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  • Ya-shi LIU, Hong-chao LI
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 406-410.

    Compared to adult economic evaluation, pediatric pharmacoeconomics evaluation has the characteristics, such as the limited disease types, difficult to accurately measure health utility, easily ignored family spillover effects, unmet medical needs, and higher appropriateness requirements. There are specialized tools and resources in the field of pediatric pharmacoeconomics evaluation including the pediatric quality appraisal questionnaire, pediatric economic database evaluation database, and pediatric economic evaluation textbook. The characteristics of pediatric pharmacoeconomics evaluation is necessary to be pay attention, and specialized tools and resources should be actively used to improve the practicality and standardization of future pediatric pharmacoeconomics.

  • Ye ZHANG, Yuan ZHANG, Ming-hua YANG, Sheng-feng WANG
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 410-416.
    AIM

    To investigate and analyze the adverse drug event (ADE) signals associated with ceftriaxone in children in the real world, and provide references for the safety evaluation of ceftriaxone in children.

    METHODS

    ADE reports in the US FDA Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2022 involving children aged 0-17 years with ceftriaxone as the primary suspected drug were extracted. ADEs were classified into organ systems using the Medical Dictionary for Regulatory Activities (MedDRA). The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were utilized to identify ADE signals associated with ceftriaxone.

    RESULTS

    A total of 999 ADE reports were collected for children aged 0-17 years with ceftriaxone as the primary suspected drug. There were 139 related ADE signals affecting 18 organ systems. The top 3 ADEs in terms of frequency were acute kidney injury, cholelithiasis, and postrenal acute renal failure. The top 3 ADEs in terms of signal strength were postrenal acute renal failure, ureteral calculus, and intravascular hemolysis. The top 10 ADEs in terms of signal strength for ceftriaxone in different age groups of children primarily involved the hepatobiliary system, renal and urinary system, and the blood and lymphatic system. After the update of the ceftriaxone package insert in July 2007, the proportion of pediatric stone-related ADEs caused by ceftriaxone decreased from 5.88% to 5.61% among all ADEs. Among the top 10 concomitant medications reported in ADEs, other types of antibiotics and nonsteroidal anti-inflammatory drugs were the most commonly used.

    CONCLUSION

    When ceftriaxone is used in children, caution should be exercised regarding its potential adverse events on the liver, gallbladder, and renal system. Additionally, attention should be paid to the risk of adverse events when used in combination with other medications.

  • Guang-bo LIU, Hong-fei XIONG, Fei CHENG, Yun-yun ZHANG, Zi-wen WEI, Wen-wen LIANG, Si-yuan LI
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 416-421.
    AIM

    To evaluate the influence of age on the effectiveness of midazolam oral solution in managing preoperative anxiety in pediatric patients.

    METHODS

    Pediatric patients, aged 1 to 6 years, scheduled for elective surgery under general anesthesia, regardless of gender, American Society of Anesthesiologists Ⅰ-Ⅱ classification, were divided into two age groups: infants (1 ≤ age ≤ 3 years) and children (3 < age ≤ 6 years). The initial dose of oral midazolam solution administered was 0.5 mg·kg-1. Subsequent dosages were determined using a bias coin design dose-up-and-down sequential method, based on the patient’s modified Ramsay sedation score, parental separation anxiety score, and facemask induction score after admission. The behavior scores and adverse reactions during sedation between the two groups were recorded and compared. The 95% effective dose (ED95) and corresponding 95% confidence interval (95% CI) of midazolam oral solution for preoperative anxiety relief in children was calculated through isostatic regression analysis.

    RESULTS

    The ED95 for infants and children was 0.83 mg·kg-1 (95%CI: 0.69 to 0.88 mg·kg-1) and 0.89 mg·kg-1 (95%CI: 0.69 to 0.97 mg·kg-1), respectively. No statistically significant difference in ED95 was observed between the two groups (P>0.05). A comprehensive analysis of both age groups yielded an overall ED95 of 0.89 mg·kg-1 (95%CI: 0.79 to 0.97 mg·kg-1) for midazolam oral solution in alleviating preoperative anxiety in children aged 1 to 6 years. There was a statistically significant difference in the behavior scores between the two groups (P<0.05), but no difference in parental satisfaction (P>0.05).Adverse events including hypoxemia, respiratory depression, nausea and vomiting were not observed in the two groups during the induction period and the anesthesia recovery period.

