patients were positive toward home sampling.</p><p><strong>Conclusions: </strong>The established VAMS conversion methods for 7 out of 10 oral targeted anticancer drugs or metabolites met the acceptance criteria. Future studies need to validate the conversion methods with an independent cohort and integrate home sampling via VAMS to provide patients with an alternative to venipuncture at the outpatient clinic.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical Documentation of a Purple Urine Bag Syndrome Case.","authors":"Alexandr Gish, Apolline Saint Omer, Juliette Faillie, Arnaud Lionet, Aghiles Hamroun, Olivier Gaillot, Marie Lenski, Jean-Michel Gaulier","doi":"10.1097/FTD.0000000000001313","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001313","url":null,"abstract":"","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olanzapine; Postinjection Syndrome; Pharmacokinetics in View: Grand Round/A Case Study.","authors":"Johanne Rozema, Cornelis Paul van Stee, Daniel J Touw, Matijs van Meurs","doi":"10.1097/FTD.0000000000001317","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001317","url":null,"abstract":"<p><strong>Abstract: </strong>Olanzapine is a second-generation antipsychotic that is frequently administered intramuscularly as a slow-release depot and maintenance treatment for schizophrenia. Therapeutic values range from 20 to 80 mcg/L and levels >100 mcg/L are considered toxic. Postinjection delirium/sedation syndrome (PDSS) is a rare but serious adverse effect after the injection of olanzapine depot formulations. The authors present a case study in which a 64-year-old patient presented to the emergency room 30 minutes after an intramuscular injection of olanzapine with signs of possible postinjection syndrome. The patient presented with hypertension, tachycardia, delirium, and was suspected to have PDSS. On admission, his serum olanzapine levels had reached 390 mcg/L, and blood samples were collected on days 0, 1, 3, and 12. The timing of his presentation at the emergency room made it possible to track the pharmacokinetics of olanzapine in detail. On the basis of Therapeutic drug monitoring, a prolonged olanzapine half-life of 7 days was calculated. Symptoms such as agitation and hypertension improved after approximately 39 hours, and the patient had made a full recovery after 72 hours. This case study can serve as a reference for healthcare providers that will aid in the recognition and treatment of PDSS and contribute to a better understanding of the clinical problems associated with PDSS. In addition, it emphasizes how Therapeutic drug monitoring may be of added value with respect to determining when medication can be safely resumed.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Age on Antipsychotic Serum Concentration in Males and Females: A Study Based on Therapeutic Drug Monitoring Data From 19,926 Patients.","authors":"Vigdis Solhaug, Ragnhild Birkeland Waade, Espen Molden, Elisabet Størset, Gudrun Høiseth, Marit Tveito","doi":"10.1097/FTD.0000000000001309","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001309","url":null,"abstract":"<p><strong>Background: </strong>Antipsychotic medications are commonly prescribed for older patients; however, documentation on their safety and efficacy in this population is limited. This study aimed to investigate and compare the effect of age on dose-adjusted serum concentrations of 6 commonly used antipsychotic medications in both sexes.</p><p><strong>Methods: </strong>Patients with serum concentration measurements of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, and zuclopenthixol were retrospectively included from a therapeutic drug monitoring service. The primary outcome measure for each antipsychotic was the dose-adjusted serum concentration (C:D ratio), assessed across groups divided by sex and age (18-49 years, 50-74 years, and ≥75 years). The data were analyzed using linear mixed modeling with restricted maximum likelihood estimation.</p><p><strong>Results: </strong>A total of 19,926 patients (53% male) with 74,194 serum concentration measurements were included. For most antipsychotics, the C:D ratios increased significantly with age, with generally larger differences observed in females compared with males. The largest impact of age was observed for risperidone, where C:D ratios in the age groups 50-74 years and ≥75 years were 20% and 81% higher for males, respectively, compared with the reference group (18-49 years). For females, the C:D ratios were 28% and 92% higher, respectively, compared with females aged 18-49 years (all P < 0.001). The smallest impact of age was observed for aripiprazole, with no significant differences in C:D ratios across age groups for males. For females treated with aripiprazole, C:D ratios were 8% and 28% higher in the 50-74 and ≥75 years age groups, respectively, compared with females aged 18-49 years (both P < 0.001).