Efficacy and safety of esketamine for sedation among patients undergoing gastrointestinal endoscopy: a systematic review and meta-analysis.

BACKGROUND: Patients who undergo gastrointestinal endoscopy often require propofol-based sedation combined with analgesics. At present, the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients remains controversial. Moreover, there is no universal agreement regarding the appropriate dose of esketamine supplementation. This study aimed to assess the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients. METHODS: Seven electronic databases and three clinical trial registry platforms were searched and the deadline was February 2023. Randomized controlled trials (RCTs) evaluating the efficacy of esketamine for sedation were included by two reviewers. Data from the eligible studies were combined to calculate the pooled risk ratio or standardized mean difference. RESULTS: Eighteen studies with 1962 esketamine participants were included in the analysis. As an adjunct to propofol, the administration of esketamine reduced the recovery time compared to normal saline (NS). However, there was no significant difference between the opioids group and ketamine group. For propofol dosage, the administration of esketamine required a lower propofol dosage compared to the NS group and opioids group].For complications, the esketamine group had fewer complications compared to the NS group and opioid group in patients, but there were no significant differences between the esketamine group and ketamine group. Notably, the coadministration of esketamine was associated with a higher risk of visual disturbance compared to the NS group. In addition, we used subgroup analysis to investigate whether 0.2-0.5 mg/kg esketamine was effective and tolerable for patients. CONCLUSION: Esketamine as an adjunct to propofol, is an appropriate effective alternative for sedation in participants undergoing gastrointestinal endoscopy. However, considering the possibility of its psychotomimetic effects, esketamine should be used with caution.

A cross-sectional study on knowledge and behavior regarding medication usage among guardians of left-behind children: evidence from China.

PURPOSE: The primary objective of this study was to evaluate knowledge and behavior of medication use among guardians of left-behind children (LBC) and non-left-behind children (NLBC). METHODS: A cross-sectional study was conducted in Chengdu, the major city of southwestern China from May 2020 to August 2020. A logistic regression model was conducted to assess medication-related knowledge and behavior of guardians between the LBC group and NLBC group, adjusted for confounders. Stratified analysis was further performed. RESULTS: The overall mean scores for knowledge and for behavior were 20.22 (standard deviation = 4.472) and 15.77 (standard deviation = 3.604), respectively. No significant difference was found in medication-related knowledge and behavior scores between LBC and NLBC guardians (P > 0.05). A significant difference was only observed after adjusting for past medical history and history of present illness (HPI). CONCLUSION: There was no significant difference in the awareness and behavior of medication use between guardians of LBC and NLBC in this study, having more contact with the doctor was an effective method of health education that could possibly improve their health literacy.

Effects of vitamin D supplementation during pregnancy on bone health and offspring growth: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Whether vitamin D supplementation during pregnancy is beneficial to bone health and offspring growth remains controversial. Moreover, there is no universal agreement regarding the appropriate dose and the time of commencement of vitamin D supplementation during pregnancy. OBJECTIVE: We aimed to systematically review the effects of vitamin D supplementation during pregnancy on bone development and offspring growth. METHODS: A literature search for randomized controlled trials (RCTs) was performed in 7 electronic databases to identify relevant studies about the effects of vitamin D supplementation during pregnancy on bone development and offspring growth from inception to May 22, 2022. A Cochrane Risk Assessment Tool was used for quality assessment. Vitamin D supplementation was compared with placebo or standard supplements. The effects are presented as the mean differences (MDs) with 95% CIs. The outcomes include bone mineral content (BMC), bone mineral density (BMD), bone area (BA), femur length (FL) and humeral length (HL); measurement indicators of growth, including length, weight and head circumference; and secondary outcome measures, including biochemical indicators of bone health, such as the serum 25(OH)D concentration. Additionally, subgroup analyses were carried out to evaluate the impact of different doses and different initiation times of supplementation with vitamin D. RESULTS: Twenty-three studies with 5390 participants met our inclusion criteria. Vitamin D supplementation during pregnancy was associated with increased humeral length (HL) (MD 0.13, 95% CI 0.06, 0.21, I2 = 0, P = 0.0007) during the fetal period (third trimester). Vitamin D supplementation during pregnancy was associated with a significantly increased length at birth (MD 0.14, 95% CI 0.04, 0.24, I2 = 24%, P = 0.005) and was associated with a higher cord blood 25(OH)D concentration (MD 48.74, 95% CI 8.47, 89.01, I2 = 100%, P = 0.02). Additionally, subgroup analysis revealed that birth length was significantly higher in the vitamin D intervention groups of ≤1000 IU/day and ≥4001 IU/day compared with the control group. Prenatal (third trimester) vitamin D supplementation was associated with a significant increase in birth length, while prenatal (second trimester) vitamin D supplementation was associated with a significant increase in birth weight. CONCLUSION: Vitamin D supplementation during pregnancy may be associated with increased humeral length (HL) in the uterus, increased body length at birth and higher cord blood 25(OH)D concentration. Evidence of its effect on long-term growth in children is lacking. Additional rigorous high-quality, long-term and larger randomized trials are required to more fully investigate the effects of vitamin D supplementation during pregnancy.