    CONCLUSION

    The efficacy of midazolam oral solution in alleviating preoperative anxiety in children is not affected by age. The dose of ED95 for relieving preoperative anxiety in children aged 1 to 6 years is 0.89 mg·kg-1.

  • Xu ZHANG, Jia-hui ZHOU, Bei ZHANG, Hai-cheng SONG, Yue-yi REN
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 422-425.
    AIM

    To explore the median effective dose (ED50) of ciprofol combined with remifentanil for sedation in painless gastroscopy of school-aged children.

    METHODS

    School-aged children scheduled for painless gastroscopy were selected, regardless of gender, aged 6-12 years old. Following the intravenous injection of remifentanil 0.5 μg·kg-1, the pediatric patient was administered with ciprofol (starting with an initial dose of 0.5 mg·kg-1, the dose for the next child was determined using the Dixon sequential method, based on the sedation situation. A decrease of 0.05 mg·kg-1 was applied for successful sedation, while an increase of 0.05 mg·kg-1 was applied for failed sedation). The ED50, 95% effective dose (ED95) and corresponding 95% confidence interval (CI) of ciprofol were calculated by Probit method. The mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) of the pediatric patients before sedation (T0), after remifentanil administration (T1), and after ciprofol administration (T2), as well as the occurrence of adverse reactions were recorded.

    RESULTS

    The ED50 of ciprofol when combined with 0.5 μg·kg-1 remifentanil in anesthesia induction for school-aged children in painless gastroscopy was 0.302 mg·kg-1 (95% CI: 0.184 to 0.356 mg·kg-1),and the ED95 was 0.461 mg·kg-1 (95% CI: 0.390 to 1.004 mg·kg-1). Compared with those at T0, the MAP, HR, and RR of the children decreased significantly at T1 and T2 (P<0.05). Compared with those at T1, only MAP decreased significantly at T2 (P<0.05).During the examination, there were 6 cases of hypotension, 5 cases of bradycardia, and 5 cases of respiratory depression (including 3 cases of transient apnea), with no injection pain or chest wall rigidity.

    CONCLUSION

    The ED50 of ciprofol combined with 0.5 μg·kg-1 remifentanil for sedation in painless gastroscopy of school-aged children was 0.302 mg·kg-1 (95% CI: 0.184 to 0.356 mg·kg-1),and the ED95 was 0.461 mg·kg-1 (95% CI: 0.390 to 1.004 mg·kg-1).

  • Hong-xia LIU, Ting XIE, Yan ZHU, Bo-yu TAN, Qiao-ling YANG, Sheng HAO
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 426-431.
    AIM

    To analyze the safety of tocilizumab in children with rheumatic immune disease and provide reference for clinical medication.

    METHODS

    The medical records of tocilizumab from January 1st, 2016 to August 9th,2022 through the medical record system were collected. Retrospective analysis of the adverse events (AE) incidence and influencing factors, distribution, occurrence time, and outcome.

    RESULTS

    A total of 53 children treated with tocilizumab were included, 48 cases of systemic juvenile idiopathic arthritis, 1 case of Sjogren’s syndrome, 2 cases of autoimmune disease (autoimmune disease), 1 case of juvenile idiopathic arthritis (polyarticular type), and 1 case of multiple arteritis. The incidence of AE was 87% (46/53). The main AE were hypertriglyceridemia (60%), liver injury (49%), hypercholesterolemia (30%), hyperbilirubinemia (8%), neutropenia (9%), hypersensitivity (8%). Hypersensitivity was the main AE leading to drug withdrawal. The occurrence of hypercholesterolemia was associated with higher dose, and the occurrence of liver injury was associated with higher age and higher body mass index. Most of AE were mild and could recover to normal without treatment, and continuous medication rate was 96% (44/46).

