Development of a model to predict vancomycin serum concentration during continuous infusion of vancomycin in critically ill pediatric patients.

Vancomycin is a frequently used antibiotic in intensive care units, and the patient's renal clearance affects the pharmacokinetic characteristics of vancomycin. Several advantages have been reported for vancomycin continuous intravenous infusion, but studies on continuous dosing regimens based on patients' renal clearance are insufficient. The aim of this study was to develop a vancomycin serum concentration prediction model by factoring in a patient's renal clearance. Children admitted to our institution between July 1, 2021, and July 31, 2022 with records of continuous infusion of vancomycin were included in the study. Sex, age, height, weight, vancomycin dose by weight, interval from the start of vancomycin administration to the time of therapeutic drug monitoring sampling, and vancomycin serum concentrations were analyzed with the linear regression analysis of the mixed effect model. Univariable regression analysis was performed using the vancomycin serum concentration as a dependent variable. It showed that vancomycin dose (p < 0.001) and serum creatinine (p = 0.007) were factors that had the most impact on vancomycin serum concentration. Vancomycin serum concentration was affected by vancomycin dose (p < 0.001) and serum creatinine (p = 0.001) with statistical significance, and a multivariable regression model was obtained as follows: Vancomycin serum concentration (mg/l) = -1.296 + 0.281 × vancomycin dose (mg/kg) + 20.458 × serum creatinine (mg/dl) (adjusted coefficient of determination, R2 = 0.66). This prediction model is expected to contribute to establishing an optimal continuous infusion regimen for vancomycin.

Evaluation of Low-Molecular-Weight Heparin for Treatment of Portal Vein Thrombosis in Liver Cirrhosis Patients.

Background and Objectives: Even though low-molecular-weight heparin (LMWH), including dalteparin, has a critical role in portal vein thrombosis (PVT) treatment in liver cirrhosis (LC) patients, the predictive factors and the proper dose of dalteparin for PVT treatment and relapse have not yet been investigated. Materials and Methods: This retrospective study evaluated the records of LC patients receiving dalteparin from July 2013 to June 2019. The odds ratio (OR) and adjusted OR were calculated from univariate and multivariable analyses, respectively. Results: Among data from 121 patients, the overall recanalization rate of all patients was 66.1% (80 patients). No history of variceal bleeding (OR 4.6, 95% CI: 1.88-11.43) and the case of newly developed thrombus before dalteparin treatment (OR 3.2, 95% CI: 1.24-8.08) were predictive factors associated with increased treatment response. Relapse of PVT occurred in 32 out of 80 patients (40%) who showed a recanalization. The risk of relapse was 3.1-3.9 times higher in those who took more than three months or more than six months from the diagnosis of PVT to dalteparin treatment compared to those who took less than these durations, respectively. In the dosing regimen, patients with the kg-based dosing regimen showed 2.6 times better response than those with the fixed dosing regimen. However, no difference in bleeding complications was observed. Conclusion: In the dosing regimen, the kg-based regimen that was the same as the venous thromboembolism regimen was a better option for the efficacy and safety of dalteparin therapy. Additionally, when treating PVT in LC patients, careful monitoring is recommended for patients with predictive factors for treatment response and relapse of PVT.

Incidence of taxane-induced peripheral neuropathy receiving treatment and prescription patterns in patients with breast cancer.

PURPOSE: Taxane-induced peripheral neuropathy (TIPN) can affect quality of life and treatment outcomes in breast cancer patients. Despite the high incidence, treatment of PN has not been established. This study aimed to evaluate the incidence, risk factors, and prescribing pattern of TIPN receiving pharmacologic treatment in real-world practice. METHODS: We conducted a retrospective chart review of 1629 breast cancer patients who received taxanes at the Seoul National University Hospital from July 2012 to June 2014. We determined the incidence and predictors for TIPN treated with anti-neuropathic pain medications during taxane treatment and the 1-year follow-up period after discontinuation of taxanes. The prescribing pattern of anti-neuropathic drugs was also analyzed. RESULTS: A total of 1516 patients with breast cancer were included, and the incidence of TIPN receiving treatment was 21.9% overall, with 42.2% of patients using paclitaxel and 15.8% using docetaxel. The median time to the first anti-neuropathic pain medication prescribed from the start of taxane treatment was 64 days and was significantly earlier in the paclitaxel group. In 21% of patients, TIPN treatment was started after the end of taxane treatment. Identified risk factors for TIPN were paclitaxel use (vs. docetaxel), old age, overweight, metastatic (vs. non-metastatic) breast cancer, and possibly a 3-weekly taxane schedule (vs. weekly). Gabapentin and pregabalin accounted for 71.7 and 24.3% of total use of anti-neuropathic agents, respectively. CONCLUSIONS: One-fifth of breast cancer patients who were treated with taxane-based chemotherapy experienced TIPN receiving treatment, and its risk factors were paclitaxel use, old age, overweight, and metastatic cancer.

