ABSTRACT
We improved the thermal dissociation cavity attenuated phase shift spectroscopy (TD-CAPS) instrument to measure atmospheric total peroxy nitrates (PNs) and organic nitrates (ONs) continuously under the condition of high NOx. In TD-CAPS, PNs and ONs are dissociated in heated quartz tubes to form NO2, and the NO2 concentration is measured by cavity attenuated phase shift spectroscopy (CAPS). The original TD-CAPS system overestimates PN and ON concentrations in the presence of high NO concentrations. Our laboratory experiments and numerical simulations showed that the main cause of the overestimation was NO oxidation to NO2 by peroxy radicals generated in the heated quartz tubes. In the improved system, NO was converted to NO2 by adding excess O3 after the quartz tubes so that CAPS detected NOx (NO and NO2) instead of NO2. The uncertainty of the improved system was less than 20% with â¼15 parts per billion by volume (ppbv) NO and â¼80 ppbv NO2. The estimated detection limit (3σ) was 0.018 ppbv with an integration time of 2 min in the presence of 64 ppbv NO2. The improved system was tested for measurement of PNs and ONs in an urban area, and the results indicated that interference from NO was successfully suppressed.
ABSTRACT
BACKGROUND: No head-to-head clinical trials have compared the differences in adverse events (AEs) between nivolumab plus ipilimumab (NIVO-IPI) and nivolumab plus cabozantinib (NIVO-CABO) in the treatment of metastatic renal cell carcinoma (mRCC). AIM: We analysed the two largest real-world databases, the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization's VigiBase, to elucidate the differences in AEs between NIVO-IPI and NIVO-CABO. METHOD: In total, 40,376 and 38,022 records were extracted from FAERS and VigiBase, and 193 AEs were analysed. The reporting odds ratios (ROR) with 95% confidence interval were calculated using a disproportionality analysis (NIVO-CABO/NIVO-IPI). RESULTS: The reported numbers of immune-related AEs, including myocarditis, colitis, and hepatitis, were significantly higher with NIVO-IPI (ROR = 0.18 for FAERS and 0.13 for VigiBase). Contrarily, the reported numbers of other AEs, including gastrointestinal disorders (ROR = 2.68 and 2.92) and skin and subcutaneous tissue disorders (ROR = 2.94 and 3.55), considered to be potentiated by the combination of NIVO and CABO, were higher with NIVO-CABO. CONCLUSION: Our findings contribute to the selection and clinical management of NIVO-IPI and NIVO-CABO, which minimizes the risk of AEs for individual patients with mRCC by considering distinctive differences in the AE profiles.
Subject(s)
Adverse Drug Reaction Reporting Systems , Anilides , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Renal Cell , Ipilimumab , Kidney Neoplasms , Nivolumab , Pharmacovigilance , Pyridines , Humans , Ipilimumab/adverse effects , Ipilimumab/administration & dosage , Nivolumab/adverse effects , Nivolumab/administration & dosage , Carcinoma, Renal Cell/drug therapy , Pyridines/adverse effects , Pyridines/administration & dosage , Male , Kidney Neoplasms/drug therapy , Female , Anilides/adverse effects , Anilides/administration & dosage , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Aged , Databases, Factual , Adult , United States/epidemiologyABSTRACT
BACKGROUND: Palbociclib and abemaciclib are cyclin-dependent kinase (CDK) 4/6 inhibitors currently used to treat breast cancer. Although their therapeutic efficacies are considered comparable, differences in adverse event (AE) profiles of the two drugs remain unclear. AIM: We analysed two real-world databases, the World Health Organization's VigiBase and the Food and Drug Administration Adverse Event Reporting System (FAERS), to identify differences in AE profiles of palbociclib and abemaciclib. METHOD: Data of patients with breast cancer receiving palbociclib or abemaciclib recorded until December 2022 were extracted from the VigiBase and FAERS databases. In total, 200 types of AEs were analysed. The reporting odds ratios were calculated using a disproportionality analysis. RESULTS: Cytopenia was frequently reported in patients receiving palbociclib, whereas interstitial lung disease and diarrhoea were frequently reported in those receiving abemaciclib. Moreover, psychiatric and nervous system disorders were more common in the palbociclib group, whereas renal and urinary disorders were more common in the abemaciclib group. CONCLUSION: This study is the first to show comprehensively the disparities in the AE profiles of palbociclib and abemaciclib. The findings highlight the importance of considering these differences when selecting a suitable CDK4/6 inhibitor to ensure safe and favourable outcomes for patients with breast cancer.
Subject(s)
Aminopyridines , Benzimidazoles , Breast Neoplasms , Piperazines , Humans , Female , Aminopyridines/adverse effects , Pyridines/adverse effects , Breast Neoplasms/drug therapy , Protein Kinase Inhibitors/adverse effectsABSTRACT
Shared decision making(SDM)plays a crucial role in treatment discussions for pregnant patients with breast cancer. A woman in her 30s was diagnosed with Stageâ breast cancer during the 20th week of her pregnancy. In SDM sessions, we proposed a total mastectomy and axillary sentinel lymph node biopsy with a radioisotope tracer. However, the patient opted for a conservative breast surgery and lymph node evaluation without tracer use. Following a comprehensive risk explanation, we performed a partial mastectomy and axillary lymph node sampling during her 22nd week of pregnancy. Post-delivery, further SDM sessions were held to discuss adjuvant therapy. Although we recommended the prompt initiation of radiotherapy, the patient chose to postpone it to continue breastfeeding. After she stopped breastfeeding, radiotherapy commenced 6 weeks post-delivery(24 weeks after surgery). After the SDM sessions, the chosen course may not align with optimal health practices. Nevertheless, SDM remains crucial, particularly for pregnancy-related breast cancer, given the limited high- grade evidence for treatment approaches in such cases.