Latest ArticlesTo assess the in vitro antibacterial activity of polymyxin B in combination with meropenem, amikacin, and fosfomycin against carbapenem-resistant Enterobacteriaceae (CRE) strains carrying various resistance genes.
A total of 76 CRE strains isolated from the clinical laboratory of our hospital between 2019 and 2021 were collected for identification and confirmation of carbapenemase genotype. The minimum inhibitory concentrations (MIC) of polymyxin B, meropenem, amikacin, and fosfomycin against CRE were determined using the broth microdilution method.The in vitro combined sensitivity tests of polymyxin B with meropenem, amikacin, and fosfomycin were performed using the microdilution checkerboard method to calculate the fractional inhibitory concentration index (FICI) for determining their interactions.
Among the 76 strains of CRE, 24 strains were identified to carry the blaKPC, while 28 strains carried the blaNDM and another 24 strains carried the blaOXA-48-like. The drug-resistance rates of CRE strains to polymyxin B, meropenem, amikacin, and fosfomycin were determined as 3%, 92%, 39%, and 45%, respectively. The highest synergistic + partial synergistic rate was observed in combination of polymyxin B with meropenem (54%), followed by fosfomycin (43%) and amikacin (18%). For CRE carrying blaKPC, blaOXA-48-like, or blaNDM, the synergistic + partial synergistic rates of polymyxin B combined with fosfomycin were 37%, 42%, and 50%, respectively, while combined with meropenem were 75%, 21%, and 64%, respectively, and combined with amikacin were 8%, 25%, and 21%, respectively. No antagonistic effect was observed between polymyxin B and these three antibiotics.
The combination of polymyxin B and meropenem exhibits the best synergistic antibacterial effect against CRE, and the combined effect is related to the drug-resistance genotype of bacteria, so active detection of drug-resistance genes can help to promote the rational use of antibiotics in clinical practice.
To evaluate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) on gastrointestinal adverse reactions in patients with type 2 diabetes mellitus (T2DM).
The databases PubMed, Embase, and Cochrane Library were systematic searched for randomized controlled trials of GLP-1RA for the treatment of T2DM from the time of construction until October 1st, 2023, with one GLP-1RA as the drug in the trial arm and placebo or another GLP-1RA as the drug in the control arm. Bayesian network meta-analysis was used to explore the risk of gastrointestinal adverse reactions, such as nausea, vomiting, anorexia, constipation, dyspepsia, and diarrhea.
Forty-five papers were included, involving 27 729 patients. The overall incidence of gastrointestinal adverse reactions caused by GLP-RA was 11.66%. Compared with placebo, tirzepatide caused the highest risk of nausea, diarrhea, dyspepsia, and anorexia, lixisenatide caused the highest risk of vomiting, and semaglutide caused the highest risk of constipation. Compared with placebo, all GLP-1RA except loxenatide significantly increased the risk of vomiting; all GLP-1RA except lixisenatide significantly increased the risk of diarrhea; all GLP-1RA significantly increased the risk of constipation except tirzepatide and lixisenatide; all GLP-1RA significantly decreased appetite and increased the risk of dyspepsia (P<0.05).
GLP-1RA significantly increased the risk of gastrointestinal adverse reactions in T2DM patients, and different drugs have different risks of various symptoms, among which tirzepatide has a higher risk of gastrointestinal symptoms, which deserves clinical attention and vigilance.
To explore the median effective dose (ED50) of ciprofol combined with remifentanil for sedation in painless gastroscopy of school-aged children.
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.
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.
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).
To analyze the safety of tocilizumab in children with rheumatic immune disease and provide reference for clinical medication.
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.
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).
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.
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.
To study the mechanism of gigantol inhibiting the proliferation of pancreatic carcinoma (PC) cells by targeting urokinase-type plasminogen activator (PLAU).
PC cells (PANC-1 and SW1990) were treated with different concentrations of gigantol. The cells activity was detected by CCK-8, and half-maximal inhibitory concentration (IC50) was calculated. Cell clone assay was performed to detect the effects of gigantol on cells growth ability. The effects of gigantol on cells growth cycle and apoptosis were detected by flow cytometer. The targets of gigantol were analyzed by bioinformatics, expressions of these targets in PC tissues and their relationship with poor clinical phenotypes were analyzed.PC cells were transfected with PLAU or vector plasmid, and divided into normal group (vector plasmid), gigantol group (45 μmol·L-1 or 50 μmol·L-1) and gigantol + PLAU (PLAU plasmid) group. The effects of gigantol on cells proliferation, clone, cells cycle and apoptosis by targeting PLAU were observed. The expression of PLAU protein in cells was detected by Western blot. The inhibitory effects of gigantol on cells proliferation in vivo were detected by xenograft assay in nude mice.The expression of proliferating cell antigen (Ki67) was detected by immunohistochemistry.
Compared with the normal group, gigantol group showed a significant decrease in cell proliferation and clone number (P<0.05), and an increase in the number of G0/G1-phase cells, a decrease in the number of S-phase cells (P<0.05), and an increase in the number of apoptotic cells (P<0.05). There were no significant difference in the number of G2/M-phase cells between the two groups (P<0.05). Bioinformatics results showed that PLAU was the target of gigantol, which was up-regulated in PC tissues and related to poor clinical phenotypes of PC. Gigantol could inhibit the expression of PLAU protein in PC cells, showing concentration and time dependence (P<0.05). PLAU protein expression, proliferation activity and clone number, and the number of S-phase cells in PC cells were higher in the gigantol +PLAU group than in the gigantol group, while the number of apoptotic cells was less than in the gigantol group (P<0.05). In the nude mice experiments, the volume and weight of transplanted tumors in the gigantol group were significantly lower than those in the normal group (P<0.05), and the relative expression of Ki67 in tumor tissues was lower than that in the normal group (P<0.05).
Gigantol can inhibit the proliferation of PC cells, affect cells cycle and promote apoptosis by targeting the expression of PLAU protein.
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.
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.
Latent tuberculosis infection (LTBI) is a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active tuberculosis. Although LTBI is not contagious, about 5%-15% patients will develop active tuberculosis. Young age and immunosuppression are risk factors for the progression of LTBI to active tuberculosis. Due to the immature immune system, rheumatic disease and anti-rheumatic drugs, children with rheumatic disease are more susceptible to Mycobacterium tuberculosis, and LTBI is also prone to develop into active tuberculosis. China is still a country with a high burden of tuberculosis, more attentions should be paid to LTBI in rheumatic children. Screening for LTBI and preventive anti-tuberculosis treatment can reduce the occurrence of active tuberculosis and ensure the health of rheumatic children.
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.
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.
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.
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.
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