Awareness of the adverse effects associated with prophylactic corticosteroid use during docetaxel therapy.

PURPOSE: Weekly or tri-weekly docetaxel treatment mandates the use of dexamethasone to prevent toxicity. However, the adverse effects of prophylactic steroid use are often overlooked. We investigated the incidence of corticosteroid-associated adverse effects during docetaxel therapy, focusing on hyperglycemia and infection as well as the identification of possible risk factors. METHODS: This study was conducted through retrospective chart review of 632 patients who started docetaxel-based chemotherapy between July 2011 and June 2012 at Seoul National University Hospital. Hyperglycemia was defined as more than two random glucose levels >200 mg/dL. All documented episodes of infection that required treatment with antibiotics were regarded as infectious episodes. RESULTS: The incidences of hyperglycemia in overall patients and in patients without previous diabetes mellitus were 13.7 and 10.9%, respectively. Infectious episodes greater than grade 2 and grade 3 developed in 29.6 and 19.9% of patients, respectively. Multivariable logistic regression analysis showed that body mass index and previous diabetes mellitus were independent risk factors for hyperglycemia, whereas corticosteroid dose was not. Treatment duration and frequency of high blood glucose levels over 200 mg/dL were independent risk factors for infection. CONCLUSIONS: Due to the significant difference in patient and treatment characteristics, we could not obtain meaningful comparisons between weekly and tri-weekly docetaxel administration regimens. This study suggests that adverse effects associated with prophylactic steroid use need to be recognized and optimally managed during docetaxel therapy.

Prognostic Significance of the Severity of Immune-Related Adverse Events in Advanced Cancer Patients Treated with PD-1/PD-L1 Inhibitors: A Real-World Data Analysis.

BACKGROUND: There is limited evidence regarding immune-related adverse events (irAEs) in Asian cancer patients treated with antibodies directed against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1). OBJECTIVE: This study aimed to investigate the clinical patterns and prognostic significance of grade 1-2 and grade ≥ 3 irAEs by PD-1/PD-L1 inhibitors in cancer patients using real-world clinical data. PATIENTS AND METHODS: We conducted a retrospective study of cancer patients who received pembrolizumab, nivolumab, or atezolizumab at a tertiary hospital in South Korea. Incidence, time to onset, and grade 1-2 and grade ≥ 3 irAE risk factors were analyzed from medical records. The association of irAE severity with progression-free survival (PFS) and prognostic factors for PFS were evaluated. RESULTS: Among a total of 431 patients, irAEs occurred in 45.2%, and 9.5% were grade ≥ 3 irAEs. There were no significant differences in the median time to onset based on severity. Risk factors for the development of grade ≥ 3 irAEs were the presence of autoimmune disorders or diabetes mellitus. The median PFS was significantly different at 13.20, 9.00 and 4.17 months for the grade 1-2, grade ≥ 3, and no irAE groups, respectively. An increase in administration cycles was associated with a reduced risk of progression in patients with grade 1-2 and grade ≥ 3 irAEs. CONCLUSIONS: The development of grade ≥ 3 irAEs was affected by comorbidities and associated with improved PFS compared with those without irAEs. Our findings identified the real-world epidemiology, risk factors, and prognostic significance of irAEs, which may guide treatment decisions of PD-1/PD-L1 inhibitors.

