Adjuvant zoledronic acid therapy for postmenopausal women with early breast cancer in China: a cost-effectiveness analysis.

Combination therapy of zoledronic acid (ZOL) plus aromatase inhibitor (AI) was found to reduce bone metastasis risk and improve overall survival for treatment-naïve postmenopausal women (PMW) with hormone receptor-positive (HR+) early breast cancer (EBC), when compared with AI alone. The objective of this study was to evaluate the cost-effectiveness of adding ZOL to AI in treating PMW with HR+ EBC in China. A 5-state Markov model was constructed to evaluate the cost-effectiveness of adding ZOL to AI for PMW-EBC (HR+) over a lifetime horizon from the perspective of Chinese healthcare provider. Data used were obtained from previous reports and public data. The primary outcomes of this study were direct medical cost, life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed to examine the robustness of the presented model. Over a lifetime horizon, adding ZOL to AI was projected to yield a gain of 1.286 LYs and 1.099 QALYs compared with AI monotherapy, which yielded ICER $11 140.75 per QALY with an incremental cost of $12 247.36. The one-way sensitivity analysis indicated that the cost of ZOL was the most influential factor in our study. The probability that adding ZOL to AI was cost-effective at a threshold of $30 425 per QALY in China was 91.1%. ZOL is likely to be cost-effective in reducing bone metastasis risk and improving overall survival for PMW-EBC (HR+) in China.

Population pharmacokinetics of valproic acid in adult Chinese epileptic patients and its application in an individualized dosage regimen.

BACKGROUND: There are several reports describing population pharmacokinetic (PPK) models of valproic acid (VPA). However, little was known in Chinese adult patients with epilepsy. The present study aimed to establish a PPK model for VPA in Chinese adult epileptic patients and to demonstrate its use for dose individualization. METHODS: Data were obtained from a prospective study of 199 adult epileptic patients at 5 hospitals. The trough concentrations at steady state were measured by fluorescence polarization immunoassay. Data were analyzed using the Nonlinear Mixed Effects Model software. The serum trough concentrations at steady state were also measured using samples (n = 20) collected prospectively from a different hospital from those providing the data for deriving the original model. These independent samples served as an evaluation group. RESULTS: The important determinants of apparent VPA clearance were daily dose, body weight, and combination with carbamazepine, phenytoin, or phenobarbital. The final model predicted the individualized doses accurately. A total of 85% of the trough concentrations in the evaluation group were accurately predicted by the final model, whereas the prediction errors of the other patients were all < ± 31%. CONCLUSIONS: A PPK model was developed to estimate the individual clearance for patients taking VPA and could be applied for individualizing doses in the target population.

Evaluation of osimertinib for advanced non-small cell lung cancer with leptomeningeal metastases: a cost-effectiveness and budget impact analysis.

Background Few regimens for non-small cell lung cancer (NSCLC) with leptomeningeal metastases (LM) patients exist up to date, most with low efficacy. A retrospective analysis showed that osimertinib significantly improved the overall survival of LM patients by 11.5 months (17.0 vs. 5.5) as compared to no osimertinib treatment. Until now, no pharmacoeconomic evaluation of osimertinib has been performed to determine its feasibility for widespread use in LM patients. Aim This study analyzed the cost-effectiveness of osimertinib in LM of NSCLC from the perspective of the Chinese health care system. Methods Based on a retrospective analysis from the Samsung Medical Center, a Markov model was constructed to estimate the lifetime benefits and costs for LM patients who were treated with osimertinib. The main outcomes were cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to verify the robustness of model. A budget impact analysis was conducted to estimate the annual incremental cost of osimertinib treatment. Results Compared with patients who were not treated with osimertinib, the survival time of patients treated with osimertinib was higher by 0.69 (1.24 vs. 0.55) QALYs. The incremental cost was $11,877 ($29,232 vs. $17,355) and the ICER was $17,214/QALY, which was below the willingness-to-pay threshold of $30,867/QALY. Osimertinib treatment will increase national cancer spending by $220 million in the first year and increase to $474 million in the fifth year. Conclusions Osimertinib treatment is deemed to be cost-effective for NSCLC with LM patients, however, its use would significantly increase annual cancer spending.

Ratiometric fluorescence assay based on carbon dots and Cu2+-catalyzed oxidation of O-phenylenediamine for the effective detection of deferasirox.

