The Effect of Genetic Variation on the Sensitivity to Opioid Analgesics in Patients With Postoperative Pain: An Updated Meta-analysis.

BACKGROUND: Responsiveness to opioid analgesics differs among patients with acute postoperative pain. OBJECTIVE: Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids. STUDY DESIGN: An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain. METHODS: PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021. RESULTS: Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human µ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms. LIMITATIONS: Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis. CONCLUSIONS: In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia. KEY WORDS: Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.

The implementation of a FIP guidance for COVID-19: insights from a nationwide survey.

BACKGROUND: The International Pharmaceutical Federation (FIP) has established an interim guidance of coronavirus disease 2019 (COVID-19) for pharmacists worldwide. The aim of this study was to identify the implementation of FIP guidance in China and provide applicable strategies for further actions. METHODS: A nationwide cross-sectional survey on Chinese pharmacists was distributed electronically through groups of WeChat between 9 December 2020 and 18 December 2020. The 29-item questionnaire for the survey was designed based on the FIP guidance and knowledge, attitudes, and practices (KAP) framework. RESULTS: A total of 237 responses from 237 pharmacists (69.20% females) were received. Most pharmacists (81.86%) participated in work related to COVID-19. Respondents referred to other guidelines or consensus more than they did to FIP guidance. Most participants were qualified for the knowledge-based questions regarding COVID-19 (67.51%), had positive attitudes towards pharmacists' roles and actions (61.18%), and were qualified in the practices of prevention measures, infection risk monitoring, and pharmacists' advice (50.63%). Several factors were revealed as having impact on pharmacists' KAP, such as the relevance of participating in work related to COVID-19, work entailments, and information source. CONCLUSIONS: The FIP guidance has a certain degree of dissemination and implementation in China, which can be improved through effective actions directed towards impact factors.

Posaconazole-associated severe hyperbilirubinemia in acute myeloid leukemia following chemotherapy: A case report.

BACKGROUND: Posaconazole is a widely used azole antifungal agent, and posaconazole-associated severe hyperbilirubinemia is usually rare in clinical practice. We herein report a 58-year-old male with acute myeloid leukemia, who developed fungal infection following chemotherapy. CASE SUMMARY: After administration of posaconazole oral suspension, the patient developed severe hyperbilirubinemia and jaundice (Common Terminology Criteria for Adverse Events, CTCAE -Grade 3) with a serum total bilirubin (T-BIL) peak level of 170 µmol/L, alkaline phosphatase level of 739 U/L, alanine aminotransferase level of 99 U/L, and gamma-glutamyl transpeptidase level of 638 U/L. After posaconazole withdrawal and symptomatic treatment with liver-protective agents, the level of T-BIL and other laboratory data decreased gradually, and related symptoms disappeared. After medication analysis and literature review, we consider that the patient had a cholestatic type of posaconazole-induced liver injury, which was related to intracellular mitochondrial DNA damage. The case demonstrates that when patients with hematological malignancy develop severe infection following chemotherapy, combination of anti-infective drugs may contribute to a higher risk of severe drug-induced liver injury. CONCLUSION: This is the first thoroughly documented case report of posaconazole-associated severe hyperbilirubinemia. Therefore, in order to avoid severe adverse events, liver and renal function should be monitored closely before and during the administration of posaconazole.