Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, has increased in cancer patients and adversely affects their prognosis. Low-molecular-weight heparins are recommended as efficacious and safe anticoagulation treatment in cancer patients. However, in practice, oral anticoagulation is preferred, especially if longterm or extended treatment is necessary. Novel oral anticoagulants have recently emerged as an alternative to the standard therapy owing to the ease of administration, predictable anticoagulation effect without the need of laboratory monitoring, and fewer drug interactions. These new agents have been shown as effective and safe for the management of cancer-associated thrombosis in ongoing head-to-head comparative trials. Here we review the advances and limitation of current anticoagulant therapies.
Anticoagulants* ; Drug Interactions ; Heparin, Low-Molecular-Weight ; Humans ; Prognosis ; Pulmonary Embolism ; Thrombosis ; Venous Thromboembolism* ; Venous Thrombosis

OBJECTIVE: Treatment with sulfonylureas in combination with metformin improves glycemic control in type 2 diabetes mellitus (T2DM), but is associated with hypoglycemia and weight gain. This retrospective study aims to compare the effectiveness of dipeptidylpeptidase-4 (DPP-4) inhibitors and sulfonylureas as an add-on therapy to metformin in patients with T2DM. METHODS: Data from medical records of 355 T2DM patients received therapy either DPP-4 inhibitors (DPP-4 inhibitor group) or sulfonylurea (SU group) in combination with metformin from 1 March 2009 to 30 September 2011 were retrospectively reviewed. Of total 355 patients, 231 patients were in DPP-4 inhibitor group and 124 patients were in SU group. Baseline Hemoglobin A1c (HbA(1c)) level in SU group was higher than DPP-4 inhibitor group with a statistically significant difference (8.6% vs. 7.8%). Comparative analysis between DPP-4 inhibitor group and SU group was performed for HbA(1c) values, amounts of HbA(1c) changes, and rates of HbA(1c) changes from baseline at 6-month intervals and incidence rates of major cardiocerebral events. RESULTS: SU group showed larger HbA(1c) changes in both amounts and rates compared to DPP-4 inhibitor group, although statistical significance was not found in all study periods. Proportions of patients with stable HbA(1c) <6.5% or 7% were significantly higher in DPP-4 inhibitor group than SU group (<6.5%: 30.4% vs. 13.4%, <7%: 72.3% vs. 41.2%). Time to achieve stable HbA(1c) <6.5% was not significantly different, but time to achieve stable HbA(1c) <7% was shorter in DPP4 inhibitor group than SU group with a significant difference. The incidence rate of cardiocerebral events in group of patients with or without previous events was 1.7%, not significantly lower than that in DPP-4 inhibitor group (4.0%). For newly encountered cardiocerebral events during the treatment, incidence rates of two groups did not differ significantly. CONCLUSION: DPP-4 inhibitors were as effective as sulfonylureas in achieving the HbA(1c) goal of less than 6.5% or 7% and cardiocerebral event rates did not differ between the two drugs.
Diabetes Mellitus, Type 2* ; Humans ; Hypoglycemia ; Incidence ; Medical Records ; Metformin* ; Retrospective Studies ; Weight Gain

BACKGROUND: Venous thromboembolism (VTE) is a common and life-threating condition in cancer patients. Low molecular weight heparins (LMWH), such as dalteparin, are recommended in the treatment of VTE. Also, rivaroxaban, an orally administered direct factor Xa inhibitor, was approved for the treatment of VTE. It showed similar efficacy to standard therapy (LMWH or warfarin) and was associated with significantly lower rates of major bleedings. However, in the real world, bleeding has been reported to occur frequently in cancer patient receiving rivaroxaban. The goal of this research was to analyze bleeding risks between rivaroxaban and dalteparin for treatment of VTE in cancer patients. METHODS: Medical records of oncology patients who were treated with rivaroxaban or dalteparin for VTE from July 2012 to June 2014 were retrospectively reviewed. Data collected were as follows: age, sex, weight, height, cancer types and stages, ECOG (eastern cooperative oncology group) PS (performance score), VTE types, concurrently used medications, study drug information (dose and duration of therapy), INR (international normalized ratio), PT (prothrombin time), and platelet counts. Bleeding was classified into major bleedings, clinically relevant non-major bleedings, and minor bleedings. RESULTS: A total of 399 patients were included in the study. Of these patients, 246 were treated with rivaroxaban and 153 with dalteparin. Bleeding rates were significantly higher in the rivaroxaban group than in the dalteparin group (adjusted odds ratio (AOR) 2.09, 95% CI 1.22-3.60) after adjusting for confounders. In addition, rivaroxaban remained independently associated with 1.78-fold (95% CI 1.14-2.76) shorter time to bleeding compared to dalteparin after adjusting other factors known to be associated with poor outcomes. CONCLUSION: This study suggested that rivaroxaban was associated with an increased risk of bleedings in cancer patients.
Dalteparin* ; Factor Xa ; Hemorrhage* ; Heparin, Low-Molecular-Weight ; Humans ; International Normalized Ratio ; Medical Records ; Odds Ratio ; Platelet Count ; Retrospective Studies ; Rivaroxaban* ; Venous Thromboembolism*