Clinical impacts of the concomitant use of L-asparaginase and total parenteral nutrition containing L-aspartic acid in patients with acute lymphoblastic leukemia.

Introduction: L-asparaginase (ASNase) depletes L-asparagine and causes the death of leukemic cells, making it a mainstay for the treatment of acute lymphoblastic leukemia (ALL). However, ASNase's activity can be inhibited by L-aspartic acid (Asp), which competes for the same substrate and reduces the drug's efficacy. While many commercially used total parenteral nutrition (TPN) products contain Asp, it is unclear how the concomitant use of TPNs containing Asp (Asp-TPN) affects ALL patients treated with ASNase. This propensity-matched retrospective cohort study evaluated the clinical effects of the interaction between ASNase and Asp-TPN. Methods: The study population included newly diagnosed adult Korean ALL patients who received VPDL induction therapy consisting of vincristine, prednisolone, daunorubicin, and Escherichia coli L-asparaginase between 2004 and 2021. Patients were divided into two groups based on their exposure to Asp-TPN: (1) Asp-TPN group and (2) control group. Data, including baseline characteristics, disease information, medication information, and laboratory data, were collected retrospectively. The primary outcomes for the effectiveness were overall and complete response rates. Relapse-free survival at six months and one year of treatment were also evaluated. The safety of both TPN and ASNase was evaluated by comparing liver function test levels between groups. A 1:1 propensity score matching analysis was conducted to minimize potential selection bias. Results: The analysis included a total of 112 ALL patients, and 34 of whom received Asp-TPN and ASNase concomitantly. After propensity score matching, 30 patients remained in each group. The concomitant use of Asp-TPN and ASNase did not affect the overall response rate (odds ratio [OR] 0.53; 95% confidence interval [CI] = 0.17-1.62) or the complete response rate (OR 0.86; 95% CI = 0.29-2.59) of the ASNase-including induction therapy. The concomitant use of Asp-TPN and ASNase also did not impact relapse-free survival (RFS) at six months and one year of treatment (OR 1.00; 95% CI = 0.36-2.78 and OR 1.24; 95% CI, 0.50-3.12, respectively). The peak levels of each liver function test (LFT) and the frequency of LFT elevations were evaluated during induction therapy and showed no difference between the two groups. Conclusion: There is no clear rationale for avoiding Asp-TPN in ASNase-treated patients.

Consultation-Based Deprescribing Service to Optimize Palliative Care for Terminal Cancer Patients.

(1) Background: A pharmacist-led deprescribing service previously developed within the Consultation-Based Palliative Care Team (CB-PCT) was implemented for terminal cancer patients. (2) Objective: To evaluate the clinical outcomes of the developed deprescribing service for terminal cancer patients in CB-PCT. (3) Methods: A retrospective analysis compared the active care (AC) group to the historical usual care (UC) group. The clinical outcomes included the deprescribing rate of preventive medications, the proportion of patients with one or more medication-related problems (MRPs) resolved upon discharge, and the clinical significance. The implementability of the service was also gauged by the acceptance rates of pharmacists' interventions. (4) Results: Preventive medications included lipid-lowering agents, gastroprotective agents, vitamins, antihypertensives, and antidiabetic agents. The AC group revealed a higher deprescribing rate (10.4% in the UC group vs. 29.6% in the AC group, p < 0.001). At discharge, more AC patients had one or more MRPs deprescribed (39.7% vs. 2.97% in UC, p < 0.001). The clinical significance consistently had a very significant rating (mean score of 2.96 out of 4). Acceptance rates were notably higher in the AC group (30.0% vs. 78.0%. p = 0.003). (5) Conclusions: The collaborative deprescribing service in CB-PCT effectively identified and deprescribed MRPs that are clinically significant and implementable in practice.

Long-Term Survival and Kidney Function in Pediatric Patients Following Liver Transplantation: A 15-Year Retrospective Cohort Study.

