Palatability plays a significant role in treatment compliance, notably in children. Poor compliance increases the risk of therapeutic failure. The European Medicines Agency considers it desirable that the acceptability of oral medicines for pediatric patients is evaluated by target age group based on the Guideline on the pharmaceutical development of medicines for paediatric use. However, the palatability test of the pediatric population is concerned about the lack of versatility, robustness and repeatability. In this study, we evaluated the palatability of sour syrups as a corrigent in children aged 3 to 6 years old. The repeatability and acceptability were tested in 50 children using 6 test drugs (25％ or 50％ simple syrup solutions, dilute hydrochloric acid solution with 25％ or 50％ simple syrup and citric acid solutions with 25％ or 50％ simple syrup solutions). The repeatability was evaluated by the correlation of the palatability score in two tests on different days. The palatability assessment was based on a 5-point scale, according to a method in a previous study by Popper R et al. As a result of the repeatability test, the palatability scores of all 6 syrups revealed a correlation (correlation coefficient (r) > 0.75). In the 4 sour syrups, a greater preference was shown for dilute hydrochloric acid solutions with simple syrups than for the citric acid solution with simple syrups. These results suggest that the syrup containing citric acid might cause avoidance. Sour syrup including citric acid and syrup have the effect of suppressing bitterness, so an acceptability test of the mixture of the drug and sour syrup is required.
We implemented a stepwise antimicrobial stewardship program (ASP). This study evaluated the effect of each intervention and the overall economic impact on carbapenem (CAR) use.Carbapenem days of therapy (CAR-DOT) were calculated to assess the effect of each intervention, and antipseudomonal DOT were calculated to assess changes in use of broad-spectrum antibiotics. We carried out segmented regression analysis of studies with interrupted time series for 3 periods: Phase 1 (infectious disease [ID] consultation service only), Phase 2 (adding monitoring and e-mail feedback), and Phase 3 (adding postprescription review and feedback [PPRF] led by ID specialist doctors and pharmacists). We also estimated cost savings over the study period due to decreased CAR use.The median monthly CAR-DOT, per month per 100 patient-days, during Phase 1, Phase 2, and Phase 3 was 5.46, 3.69, and 2.78, respectively. The CAR-DOT decreased significantly immediately after the start of Phase 2, but a major decrease was not observed during this period. Although the immediate change was not apparent after Phase 3 started, CAR-DOT decreased significantly over this period. Furthermore, the monthly DOT of 3 alternative antipseudomonal agents also decreased significantly over the study period, but the incidence of antimicrobial resistance did not decrease. Cost savings over the study period, due to decreased CAR use, was estimated to be US $150 000.Adding PPRF on the conventional ASP may accelerate antimicrobial stewardship. Our CAR stewardship program has had positive results, and implementation is ongoing.
In order to reduce toxic effects while attaining maximal therapeutic effects, epirubicin 10 mg/day, cyclophosphamide 100 mg/day and prednisolone 10 mg/day were administered through in indwelling catheter inserted into the internal mammary artery and/or subclavian artery for 3-4 weeks, employing the implantable port system for the treatment of unresectable breast cancer and recurrent cancer. Ten out of 11 patients (91%) with unresectable breast cancer showed a response (CR 3, PR 7, NC 1) to this modality of intra-arterial infusion chemotherapy. Seven out of 11 patients (64%) with recurrent cancer of the breast showed a response (CR 1, PR 6, NC 4). Intraarterial infusion chemotherapy for the unresectable advanced breast cancer and recurrent breast cancer proved to be an effective modality of treatment.
Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens have often been selected as antiretroviral therapy (ART) for HIV-1 infection recently, but data for characteristics have been lacking. This study aimed to document the current status of NRTI-sparing regimens in the era of standard 3-drug combination therapies. We cross-sectionally compared characteristics of patients treated with NRTI-sparing regimens (NRTI-sparing group) with dolutegravir plus tenofovir alafenamide fumarate/emtricitabine as a standard ART group in 2018. The NRTI-sparing and the standard ART groups included 61 and 469 patients, respectively. The mean (± standard deviation) age and serum creatinine of the NRTI-sparing group were significantly higher than those of the standard ART group (57.6 ± 12.8 years vs 42.8 ± 10.4 years (p < 0.05) and 2.09 ± 3.10 mg/dL vs. 0.93 ± 0.19 mg/dL (p < 0.05), respectively. The percentage of patients with NRTI-sparing regimens increased with age; with less than 5% in their 50s or younger, 8.4% in their 60s, and 14.1% aged ≥ 70 years. The primary reason for switching to the NRTI-sparing regimen was due to reduced renal function. According to the limited data, viral suppression was achieved at week 48 in all patients in the NRTI-sparing group. No patient had treatment failure nor developed drug resistance. The use of NRTI-sparing regimens increased with age. They were more frequently used in patients aged ≥ 60 years and those with decreased renal function.
