We developed a Markov model to evaluate the cost-effectiveness of nivolumab in patients with advanced or recurrent esophageal cancer receiving second-line treatment in Japan. We assessed an incremental cost-effective ratio (ICER) for nivolumab versus docetaxel from the health insurers' perspective. A threshold ICER was set at 7.5 million JPY. The ICER was calculated to be 12.45 million JPY per quality-adjusted life year, which was above the threshold. In a one-way sensitivity analysis, the results were most sensitive to the utility scores for nivolumab. If the cost of nivolumab per 240 mg could be reduced below 282,817 JPY or nivolumab could prolong the overall survival up to 4.1 months, the ICER fell below the threshold. The probabilistic sensitivity analysis revealed a 17.6％ probability that nivolumab was cost-effective as compared to docetaxel. Our study suggests that nivolumab is not cost-effective in patients with advanced or recurrent esophageal cancer receiving second-line treatment as of this moment. Therefore, for future study, it is advisable to review drug prices and select patients who are expected to have high therapeutic effects.
One of the most important operations for pharmacists is drug management. Specifically, pharmacists need to carefully and strictly manage and record narcotic drugs according to the “Narcotics and Psychotropics Control Law”, which places both operational and mental burdens on medical staff. In this study, we verified the practicality of the “Shachihata Authentication Management Program” system, which can identify minute non-uniformity in print, for the management of Fentanyl Injection ampules individually and for visualization of them in hospital. To evaluate accuracy of the system, 300 Fentanyl Injection labels were registered and authenticated. Then to verify traceability, each Fentanyl Injection label was registered when stocking in drug safe for narcotic drugs, then they were authenticated when dispatched to wards and operation rooms, when returned to the pharmacy as non-used, and when disposed as used at the pharmacy. As a result of evaluation of accuracy, all 300 ampules were completely identified individually. The traceability of all 189 ampules, which were stocked in drug safe during the study period, was certified individually in hospital. Additionally, the system could record and output the data in the format of narcotic drug accounts, and revealed a stagnation of ampules in drug safe in the operation room. Furthermore, the time required to register or authenticate per one ampule was about 10 seconds. The results indicate that the system realized the traceability of Fentanyl Injection individually in real-time in hospital, suggesting that the system contributes to appropriate individual management for strictly managed drugs without operational and mental pressure.
Enzalutamide is an orally administered drug that effectively treats castration-resistant prostate cancer. The prescribed dose of enzalutamide in Japan is the same as that in other countries, possibly causing an overdose of enzalutamide and adverse drug reactions (ADRs) in Japanese patients. In the present study, for the pharmacokinetic study to investigate the relationship between the effectiveness/ADRs and the concentrations of enzalutamide, we developed a method to measure plasma concentrations of enzalutamide and its main active metabolite (N-desmethyl enzalutamide) using high performance liquid chromatography (HPLC). The HPLC-UV system used was Shimadzu LC-20Avp equipped with a 5C18 column using 20 mM ammonium acetate (pH 5.0) containing 43％ acetonitrile as the mobile phase. Enzalutamide and N-desmethyl enzalutamide were detected at 237 nm. Plasma samples were deproteinized by adding acetonitrile containing an internal standard substance (IS), nilutamide. After the centrifugation, the supernatant was collected and evaporated to dryness under a stream of nitrogen gas. The residue was reconstituted with the mobile phase and injected into the HPLC system. Peaks of IS, N-desmethyl enzalutamide and enzalutamide were detected at a retention time of 9.5, 12.7 and 16.8 min, respectively. The established method was validated based on FDA guidelines and found to have good linearity (0.25-25 μg/mL), precision and accuracy. We also confirmed that our method was applicable to the measurement of patient plasma. These results suggest that the established method would be suitable to measure enzalutamide and N-desmethyl enzalutamide in plasma for the research to promote the proper use of enzalutamide.
The clinical efficacy of shitei decoction for the treatment of hiccups in patients undergoing cancer chemotherapy was retrospectively investigated. The control group was treated with metoclopramide. The clinical efficacy was assessed based on complete remission (hiccups disappeared within 2 days of administration of shitei decoction or metoclopramide), remission (hiccups disappeared > 3 days after the administration of shitei decoction or metoclopramide), and no effect (hiccups did not disappear after the administration of shitei decoction or metoclopramide and required other drugs to be added to the shitei decoction or metoclopramide). Among the 85 patients treated with shitei decoction, 43 had complete remission, 35 had remission, and 7 had no effect. Conversely, among the 19 patients treated with metoclopramide, 5 had complete remission, 8 had remission, and 6 had no effect. Compared with metoclopramide, shitei decoction was found to be significantly more effective. Thus, these data suggest that shitei decoction is effective for the treatment of hiccups in patients undergoing cancer chemotherapy.
The methods of administering the chemical antibiotic agent TAZ/PIPC were investigated through PK/PD analysis, in order to promote an improved efficacy of the drug. The subjects were patients with suspected bacteremia who received rapid (30 - 60 min, n = 24) and extended (4 hr, n = 33) administrations of TAZ/PIPC. The clinical outcomes in the two groups were analyzed and compared to evaluate the efficacy of the two methods of administration. An analysis of WBC, CRP, and body temperature on the 7 - 9th day of administration revealed no significant difference between the two groups in terms of the decrease in each parameter. However, 67％ of the patients with a SIRS score ≧ 3 in the extended administration (n = 18) group showed improvement in at least two of the three parameters, compared to only 33％ of those in the rapid administration group (n = 12). Thus, there was a marginally higher rate of improvement in the extended administration group (P = 0.073) than in the rapid administration group. Similarly, among the patients with a SIRS score ≥ 3, CRP improved significantly in the extended administration group on the 7 - 9th day of administration (P = 0.0042). These results suggest that extended administration of TAZ/PIPC may improve clinical outcomes more effectively than rapid administration in patients with severe bacteremia.
In this research, we examined the effects of collaborative intervention by pharmacists in hospitals and insurance pharmacies on the quality of life (QOL) and medication adherence of heart failure patients. Heart failure inpatients were assigned to the collaborative intervention group (Group A) and the control group (Group B), with each group containing 35 subjects. Both groups were examined 12 months after they were admitted to hospital, and the conditions at the time of admission were used as the baseline. The primary endpoint was QOL, which was evaluated by the Minnesota Living with Heart Failure (MLHF) scale, and the secondary endpoints were medication adherence and prescription complexity index, which were assessed using the medication regimen complexity index (MRCI) and the Morisky Medication Adherence Scale (MMAS-4), respectively. The number of target patients that could be analyzed was 31 in group A (18 men and 13 women with an average age of 78.1 ± 9.9 years), and 29 in group B (17 men and 12 women with an average age of 79.6 ± 8.1 years). The QOL at the time of admission and discharge from the hospital was significantly improved in group A and B (P < 0.05). MMAS-4 improved significantly in group A (P < 0.05) but did not change significantly in group B. MRCI was significantly increased in group B (P < 0.05). It is suggested that the intervention by pharmacists in hospitals and insurance pharmacy pharmacists for heart failure patients may have an impact on improving the quality of life.