</p><p><strong>Conclusions: </strong>The age-dependent increase in dose-adjusted serum concentrations among males and females varied across different antipsychotics and was highest for risperidone. These findings emphasize the importance of proper monitoring of antipsychotic use in older adults.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Sensitive Ultrafiltration Plus RP-HPLC-FLD Method to Quantify Total and Free Perampanel Concentrations in the Plasma of Patients With Epilepsy: A Fully Validated Assay With Clinical Application.","authors":"Zhonghua Dong, Peng Wang, Xueyan Cui, Jinjuan Liu, Haiyan Shi, Yilei Yang, Jingya Xu, Qiaoyan Yi","doi":"10.1097/FTD.0000000000001311","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001311","url":null,"abstract":"<p><strong>Background: </strong>Perampanel (PER), a novel antiepileptic drug, exhibits high protein binding. Given the drug's susceptibility to various factors, including drug interactions, and the considerable variability in blood concentrations among individuals, solely measuring the total plasma concentration of PER may not provide comprehensive insights. This study aimed to establish an HPLC-FLD method to quantify both total and free PER in clinical samples.</p><p><strong>Methods: </strong>Analysis of total PER involved a straightforward sample preparation process involving plasma protein precipitation. Plasma samples were ultrafiltered to isolate the free portion of PER. Chromatographic separation was achieved on an InertSustain C18 column at a 1-mL/min flow rate using a gradient of acetonitrile and aqueous sodium acetate buffer at pH 4.4.</p><p><strong>Results: </strong>Calibration curves for total and free PER in plasma exhibited excellent linearity over the concentration ranges of 10-3000 and 0.5-100 ng/mL, respectively. The method was applied to analyze blood samples from patients with epilepsy quantitatively; the total concentration of perampanel in the plasma of the patients was in the range of 90.45-563.39 ng/mL, whereas the free concentration was in the range of 1.82-15.29 ng/mL. The plasma protein binding ratio of perampanel was normally between 97.09% and 99.29% and decreased in cases of hypoproteinemia.</p><p><strong>Conclusions: </strong>The method was rigorously validated for selectivity, accuracy, precision, and stability in accordance with established FDA and EMA guidelines. The developed method enables the rapid and accurate quantification of both total and free PER concentrations in the plasma of patients with epilepsy, offering technical support for its subsequent clinical application.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining Different Methods to Assess Busulfan Exposure in Pediatric Hematopoietic Stem Cell Transplant Recipients.","authors":"Maxwell Thompson, Christine E Staatz, Christopher J Fraser, Stefanie Hennig, Rachael Lawson","doi":"10.1097/FTD.0000000000001304","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001304","url":null,"abstract":"<p><strong>Background: </strong>Noncompartmental analysis (NCA) and model-based method (MBM) can be used to estimate the cumulative area under the concentration-time curve (AUCcum) during therapeutic drug monitoring. Understanding predictive differences among these techniques should assist in switching between them and interpreting their results. The aim of this study was to compare busulfan AUCcum prediction based on NCA technique (Kinetica) and MBM (NextDose) applied to the same concentration-time data from pediatric hematopoietic stem cell transplant (HSCT) recipients.</p><p><strong>Methods: </strong>Data on busulfan therapy administered once daily through intermittent infusion were obtained from 4 hospitals in Australia and New Zealand. Busulfan concentrations were measured at 3, 3.25, 4, 5, 6, and 8 hours after infusion initiation over 4 treatment days. Information on busulfan dose, pharmacokinetic profile, and patient covariate factors (if required) were supplied sequentially to Kinetica and NextDose to generate NCA-based and MBM-based predictions of busulfan exposure; differences in AUCcum estimates at the end of the treatment course were compared using Bland-Altman plots, box plots, and Wilcoxon signed-rank sum test.