Earticle

Polypharmacy is increasing owing to an increase in the elderly population and multimorbidities associated with the increased risk of administration of potentially inappropriate medications (PIMs). The negative effects of polypharmacy on various health conditions and aspects, such as fall, fracture, mortality, cognitive function, and dementia, have been reported. The management of excess and inappropriate polypharmacy through proper interventions and local or national guidelines has been highlighted. The purpose of polypharmacy management is to appropriately prescribe medicines that are essential to treat diseases in patients and to avoid inappropriate polypharmacy, such as interactive or duplicate medicines under prescription and PIMs for specific diseases. Community pharmacists in Australia, the EU, USA, and Japan are collaborating with prescribers to review medications to ensure that the patients can be prescribed appropriate medications. The service cost is reimbursed by public or private insurers. A study in the United States has shown that even with medication review costs, the overall medication cost has reduced. In Korea, various projects such as Drug Utilization Review service and safe use of medicines have been conducted; however, no national guidelines or management measures have been established. It is necessary to implement a national long-term plan on polypharmacy management. Furthermore, a phased implementation plan is required. Shortly, active medication review services and education programs for healthcare professionals with the support of the government should be considered in Korea with reference to other countries in order to raise awareness of seriousness and risks of inappropriate polypharmacy.

Background: Vitamin D has been associated with sepsis in pediatric and adult patients. The association with neonates is unclear. This systematic review and meta-analysis examined the effect of neonatal and maternal vitamin D levels on neonatal early-onset sepsis. Methods: We searched studies published up to November 2017 in PubMed/Medline, Embase, and the Cochrane Library databases. All studies that reported 25-hydroxyvitamin D levels in neonates with or without early-onset sepsis were included. Meta-analysis was performed using RevMan 5.3 software. Results: Four studies were eligible. The weighted mean difference of 25-hydroxyvitamin D levels in neonates with early-onset sepsis and controls was -7.27 ng/mL (95% confidence interval = -7.62, - 6.92). Maternal vitamin D levels in neonates with early-onset sepsis were significantly lower than those in controls (weighted mean difference -7.24 ng/mL, 95% confidence interval -8.45, -6.03). All neonates with early onset sepsis had vitamin D deficiency (25- hydroxyvitamin D <20 ng/mL). Conclusion: Lower neonatal and maternal 25-hydroxyvitamin D levels were associated with neonatal early-onset sepsis. Vitamin D supplementation during pregnancy may be helpful to prevent neonatal early-onset sepsis. The effects of vitamin D supplementation on early-onset sepsis in neonates warrant further study.

Objective: Opioid analgesics, for postoperative pain management, are an indispensable group of medication; however, they also have a variety of adverse drug reactions (ADR). Multimodal methods, combining non-opioid analgesics with opioid analgesics, have been investigated to increase the effects of analgesics and reduce ADR with opioid-sparing effects. The purpose of this study was to compare the effects of patient-controlled analgesia (PCA) with fentanyl alone, and PCA with fentanyl and intravenous (i.v.) propacetamol to determine the effects of pain control, cumulative opioid usage, and opioid ADR. Methods: The subjects were patients who underwent total knee arthroplasty at the Seoul Veterans hospital from January 1, 2015 to December 31, 2016. The study period was from postoperative day 0 (POD0) to day 3 (POD3), and the retrospective study was conducted using electronic medical records. Results: Pain severity was significantly low at POD1 (p = 0.017), POD2 (p = 0.003), and POD3 (p = 0.002) in the multimodal group. The fentanyl only group frequently reported both moderate and severe pain at a statistically significant level. This was consistent with the analysis of the pro re nata (PRN) intramuscular analgesia usage at the time of numerical rating scale (NRS) 4 and above. The opioid-sparing effect confirmed that the average opioid dose equivalent to i.v. morphine dose was 9.4 mg more than that used for the multimodal group in the fentanyl only group. The ADRs and length of stay between the two groups were not statistically different. Conclusion: The results of this study suggest that the combination therapy of fentanyl and i.v. propacetamol is superior to fentanyl monotherapy.

Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)−a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant antifungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a twocompartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: CL (L/h) = 5.9 × (BSA / 1.2)0.9, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, ka (h-1) = 0.000377. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

Background: Clinical Pharmacy Practice Experience (CPPE) is an important curriculum that offers students patient-centered disease prevention and treatment with evidence-based optimal pharmacotherapy for better clinical outcomes. However, few studies have evaluated the perception of pharmacy students regarding CPPE in tertiary and secondary hospitals. This study aimed to evaluate the perception of pharmacy students regarding the learning program of CPPE. Methods: The survey questionnaire consisted of 15 self-administered questions regarding pharmacy practices, barriers, and improvement of practical training. Fourteen institutional pharmacies located in seven regions responded to a survey questionnaire from March 1 to June 30, 2017. The participants were pharmacy students doing clerkship in a hospital setting. Results: The response rate was 73.6%. Thirty-five participants (22.4%) had used a hospital library, but 121 (77.6%) had never used the library for drug information resources. Eightyone (50.0%) responded that clinical knowledge and drug information was the most beneficial practice. Thirty-seven (31.1%) respondents in the tertiary hospitals and 19 (46.3%) in the secondary hospitals answered that they were filling prescriptions during the daily break. On the other hand, 72 respondents (60.5%) in the tertiary hospitals and 17 (41.5%) in the secondary hospitals did literature research to prepare for presentation. Conclusion: More students in secondary hospitals continue to fill prescriptions during the daily break, as compared to those in tertiary hospitals. Therefore, the authors suggest self-directed learning to improve clinical performance and each institution considers offering onsite or online library service to improve evidence-based CPPE for pharmacy school students.

Objective: This study presented the analysis period, the complexity of combined therapy and comparator choice as the key limitations in the economic evaluation of new drugs, and discussed programs for coping with these limitations. Methods: This study evaluated the post-evaluation, risk-sharing agreement, extra funding program, and flexible incremental cost-effectiveness ratio (ICER) threshold as actions or programs that would increase accessibility to costly new drugs. The study also presented the cases of other countries. The application of the post-evaluation was considered to deal with high uncertainty regarding new drugs. Results: The risk-sharing agreement was introduced in European countries as well as South Korea and has been responsible for the shift from using the financial schemes to outcome-based schemes. The drug funding program has had troubled in securing stable extra funds. The application of higher ICER in the economic evaluation of expensive and innovative oncology drugs was criticized because of the inequity between oncology patients and patients with other diseases. Conclusion: Therefore, introducing and applying actions that would increase the accessibility to costly new drugs in South Korea have been deemed necessary after careful reviews and discussions with various stakeholders (insurer, policy makers, pharmaceutical companies and patients).

Objective: An automated process for medication preparation and dispensing is essential to improve the quality of work. To reduce night pharmacy workload, a new automated dispensing cabinet system was implemented in a hospital emergency medical center. The purpose of this study is to verify that implementation of an automated dispensing cabinet system will influence the efficiency of night pharmacy work. Methods: To evaluate the new system implementation, a retrospective study and survey was performed in the Ewha Womans University medical center. We compared the dispensing and near-miss error rates between the automated dispensing cabinet system and a night pharmacy. The degree of satisfaction of night shift workers with the new system was surveyed. Results: This study showed significantly reduced dispensing rates of night medications (56.1% and 37.3%; p < 0.01) and near-miss night medications (0.27% and 0.17%; p<0.01). Thirty-two persons responded to the survey, and the satisfaction score for the new system was 4.0 (±0.8). The scores were high in order of efficiency, management, and convenience. Time requirement was also reduced because of the simple step of only reviewing in the pharmacy with the new system. Conclusion: Due to system implementation, workload was reduced and time was saved for not only night shift workers but also patients receiving emergency discharge medicine. It was suggested that this will have a positive effect on pharmacist medical service and patient safety.

Background: Patients experience significant differences in aspects of mortality, quality of life, and costs between during the year of receiving liver transplant (LT) and the subsequent years (post-LT). This study aimed to estimate the medical utilization and cost of LT for patients compared to post-LT patients by using a recent National Patient Sample (NPS) data provided by the Korean Health Insurance Review and Assessment Service (HIRA). Methods: This study used a subset of the 2015 HIRA-NPS. Patient claims data that included Z944 (Korean Standard Classification of Diseases code for LT status) were selected. Within the selected data, LT patients were identified based on whether the national health insurance number code of Q80 (procedure code for LT surgery) was included, and they were compared to post-LT patients. Results: In the analysis, 330 patients were included. The average cost per patient was 90,066±36,959 thousand KRW and 10,557±9,668 thousand KRW for LT and post-LT patients, respectively. Especially, LT patients’ costs for injection/procedure, surgery/treatment, and examination were higher than other costs, being 35,983±18,115 thousand KRW, 28,246±9,408 thousand KRW, and 12,131±6,604 thousand KRW, respectively. For inpatients, the average number of hospitalized days was 63.5±66.0 days for LT patients and 22.3±35.1 days for post-LT patients. Conclusion: Compared to post- LT patients, LT patients had higher costs, especially for injection/procedure, surgery/treatment, and examination. Additionally, the LT group had longer hospitalization duration and higher costs for their hospital admission, whereas they did not show a significant difference in number of visits and medical costs for outpatient-care.

Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.