Search

Background: Posaconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of posaconazole TDM and the target of posaconazole plasma concentration for clinical successful prophylaxis remain uncertain and controversial. The aim of this study was to evaluate posaconazole exposure-response relationship and determine an optimum posaconazole concentration for prophylaxis against invasive fungal infections (IFIs).Methods: Bibliographic databases were searched (from inception to September 2017) to select studies including the clinical outcomes below and above concentration cut-off value of 0.5 mg/L and 0.7 mg/L. The reliability of the results were evaluated with trial sequential analysis (TSA).Results: Twenty-eight studies with 1930 patients included were analyzed. The results of our pooled analysis demonstrated that patients with posaconazole plasma concentrations over 0.5 mg/L were twice more likely to achieve successful responses compared with those with lower concentrations (odds ratio, OR = 1.98, 95% confidence interval, CI 1.09-3.58, P = 0.02) while the threshold, 0.7 mg/L showed no significant difference (OR = 1.84, 95% CI 0.94-3.63, P = 0.08). The TSA results showed that there was sufficient information to support these findings.Conclusions: An optimal posaconazole concentration target of 0.5 mg/L is suggested to ensure the clinical prophylactic efficacy and may help reduce the dosage and dose-dependent toxicity comparing with the target of 0.7 mg/L. [ABSTRACT FROM AUTHOR]

Background: As a novel biomarker of inflammation, procalcitonin (PCT) has proven useful to guide antibiotic therapy in intensive care unit (ICU). However, there are controversial on mortality. The aim of this study was to evaluate the utility of PCT-guided antibiotic therapy in critically ill adults and determine whether studies are sufficient.Methods: A systematic search in PubMed, Embase and Cochrane was performed. We included only randomized controlled trials which compared the safety and efficacy between PCT-guided or standard antibiotic therapy groups in ICU adults. Trial sequential analysis and GARDE approach were performed.Results: Fifteen studies met our criteria for inclusion finally, with a cumulative number of 5486 ICU patients. There was no difference in 28-day mortality between two compared groups (P = 0.626), but significant decreases were observed in the duration of antibiotic therapy for the first episode of infection (P < 0.001) and length of hospitalization (P = 0.049). No significant deference was found in secondary endpoints except total duration of antibiotic therapy (P < 0.001). TSA revealed that the pooled sample sizes of 28-day mortality and the duration of antibiotic therapy for the first episode of infection exceeded the estimated required information size, but not the length of hospitalization.Conclusions: PCT-guided therapy is a better and safer algorithm to be applied into ICU patients, which appears no effect on 28-day mortality while performing preferable utility in reducing the duration of antibiotic therapy for the first episode of infection. More studies on these endpoints were not recommended. [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma (SCC) is a main pathological type of non-small cell lung cancer. It is common among elderly patients with poor prognosis. We aimed to establish an accurate nomogram to predict survival for elderly patients (≥ 60 years old) with SCC based on the Surveillance, Epidemiology, and End Results (SEER) database.Methods: The gerontal patients diagnosed with SCC from 2010 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The independent prognostic factors were identified using multivariate Cox proportional hazards regression analysis, which were utilized to conduct a nomogram for predicting survival. The novel nomogram was evaluated by Concordance index (C-index), calibration curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA).Results: 32,474 elderly SCC patients were included in the analysis, who were randomly assigned to training cohort (n = 22,732) and validation cohort (n = 9742). The following factors were contained in the final prognostic model: age, sex, race, marital status, tumor site, AJCC stage, surgery, radiation and chemotherapy. Compared to AJCC stage, the novel nomogram exhibited better performance: C-index (training group: 0.789 vs. 0.730, validation group: 0.791 vs. 0.733), the areas under the receiver operating characteristic curve of the training set (1-year AUC: 0.846 vs. 0.791, 3-year AUC: 0.860 vs. 0.801, 5-year AUC: 0.859 vs. 0.794) and the validation set (1-year AUC: 0.846 vs. 0.793, 3-year AUC: 0.863 vs. 0.806, 5-year AUC: 0.866 vs. 0.801), and the 1-, 3- and 5-year calibration plots. Additionally, the NRI and IDI and 1-, 3- and 5-year DCA curves all confirmed that the nomogram was a great prognosis tool.Conclusions: We constructed a novel nomogram that could be practical and helpful for precise evaluation of elderly SCC patient prognosis, thus helping clinicians in determining the appropriate therapy strategies for individual SCC patients. [ABSTRACT FROM AUTHOR]