Anticoagulant drugs, like vitamin K antagonists and heparin, have been the mainstay for the treatment and prevention of venous thromboembolic disease for many years. Although effective if appropriately used, traditional anticoagulants have several limitations such as unpredictable pharmacologic and pharmacokinetic responses and various adverse effects including serious bleeding complications. New oral anticoagulants have recently emerged as an alternative because of their rapid onset/offset of action, predictable linear dose-response relationships and fewer drug interactions. However, they are still associated with problems such as bleeding, lack of reversal agents and standard laboratory monitoring. In an attempt to overcome these drawbacks, key steps of the hemostatic pathway are investigated as targets for anticoagulation. Here we reviewed the traditional and new anticoagulants with respect to their targets in the coagulation cascade, along with their therapeutic advantages and disadvantages. In addition, investigational anticoagulant drugs currently in the development stages were introduced.
Anticoagulants* ; Drug Interactions ; Hemorrhage ; Heparin ; Venous Thromboembolism* ; Vitamin K

OBJECTIVE: This study aimed to compare effects on glycemic control and weight loss between the metformin/dapagliflozin combination and the metformin/sitagliptin combination in type 2 diabetic patients. METHODS: This study retrospectively reviewed the medical records, from January 1(st) 2015 to March 31(st) 2016, of type 2 diabetic patients who were older than 18 and were prescribed with dapagliflozin or sitagliptin in combination with metformin. Hemoglobin A(1c) (HbA(1c)) levels and weights were measured every 3 months. RESULTS: The dapagliflozin group showed a greater decrease in HbA(1c) levels after 3 months (-0.75% vs. 0.01%, P<0.001), 6 months (-0.36% vs. 0.08%, P=0.029), and 9 months (-0.53% vs. 0.08%, P=0.046) compared to the sitagliptin group. Also, the dapagliflozin group showed a greater significant decrease in the rate of change in HbA1c levels after 3 months (-0.09 vs. 0.01, P<0.001), 6 months (-0.04 vs. 0.01, P=0.031), 9 months (-0.07 vs. 0.02, P=0.029), and 12 months (-0.05 vs. 0.05, P=0.047). Furthermore, the dapagliflozin group showed a greater decrease in amount of weight change after 3 months (-2.46 kg vs. 0.37 kg, P<0.001), 6 months (-3.02 kg vs. 0.13 kg, P<0.001), and 9 months (-2.27 kg vs. 0.50 kg, P=0.002). Finally, the dapagliflozin group showed a greater decrease in the rate of change in weight after 3 months (-3.10% vs. 0.52%, P<0.001), 6 months (-3.83% vs. 0.21%, P<0.001), 9 months (-2.84% vs. 0.79%, P=0.002), and 12 months (-4.91% vs. 0.44%, P<0.001). CONCLUSION: It was concluded that dapagliflozin is more effective than sitagliptin for type 2 diabetic patients.
Diabetes Mellitus, Type 2* ; Humans ; Medical Records ; Metformin* ; Retrospective Studies ; Sitagliptin Phosphate* ; Weight Loss ; Weights and Measures