    CONCLUSION

    The incidence of AE related to the use of tocilizumab in children is high. Hypersensitivity reactions may lead to drug withdrawal, and attention should be paid during the medication period. Although most children only suffer from mild liver injury, it is still necessary to be alert to the possibility of severe liver failure.

  • Yuan-yuan LI, Qun GU, Lin HUANG
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 432-436.

    Ganaxolone is an oral GABAA receptor positive variant modulator developed by Marinas Pharmaceuticals in the United States, and it can specifically modulate GABAA receptors in the central nervous system to enhance temporal and tonic inhibition for seizure control. In March 2022, the U.S. Food and Drug Administration approved it as the first drug to treat cyclin-dependent kinase-like 5 deficiency based on the results of a major phase Ⅲ clinical trial. Clinical trials have shown that ganaxolone is well tolerated, and the treatment regimen based on this drug is effective in controlling seizure frequency of patients and improving their quality of life.

  • Bo SUN, Yi-feng CHEN, Gang LI
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 436-441.

    Traditional clinical trials are often expensive, relatively inefficient, and may also cause additional burden for trial participants. The use of new technologies and methods in remote decentralized clinical trials (DCT) can help to improve clinical trials efficiency. The application of DCT brings several benefits, but also poses new challenges for the regulation of clinical trials. In this study, the current situation and issues surrounding the use of digital technology in clinical trials were analyzed, as well as the regulatory practices and regulatory scientific research on DCT in Europe and the United States. The proposed regulatory strategies for DCT in China were investigated, taking into account the current development and regulatory considerations of DCT in China.

  • Dan SU, Tao LIANG, Chao-ran CHEN, Zhong-hua JI, Wei ZHANG, Xiu-xiu YAO, Ying-lin WANG
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 442-445.
    AIM

    To evaluate the effects of remimazolam on painless gastroenteroscopy in elderly patients.

    METHODS

    The aged patients scheduled for painless gastroenteroscopy were enrolled and randomly divided into 2 groups.The anesthesia induction regimen of the control group was sufentanil 0.1 μg·kg-1+ propofol 1.5 mg·kg-1, and the additional dose of propofol was 0.5 mg·kg-1 each time during the examination. The administration regimen of the experimental group was sufentanil 0.1 μg·kg-1 + remimazolam 0.15 mg·kg-1 induction, and each additional dose of remimazolam was 1/3 of the first dose during the examination. Heart rate, respiratory rate, mean arterial pressure, and blood oxygen saturation during anesthesia were recorded. The time of induction, recovery and exit, and adverse reactions such as injection pain, hypoxemia and hypotension were observed.

    RESULTS

    A total of 441 patients were included in the analysis, 225 in the control group and 116 in the experimental group. Compared with the control group, the mean arterial pressure of the experimental group was higher than that of the control group at 5 and 10 min after administration, and the difference was significant (P<0.05).The induction, recovery and exit time of the experimental group were (41.8±4.3) s, (5.7±4.4) and (10.2±6.5) min, and those in the control group were (32.6±2.7) s, (6.6±3.9) and (12.9±7.4) min, respectively. The induction time of the experimental group was longer than that of the control group, and the recovery and exit time of the control group were shorter, with significant differences (P<0.05). Compared with the control group, the incidence of injection pain (54.2% vs. 2.3%), hypotension (16.4% vs. 6.9%) and hypoxemia (19.6% vs. 14.8%) in the experimental groups was significantly reduced (P<0.05).

    CONCLUSION

    Remimazolam is safe and effective for painless gastroenteroscopy in elderly patients, and has the advantages of fast recovery and low incidence of adverse reactions.

  • Guo-li WANG, Quan-yang LIN, Qing-qi ZHENG, Bao-xin MA
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 446-449.
    AIM

    To investigate the effects of sub-anesthetic doses of esketamine on cerebral oxygenation and hemodynamics in elderly patients undergoing hip arthroplasty.

