AbstractCentral venous catheter (CVC) dysfunction is often associated with thrombosis, which in turn has been linked with poorer survival outcomes in cancer patients. Our objective was to examine the association of tissue plasminogen activator (tPA) administration as a surrogate measure of CVC dysfunction with survival in pediatric cancer patients. The present study uses data from a population-based retrospective cohort of pediatric oncology patients from the Canadian Maritime provinces treated between 2000 and 2017 at the IWK Health Centre, Halifax, NS. Demographics, diagnosis, date of death or date of last visit, and tPA use for CVC dysfunction were obtained from clinical databases and the provincial Cancer in Young People in Canada registry. The association between tPA administration and survival was examined using a Cox regression model adjusted for sex, age at diagnosis, cancer type, thrombosis, CVC duration, diagnosis era, and treatment modalities. Out of 821 patients, 206 received one or more doses of tPA during upfront therapy. The death rate was 21% and 15% respectively in patients who did and did not receive tPA. In the adjusted regression model, after receiving one or more doses of tPA, children had significantly poorer survival as compared to those that did not receive tPA (HR: 1.496, 95% CI: 1.019, 2.197). CVC dysfunction may be associated with a poorer prognosis in pediatric cancer patients. Future studies should corroborate these findings in other populations, examine the influence of other potential confounders, and determine the role of CVC dysfunction in prognostic models of cancer survival. 相似文献
Objectives: To establish the first plasma and cerebrospinal fluid (CSF) oxycodone population pharmacokinetic (PopPK) model after epidural (EPI) and intravenous (IV) oxycodone administration.
Methods: The study was conducted with 30 female subjects undergoing elective gynecological surgery with epidural analgesia. A parallel single dose of EPI oxycodone with IV placebo (EPI group; n = 18) or IV oxycodone with EPI placebo (IV group; n = 12) was administered. An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for CSF sampling at L3/4. Plasma and CSF for oxycodone analysis were frequently collected. A PopPK model was built using the NONMEM software package.
Results: Plasma and CSF oxycodone concentrations were evaluated using separate central plasma and CSF compartments and separate peripheral plasma and CSF compartments. Epidural space served as a depot compartment with transfer to both the plasma and CSF central compartments. The population parameters for plasma clearance and apparent distribution volumes for central and peripheral compartments for plasma and CSF were 37.4 L/h, 90.2 L, 68.9 L, 0.035 L (fixed based on literature), and 0.039 L, respectively.
Conclusion: A PopPK model was developed and found to precisely and accurately describe oxycodone time-concentration data in plasma and CSF. 相似文献