Comparison of dexmedetomidine with chloral hydrate as sedatives for pediatric patients: A systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine (Dex) and chloral hydrate (CH) are the most frequently used sedative agents in pediatric patients. We aimed to systematically review the literature comparing the efficacy and safety of Dex and CH for sedation in pediatric patients. METHODS: Seven electronic databases and 3 clinical trial registry platforms were searched for articles published prior to October 2019. Randomized controlled trials (RCTs) evaluating the efficacy and safety of Dex versus CH for sedation in children were examined by 2 reviewers. The extracted information included the success rate of sedation, sedation latency, sedation duration, sedation recovery time, and adverse events. Moreover, the extracted data included 5 subgroups: the effects of 1, 1.5, 2, 2.5, and 3 µg/kg doses of Dex were compared with the effect of CH on the success rate of sedation. We also formed separate subgroups for different types of adverse events (incidence of vomiting, hypotension, bradycardia, etc). The outcomes were analyzed by Review Manager 5.3 software and are expressed as relative risks (RR) or the mean difference (MD) with the 95% confidence interval (CI). Heterogeneity was assessed with I-squared (I) statistics. RESULTS: A total of 15 RCTs involving 2128 children with Dex versus CH for sedation were included in the meta-analysis. The dose range of Dex ranged from 1 to 3 µg/kg. Compared with CH, the Dex group had a significantly higher success rate of sedation (RR = 1.14, 95% CI [1.05, 1.25], I = 79%, P = .003). Additionally, subgroup analysis revealed that there was no significant difference in the success rate of sedation between the CH group and the 1, 1.5, 2.5, and 3 µg/kg Dex groups; only the 2 µg/kg Dex group had a significantly higher success rate than the CH group (RR = 1.15, 95% CI [1.03, 1.29], I = 80%, P = .02). There was no significant difference in the number of subjects who required 2 doses or the duration of sedation between the CH and Dex groups. Furthermore, compared with the Dex group, the CH group had a significantly longer sedation latency (MD = -3.54, 95% CI [-5.94, -1.15], I = 95%, P = .004), sedation recovery time (MD = -30.08, 95% CI [-46.77, -13.39], I = 99%, P = .0004), and total time from sedative administration to discharge (MD = -12.73, 95% CI [-15.48, -9.97], I = 0%, P < .05), as well as a higher number of adverse events in total (RR = 0.25, 95% CI [0.11, 0.61], I = 89%, P = .002). Moreover, the subgroup analysis of adverse events revealed that CH was associated with higher risks of vomiting (RR = 0.07, 95% CI [0.03, 0.17], I = 0%, P < .0001), crying or resisting (RR = 0.22, 95% CI [0.07, 0.71], I = 60%, P = .01), and cough (RR = 0.15, 95% CI [0.05, 0.44], I = 0%, P = .0006); there was no significant difference in the risk of hypotension, supplemental oxygen, or respiratory events between CH and Dex. However, Dex was associated with a higher risk of bradycardia (RR = 4.08, 95% CI [1.63, 10.21], I = 0%, P = .003). CONCLUSIONS: Dex is an appropriate effective alternative to CH for sedation in pediatrics. However, considering the possibility of bradycardia, Dex should be used with caution.