Dose adjustment of vancomycin (VCM) is important in improving clinical outcomes and avoiding adverse effects such as nephrotoxicity. Although pharmacist-managed VCM therapy has been reported to optimize treatment, there are no studies focused on pharmacist expertise to date. In this study, we compared the contribution of pharmacists trained for infectious diseases and general pharmacists to dose adjustment of VCM.We retrospectively investigated VCM trough concentration after dose adjustment by both trained (n = 67) and general (without special training for infectious diseases; n = 85) pharmacists. We also compared the incidence of nephrotoxicity during VCM treatment in both groups.The rate of achieving therapeutic VCM trough concentration (10-20 μg/mL) was higher in the trained group than in the control group (80.6 vs. 54.1%, p < 0.001). No significant differences in incidence of nephrotoxicity were observed between the two groups (p = 0.744). Trained pharmacists could contribute more successfully to the achievement of therapeutic VCM concentration ranges without increasing the risk of nephrotoxicity.
Background Olaparib-induced anemia is a frequently occurring complication in patients with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and is associated with a marked deterioration in patients’ health-related quality of life. This study aimed to clarify patient-specific risk factors for severe anemia in patients with advanced ovarian or breast cancer receiving olaparib monotherapy in a real-world setting. Methods This multicenter, retrospective, observational study enrolled consecutively presenting patients with advanced ovarian or breast cancer who received olaparib monotherapy as maintenance or palliative treatment between April 2018 and December 2020 at three participating medical institutions in Japan. The primary endpoint was patient-associated risk factors underlying the onset of grade ≥3 anemia from olaparib treatment initiation to 90 days after treatment. Receiver operating characteristic curves were constructed and univariable and multivariable logistic regression analyses were performed to evaluate the association between patient-associated risk factors and grade ≥3 anemia. Results Of 113 patients evaluated in this study, 32.7% ( n = 37) had grade ≥3 anemia. Multivariable logistic regression analysis revealed that low baseline red blood cell (RBC) count (<3.3 × 10 6 cells/μL), low baseline hematocrit level (<35%), low baseline hemoglobin level (<11.6 g/dL), and breast cancer susceptibility ( BRCA1/2 ) mutation were significantly associated with the onset of grade ≥3 anemia (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 1.28–9.62; P = 0.017, adjusted OR, 3.63; 95% CI, 1.28–11.64; P = 0.021, adjusted OR, 3.89; 95% CI, 1.39–12.21; P = 0.014, and adjusted OR, 4.09; 95% CI, 1.55–11.67; P = 0.006, respectively). Conclusions Our findings suggest that low baseline RBC count, low baseline hematocrit level, and low baseline hemoglobin level might be the patient-associated risk factors for severe anemia induced by olaparib monotherapy. Additionally, BRCA1/2 mutation was suggested to be a patient-related risk factor for anemia regardless of severity. Therefore, applying these patient-associated risk factors would help classify and screen patients at risk of severe anemia.
Paclitaxel (PTX) is a key drug used in the treatment of ovarian cancer. One well-known adverse effect is chemotherapy-induced peripheral neuropathy (CIPN), which can often lead to the discontinuation of chemotherapy or decreased quality of life. There are some pivotal clinical trial data for patients with ovarian cancer, which have shown the incidence of CIPN according to severity but have not shown detailed data. Therefore, we retrospectively investigated the incidence, timing, and severity of CIPN associated with PTX-containing regimens in 142 patients with ovarian cancer. Patients received dose-dense paclitaxel/carboplatin (TC) (n = 93, 65.5％), TC (n = 36, 5.4％), or weekly TC (n = 13, 9.1％). CIPN occurred in 130 patients (91.5％); 67 of 130 patients (51.5％) had CIPN of Grade 2 or higher. The median cumulative dose associated with the onset of CIPN was 320 mg/m2. The median cumulative dose associated with the onset of CIPN was 400 mg/m2 for Grade 1, 320 mg/m2 for Grade 2, and 175 mg/m2 for Grade 3. Patients with CIPN onset at lower doses of PTX developed more severe CIPN (P < 0.05). Further investigation of optimal timing to prevent and therapeutic strategy to treat CIPN is required.
