Therapeutic Advances in Drug Safety最新文献

Background: The use of antineoplastic agents is one of the important triggers of tumor lysis syndrome (TLS), but there is still a lack of comprehensive understanding of antineoplastic agents that may trigger TLS and the TLS risk differences between different antineoplastic agents.

Objectives: This study aims to investigate the TLS risk of different antineoplastic agents and provide reference information for clinical practice.

Design: Real-world adverse events data in the FDA Adverse Event Reporting System (FAERS) database were used as the basis for the disproportionality analysis.

Methods: We reviewed the TLS reports in the FAERS database from 2004 to 2022 to summarize an antineoplastic agent list that was reported to trigger TLS, based on which we conducted disproportionality analysis to assess the TLS risk of each antineoplastic agent.

Results: In all, 164 antineoplastic agents were reported to trigger TLS. On the whole, rituximab was the most reported antineoplastic agent in TLS reports, followed by cyclophosphamide, venetoclax, doxorubicin, and etoposide, while tagraxofusp was the antineoplastic agent with the highest adverse drug reaction (ADR) signal strength in signal detection, followed by floxuridine, pentostatin, tebentafusp, and venetoclax. Integrating ADR signal detection results, 129 of 164 antineoplastic agents showed at least one positive ADR signal, and six antineoplastic agents (bevacizumab, carboplatin, cisplatin, fluorouracil, lenvatinib, and paclitaxel) have the highest total number of positive signals. Further classifying the 164 antineoplastic agents into 46 chemical subgroups to conduct ADR signal detection, nitrogen mustard analogs were the most reported antineoplastic agent subclasses, followed by clusters of differentiation 20 inhibitors, and pyrimidine analogs, while clusters of differentiation 22 inhibitors were the antineoplastic agent subclass with the highest ADR signal strength, followed by podophyllotoxin derivatives and actinomycines.

Conclusion: Our study showed the TLS risk characteristics of 164 antineoplastic agents by detecting and integrating ADR signals, which may help to optimize clinical practice.

Background: Oxaliplatin-associated shock (referred to as shock) is a rare but life-threatening adverse event.

Objectives: This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock, and assess the cycle-to-shock during oxaliplatin treatment.

Design: The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders.

Methods: All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012-2016). Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for oxaliplatin's link to shock incidence.

Results: Among 6932 oxaliplatin recipients, 331 suffered shock. In all, 3309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock (adjusted OR: 2.08, 95% CI: 1.23-3.52). Two independent risk factors were male sex (adjusted OR: 1.33, 95% CI: 1.05-1.69) and heart diseases (adjusted OR: 1.65, 95% CI: 1.17-2.32). The case-crossover analysis revealed a more than fourfold risk (OR: 4.4, 95% CI: 1.67-11.62). In total, 22 of 331 shock cases were exposed to oxaliplatin within 2 days of shock onset, with a median cycle-to-shock time at the seventh cycle.

Conclusion: Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and heart disease are two independent risk factors.

Background: Numerous studies report that anticholinergic burden (ACB) has been linked with several health consequences, including increased hospital admissions, prolonged hospitalization, and physical and cognitive impairment. However, low- and middle-income settings, as well as younger individuals, are underrepresented.

Objectives: To assess the prevalence and determinants of ACB, and to assess the impact of ACB on in-hospital mortality among adult in-patients at University of Gondar Comprehensive Specialized Hospital (UOGCSH).

Design: A cross-sectional study was conducted from June to August 2022 at UOGCSH among adult in-patients.

Methods: A pre-tested questionnaire was utilized to collect data from patients and their corresponding medical charts. A consecutive sampling technique was used to select the participants. Descriptive statistics were used to summarize socio-demographic and clinical characteristics. Chi-squared, Fisher's exact, and Wilcoxon rank sum tests, as appropriate, were used to determine associations between independent variables and ACB. Kaplan-Meier survival curve and Cox proportional hazards regression test were used to assess the impact of ACB on in-hospital mortality.

Results: A total of 420 adult in-patients, median (interquartile range) age of 38 (26, 55) years, participated in this study. Over half (58.3%) were exposed to anticholinergic medicines, with a high ACB (⩾3) seen in 11.2% of participants. High ACB was associated with higher median number of medicines per patient (p = 0.003) higher median hospital length of stay (p = 0.033), and having mental and behavioral disorders (p < 0.001). No significant association was found between ACB and in-hospital mortality (log-rank test p = 0.26, Cox regression adjusted hazard ratio: 1.47, 95% CI: 0.335-6.453, p = 0.61).

Conclusion: Among adult in-patients, a significant majority (58.3%) were subjected to medications possessing anticholinergic properties, with a noteworthy 11.2% of the study subjects exhibiting a high ACB. Participants with higher median length of hospital stay were more likely to have high ACB even in this relatively younger adult patient population.

Background: Cefuroxime has played a crucial role in the prevention and treatment of bacterial infections. However, the differences in adverse events across formulations and routes remain unclear.

Objectives: This study aimed to investigate the post-marketing safety of cefuroxime, particularly concerning formulations and routes.

Design: A retrospective pharmacovigilance study of cefuroxime was conducted using the data from Food and Drug Administration Adverse Event Reporting System database.

Methods: The clinical characteristics and concomitant drugs reported with cefuroxime were investigated. Adverse event signals of cefuroxime were identified based on four disproportionality algorithms. The signal differences of cefuroxime across formulations and routes were further examined.

Results: A total of 1810 adverse event reports associated with cefuroxime were identified, and 181 cefuroxime-associated signals were detected. Compared with tablets, injections were more likely to cause preferred terms 'blood pressure decreased' and 'anaphylactic shock'. In addition, system organ class 'eye disorders' significantly increased when cefuroxime was administered intraocularly, underscoring the importance of exercising caution regarding ocular toxicity.

Conclusion: The adverse events associated with cefuroxime were significantly different across formulations and routes, which deserve special attention in clinical use.

Background: Venous thromboembolism (VTE) has a serious impact on the prognosis of patients with spontaneous intracranial hemorrhage (sICH). However, the use of prophylactic heparin remains controversial.

Objectives: This study investigated the safety and timing of prophylactic heparin for VTE in patients with sICH.

Design: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines.

Methods: Two authors systematically searched Web of Science, Cochrane Library, Embase, and PubMed to find all published research before June 2023. The incidence of deep venous thrombosis (DVT) and mortality were set as primary endpoints.

Results: This meta-analysis included seven randomized controlled trials (RCTs) and five observational studies involving a total of 4419 sICH patients in the heparin (n = 2808) and control (n = 1183) groups. Among these patients, 205 received early heparin administration, while 223 received late heparin administration. The results suggested that, compared to the control group, patients in the heparin group had a lower incidence of VTE [odds ratio (OR), 0.47; 95% CI, 0.31-0.71; p < 0.001], DVT (OR, 0.53; 95% CI, 0.33-0.85; p = 0.009), pulmonary embolism (OR, 0.31 95% CI, 0.15-0.65; p = 0.002), and mortality (OR, 0.70; 95% CI, 0.54-0.90; p = 0.006), but there were no statistical differences in hematoma enlargement, extracranial hematoma, and major disability (p > 0.05). There was no statistically significant difference in DVT, mortality, hematoma enlargement, and extracranial hemorrhage between the early heparin group (<24-48 h) and the late heparin group (p > 0.05).

Conclusion: In patients with sICH, prophylactic use of heparin may be beneficial because it reduces the incidence of VTE and mortality without increasing the risk of additional bleeding. In addition, early prophylactic use of heparin appears to be safe. However, large-scale RCTs are lacking to support this evidence.