Subcutaneously injected ivermectin-loaded mixed micelles: formulation, pharmacokinetics and local irritation study.

Clinical application of ivermectin (IVM) is limited by several unfavorable properties, induced by its insolubility in water. Slight differences in formulation may change the plasma pharmacokinetics and efficacy. In this study, an IVM-loaded Soy phosphatidylcholine-sodium deoxycholate mixed micelles (IVM-SPC-SDC-MMs) were developed to improve its aqueous solubility, aiming to make it more applicable for clinical use. First, IVM-SPC-SDC-MMs were prepared using the co-precipitation method. After formulation optimization, the particle size was 9.46 ± 0.16 nm according to dynamic light scattering. The water solubility of IVM in SPC-SDC-MMs (4.79 ± 0.02 mg/mL) was improved by 1200-fold, comparing with free IVM (0.004 mg/mL). After subcutaneous administration, the pharmacokinetic study showed that IVM-SPC-SDC-MMs and commercially available IVM injection were bioequivalent. Also, the local irritation study confirmed that IVM-SPC-SDC-MMs reduced side reactions of the commercially available IVM injection. These results indicated that IVM-SPC-SDC-MMs represented a promising new drug formulation suitable for subcutaneous delivery of IVM.

Co-delivery of Pirarubicin and Paclitaxel by Human Serum Albumin Nanoparticles to Enhance Antitumor Effect and Reduce Systemic Toxicity in Breast Cancers.

In our study, we aimed to develop a codelivery nanoparticulate system of pirarubicin (THP) and paclitaxel (PTX) (Co-AN) using human serum albumin to improve the therapeutic effect and reduce systemic toxicities. The prepared Co-AN demonstrated a narrow size distribution around 156.9 ± 3.2 nm (PDI = 0.16 ± 0.02) and high loading efficiency (87.91 ± 2.85% for THP and 80.20 ± 2.21% for PTX) with sustained release profiles. Significantly higher drug accumulation in tumors and decreased distribution in normal tissues were observed for Co-AN in xenograft 4T1 murine breast cancer bearing BALB/c mice. Cytotoxicity test against 4T1 cells in vitro and antitumor assay on 4T1 breast cancer in vivo demonstrated that the antitumor effect of Co-AN was superior to that of the single drug or free combination. Also, Co-AN induced increased apoptosis and G2/M cell cycle arrest against 4T1 cells compared to that of the single drug formulation. Remarkably, Co-AN exhibited significantly lower side effects regarding bone marrow suppression and organ and gastrointestinal toxicities. This human serum albumin-based codelivery system represents a promising platform for combination chemotherapy in breast cancers.

Soluplus(®) based 9-nitrocamptothecin solid dispersion for peroral administration: preparation, characterization, in vitro and in vivo evaluation.

Our study aimed to develop an amorphous 9-nitrocamptothecin solid dispersion (9-NC-SD) using polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus(®)) for improving its oral bioavailability and antitumor efficacy in vivo. Freeze-dried 9-NC-SD with an optimized drug/polymer ratio at 1:15 (w/w) was characterized by powder X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. The amorphous form of 9-NC was obtained by freeze-drying and the aqueous solubility of 9-NC was increased to 1.42 mg/mL. Upon dilution, 9-NC-SD was proven to form micellar structures with an average size distribution around 58 nm ± 5 nm (PDI=0.107 ± 0.016). Moreover, 9-NC-SD showed significantly increased intracellular uptake efficiency in Caco-2 cells compared to free 9-NC. Furthermore, the AUC0-8h of 9-NC-SD following oral administration showed a 2.68-fold increase in the lactone form of 9-NC compared to that of free 9-NC in Sprague-Dawley rats. The 9-NC-SD did not show obvious inflammatory responses and gastrointestinal toxicity following oral administration as demonstrated by the histological analysis of the rat intestinal sections. Thus, 9-NC-SD represents a promising approach for improving the solubility and oral bioavailability of drugs with poor solubility.