    METHODS

    Sixty patients ( age ≥ 65 years and ASA classification Ⅱ to Ⅲ) for elective hip arthroplasty were selected and randomly divided into 2 groups of 30 patients each.Anesthesia was induced and maintained essentially in the same way in the two groups, with the addition of esketamine 0.5 mg·kg-1 intravenously at the time of induction followed by continuous pumping with esketamine 0.25 mg·kg-1·h-1 in the experimental group, and an equal amount of sodium chloride injection given at the corresponding time point in the control group. The mean arterial pressure (MAP), heart rate (HR), surgical volume index (SPI), and regional cerebral oxygen saturation (rSO2) were collected at the patient’s admission to the operating room (T0), 3 min after the procedure of induction (T1), intubation were immediately applied (T2), 10 min after induction (T3), skin incision (T4) and 1 h after surgery (T5). The intraoperative drug use and recovery quality during awakening were observed.

    RESULTS

    Compared with that at T0, MAP (except T4 in the experimental group) and SPI was significantly lower (P<0.05) and rSO2 was significantly higher (P<0.05) at all time points from T1 to T5 in the two groups. Compared with the control group, MAP was significantly increased at T1, T2, T3 in the experimental group (P<0.05). There was no significant difference in SPI, HR, and rSO2 between the two groups from T1 to T5 (P>0.05). The intraoperative usage rates of atropine and ephedrine, and the dosages of propofol and remifentanil in the experimental group were significantly lower than those in the control group (P<0.05).There was no significant difference in postoperative eye opening time and extubation time between the two groups (P>0.05).

    CONCLUSION

    The sub-anesthetic doses of esketamine has no significant effect on the rSO2 in elderly patients undergoing hip arthroplasty, which can provide more stable hemodynamics for patients undergoing anesthesia, and help maintain the balance between supply and demand of oxygen in brain tissue during perioperative period.

  • Man-hua ZHU, Qi-lu YING, Ling-zhi WANG, Rui-fen ZHOU
    Chinese Journal of New Drugs and Clinical Remedies. 2024, 43(6): 450-454.
    AIM

    To evaluate the effects of flurbiprofen combined with quadratus lumborum block (QLB) on postoperative neurocognitive function and inflammatory response in elderly patients undergoing nephrectomy.

    METHODS

    Sixty elderly patients undergoing laparoscopic nephrectomy were randomized into group Q (QLB group) and group FQ (flurbiprofen combined with QLB group), 30 patients in each group. Ultrasound guided anterior QLB were performed in all patients on the surgical side. Patients in group FQ received flurbiprofen 1 mg·kg-1 iv 10 min before surgery. Then both groups received general anesthesia. The dosages of propofol and remifentanil during surgery and the effective number of analgesia pump presses were recorded. The scores of visual analogue scale (VAS) and Bruggrmann comfort scale (BCS) were evaluated at 6, 24, 48 h after surgery. The neurocognitive function was evaluated at 1 d before surgery and 1 d and 7 d after surgery using the mini-mental state examination (MMSE), and the incidence of postoperative neurocognitive disorder (PND) within 7 d after surgery was recorded. Venous blood was collected and the serum levels of high mobility group box protein 1 (HMGB1) and interleukin 6 (IL-6) were tested 1 h before surgery and 30 min and 24 h after the surgery.

    RESULTS

    Compared with group Q, the dosage of remifentanil was significantly reduced in group FQ (P<0.05), and the effective numbers of analgesia pump presses were reduced in group FQ (P<0.05). At 6, 24 h after surgery, the VAS score was lower, and the BCS score was higher in group FQ than group Q (P<0.05). Compared with group Q, the MMSE score at 1, 7 d after surgery was significantly higher in the group FQ (P<0.05), the incidence of PND within 7 d after surgery was lower in group FQ (P<0.05). The HMGB1 and IL-6 levels at 30 min, 24 h after the surgery were significantly lower in group FQ than group Q (P<0.05).

    CONCLUSION

    Flurbiprofen combined with QLB can reduce the incidence of PND in elderly patients undergoing nephrectomy, which may be related to the perfect early postoperative analgesia and the decreased levels of inflammatory cytokines.