We conducted this multicenter retrospective study to evaluate the prevalence, clinical patterns, and risk factors for tigecycline-induced liver injury, which is a type of drug-induced liver injury (DILI). Inpatients receiving intravenous tigecycline for ≥7 days were included. Patient information was collected to assess possible DILIs. The pattern and severity of tigecycline DILI were evaluated. A multivariable logistic regression model was used to identify the independent risk factors associated with tigecycline DILI. A total of 986 patients were identified and 397 patients were included in this study. The prevalence of tigecycline DILI was 10.3% (95% confidence interval [CI] = 7.51-13.7%). The most common type of tigecycline DILI was cholestatic, with mild severity observed in most cases. Abnormal baseline alanine aminotransferase levels (odds ratio [OR] = 3.11, 95% CI = 1.55-6.24, P = 0.001), intensive care unit admission (OR = 2.63, 95% CI = 1.32-5.36, P = 0.006), and treatment length (in weeks) (OR = 1.25, 95% CI = 1.05-1.49, P = 0.011) were independent risk factors for tigecycline DILI. Our results indicate that the prevalence of tigecycline DILI is high, and that the patients at risk should receive special attention.

Background: Vancomycin dosing is difficult in critically ill patients receiving continuous renal replacement therapy (CRRT). Previous population pharmacokinetic (PopPK) models seldom consider the effect of residual diuresis, a significant factor of elimination, and thus have poor external utility. This study aimed to build a PopPK model of vancomycin that incorporates daily urine volume to better describe the elimination of vancomycin in these patients.Methods: We performed a multicenter retrospective study that included critically ill patients who received intermittent intravenous vancomycin and CRRT. The PopPK model was developed using the NONMEM program. Goodness-of-fit plots and bootstrap analysis were employed to evaluate the final model. Monte Carlo simulation was performed to explore the optimal dosage regimen with a target area under the curve of ≥400 mg/L h and 400–600 mg/L h.Results: Overall, 113 observations available from 71 patients were included in the PopPK model. The pharmacokinetics could be well illustrated by a one-compartment model with first-order elimination, with the 24-h urine volume as a significant covariate of clearance. The final typical clearance was 1.05 L/h, and the mean volume of distribution was 69.0 L. For patients with anuria or oliguria, a maintenance dosage regimen of 750 mg q12h is recommended.Conclusion: Vancomycin pharmacokinetics in critically ill patients receiving CRRT were well described by the developed PopPK model, which incorporates 24-h urine volume as a covariate. This study will help to better understand vancomycin elimination and benefit precision dosing in these patients.

Objective: The use of attention-deficit hyperactivity disorder (ADHD) medication is increasing worldwide, but its status in China is unknown. This research aimed to assess the trends of ADHD medication use in young Chinese patients between 2010 and 2019. Methods: Dispensing data related to ADHD medication use were extracted from the Hospital Prescription Analysis Cooperative Project of China. The trends in the yearly prescription number of ADHD drugs and corresponding cost were analyzed. We further stratified the data by age, sex, and specific drug. Results: From 2010 to 2019, sampled prescriptions for ADHD medication increased from 902 to 4531, and the total expenditure increased rapidly from 276,580 to 2,412,308 Chinese Yuan. Prescriptions for males were almost fourfold more than that for females. Patients aged 6–11 years had the highest number of prescriptions for ADHD medication each year, accounting for more than 50% of the total number of prescriptions. The percentage of methylphenidate prescriptions decreased from 91.9% in 2010 to 76.9% in 2019, and the corresponding cost declined from 77.3% to 66.8%. In contrast, atomoxetine prescriptions increased progressively and accounted for about 24.5% of the total prescriptions at the end of the study. Conclusions: The use of ADHD drugs and the corresponding cost increased rapidly in China, and methylphenidate was the most frequently prescribed medicine. The increase in ADHD prescriptions requires attention to ensure that it reflects appropriate use, especially in patients aged 6–11 years.

Topical anti-infectives are important in the management of ocular infections, but little is known about their current status and trends in their use in China. Thus, we carried out a prescription-based, cross-sectional study using the database of Hospital Prescription Analysis Projection of China, and aimed to analyze the trend in the use of ocular topical anti-infectives for outpatients of the ophthalmology department from 2013 to 2019. A total of 2,341,719 prescriptions from 61 hospitals located in six major areas written by ophthalmologists for outpatients were identified, and 1,002,254 of the prescriptions contained at least one anti-infective. The yearly anti-infective prescriptions increased continuously from 126,828 prescriptions in 2013 to 163,434 prescriptions in 2019. The cost also increased from 4,503,711 Chinese Yuan (CNY) in 2013 to CNY 5,860,945 in 2019. However, the use rate of anti-infectives decreased slightly from 46.5% in 2013 to 41.1% in 2019. Patients aged between 19 and 45 years old had the highest anti-infective use rate. Levofloxacin was the most frequently used anti-infective and kept on increasing among all age groups, occupying 67.1% of the total cost at the end of the study. Tobramycin was more frequently used in pediatric patients than in adults, but the use still decreased. Ganciclovir was the preferred anti-viral drug over acyclovir. In conclusion, the prescriptions and cost of ocular topical anti-infectives for outpatients both increased progressively. The increasingly widespread use of levofloxacin raised concerns regarding safety in pediatrics and resistance development. The observed trends can lead to the more efficient management of ocular anti-topical anti-infectives in China.

Objective: The efficacy of perampanel (PER) in pediatric epilepsy with specific etiologies has not been well established. Here, we investigated outcome and pre-dictors of PER treatment in a pediatric cohort with known and presumed genetic etiology. Methods: We included pediatric patients with potential genetic epilepsy who received PER treatment and underwent whole-exome sequencing (WES) from January 2020 to September 2021. All patients were followed up for >12 months. Results: A total of 124 patients were included. Overall response rates were 51.6% and 49.6% at 6 months and 12 months, respectively. Patho-genic or likely pathogenic variants in 27 multiple genes were detected among 58 patients (46.8%) by WES. On performing multivariate logistic regression analysis, only developmental delay (OR = 0.406, P = 0.042) was a negative pre-dictor of treatment response. However, the seizure onset age, positive WES results, and number of ASMs before PER administration were not significantly. Thirteen carriers with variants in the SCN1A gene showed a better response compared to eight patients with other sodium channels (P = 0.007), and to the other 45 patients with positive WES results (OR = 7.124, 95% CI = 1.306- 38.860, P = 0.023). Adverse events were only reported in 23 patients, the most common being emotional problems. Interpretation: PER is safe and efficacious in pediatric patients with known and presumed genetic etiology. The response rate is comparable to that reported in other pediatric populations, and lower among those with developmental delay. A gene-specific response to PER is found along with better efficacy links to pathogenic variants in the SCN1A gene.