{"title":"Erratum: A randomized direct comparison of the pharmacokinetics and pharmacodynamics of apixaban and rivaroxaban [Corrigendum.","authors":"","doi":"10.2147/CPAA.S168295","DOIUrl":"https://doi.org/10.2147/CPAA.S168295","url":null,"abstract":"<p><p>[This corrects the article on p. 179 in vol. 6, PMID: 25419161.].</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"71"},"PeriodicalIF":2.0,"publicationDate":"2018-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S168295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36244833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-factor Xa levels in obese patients receiving enoxaparin for treatment and prophylaxis indications.","authors":"Linda Tahaineh, Sahar M Edaily, Shadi F Gharaibeh","doi":"10.2147/CPAA.S161599","DOIUrl":"10.2147/CPAA.S161599","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the degree of anticoagulation achieved with different enoxaparin dosing regimens used in obese and morbidly obese patients in a hospital setting in Jordan.</p><p><strong>Methods: </strong>All obese adult patients who were prescribed enoxaparin for various indications were invited to participate in the study. The anti-factor Xa (anti-Xa) level was checked once after 4-6 hours of the third or fourth dose of enoxaparin (at steady state). Patients were followed daily to evaluate drug efficacy and safety through their hospital course.</p><p><strong>Results: </strong>Enoxaparin daily dose used for prophylaxis indications ranged from 0.3 to 0.85 mg/kg and from 0.31 to 2.25 mg/kg in case of certain treatment indications. Most participants who received enoxaparin for treatment indications (76.9%) were on capping dosing regimens, which was <1 mg/kg twice daily. On the other hand, most patients (88.5%) who received enoxaparin for prophylaxis indications were on a fixed 40 mg/d dose. Among the 52 patients who completed the study, 19 patients (36.5%) had therapeutic anti-Xa levels. The results showed no statistically significant associations between regimens that were used and achieving therapeutic anti-Xa level (<i>p</i>>0.05). No bleeding events or thrombocytopenia were noticed, and there was one case of recurrent thrombosis.</p><p><strong>Conclusion: </strong>Enoxaparin dosing regimens that were used for obese patients varied based on prescribing physicians. Regardless of the regimen used, the majority of participants had nontherapeutic anti-Xa. Individualized dosing regimens based on anti-Xa levels are warranted for obese patients on enoxaparin.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"63-70"},"PeriodicalIF":3.1,"publicationDate":"2018-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/c2/cpaa-10-063.PMC5965377.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36178730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Li, Xiaomin Wang, Liangang Liu, Josephine Reyes, Maria Palmisano, Simon Zhou
{"title":"Distribution of pomalidomide into semen of healthy male subjects after multiple doses.","authors":"Yan Li, Xiaomin Wang, Liangang Liu, Josephine Reyes, Maria Palmisano, Simon Zhou","doi":"10.2147/CPAA.S167017","DOIUrl":"https://doi.org/10.2147/CPAA.S167017","url":null,"abstract":"<p><strong>Objective: </strong>To assess whether pomalidomide can distribute into human semen and its duration in human semen.</p><p><strong>Method: </strong>A phase 1, randomized, double-blind, placebo-controlled study (CC-4047-CP-006) was conducted to evaluate the safety, tolerability, and pharmacokinetics of pomalidomide (CC-4047) following multiple daily doses in healthy male subjects. Semen samples were collected on Day -1 and 4 hours after dosing on Day 4 to quantify the pomalidomide concentrations in ejaculate after multiple oral doses of pomalidomide.</p><p><strong>Result: </strong>Our study showed that pomalidomide was present in male subjects' semen samples, and the average amount of pomalidomide in a single ejaculate 4 hours after dosing was less than 0.0022% of the daily 2 mg dose. There was a good correlation between the semen concentrations and the plasma concentrations, suggesting that the plasma concentration may be the main driving force for the distribution of pomalidomide into the seminal reservoirs. Simulation results suggest that pomalidomide was undetectable in semen 48 hours after stopping dosing.</p><p><strong>Conclusion: </strong>Based on the results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration includes a statement that \"pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Male patients taking POMALYST must not donate sperm.\"</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"53-62"},"PeriodicalIF":2.0,"publicationDate":"2018-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S167017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raymond R Tjandrawinata, Arini Setiawati, Dwi Nofiarny, Liana W Susanto, Effi Setiawati