</p><p><strong>Results: </strong>Data from 90 HSCT recipients (2131 busulfan samples) were included. The median patient age and weight were 4.3 years and 17.0 kg, respectively. Median AUCcum estimated based on NCA and MBM were 78.0 mg.h/L [range: 51.7-107.0] and 85.5 mg.h/L [range: 60.6-120.8], respectively, with statistically significant difference in AUCcum values (P < 0.001). The mean percentage difference in AUCcum values between the 2 different methods suggested that if the AUCcum target using MBMs (NextDose) is 78-101 mg.h/L, then an equivalent target using NCA (Kinetica) would be reduced by 9.1%.</p><p><strong>Conclusions: </strong>When switching between NCA and MBMs to estimate busulfan AUCcum in pediatric HSCT recipients, a change in the target AUCcum is likely required to maintain a similar drug exposure during therapeutic drug monitoring.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Performance of Bayesian Dosing Software for Vancomycin in Intensive Care Unit Patients.","authors":"Gali Bai, Hui Qi, Yaqun Huang, Jiao Zhang, Huiying Zhao, Ruiting Wen, Xiaohong Zhang","doi":"10.1097/FTD.0000000000001310","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001310","url":null,"abstract":"<p><strong>Background: </strong>According to the updated guidelines, Bayesian-derived area under the curve estimation is recommended to guide vancomycin dosing. However, the Bayesian dosing software that facilitates this procedure has not been adequately assessed in intensive care unit (ICU) patients. This study evaluated the performance of 3 commonly used Bayesian software programs in predicting vancomycin concentrations in ICU patients before they could be utilized for personalized dosing in this population.</p><p><strong>Methods: </strong>Retrospective data from adult ICU patients who were administered vancomycin intravenously were obtained to predict serum concentrations a priori (based solely on patient characteristics) or a posteriori (Bayesian forecasting using measured concentrations). The predictive performance was evaluated via bias and precision using relative bias (rBias) and relative root mean squared error, respectively.</p><p><strong>Results: </strong>Data from 139 patients with 284 vancomycin concentrations were evaluated using 3 software programs: SmartDose (He model), Pharmado (Yasuhara model), and PrecisePK (Rodvald and Goti model). All 3 programs showed clinically acceptable bias with the exception of the Goti model of PrecisePK in an a priori estimation (rBias, 27.44%). A relatively low level of precision in terms of relative root mean squared error was observed in all these programs, but with a marked improvement in the a posteriori estimation (27.69%-37.64%) compared with the a priori situation (45.12%-68.59%).</p><p><strong>Conclusions: </strong>Bayesian dosing software is a potential tool for vancomycin dose optimization in ICU patients. Patients with different physiological and pathological features may be referred to specific Bayesian programs.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significant Influence of Abemaciclib on Rivaroxaban.","authors":"Xiaoshuang He, Yongjie Ding, Jie Fang, Juntao Zhao, Xiaoli Ma, Fengmei Hu, Qing Qu, Xiaolan Bian, Qiuya Lu","doi":"10.1097/FTD.0000000000001301","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001301","url":null,"abstract":"<p><strong>Background: </strong>A patient was treated with abemaciclib and rivaroxaban. Therapeutic drug monitoring revealed high total plasma concentrations of rivaroxaban, which was identified as likely cause of abnormal bleeding. This result indicating that it was caused by drug-drug interaction.</p><p><strong>Methods: </strong>According to the pharmacokinetic profile, the concentrations of rivaroxaban, abemaciclib, and its metabolite (M2) were monitored.</p><p><strong>Results: </strong>The concentrations of abemaciclib and its metabolite (M2) decreased with the reduction in rivaroxaban dosage.</p><p><strong>Conclusions: </strong>This case study demonstrates the interactions between abemaciclib and rivaroxaban. For patients with complex medications, therapeutic drug monitoring can reduce the occurrence of adverse effects.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}