Implementation of pharmacists' monitoring for intravenous drug compatibility.

BACKGROUND: Injectable medication errors primarily occur during preparation and administration. Currently, South Korea is experiencing chronic pharmacist shortages. Moreover, pharmacists have not routinely conducted prescription monitoring for intravenous compatibility. In the present study, we analysed the implementation of a pre-issue monitoring program using recently released cloud-based software to provide information on intravenous compatibility in the pharmacy at a general hospital in South Korea. OBJECTIVES: The aims of this study were to determine whether adding an intravenous drug prescription review to pharmacists' actual work scope could promote patient safety, and to assess the impact of this new task on pharmacists' workload. METHODS: Data on intravenous drugs prescribed in the intensive care unit and haematology-oncology ward were prospectively collected during January 2020. Four quantitative items were evaluated: the run-time, intervention ratio, acceptance ratio, and the information completeness ratio with regard to the compatibility of intravenous drugs. RESULTS: The mean run-time of two pharmacists was 18.1 min in the intensive care unit and 8.7 min in the haematology-oncology ward (p<0.001). Significant differences were also found between the intensive care unit and the haematology-oncology wards in terms of the mean intervention ratio (25.3% vs 5.3%, respectively; p<0.001) and the information completeness ratio (38.3% vs 34.0%, respectively; p=0.007). However, the mean acceptance ratio was comparable (90.4% in the intensive care unit and 100% in the haematology-oncology ward; p=0.239). The intravenous pairs that most frequently triggered interventions were tazobactam/piperacillin and famotidine in the intensive care unit, and vincristine and sodium bicarbonate in the haematology-oncology ward. CONCLUSION: This study suggests that despite a shortage of pharmacists, intravenous compatibility can be monitored before issuing injectable products in all wards. Because the prescribing pattern of injections varies across wards, pharmacists' tasks should be established accordingly. To improve the completeness of information, efforts to generate more evidence should continue.

Impact of pharmacist intervention in antibiotic stewardship programmes for critically ill neonates: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Antibiotic stewardship programmes (ASPs) are introduced to ensure effective antibiotic use. Pharmacists can be involved in ASPs to facilitate the appropriate antibiotic use. Prolonged use of antibiotics causes adverse events in critically ill neonates. Hence, this systematic review and meta-analysis was aimed at investigating pharmacists' functions in ASPs in critically ill neonates and the effect of ASP implementation on antibiotic use. METHODS: A comprehensive search of PubMed/Medline, Embase, and Cochrane Library databases until January 2021 was conducted and studies that reported the functions of pharmacists in ASPs for critically ill neonates and the results of ASP implementation were included in this review. All processes were performed by two reviewers independently, and any discordance between the two was resolved by discussion. RESULTS AND DISCUSSION: In all, 19 studies were included in this review. Pharmacists were found to have various functions in ASPs, such as participating in the development of antibiotic use guidelines, auditing antibiotic prescriptions, participating in multidisciplinary ward rounds, educating other ASP team members, checking blood culture or laboratory data, and monitoring antibiotic use. A meta-analysis revealed that ASP implementation in critically ill neonates was significantly associated with a 23% reduction in the overall antibiotic use rate (ratio of means: 0.77, 95% confidence interval: 0.69-0.87, p < 0.001). Moreover, the overall duration of antibiotic therapy significantly reduced by 15% with ASP implementation (ratio of means: 0.85, 95% confidence interval: 0.78-0.91, p < 0.001). WHAT IS NEW AND CONCLUSION: The implementation of ASPs involving pharmacists, especially in critically ill neonates, was associated with the reduced use and duration of antibiotic treatment. Thus, pharmacists played a key role in ASPs in critically ill neonates.

Vancomycin pharmacokinetics in critically ill neonates receiving extracorporeal membrane oxygenation.

Objective: This study aimed to characterise vancomycin pharmacokinetics in critically ill neonates undergoing extracorporeal membrane oxygenation. Methods: In a retrospective analysis, the pharmacokinetics of vancomycin were determined in 25 full-term neonates receiving extracorporeal membrane oxygenation and compared with those of matched controls (n = 25) not receiving extracorporeal membrane oxygenation. Results: The half-life of vancomycin in the neonates undergoing extracorporeal membrane oxygenation was significantly prolonged compared with that in the controls (17.45 ± 11.01 hour vs 5.92 ± 2.70 hour, P<0.001). Clearance decreased significantly in the extracorporeal membrane oxygenation group relative to the control group (0.03 ± 0.02 L/kg/hr vs 0.08 ± 0.05 L/kg/hr, P<0.001). No significant difference was found in the volume of distribution between the two groups (0.63 ± 0.30 L/kg in the extracorporeal membrane oxygenation group vs 0.57 ± 0.14 L/kg/hr in control, P=0.596). Clearance values were significantly correlated with serum creatinine (r = - 0.528, P<0.001). In the subgroup analysis using patients with serum creatinine < 0.5 mg/dL, similar results were obtained including significantly prolonged half-life (11.52 ± 6.31 hour vs 5.44 ± 2.36 hour, P<0.001) and decreased clearance (0.05 ± 0.02 L/kg/hr vs 0.09 ± 0.05 L/kg/hr, P<0.001) in the extracorporeal membrane oxygenation group relative to the control group. Conclusions: Vancomycin clearance decreased significantly in the neonates undergoing extracorporeal membrane oxygenation compared with the controls. Dosing adjustments of vancomycin and close therapeutic drug monitoring are required for the safe and effective management of neonates during extracorporeal membrane oxygenation.

