A BSTRACT Objective: Chemotherapy-induced nausea and vomiting (CINV) is a distressing complication of chemotherapy. It can compromise treatment adherence and impair patients’ quality of life. Despite guideline-recommended drug prophylaxis, many patients still suffer from CINV. This double-blind, randomized crossover clinical trial aims to compare the safety and efficacy of mirtazapine versus olanzapine among patients treated with highly emetogenic chemotherapy (HEC). Methods: Sixty patients undergoing anthracycline-cyclophosphamide (AC) or cisplatin-containing regimen were enrolled. Half of the patients received olanzapine (5 mg/day) plus mirtazapine placebo during cycle 1, followed by mirtazapine (15 mg/day) plus olanzapine placebo in cycle 2 on days 1–4 after chemotherapy. The other half of the patients received the reverse order. Furthermore, all patients received a triplet antiemetic regimen consisting of aprepitant, granisetron, and dexamethasone. The endpoints included rate of complete control (CC), complete response, severity of nausea and vomiting based on NCI-CTCAE, visual analog scale nausea score, and adverse effects across the acute, delayed, and overall phases during the first two cycles of chemotherapy. Patients’ quality of life affected by CINV was assessed using the Functional Living Index-Emesis questionnaire. Findings: Overall CC was 56.7% for olanzapine and 53.6% for mirtazapine in cycle 1 ( P = 0.813) and 54.5% for mirtazapine and 56.3% for olanzapine in cycle 2 ( P = 0.917). The overall CC rate did not differ significantly between olanzapine and mirtazapine (odds ratio = 1.14, 95% confidence interval 0.89–1.35, P = 0.31). Similar findings were observed across all other evaluated outcomes. Sedation was the most common adverse effect. No significant difference was observed between olanzapine and mirtazapine ( P = 0.563 for the first cycle and 0.061 for the second cycle). Conclusion: Our findings support that mirtazapine may have comparable outcomes with olanzapine in preventing CINV following HEC.
A BSTRACT Objective: The objective of this study was to estimate the prevalence, severity, mechanisms, actionable high-severity pairs, and associated factors of clinically significant potential drug–drug interactions (DDIs) in older outpatients in Vietnam. Methods: We conducted a descriptive cross-sectional prescription study using systematic random sampling of 909 health-insurance outpatient prescriptions for patients aged 60 years or older at a provincial referral general hospital from April 2021 to April 2022. Potential DDIs were screened with Drugs.com and Medscape (final access: June 30, 2022). Severity ratings were harmonized into three levels; level 1 and level 2 interactions were considered clinically significant. Associated factors were evaluated using multivariable logistic regression. Findings: The mean age was 72.92 ± 8.88 years, and 236 patients (26.0%) were women. Polypharmacy (five or more medicines) occurred in 685 prescriptions (75.4%). Overall, 725 prescriptions (79.8%) contained at least one clinically significant potential DDI, including 84 (9.2%) with at least one level 1 pair. The mean number of clinically significant potential DDIs per prescription was 2.51 ± 2.41. Among 2745 DDI occurrences involving 325 unique pairs, pharmacodynamic mechanisms predominated, especially synergism (1382; 50.4%), and antagonism (527; 19.2%). Polypharmacy was the strongest associated factor (adjusted odds ratio 9.69, 95% confidence interval 6.21–15.11; P < 0.001). Conclusion: Clinically significant potential DDIs were frequent in older Vietnamese outpatients. Combining polypharmacy-based triage with a locally prioritized list of high-severity pairs may help outpatient pharmacists and prescribers convert routine database screening into focused medication-safety actions.
Objectives: The efficacy of intravenous magnesium sulfate in reducing sedative and analgesic requirements was examined in patients under mechanical ventilation. Methods: In this randomized clinical trial, patients requiring mechanical ventilation received either magnesium sulfate (serum magnesium target level: near 3 mg/dL) or placebo concurrently with the hospital analgosedation protocol. The calculated dose of magnesium in the intervention group was infused over 24 h. The primary outcome of the study was the cumulative opioid requirement at 24 and 48 h after intubation. Findings: A total of 110 patients were randomly assigned to either the placebo ( n = 54) or the magnesium sulfate ( n = 56) group. The results showed that the cumulative opioid consumption in the magnesium group was significantly less than in the control group at 24 h postintervention (120 mg vs. 214 mg, P < 0.001). This difference remained significant at 48 h postintervention (240 mg vs. 433 mg, P < 0.001). In addition, in the adjusted analysis using analysis of covariance, after adjustment for the model for acetaminophen dose and additive sedatives as confounders, this still remained statistically significant ( P < 0.001). Conclusion: Administration of magnesium sulfate targeting a serum magnesium level near 3 mg/dL in patients under mechanical ventilation reduced opioid requirements and may be considered as an analgesic and sedative-sparing agent.
