Trends of anti-seizure medication prescribing pattern in traumatic brain injury patients for the prevention of posttraumatic seizure in Taiwan.

Traumatic brain injury (TBI) patients are recommended to receive anti-seizure medication (ASM) as posttraumatic seizure (PTS) prophylaxis. However, the utilization of ASM, including the prescription patterns and associated clinical characteristics, is limited in Taiwan. Thus, this study aimed to investigate the ASM trends and clinical characteristics. This retrospective cohort study enrolled TBI patients who received levetiracetam, phenytoin, and valproic acid during hospitalization using the National Health Insurance Research Database between 2012 and 2019. The primary outcome was the trend of the ASMs based on the index year. The duration of levetiracetam prescription was categorized as short-term (seven days or less) or long-term (more than seven days). Logistic regression identified the factors associated with long-term usage. A total of 64,461 TBI patients were included. Levetiracetam usage increased yearly, while phenytoin declined. Among the levetiracetam users, 5681 (30.38%) were short-term users, and 13,016 (69.62%) were long-term users. Diagnoses of contusions, intracranial hemorrhage, other intracranial injuries, receiving operations, and a history of cerebrovascular disease were significantly associated with longer duration. Conclusions This study revealed the rising trend of levetiracetam usage, indicating its potential as an alternative to phenytoin. TBI patients with more severe conditions were more likely to receive longer prescriptions.

Prediction of vancomycin initial dosage using artificial intelligence models applying ensemble strategy.

BACKGROUND: Antibiotic resistance has become a global concern. Vancomycin is known as the last line of antibiotics, but its treatment index is narrow. Therefore, clinical dosing decisions must be made with the utmost care; such decisions are said to be "suitable" only when both "efficacy" and "safety" are considered. This study presents a model, namely the "ensemble strategy model," to predict the suitability of vancomycin regimens. The experimental data consisted of 2141 "suitable" and "unsuitable" patients tagged with a vancomycin regimen, including six diagnostic input attributes (sex, age, weight, serum creatinine, dosing interval, and total daily dose), and the dataset was normalized into a training dataset, a validation dataset, and a test dataset. AdaBoost.M1, Bagging, fastAdaboost, Neyman-Pearson, and Stacking were used for model training. The "ensemble strategy concept" was then used to arrive at the final decision by voting to build a model for predicting the suitability of vancomycin treatment regimens. RESULTS: The results of the tenfold cross-validation showed that the average accuracy of the proposed "ensemble strategy model" was 86.51% with a standard deviation of 0.006, and it was robust. In addition, the experimental results of the test dataset revealed that the accuracy, sensitivity, and specificity of the proposed method were 87.54%, 89.25%, and 85.19%, respectively. The accuracy of the five algorithms ranged from 81 to 86%, the sensitivity from 81 to 92%, and the specificity from 77 to 88%. Thus, the experimental results suggest that the model proposed in this study has high accuracy, high sensitivity, and high specificity. CONCLUSIONS: The "ensemble strategy model" can be used as a reference for the determination of vancomycin doses in clinical treatment.

Decrease in serum valproic acid levels during treatment with ertapenem.

PURPOSE: A possible interaction between valproic acid and ertapenem resulting in reduced serum valproic acid levels in two patients is reported. SUMMARY: In the first case, a 47-year-old woman was brought to the emergency department (ED) with fever, pain, redness, swelling, and local heat in the tissue around her tracheostomy tube and left foot. One month prior she was hospitalized with pneumonia and had a generalized tonic-clonic seizure. She was given teicoplanin and amoxicillin-clavulanate potassium as empirical therapy for cellulitis. On day 3, the patient developed a fever. Amoxicillin-clavulanate potassium was discontinued and replaced by i.v. ertapenem. On day 5, due to a suspected drug-induced fever, carbamazepine was discontinued, and oral valproate sodium was initiated. On day 16, the patient was afebrile, so ertapenem was discontinued. Her serum valproic acid concentration was <1 mg/L, but seizures did not recur. Three days after ertapenem was discontinued, her serum valproic acid concentration increased to 33.6 mg/L. In the second case, a 72-year-old woman was brought to the ED after a sudden loss of consciousness and convulsive seizure. The patient was diagnosed with status epilepticus and admitted to the intensive care unit. A urine culture revealed Pseudomonas aeruginosa, and she was given cefpirome and valproate sodium. On day 15, cefpirome was replaced with ertapenem. On day 21, she had a seizure, and her serum valproic acid levels was found to be <1 mg/L. Ertapenem was discontinued after 14 days. Her serum valproic acid levels continued to increase until discharge on day 42. CONCLUSION: After initiation of ertapenem, decreased serum valproic acid levels were observed in two patients.

Determination of free and total levels of phenytoin in human plasma from patients with epilepsy by MEKC: an adequate alternative to HPLC.

Phenytoin is a widely used anti-seizure agent, and a good correlation is observed between its concentration in plasma and the clinical effect. We developed a selective CE with UV detection at 200 nm for analysis of free and total levels of phenytoin in human plasma based on MEKC. A sample pretreatment by liquid-liquid extraction with ethyl acetate for determination of total level of phenytoin and serum ultrafiltrate was prepared by ultrafiltration technique (ultrafiltration membrane 30 kDa; 2000 g, 10 min) for determination of free level of phenytoin and subsequent quantification by MEKC was used. MEKC was performed in Tris buffer (25 mM; pH 10.5) containing SDS (180 mM) and EG (13%) as BGE. Hydrodynamic injection for phenytoin determination (0.5 psi 5 s for total level, 2 psi 5 s for free level) was used to introduce samples. The separation voltage was set at 20 kV. Data obtained by MEKC were compared with the results by a validated HPLC method. The MEKC assay of phenytoin exhibited a very good correlation with respect to HPLC by Bland-Altman method. The equations for the Passing-Bablok regression line were as follows: for total level: MEKC=1.0143 x HPLC+0.0976, r(2)=1; for free level: MEKC=1.0013 x HPLC-0.0016, r(2)=1. The proposed method was applied successfully to monitor free and total levels of phentoin in 20 patients with seizures.

CE with direct sample injection for the determination of metformin in plasma for type 2 diabetic mellitus: An adequate alternative to HPLC.

We developed a simple and selective CE with UV detection at 233 nm for the analysis of metformin in plasma based on direct sample injection without any pretreatment. The sample was employed with an electrokinetic injection of 10 kV for 100 s. CE separation of metformin from biological matrix was performed at 25 degrees C using a BGE consisting of 25 mM Tris buffer at pH 4.0. The linear range of the CE method for the determination of metformin in plasma was over the range of 0.1-2.0 mug/mL; the LOD of the drug in plasma (S/N = 3; injection 10 kV, 100 s) was 30 ng/mL. Data by CE were compared with the results obtained by a validated HPLC method. CE assay of metformin exhibited a very good correlation (r(2 )= 1) with respect to HPLC. CE determination of metformin is a robust, sensitive, and reproducible method with the advantage over HPLC of being fast, without prior extraction, or precipitation of proteins, also enabling quick assessment of metformin for pharmacokinetic and clinical studies.