Effects of proton pump inhibitor use on risk of Clostridium difficile infection: a hospital cohort study.

BACKGROUND: Although there are several studies on the association between use of proton pump inhibitors (PPIs) and increased Clostridium difficile infection (CDI) risk, detailed studies analyzing the effects of PPI use on CDI risk are lacking. The present study investigated the association of the dose, duration, and types of PPIs with CDI risk. METHODS: A single-center, cohort study was conducted on patients admitted to a hospital. The exposed cohort comprised patients who were prescribed PPIs at least once during the study period, and a control cohort was prepared by randomly assigning an index date to patients who did not use PPIs ensuring the same distribution of index dates as in the exposed cohort and matching sex, age, hospitalization period, and date of admission. RESULTS: PPI use increased the risk of CDI by 1.8-fold [95% confidence interval (CI) 1.5-2.2]. CDI risk increased by 1.8-fold with esomeprazole (95% CI 1.4-2.2) and 2.0-fold with pantoprazole (95% CI 1.5-2.8). Patients who used a high dose had a higher risk than those who used a medium dose [adjusted hazard ratio (HR) 2.0 vs 1.3]. The risk of CDI increased 4.2-fold when the PPI exposure period was 6 days or shorter than 6 days. CONCLUSIONS: Our study showed that PPI use was associated with an increased risk of developing CDI and the risk of CDI was dose dependent. Therefore, PPIs should only be used at proper doses and only for the necessary indications to avoid CDI risk.

Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients.

Traditionally, dosage for pediatric patients has been optimized using simple weight-scaled methods, but these methods do not always meet the requirements of children. To overcome this discrepancy, population pharmacokinetic (PK) modeling of size and maturation functions has been proposed. The main objective of the present study was to evaluate a new modeling method for pediatric patients using clinical data from three different clinical studies. To develop the PK models, a nonlinear mixed effect modeling method was employed, and to explore PK differences in pediatric patients, size with allometric and maturation with Michaelis-Menten type functions were evaluated. Goodness of fit plots, visual predictive check and bootstrap were used for model evaluation. Single application of size scaling to PK parameters was statistically significant for the over one year old group. On the other hand, simultaneous use of size and maturation functions was statistically significant for infants younger than one year old. In conclusion, population PK modeling for pediatric patients was successfully performed using clinical data. Size and maturation functions were applied according to established criteria, and single use of size function was applicable for over one year ages, while size and maturation functions were more effective for PK analysis of neonates and infants.

Risk factors for neutropenia and febrile neutropenia following prophylactic pegfilgrastim.

AIM: Neutropenia is a common side effect of myelosuppressive chemotherapy. Administration of granulocyte colony-stimulating factor is being used for neutropenia prophylaxis, but there are patients who develop neutropenia or febrile neutropenia despite prophylaxis. We attempted to identify potential risk factors for chemotherapy-induced neutropenia in patients with pegfilgrastim prophylaxis. METHODS: This was a single-center, retrospective, observational study of patients with breast cancer or diffuse large B-cell lymphoma. We obtained patients' data from electronic medical records, including baseline demographics and clinical characteristics regarding diseases, treatments and laboratory values. The outcome measures assessed were the incidence of neutropenia and febrile neutropenia. RESULTS: There were a total of 127 patients, including 77 patients with diffuse large B-cell lymphoma (DLBCL) and 50 patients with breast cancer, and we analyzed 722 chemotherapy cycles. We found 88 cases (12.2%) of grade 3 or 4 neutropenia and 39 cases of febrile neutropenia (5.4%). In the univariate analysis, variables associated with both grade 3 or 4 neutropenia and febrile neutropenia were age, cancer type, cancer stage, radiotherapy and platelet count. A multivariate logistic regression model revealed that age, radiotherapy and platelet count were significant factors in severe neutropenia, whereas platelet count was the only statistically significant factor in febrile neutropenia. Platelet counts of less than 150 000/mm3 increased the risk of neutropenia and febrile neutropenia approximately fourfold. In the subgroup analysis of patients with DLBCL, it was found that platelet count was a significant factor for both neutropenia and febrile neutropenia. CONCLUSION: Among cancer patients with pegfilgrastim prophylaxis, advanced age, absence of radiation therapy and low platelet count were independent predictors of neutropenia, and low platelet count was the predictor of febrile neutropenia.