The monitoring of deferasirox (DEF) has important clinical roles in patients who need iron excretion. However, analytical methods with practicability and simplicity are limited. Moreover, ratiometric fluorescence strategies based on Förster resonance energy transfer (FRET) from carbon dots (CDs) as a donor are rarely reported as a drug monitor. In this work, CDs with an appropriate emitting wavelength at 480 nm and excitation around 370 nm were prepared by hydrothermal approach and HCl post-treatment. O-Phenylenediamine (OPD) can be oxidized by Cu2+ to produce yellow fluorescent 2,3-diaminophenazine (oxOPD) in the system of Cu2+ and OPD (Cu-OPD). Correspondingly, a remarkable FRET from CDs to oxOPD in the system of CDs, Cu2+ and OPD (CDs-Cu-OPD) was fabricated with the quenching illustration of CDs, but emitting property of oxOPD. Attributed to the chelation ability of DEF on Cu2+, the inhibitory effects of DEF on the Cu2+-triggered oxidative capability reduced the FRET system by the decreased oxOPD. Thus, the recovered CDs at F 480 and decreased oxOPD at F 560 were found through a ratiometric mode by the addition of DEF in CDs-Cu-OPD for the DEF assay. The FRET behavior of CDs and oxOPD in CDs-Cu-OPD was proved clearly through the calculation of the association constant, binding constant, number of binding sites, and the distance between the donor and acceptor. Furthermore, this ratiometric method exhibited promising analytical performance for DEF with the application in real samples. The implementation of this work expands the application field of CDs and OPD oxidation in drug monitoring, and even other biological analyses through ratiometric strategy.

Predictors of Poor-Grade Aneurysmal Subarachnoid Hemorrhage Caused by Anterior Communicating Artery Aneurysm.

BACKGROUND: Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) are considered to have a poor prognosis. However, the underlying reason for the association between the aneurysmal characteristics and poor-grade aSAH is still unclear. In the present study, we retrospectively evaluated the independent risk factors for patients with anterior communicating artery (ACoA) aneurysms with poor-grade aSAH. METHODS: From January 2009 to January 2016, 477 consecutive patients with ruptured ACoA aneurysms were included in the present study. Poor-grade aSAH was defined as a World Federation of Neurosurgical Society grade of IV or V, and good-grade aSAH was defined as a grade of I-III. Univariate and multivariable regression analyses were used to investigate the differences in aneurysm morphology and clinical characteristics between the 2 groups. RESULTS: On univariate analysis, older patients (P = 0.038), larger aneurysm size (P = 0.013), larger size ratio (P = 0.007), larger aspect ratio (P = 0.009), positive history of stroke (P = 0.001), and posterior projection aneurysms (P = 0.001) were associated with poor-grade aSAH. Multivariate analyses revealed that older patients (odds ratio [OR], 1.654; 95% confidence interval [CI], 1.004-2.728; P = 0.048), larger size ratio (OR, 1.280; 95% CI, 1.111-1.475; P = 0.001), positive history of stroke (OR, 6.051; 95% CI, 1.712-21.381; P = 0.005), and posterior projection aneurysms (OR, 2.718; 95% CI, 1.607-4.598; P < 0.001) were independently associated with poor-grade aSAH. CONCLUSIONS: Poor-grade aSAH was independently associated with older patients, a larger size ratio, a positive history of stroke, and posterior projection aneurysms in patients with a ruptured ACoA aneurysm. These parameters could contribute to screening for patients with the potential for poor-grade aSAH.

A signal-off fluorescent strategy for deferasirox effective detection using carbon dots as probe and Cu2+ as medium.

The content of deferasirox (DEF) in plasma is significant in ß-thalassemia patient that needs long-term transfusion therapy, while the effective and simple strategy for DEF monitoring is still limited. The carbon dots (CDs) prepared from citric acid monohydrate and glutathione exhibit weakly modulated fluorescence intensity to several common metal ions containing Cu2+. Interestingly, the process of interaction of Cu2+ and DEF forms the chelation of Cu2+ and DEF (Cu-DEF) with the absorbance wavelength of DEF at 320 nm shifting to 332 nm for Cu-DEF. And the obtained Cu-DEF will effectively quench CDs through inner filter effect (IFE). Accordingly, a facile signal-off fluorescent method based on CDs as probe is developed for DEF detection using Cu2+ as medium. And the proposed method exhibits linear range of 0.5-20 µg/mL with the detection limit of 0.33 µg/mL for DEF under the optimized conditions. Moreover, the developed assay is further expanded to test the content of DEF in dispersible tablet and plasma with accuracy and reproducibility. Such cost-effective and sensitive fluorescent assay just through simple mixing operation present a valuable strategy for drug monitoring.

Predicting Long-Term Outcomes After Poor-Grade Aneurysmal Subarachnoid Hemorrhage Using Decision Tree Modeling.