{"title":"Pharmacokinetic equivalence study of nonsteroidal anti-inflammatory drug etoricoxib.","authors":"Raymond R Tjandrawinata, Arini Setiawati, Dwi Nofiarny, Liana W Susanto, Effi Setiawati","doi":"10.2147/CPAA.S161024","DOIUrl":"10.2147/CPAA.S161024","url":null,"abstract":"<p><strong>Purpose: </strong>The current study aimed to evaluate whether a generic product of etoricoxib 120 mg film-coated tablet (the test drug) was bioequivalent to the reference product (Arcoxia® film-coated tablet 120 mg).</p><p><strong>Methods: </strong>This was a randomized, open-label, two-sequence, crossover study under fasting condition, with a 14-day washout period, involving 26 healthy adult male and female subjects. Blood samples were taken and analyzed for plasma concentrations of etoricoxib (Chemical Abstracts Service [CAS] 202409-33-4) using a high-pressure liquid chromatography-ultraviolet detector (HPLC-UV) system capable of measuring etoricoxib concentrations ranging from 5.00 to 5002.90 ng/mL, with the lowest limit of quantitation of 5.00 ng/mL. A noncompartmental method was used to determine the pharmacokinetic parameters of a single-dose administration of the drug, including the area under plasma concentration-time curve from time zero to the time of last observed concentration (AUC<sub>0-</sub><i><sub>t</sub></i> ), the area under plasma concentration-time curve from time zero to infinity (AUC<sub>0-∞</sub>), the maximum plasma concentration (<i>C</i><sub>max</sub>), the time to reach the maximum plasma concentration (<i>t</i><sub>max</sub>), and the terminal half-life (<i>t</i><sub>½</sub>).</p><p><strong>Results: </strong>After a single-dose administration of etoricoxib 120 mg film-coated tablet, the mean (SD) values for the AUC<sub>0-72h</sub> and <i>C</i><sub>max</sub> of the test drug were 45913.42 (13142.19) ng·h/mL and 3155.93 (752.81) ng/mL, respectively; the values for the reference drug were 44577.20 (13541.85) ng·h/mL and 2915.13 (772.81) ng/mL, respectively. The geometric mean ratios (90% CIs) of the test drug/reference drug were 103.40% (98.70%-108.32%) for AUC<sub>0-72h</sub> and 109.26% (100.18%-119.18%) for <i>C</i><sub>max</sub>. No clinically significant differences in <i>t</i><sub>max</sub> and <i>t</i><sub>½</sub>values were found between the test drug and the reference drug. No adverse events were experienced by the subjects during this study.</p><p><strong>Conclusion: </strong>The present study demonstrated that the evaluated generic etoricoxib 120 mg film-coated tablets were bioequivalent to the reference drug.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"43-51"},"PeriodicalIF":2.0,"publicationDate":"2018-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/22/cpaa-10-043.PMC5896653.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36022483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Safinamide: an add-on treatment for managing Parkinson's disease.","authors":"Thomas Müller","doi":"10.2147/CPAA.S137740","DOIUrl":"10.2147/CPAA.S137740","url":null,"abstract":"<p><p>Heterogeneous expression of neurotransmitter deficits results from onset and progression of Parkinson's disease. Intervals, characterized by reappearance of motor and associated certain nonmotor symptoms, determine the end of good tolerability and efficacy of oral levodopa therapy. These \"OFF\" states result from levodopa pharmacokinetics and disease progression-related deterioration of the central buffering capacity for fluctuations of dopamine levels. This review discusses safinamide as an add-on therapeutic agent in orally levodopa-treated patients with \"OFF\" phenomena. Safinamide provided beneficial effects on \"OFF\" symptoms in pivotal trials with doses of 50 or 100 mg once daily. Safinamide reversibly inhibits mono-amine oxidase B and declines abnormal glutamate release by modulation of potassium- and sodium ion channels. An ideal candidate for combination with safinamide is opicapone. This inhibitor of peripheral catechol-O-methyltransferase supports continuous brain delivery of levodopa and, thus, the continuous dopaminergic stimulation concept. Both compounds with their once-daily application and good tolerability may complement each other by reduction of necessary oral levodopa intakes and \"OFF\" times. Thus, a promising, future option will be combination of safinamide and opicapone in one formulation. It will reduce adherence issues and may complement levodopa treatment. It will probably cause less nausea and edema than a dopamine agonist/levodopa regimen.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"31-41"},"PeriodicalIF":2.0,"publicationDate":"2018-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S137740","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36022062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maha S Al-Keilani, Dua H Alsmadi, Ruba S Darweesh, Karem H Alzoubi
