Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID-19: A systematic review and meta-analysis.

This study aimed to compare the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) with molnupiravir in the treatment of coronavirus disease 2019 (COVID-19). To end this, PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar were systematically searched to collect relevant evidence up to February 15, 2023. The risk of bias was evaluated using the risk of bias in nonrandomized studies of interventions tool. Data were analyzed using Comprehensive Meta-Analysis software. Eighteen studies involving 57 659 patients were included in the meta-analysis. The meta-analysis showed a significant difference between nirmatrelvir/ritonavir and molnupiravir in terms of all-cause mortality rate (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.44-0.67), all-cause hospitalization rate (OR = 0.61, 95% CI: 0.54-0.69), death or hospitalization rate (OR = 0.61, 95% CI: 0.38-0.99), and negative polymerase chain reaction conversion time (mean difference = -1.55, 95% CI: -1.74 to -1.37). However, no significant difference was observed between the two groups in terms of COVID-19 rebound (OR = 0.87, 95% CI: 0.71-1.07). In terms of safety, although the incidence of any adverse events was higher in the nirmatrelvir/ritonavir group (OR = 2.52, 95% CI: 1.57-4.06), no significant difference was observed between the two treatments in terms of adverse events leading to treatment discontinuation (OR = 1.18, 95% CI: 0.69-2.00). The present meta-analysis demonstrated the significant superiority of nirmatrelvir/ritonavir over molnupiravir in improving clinical efficacy in COVID-19 patients during the prevalence of Omicron variant. These findings, however, need to be further confirmed.

Morphine in Plasma and Cerebrospinal Fluid of Patients Addicted to Opiates Undergoing Surgery: High-performance Liquid Chromatography Method.

BACKGROUND: The prevalence of opium addiction among Iranians is considerable. Since endogenous opioid systems may be altered as a consequence of addiction, it is very important to determine the plasma and cerebrospinal fluid (CSF) levels of morphine in Iranian patients addicted to opiates who will undergo surgery. METHODS: We obtained CSF and plasma samples from 50 volunteers with an established opioid addiction pattern. Samples were analyzed using high-performance liquid chromatography (HPLC). Additionally, frequency of nausea and vomiting, baseline heart rate (BHR), and systolic blood pressure (SBP) were recorded within the surgery and postoperatively during a 10-min interval. FINDINGS: 84% of participants were men with a median age of 39.08 years. Mean score of body mass index (BMI) was 23.30 and most of the participants (46%) used opium in its traditional inhaled form. A higher concentration of morphine in blood was found in comparison with CSF (P < 0.001) in relation to the way of use. However, no statistically significant differences were found in relation to the type of addictive substance. No other association was found between the levels of morphine and the clinical characteristics of the patients. Moreover, results revealed no difference between hemodynamic-related data with blood and CSF level in opium-dependent patients. CONCLUSION: Quantification of plasma and CSF morphine, both immediately before initiation of surgery and subsequently on recovery room, showed that although clinical efficacy of systemic morphine was poor in addicted patients, it had no effect on patients' hemodynamic variable and following complications after surgery.