Long-term preservation of kidney function after liver transplantation (LT) has not been well studied. We thus evaluated the rates of kidney function preservation and long-term survival after pediatric LT. We also investigated the risk factors associated with the progression of chronic kidney disease (CKD). We conducted a retrospective study of 184 pediatric patients who had undergone LT from 2003 to 2018 at a university hospital. We collected demographics, primary indications for LT, liver disease scores, renal function test results, immunosuppressive drug prescriptions, and diagnosis of post-LT complications. The 15-year survival rate was 90.8%. Furthermore, the rate of kidney function preservation at 14 years post-LT in patients at high risk of renal disease was 79.3%, and that in those with less risk of kidney diseases was 96.0%. Arterial hypertension was an independent risk factor associated with CKD progression. However, when arterial hypertension was excluded, the use of cyclosporine and liver disease with renal involvement were risk factors for CKD progression. We found that kidney function after pediatric LT was well preserved. We encourage the early detection of underlying kidney involvement, routine monitoring of renal function for high-risk patients, active control of hypertension, and appropriate immunosuppressive regimens for pediatric patients with LT.

Clinical and economic impact of pharmacists' intervention in a large volume chemotherapy preparation unit.

Background Even though pharmacists have devoted considerable time to ensuring patient safety during the process of preparing and dispensing chemotherapy, only a few studies have evaluated their efforts. Objective To evaluate the clinical and economic impact of pharmacists' interventions in a large volume chemotherapy preparation unit. Setting A 1600-bed tertiary hospital in Seoul, Korea. Method Pharmacist intervention records from May 2012 to April 2013 were retrospectively reviewed. The clinical significance of interventions was rated by one physician and one pharmacist. A cost-benefit analysis was conducted. The benefit from interventions was estimated through both cost avoidance based on the potential to avoid an adverse drug event (ADE) and cost savings related to reducing discarded products. Cost was estimated from the pharmacists' salary corresponding to the time spent in reviewing chemotherapy prescriptions. Main outcome measure Acceptance rate, clinical significance, net cost-benefit, and cost-benefit ratio of pharmacist interventions. Results Among 39,649 cancer chemotherapy prescriptions in 6364 patients, 631 interventions were performed for 435 patients. The acceptance rate was 72.1 %. Most cases of declined interventions were related to dosage adjustment within the range of <10 % of the prescribed dosage. More than half of the interventions were considered as clinically more than "significant" (50.4 %). The cost-benefit analysis showed a clear cost benefit with a net cost-benefit of $116,493 and a cost-benefit ratio of 3.64:1. Conclusion Pharmacists' interventions in a large volume ambulatory-based chemotherapy preparation unit provided a positive economic impact on health care budget and were effective in preventing clinically significant ADEs.

Bortezomib-associated peripheral neuropathy requiring medical treatment is decreased by administering the medication by subcutaneous injection in Korean multiple myeloma patients.

PURPOSE: Bortezomib-induced peripheral neuropathy (BIPN) is a significant neurotoxicity, requiring dose reduction or the delay of treatment. In a multicentre trial including 97 % Caucasians and 3 % Asians, BIPN was shown to occur less frequently in cases in which bortezomib was administered subcutaneously. Considering the different pharmacokinetics between Caucasians and Asians, we analysed BIPN according to the administration route, specifically in Korean myeloma patients. METHODS: We surveyed the prescribed anticonvulsants for the treatment of BIPN and analysed the data after stratifying the results by the cumulative dose of bortezomib. Exclusion criteria were as follows: treated with <2 doses of bortezomib, change in the administration route during the treatment, or receiving anticonvulsants for other reasons prior to bortezomib administration. RESULTS: A total of 101 patients were enrolled; 60 were treated with bortezomib and dexamethasone, and 37 were treated with bortezomib, melphalan, and prednisolone. The median number of treatment courses was four for each regimens. The median exposure to bortezomib for all patients was 19 mg/m(2). Progression-free survival (PFS) and overall survival rates were not statistically different between the groups. There was no difference in the proportion of patients requiring medical treatment (p = 0.388). After stratifying the results, BIPN developed less frequently when bortezomib was administered subcutaneously rather than intravenously in patients receiving more than 23.4 mg/m(2) of bortezomib (p < 0.05). CONCLUSION: Since the responses were potent regardless of administration route, the subcutaneous injection of bortezomib should be considered in Asian myeloma patients who are expected to achieve a longer PFS with bortezomib.