Multiple sclerosis (MS) predominantly affects women of childbearing age, and decision-making regarding disease-modifying therapies during pregnancy and lactation, particularly for highly effective anti-CD20 therapies such as rituximab and ocrelizumab, remains challenging. This review aims to synthesize available evidence on the course of MS, pregnancy, and neonatal outcomes, complications, and safety considerations in pregnant and breastfeeding women with MS exposed to rituximab or ocrelizumab. This structured narrative review was conducted in accordance with the PRISMA reporting framework. A systematic search of major scientific databases was performed for studies published between 2000 and 2026. Included study designs comprised cohorts, registries, case series, case reports, and systematic reviews. Data were extracted based on exposure type (preconception, during pregnancy, postpartum, and during breastfeeding) and key outcomes (relapse and disease activity, live birth, miscarriage, preterm delivery, congenital anomalies, infections, and neonatal immune parameters) and were narratively synthesized. The body of evidence indicates that exposure to rituximab or ocrelizumab, particularly when treatment was administered prior to pregnancy and conception occurred at an interval from the last dose, is often associated with better disease stability during pregnancy and a reduced risk of postpartum relapse. Most reports have not identified a consistent pattern of increased major congenital anomalies, and pregnancy outcomes have generally fallen within expected ranges. The most important neonatal consideration is transient B-cell lymphopenia in some exposures occurring close to late pregnancy; this finding has usually been reported as reversible and requires attention to the timing of live vaccinations. During breastfeeding, existing evidence supports minimal drug transfer into breast milk and the absence of clinically meaningful adverse outcomes in infants. Current evidence suggests that rituximab and ocrelizumab may be considered as strategies for disease control around pregnancy and in the postpartum period in women with active MS. However, decision-making should be individualized, based on disease severity, timing of exposure, maternal benefit, and neonatal monitoring considerations. Prospective studies and expanded pregnancy registries are needed to better evaluate long-term maternal and infant outcomes.
To assess the efficacy and safety of each therapeutic options in the treatment of COVID-19 by assessing the evidence from existing systematic reviews and meta-analyses, and to carry out an umbrella meta-analysis of all meta-analysis studies to assess the efficacy of each drug. A comprehensive search was carried out in electronic databases for systematic reviews and meta-analyses which compared the efficacy and/or safety of therapeutic options in the treatment of COVID-19. Findings from the reviews were synthesized using tables and forest plots and the pooled estimate of effect size using the DerSimonian and Laird method was used for the updated meta-analysis. The main outcome was mortality. 285 reviews with 152 meta-analyses were included, The analysis of systematic reviews contents indicated that most reviewed drugs were as follows: chroquine/hydroxychloroquine ( n = 48), tocilizumab ( n = 39), remdesivir ( n = 25), corticosteroids ( n = 25), JAK inhibitors ( n = 12), colchicine ( n = 11), ivermectin ( n = 8), anakinra ( n = 7), favipravir ( n = 7), lopinavir/ritonavir ( n = 6), ACEI/ARB ( n = 6), azithromycin ( n = 4), sofosbuvir ( n = 4), and Vitamin D ( n = 4). Findings from the included reviews suggested that tocilizumab, remdesivir, corticosteroids, JAKI, anakinra, colchicine, ivermectin, and sofosbuvir decreased the rate of mortality significantly in those taking the drugs; otherwise hydroxylchroquine increased the risk of mortality significantly, while Lopinavir/Ritonavir had no benefit and ACEI and azithromycin decreased mortality rate not significantly. lower requirement for mechanical ventilation and intensive care unit admission and a shorter hospital length of stay was observed with the tocilizumab, JAKIs, anakinra, corticosteroids and sofosbuvir Only one third of the included reviews had 70% quality based on the AMSTAR scale assessment. The results of this study have the potential to be a useful tool for the translation of health evidence and for designing the decision support systems for evidence synthesis.