{"title":"Pramlintide, an antidiabetic, is antineoplastic in colorectal cancer and synergizes with conventional chemotherapy.","authors":"Maha S Al-Keilani, Dua H Alsmadi, Ruba S Darweesh, Karem H Alzoubi","doi":"10.2147/CPAA.S153780","DOIUrl":"https://doi.org/10.2147/CPAA.S153780","url":null,"abstract":"<p><strong>Background: </strong>Approximately 90% of patients with metastatic colorectal cancer fail therapy mainly due to resistance. Taking advantage of currently approved agents for treatment of disease conditions other than cancer for the identification of new adjuvant anticancer therapies is highly encouraged. Pramlintide is a parenteral antidiabetic agent that is currently approved for treatment of types 1 and 2 diabetes mellitus.</p><p><strong>Objectives: </strong>To address the antineoplastic potential of pramlintide in colorectal cancer and to evaluate the ability of pramlintide to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53.</p><p><strong>Materials and methods: </strong>The antiproliferative effect of pramlintide alone or in combination with 5-fluorouracil, oxaliplatin, or irinotecan in HCT-116 and HT-29 colorectal cancer cell lines was investigated using MTT cell proliferation assay. IC50 values were calculated using Compusyn software 1.0. Synergy values (R) were calculated using the ratio of IC50 of each primary drug alone divided by combination IC50s. For each two pairs of experiments, Student's <i>t</i>-test was used for analysis. For combination studies, one-way analysis of variance and Tukey post hoc testing was performed using R 3.3.2 software. A <i>p</i>-value of <0.05 was considered significant.</p><p><strong>Results: </strong>Pramlintide inhibited the growth of HCT-116 and HT-29 in a dose-dependent manner, with higher efficacy against the latter (IC50s; 48.67 and 9.10 μg/mL, respectively; <i>p</i>-value =0.013). Moreover, the addition of 5, 10, and 20 μg/mL of pramlintide to HCT-116 and HT-29 with 5-fluorouracil, oxaliplatin, or irinotecan induced the antiproliferative effect synergistically (<i>R</i>>1.6, <i>p</i>-value <0.05).</p><p><strong>Conclusion: </strong>Pramlintide enhances the cytotoxicity of conventional chemotherapy against colorectal cancer cell lines harboring wild-type or mutant p53. Thus, pramlintide is a promising potential adjuvant chemotherapy in colorectal cancer.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"23-29"},"PeriodicalIF":2.0,"publicationDate":"2018-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S153780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35924725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pavel Klein, Anyzeila Diaz, Teresa Gasalla, John Whitesides
{"title":"A review of the pharmacology and clinical efficacy of brivaracetam.","authors":"Pavel Klein, Anyzeila Diaz, Teresa Gasalla, John Whitesides","doi":"10.2147/CPAA.S114072","DOIUrl":"10.2147/CPAA.S114072","url":null,"abstract":"<p><p>Brivaracetam (BRV; Briviact) is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10-1,000 mg) and multiple (200-800 mg/day) oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50-200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic-clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug-drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"1-22"},"PeriodicalIF":3.1,"publicationDate":"2018-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/51/cpaa-10-001.PMC5783144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35797828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CRTH2 antagonists in asthma: current perspectives.","authors":"Dave Singh, Arjun Ravi, Thomas Southworth","doi":"10.2147/CPAA.S119295","DOIUrl":"https://doi.org/10.2147/CPAA.S119295","url":null,"abstract":"<p><p>Chemoattractant receptor-homologous molecule expressed on T<sub>H</sub>2 cells (CRTH2) binds to prostaglandin D<sub>2</sub>. CRTH2 is expressed on various cell types including eosinophils, mast