Acute Kidney Injury in Non-Intensive Care and Intensive Care Patients Treated with Vancomycin and Piperacillin-Tazobactam.

BACKGROUND: We investigated the incidence of acute kidney injury (AKI) and risk factors associated with vancomycin (VAN) and piperacillin-tazobactam (TZP) combination therapy in non-intensive care unit (ICU) and ICU settings. METHODS: In this single-center retrospective cohort study, adults who received VAN for ≥48 h during the period from 1 January 2016 through 31 December 2017 were included. The primary endpoint was incidence of AKI. RESULTS: Data from 593 adults were analyzed. The incidence of AKI was 10.6% overall, 8.0% in the non-TZP group, and 19.8% in the TZP group. In univariate analysis, the odds ratio (OR) for AKI was higher in the TZP group than in the non-TZP group (2.84, 95% CI = 1.64-4.90). In both the non-ICU and ICU settings, the OR for AKI was higher in the TZP group than in the non-TZP group (non-ICU: OR = 3.04, 95% CI = 1.52-6.09; ICU: OR = 2.51, 95% CI = 1.03-6.08). Furthermore, in propensity score analysis, the OR for AKI was higher in the TZP group than in the non-TZP group (OR = 2.81, 95% CI = 1.52-5.17). In both the non-ICU and ICU settings, the OR for AKI was higher in the TZP group than in the non-TZP group (non-ICU: OR = 2.57, 95% CI = 1.17-5.64; ICU: OR = 3.51, 95% CI = 1.05-11.6). CONCLUSIONS: Combined use of TZP in patients receiving VAN increased AKI incidence in non-ICU and ICU settings.

Pharmacokinetic and pharmacodynamic studies of pregabalin suppositories based on pharmacological research.

OBJECTIVES: As commercially available pregabalin preparations are limited to oral administration, it is impossible to use it as an adjuvant analgesic for neuropathic cancer-related pain in terminally ill cancer patients with oral feeding difficulties. The objective of this study was to develop a pregabalin suppository to be available at hospitals. METHODS: Pregabalin suppositories were prepared using bases comprising six different compositions of Witepsol H-15, Witepsol S-55, and Witepsol E-75. The suppository release test and stability test were performed in vitro. The pharmacokinetics and pharmacodynamics of the suppositories were assessed in rats. KEY FINDINGS: In the in vitro releasing test, the pregabalin suppositories with H-15, H-15 : S-55 = 1 : 1, H-15 : S-55 = 2 : 1, H-15 : S-55 = 1 : 2 released approximately 100% of the pregabalin within 180 min. Among these pregabalin suppositories, only the suppository with H-15 : S-55 = 2 : 1 demonstrated an equivalent AUC0-∞ with the oral administration group. Consistent with the results of the pharmacokinetic study, the pregabalin suppository with H-15 : S-55 = 2 : 1 exhibited antinociceptive effects. In addition, the pregabalin suppository with H-15 : S-55 = 2 : 1 was stable for 12 weeks when refrigerated with light shielding. CONCLUSIONS: The pregabalin suppositories prepared in this study may be applicable for pain control for terminally cancer ill patients with oral feeding difficulties.

Pregabalin prescription for terminally ill cancer patients receiving specialist palliative care in an acute hospital.

BACKGROUND: Pregabalin is recommended as an adjuvant analgesic for neuropathic cancer-related pain, and may be taken at all steps of the World Health Organization analgesic ladder. However, unlike opioids, pregabalin treatments are limited to an oral administration route. If patients have oral feeding difficulties, it is not possible to administer any drug as an adjuvant analgesic for neuropathic cancer-related pain. Therefore, the aim of the present study was to clarify the problems of pain control after pregabalin discontinuation in terminally ill cancer patients. METHODS: Our subjects comprised cancer patients who died during their hospital stay and were referred between April 2013 and October 2015 to the palliative care team of the 899-bed Cancer Hospital at the Nippon Medical School Hospital in Japan. The medical records of each patient were retrospectively reviewed, and patient characteristics were recorded. RESULTS: We obtained data on 183 patients during the study period. Thirty-eight (20.8 %) patients were treated with pregabalin. Thirty-three (86.8 %) out of 38 patients were prescribed pregabalin for neuropathic cancer-related pain. The incidence of bony metastases was significantly higher in patients administered pregabalin than in those not taking the drug (non-pregabalin group 32.4 % vs pregabalin group 57.9 %). Pregabalin was ultimately discontinued in all patients, with the main reason being oral feeding difficulties (81.6 %). After the discontinuation of pregabalin, the amount of opioid drugs administered was increased in 56.5 % of patients with oral feeding difficulties. CONCLUSION: Our results demonstrated that the amount of opioid drugs administered was increased in more than 50 % of patients following the discontinuation of pregabalin, and was repeatedly increased for some patients. A new administration route is required for cancer patients unable to take oral medication. TRIAL REGISTRATION: UMIN000022507. May 28, 2016 retrospectively registered.

[Basic Studies on the Stability of Flavored Oral Solutions of Rebamipide].