Influence of UDP-Glucuronosyltransferase Polymorphisms on Stable Warfarin Doses in Patients with Mechanical Cardiac Valves.

AIM: This study aimed to evaluate the effect of uridine diphosphate (UDP)-glucuronosyltransferase (UGT) polymorphisms on warfarin dosing requirements in patients with mechanical cardiac valves. METHODS: A total of 191 patients with stable warfarin doses from the EAST Group of Warfarin were included in this study. The influence of genetic polymorphisms on stable warfarin doses was investigated by genotyping 6 single nucleotide polymorphisms (SNPs): vitamin K epoxide reductase complex 1 (VKORC1) rs9934438, cytochrome P450 (CYP) 2C9 rs1057910, CYP4F2 rs2108622, and UGT1A1 (rs887829, rs4148323, and rs4124874). An additional subgroup analysis was carried out using patients with wild-type homozygote carriers of CYP2C9. RESULTS: One UGT1A1 SNP of rs887829 (C>T) exhibited significant association with stable warfarin doses in the study population and subgroup. Patients with the T allele in UGT1A1 rs887829 (CT or TT) required higher doses than those with the CC genotype in the study population (6.3 ± 2.4 mg vs. 5.2 ± 1.6 mg, P = 0.003). Similarly, in the subpopulation of AA carriers in the CYP2C9 gene, patients with the T allele required significantly higher doses of warfarin than those with other genotypes of rs887829 (6.5 ± 2.4 vs. 5.3 ± 1.5 mg, P = 0.002). Approximately 45.1% of overall interindividual variability in warfarin dose requirement was explained by the multivariate regression model. VKORC1, CYP2C9, UGT1A1 rs887829, age, and CYP4F2 accounted for 28.2%, 6.6%, 5.5%, 3.0%, and 1.8% of the variability, respectively. CONCLUSION: Our results suggest that UGT1A1 could be a determinant of stable warfarin doses.

Effect of biocompatible peritoneal dialysis solution on residual renal function: a systematic review of randomized controlled trials.

INTRODUCTION: Residual renal function (RRF) plays an important role in outcome of peritoneal dialysis (PD) including mortality. It is, therefore, important to provide a strategy for the preservation of RRF. The objective of this study was to evaluate relative protective effects of new glucose-based multicompartmental PD solution (PDS), which is well known to be more biocompatible than glucose-based conventional PDS, on RRF compared to conventional PDS by performing a systematic review (SR) of randomized controlled trials. METHODS: We searched studies presented up to January 2014 in MEDLINE, EMBASE, the COCHRANE library, and local databases. Three independent reviewers reviewed and extracted prespecified data from each study. The random effects model, a more conservative analysis model, was used to combine trials and to perform stratified analyses based on the duration of follow-up. Study quality was assessed using the Cochrane Handbook for risk of bias. Eleven articles with 1,034 patients were identified for the SR. RESULTS: The heterogeneity of the studies under 12 months was very high, and the heterogeneity decreased substantially when we stratified studies by the duration of follow-up. The mean difference of the studies after 12 months was 0.46 mL/min/1.73 m(2) (95% confidence interval = 0.25 to + 0.67). CONCLUSION: New PDS showed the effect to preserve and improve RRF for long-term use compared to conventional PDS, even though it did not show a significant difference to preserve RRF for short-term use.

Outcomes of a new dosage regimen of amikacin based on pharmacokinetic parameters of Korean neonates.

PURPOSE: Study results indicating improved neonatal amikacin therapy outcomes through the use of a dosage regimen tailored to population-specific pharmacokinetic parameters are presented. METHODS: In a retrospective analysis, outcomes of amikacin therapy were evaluated in two groups of Korean neonates: group 1 (n = 107), who received amikacin according to standard neonatal dosing recommendations and empirical dosing guidelines, which often resulted in a need for dosage adjustments; and group 2 (n = 74), who were treated under a revised dosage regimen derived from pharmacokinetic data on group 1 and taking into account unusually high interpatient variability in amikacin clearance among Korean newborns relative to Caucasian populations. The influences of postconceptional and postnatal age on amikacin pharmacokinetics were also evaluated. RESULTS: Relative to standard and empirical amikacin dosing, the revised dosage regimen resulted in a significantly higher percentage of neonates achieving peak concentrations within the target range of 20-30 mg/L (81.3% in group 2 versus 50.7% in group 1, p < 0.001). The percentage of neonates with a peak concentration of <20 mg/L was significantly lower in group 2 (3.8%) versus group 1 (21.6%, p < 0.001), as were the proportion of neonates with peak concentrations of >30 mg/L (15.0% versus 27.6%, p < 0.001) and the need for dosage adjustment by a pharmacist (31.6% versus 59.7%, p = 0.056). CONCLUSION: A new amikacin dosing regimen based on the pharmacokinetic parameters of Korean neonates was effective in achieving peak and trough amikacin concentrations within the target range.