BACKGROUND: Despite advances in the treatment of poor-grade aneurysmal subarachnoid hemorrhage (aSAH), predicting the long-term outcome of aSAH remains challenging, although essential. OBJECTIVE: To predict long-term outcomes after poor-grade aSAH using decision tree modeling. METHODS: This was a retrospective analysis of a prospective multicenter observational registry of patients with poor-grade aSAH with a World Federation of Neurosurgical Societies (WFNS) grade IV or V. Outcome was assessed by the modified Rankin Scale (mRS) at 12 mo, and an unfavorable outcome was defined as an mRS of 4 or 5 or death. Long-term prognostic models were developed using multivariate logistic regression and decision tree algorithms. An additional independent testing dataset was collected for external validation. Overall accuracy, sensitivity, specificity, and area under receiver operating characteristic curves (AUC) were used to assess model performance. RESULTS: Of the 266 patients, 139 (52.3%) had an unfavorable outcome. Older age, absence of pupillary reactivity, lower Glasgow coma score (GCS), and higher modified Fisher grade were independent predictors of unfavorable outcome. Modified Fisher grade, pupillary reactivity, GCS, and age were used in the decision tree model, which achieved an overall accuracy of 0.833, sensitivity of 0.821, specificity of 0.846, and AUC of 0.88 in the internal test. There was similar predictive performance between the logistic regression and decision tree models. Both models achieved a high overall accuracy of 0.895 in the external test. CONCLUSION: Decision tree model is a simple tool for predicting long-term outcomes after poor-grade aSAH and may be considered for treatment decision-making.

First-Line Treatment With Atezolizumab Plus Nab-Paclitaxel for Advanced Triple-Negative Breast Cancer: A Cost-Effectiveness Analysis.

OBJECTIVE: The authors conducted a cost-effectiveness analysis incorporating recent phase III clinical trial (IMpassion130) data to evaluate the cost-effectiveness of atezolizumab in combination with nab-paclitaxel (AnP) against nab-paclitaxel alone as the first-line treatment for advanced triple-negative breast cancer in developed and developing countries. MATERIALS AND METHODS: A decision-analytic Markov model was developed using IMpassion130 data to evaluate the cost-effectiveness of AnP over a lifetime from the US health care payer and Chinese health care system perspective. Model inputs were derived from IMpassion130 and published literature. The primary outcomes of the model were quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed using univariate and probabilistic sensitivity analyses. RESULTS: For the intention-to-treat (ITT) population, the projected mean outcome was better with AnP (1.41 QALYs) than with nab-paclitaxel alone (0.99 QALYs). Similar results were obtained for the programmed death ligand 1 (PD-L1)-positive population, with the obtained mean outcomes of 1.66 and 0.88 QALYs, respectively. For the Unites States, the ICER values comparing AnP with nab-paclitaxel were US$331,996.89 and US$229,359.88 per QALY gained for the ITT and PD-L1-positive populations, respectively. For China, the ICER values were US$106,339.26 and US$72,971.88 per QALY gained for the ITT and PD-L1-positive populations, respectively. The univariate sensitivity analysis indicated that the price of atezolizumab was the most influential factor in our study. AnP had 0% cost-effectiveness at the willingness-to-pay thresholds of US$150,000/QALY in the United States and US$29,383/QALY in China. CONCLUSION: AnP is not a cost-effective choice as the first-line treatment for advanced triple-negative breast cancer in the United States and China.

Whole-brain CT perfusion imaging using increased sampling intervals: A pilot study.

The aim of the present study was to investigate the feasibility of whole-brain perfusion imaging using the increased sampling interval protocol for 320-detector row dynamic-volume computed tomography (CT). A total of 12 volunteers were recruited. The novel protocols with 11 volumes (defined as protocol P11) and 15 volumes (defined as protocol P15) were performed on the volunteers to evaluate whether P11 and P15 are able to acquire comparable results to the standard protocol with 19 volumes (defined as protocol P19) according to the as-low-as-reasonably-achievable principle. All data were acquired using a dynamic-volume CT scanner with a 16 cm-wide detector with 320 rows. The scanned transverse images from volunteers were analyzed using the Volume-Engineered System workstation. The MedCalc software package was used for Bland-Altman analysis of all variables. The data inconsistency of mean transit time (MTT), cerebral blood volume (CBV), cerebral blood flow (CBF), and time to peak (TTP) between P11/P15 and P19 were all <5%, and the data were trustworthy. The mean differences of MTT, CBV, CBF and TTP between P15 and P19 were less than those between P11 and P19. The consistencies of perfusion parameters acquired with protocols P15 and P19 were higher compared with those acquired with P11. In whole-brain perfusion, the new protocol P15 has higher consistency with P19 than P11, and the radiation dose may be reduced by ~16% without degradation of perfusion parameters. Therefore, P15 should be recommended as a routine procedure in whole-brain perfusion imaging.