Stomatitis frequently occurs during chemotherapy and radiotherapy for cancer. Because of its pharmacological properties including anti-inflammatory activity and stimulatory effects on endogenous prostaglandin synthesis, rebamipide has been suggested as a potentially effective treatment against stomatitis. In the present study we tested the stability of oral rebamipide solutions prepared in our hospital pharmacy using sodium alginate as a thickener to increase retention of this agent in the oral cavity, and the addition of different flavoring mixtures intended for use in enteral diets to reduce the bitterness of rebamipide and sodium alginate. Samples of oral rebamipide solution prepared with 13 kinds of flavoring and sodium alginate were evaluated in terms of their appearance, redispersibility, pH, viscosity, and rebamipide content immediately after preparation and 1, 3, 7, and 10 days after storage at room temperature under ambient light or in a cool, dark place. After 10 days of storage, favorable stability was observed in four sample solutions supplemented with green apple, pineapple, yogurt, and tomato flavoring mixtures intended for use in Elental(®) diets. These oral solutions may have potential clinical application.

[A three-week regimen of S-1 monotherapy reduced gastrointestinal toxicity and maintained efficacy in patients with gemcitabine-refractory advanced pancreatic cancer].

S-1 administration for 28 consecutive days followed by 14 days of rest (6-week cycle) is often chosen as second-line chemotherapy for advanced pancreatic cancer (PC), but it causes gastrointestinal toxicity. In comparison, in gastric cancer or head and neck cancer, S-1 administration for 14 consecutive days followed by a 7-day rest period (3-week cycle) reduced gastrointestinal toxicity. This study retrospectively evaluated the efficacy and safety of a 3-week S-1 schedule compared to a 6-week schedule in patients with gemcitabine (GEM)-refractory advanced PC. Fifty-seven patients were treated with the 6- week S-1 schedule and 68 patients were treated with the 3-week S-1 schedule. There were no statistical differences in overall survival (p=0.13) and progression-free survival (p=0.190). With regard to adverse events, the rates of nausea (p<0.01) and vomiting (p=0.04) were lower with the 3-week schedule than with the 6-week schedule. Thus, S-1 therapy with a 3- week schedule as second-line chemotherapy in patients with GEM-refractory advanced PC was associated with reduced gastrointestinal toxicity and similar efficacy, when compared to a 6-week schedule.

[Cost-effectiveness analysis comparing carboplatin and weekly paclitaxel with cisplatin and docetaxel in the treatment of advanced non-small cell lung carcinoma].

Carboplatin plus weekly paclitaxel (CBDCA/wPTX) and cisplatin plus docetaxel (CDDP/DTX) are the standard regimens used in the first-line treatment of advanced non-small cell lung carcinoma (NSCLC), with no significant difference in efficacy between the two. However, because there has been no study of the cost-effectiveness of CBDCA/wPTX versus CDDP/DTX to data, we compared these two regimens in the present study. Expected costs were calculated based on data from patients with Stage III b/IV NSCLC who were treated with either CBDCA/wPTX or CDDP/DTX in the Nippon Medical School Hospital. Efficacy (1-year survival rate) was determined by pooled analysis of studies extracted from the database. The cost-effectiveness ratio was calculated from expected costs and 1-year survival rates for both the CBDCA/wPTX and CDDP/DTX regimens. The expected costs per patient of the CBDCA/wPTX and CDDP/DTX regimens were ¥2, 847, 514 and ¥3, 513, 195, respectively, with 1-year survival rates of 38.6% and 42.5%, respectively. Thus, the cost-effectiveness ratio for the CBDCA/wPTX and CDDP/DTX regimens is ¥6, 750, 863 and ¥8, 329, 054, respectively. These findings clearly suggest that, CBDCA/wPTX is a more cost-effective regimen than CDDP/DTX.

[Development of new mixing method of Busulfex injection for the purpose of improvement of medical safety method: the prefilled syringe method].

Busulfex is a new type of busulfan which can be administered intravenously. Usually it is administered over 2 hours every 6 hours. Its injection should be finished within 8 hours after mixture with a saline, which may bring some troublesome in clinical practice. We, here, introduce the prefilled-syringe method; Busulfex is filled into an injection syringe made of polypropylene beforehand under a sterile condition, and mixed with a saline just before the administration at the bed side. To evaluate the safety of this method we studied the stability of busulfan solution in the syringe physically and chemically. The drug solution was made with the same ingredients as Busulfex, filled into a syringe, and stored at 4 degrees C until use. Then, the transparency of this solution was studied with spectroscopy and the concentration of busulfan was analyzed directly by HPLC. Busulfan solution stored in non-colored injection syringe at 4 degrees C was stable for up to 96 hours both physically and chemically. We concluded that prefilled-syringe method is ease and safe way to administer Busulfex on scheduled time.

[Pharmacoeconomical evaluation of clinical pathway in gastrectomy patients].

The aim of the present study was to ascertain the pharmacoeconomical efficacy of a clinical pathway (CP) employing medication management and instruction tasks (i. e. pharmaceutical care and counseling for inpatients) in gastrectomy patients. Pharmaceutical services of a uniform quality were provided. These included a CP check sheet, medication management, and a history of the drugs chiefly prescribed by pharmacists. As a result, the average number of hospitalized days among the patients who were offered pharmaceutical care compared with those who were not was significantly shortened from 35.4 days to 26.1 days (P<0.001). Moreover, the average cost of medication was also significantly reduced from 270,631 yen to 190,331 yen (P<0.05). These data provide the first evidence that a CP employing medication management and instruction tasks for gastrectomy patients may play a substantial role in saving on medical costs.