cells, and basophils. CRTH2 and prostaglandin D<sub>2</sub> are involved in allergic inflammation and eosinophil activation. Orally administered CRTH2 antagonists are in clinical development for the treatment of asthma. The biology and clinical trial data indicate that CRTH2 antagonists should be targeted toward eosinophilic asthma. This article reviews the clinical evidence for CRTH2 involvement in asthma pathophysiology and clinical trials of CRTH2 antagonists in asthma. CRTH2 antagonists could provide a practical alternative to biological treatments for patients with severe asthma. Future perspectives for this class of drug are considered, including the selection of the subgroup of patients most likely to show a meaningful treatment response.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"165-173"},"PeriodicalIF":2.0,"publicationDate":"2017-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S119295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35687177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Olaratumab: a platelet-derived growth factor receptor-α-blocking antibody for the treatment of soft tissue sarcoma.","authors":"Alexandra Pender, Robin L Jones","doi":"10.2147/CPAA.S130178","DOIUrl":"https://doi.org/10.2147/CPAA.S130178","url":null,"abstract":"<p><p>The outcome of patients with unresectable or metastatic soft tissue sarcoma (STS) remains poor with few treatment options. A number of randomized trials in the first-line setting have shown no difference in overall survival between combination anthracycline schedules and single-agent doxorubicin. A Phase Ib/randomized Phase II trial of doxorubicin with or without the platelet-derived growth factor receptor-α (PDGFRα)-blocking antibody, olaratumab, demonstrated a significant difference in median overall survival in favor of the olaratumab arm. The results of this trial led to the approval of olaratumab in combination with doxorubicin in adult anthracycline-naïve unresectable STS. In this review, we discuss the potential role of PDGFRα signaling, early clinical data with olaratumab in sarcomas, the Phase Ib/II trial and ongoing trials with olaratumab in sarcomas.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"159-164"},"PeriodicalIF":2.0,"publicationDate":"2017-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S130178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35681843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of afatinib in the treatment of advanced lung squamous cell carcinoma.","authors":"Tiziana Vavalà","doi":"10.2147/CPAA.S112715","DOIUrl":"https://doi.org/10.2147/CPAA.S112715","url":null,"abstract":"<p><p>Lung cancer treatment has considerably changed over the last few years: the identification of druggable oncogenic alterations and innovative immunotherapic approaches granted lung cancer patients the possibility of more efficient and less toxic therapeutic options than chemotherapy. Nowadays, lung squamous cell carcinomas (SqCCs) patients have the chance to benefit from novel treatment alternatives, including immune checkpoint blockade and anti-angiogenic agents and, given positive trial results, from afatinib, a second generation tyrosine kinase inhibitor (TKI) that irreversibly antagonizes ErbB family tyrosine kinase receptors. Considering the role of the ErbB-signaling cascade in lung SqCC, it is relevant to note that ErbB1 (epidermal growth factor receptor [EGFR]) is overexpressed in 85% of non-small-cell lung carcinomas (NSCLCs), particularly in patients with squamous histology, and is associated with poor prognosis. For this reason, EGFR activity has been investigated as a therapeutic strategy in lung SqCC. Even taking into account statistically positive trial results, anti-EGFR approach still remains controversial in unselected/wild-type EGFR lung SqCC patients, as well as the optimal timing and sequencing of all available targeted therapies considering the approval of immunotherapeutic agents. This review analyzes current data about EGFR inhibition in lung SqCC with a specific focus on afatinib in order to elucidate available clinical evidence supporting EGFR targeting in this setting as well as a future management of advanced lung SqCCs in the context of new emerging immunotherapeutic drugs.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"9 ","pages":"147-157"},"PeriodicalIF":2.0,"publicationDate":"2017-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S112715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35240789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}