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.