Voriconazole is a broad-spectrum triazole antifungal and the first line treatment for invasive aspergillosis (IA). The aim of this research was to study the dose adjustments of voriconazole as well as the affecting factors influencing voriconazole trough concentrations in Asian children to optimize its daily administration. Clinical data were analyzed of inpatients aged 2-14 years who were subjected to voriconazole trough concentrations monitoring from June 1, 2015 to December 1, 2017. A total of 138 voriconazole trough concentrations from 42 paediatric patients were included. Voriconazole trough concentrations at steady state ranged from 0.02 to 9.35mg/liter with high inter- and intra-individual variability. Only 50.0% of children achieved the target range (1.0∼5.5 mg/liter) at initial dosing, while 35.7% of children were subtherapeutic, and 14.3% of children were supratherapeutic at initial dosing. There was no correlation between initial trough concentrations and initial dosing. A total of 28.6% of children (12/42) adjusted the dose according to trough concentrations. Children aged 12 years old required median oral maintenance dose to achieve the target range of 11.1, 7.2 and 5.3 mg/kg twice daily respectively (P=0.043). The average doses required to achieved the target range were 7.7 mg/kg and 5.6 mg/kg, respectively, and were lower than the recommended dosage (P=0.033, 0.003). Affecting factors such as administration routes and co-administration with proton pump inhibitors (PPIs) explained 55.3% of variability in voriconazole exposure. Therapeutic drug monitoring (TDM) of voriconazole could help to individualize antifungal therapy for children and provide guidelines for TDM and dosing optimization in Asian children.

Atezolizumab compared to chemotherapy for first-line treatment in non-small cell lung cancer with high PD-L1 expression: a cost-effectiveness analysis from US and Chinese perspectives Shuqiao Cheng, Rui Pei, Jianhuang Li, Bin Li, Lanhua Tang, Tao Yin, Shao Liu

The mechanisms underlying the association between immune activation and postpartum depression remained elusive. Although Ω-3 fatty acids possess anti-inflammatory properties, there is limited evidence directly linking the modulating effects of Ω-3 fatty acids on neuroimmune and neurochemistry to the antidepressant actions. A between-groups design was used to assess the effects of reproductive status (virgin or parous) and Ω-3 fatty acids content (control and supplementary). Serum inflammatory cytokine levels (IL-1a, IL-1β, IL-2, IL-6, IL-12, TNF-a, IFN-γ) were evaluated using the Bio-Plex Luminex System. Moreover, we also measured the protein levels of Purinergic type 2X7 receptor (P2X7R), NOD-like receptor pyrin domain containing 3 (NLRP3) and Nuclear factor-kappaB (NF-κB). Lastly, we assessed the function of various neurotransmitter systems to link the inflammatory response and neurotransmitter metabolism. Pro-inflammatory cyrokines, including IL-1a, IL-6, TNF-a and IFN-γ were markedly induced in the serum of parous rats, although no significantly depressive-like behavior was found. Meanwhile, NLRP3 and NF-κB were decreased in certain brain areas. Moreover, gestational stress significantly induced neurochemical disturbance, which is partly restored by Ω-3 fatty acids supplementation. These findings strengthen the link between inflammation, neurochemistry and postpartum depression, and further provide novel insights into the antidepressant effect of Ω-3 fatty acids.

Objectives Tacrolimus is one of the three basic immunosuppressants used following kidney transplantation, and its plasma concentration is susceptible to antifungal drugs. Abnormal tacrolimus concentrations may lead to adverse outcomes for patients. Adjustment of the tacrolimus dose after administering antifungal drugs to patients with fungal infection after transplantations therefore has important clinical significance. Our objective is to measure the impact of antifungal drugs on the plasma concentration of tacrolimus in kidney transplant patients. Methods A retrospective study was carried out in 109 kidney transplant recipients treated with a tacrolimus-based regimen and antifungal drugs simultaneously. Tacrolimus levels and dosage requirements were compared before and during antifungal therapy. Results The plasma levels of tacrolimus were significantly increased after the combination with voriconazole and fluconazole (p<0.05). Consequently, the daily dose of tacrolimus was significantly reduced after the combination (p<0.05). However, although the tacrolimus concentration was significantly decreased after the administration of caspofungin (p0.05). Conclusions Our results suggest that there is considerable variability in the interaction between tacrolimus and different antifungal drugs. The dose of tacrolimus should be reduced by two-thirds and one-third before the combination with voriconazole and fluconazole, respectively. It is not recommended that the dose should be adjusted before combination with other antifungal drugs, and the dose should be adjusted under the guidance of therapeutic drug monitoring.

Objective: To understand the status of therapeutic drug monitoring (TDM) in China Mainland, and thus lay down the foundation for further improvement in TDM. Methods: In the present study, a nationwide questionnaire survey was conducted, which was distributed and collected using a mobile‐based application. Clinicians, pharmacists, and clinical laboratory physicians belonging to different levels of public hospitals were involved as subjects/objects. The contents of the survey included TDM implementation in their hospital and information regarding their opinions and suggestions on TDM work. Mann–Whitney test was used to compare the difference between top tertiary hospitals and non–top tertiary hospitals. Results: A total of 475 questionnaires were collected, 383 from top tertiary hospitals (3A hospitals) and 92 from non–top tertiary hospitals (other than 3A hospitals). A total of 240 clinicians, TDM pharmacists, and clinical laboratory physicians were involved, with an effective rate of 50.5%. Top tertiary hospitals were associated with certain advantages, such as the number of TDM testing facilities, annual sample size, number of monitoring varieties, and interpretation rate of monitoring reports, compared with non–top tertiary hospitals. In particular, β-lactamase inhibitor, olanzapine, carbamazepine, and glucocorticoids seemed to be the main projects that clinicians wanted to assess. The drugs for which TDM was commonly performed included vancomycin, valproic acid, carbamazepine, phenytoin sodium, and methotrexate. The most commonly used detection methods include high-performance liquid chromatography, immunization, 2D-LC, and LC-MS. The monitoring concentration range was found to be inconsistent for most of the drugs. Currently, no unified regulation exists for TDM charges in China, which is no more than ¥200 in general. Clinicians rely on pharmacists for professional guidance. Importantly, improvement in the interpretation of monitoring reports, proficiency testing, and cooperation with clinical departments may aid in improving the level of TDM service. Conclusions: This survey objectively reflected the current status of TDM work in hospitals in China, and provided a strong reference base for devising strategies for improvement and effective execution of TDM work.