OBJECTIVE: The aim of this study was to investigate the difference of perception on direct-to-consumer advertisement (DTCA) of prescription drugs between healthcare providers and consumers. METHODS: The online and offline survey was conducted from May 26th to June 5th, 2013. The questionnaire was composed of 15 items about perception on DTCA of prescription drugs. RESULTS: A total of 215 healthcare providers and 202 consumers responded to the questionnaire. Consumers had an overall positive attitude on permitting DTCA of prescription drugs and carried favorable views about the influence of the DTCA of prescription drugs on providing drug information, promoting communications between healthcare providers and consumers, and improving images of healthcare providers. Healthcare providers displayed negative perception for the needs of permitting the DTCA of prescription drugs compared to consumers. They showed somewhat skeptical perception about the influence of the DTCA of prescription drugs on necessities and efficiencies of delivering drug information, promoting communications between healthcare providers and consumers, and improving images of healthcare providers. Both healthcare providers and consumers were concerned about the increase of drug prices following the increase in advertisement expenses of pharmaceutical products. CONCLUSION: This study identified the perception differences on direct-to-consumer advertisements of prescription drugs between healthcare providers and consumers. This study could be of much help in the process of review on permitting DTCA of prescription drugs in Korea.
Delivery of Health Care* ; Health Personnel* ; Humans ; Korea ; Pharmaceutical Preparations ; Prescription Drugs* ; Prescriptions*

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 two-compartment 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: Small-molecule tyrosine kinase inhibitors (TKIs) have had major impacts on anticancer therapy by targeting the catalytic activities of dysregulated tyrosine kinases. TKIs have not presented traditional toxicities; however, some serious adverse effects, including hepatotoxicity, have been documented in clinical trials and post-marketing surveillance. Although TKI-induced hepatotoxicity can cause severe clinical complications in patients, the underlying mechanism is still unclear. METHODS: Studies on TKI-induced hepatotoxicity were identified by Pubmed search, and relevant articles were reviewed. RESULTS: Immunoallergic reaction, cytochrome P (CYP) 450 polymorphisms, and formation of reactive metabolites are under consideration as mechanisms of TKI-induced hepatotoxicity. Host protein-drug metabolite conjugates are recognized as antigens by class II major histocompatibility complexes and are believed to cause liver injuries. Polymorphisms in CYP, which influences TKI metabolism, can slow TKI metabolism and may induce development of hepatotoxicity. The formation of reactive metabolites during drug metabolism can induce hepatotoxicity by directly causing cytotoxicity, leading to cell dysfunction, and indirect toxicity by mediating secondary immune reactions. Concurrent use of various medications with TKI can also cause hepatotoxicity by affecting drug transporter or enzyme activities. CONCLUSION Periodic monitoring of patients taking TKIs and risk/benefit reassessments though post marketing surveillance are necessary to prevent hepatotoxicity.

Background: Although the identification of clinical and laboratory features in pediatric COVID-19 patients is essential in establishing an appropriate treatment plan, a systematic review and meta-analysis on the topic has yet to be reported. Methods: We searched MEDLINE, Embase, and Web of Science to access clinical and laboratory characteristics as well as clinical outcomes of children with COVID-19 infection. A meta-analysis using random-effect model was performed to estimate pooled prevalence and 95% confidence intervals. Results: Among the 532 studies initially collected, 12 articles were finally included in the meta-analysis. Among the investigated 320 pediatric patients with COVID-19, fever (48.2%) and cough (39.3%) were the most common symptoms.Almost one third of patients (30.4%) were asymptomatic. In laboratory findings, only 11.4% of pediatric patients experienced lymphocytopenia. Increased inflammatory markers including c-reactive protein (18.6%) and procalcitonin (32.4%) were observed.Only a few patients needed mechanical ventilation and intensive care support, and only one death was reported. Conclusion Pediatric patients with COVID-19 infection exhibited milder symptoms and more favorable outcomes compared to adults. However, considering the high rate of asymptomatic pediatric patients, close monitoring is required to prevent community infection in asymptomatic conditions and hidden disease progression.

Background: Pharmacogenomics is the study of how genetic mutations in patients affect their response to drugs. Pharmacogenomic studies aim to maximize drug effects and minimize adverse drug events. The Food and Drug Administration and the European Medicine Agency published guidelines for pharmacogenetics in 2005 and 2006, respectively; the Korean Ministry of Food and Drug Safety followed suit in 2015. Methods: This study analyzed pharmacogenomic information in the Korean Ministry of Food and Drug Safety’s integrated drug information system to evaluate whether domestic pharmaceutical products reflect the current research on pharmacogenomic differences. Results: In June 2020, the Korean pharmacogenomic database contained genomic data on 90 compounds. Of these, 45 compounds were classified as “Antineoplastic and immunomodulating agents.” The other 45 nonantineoplastic agents were in the following categories: Anti-infectives, Mental & behavior disorder, Hormone & metabolism related diseases, Cardiovascular system, Skin & subcutaneous tissue disease, Genito-urinary system and sex hormones, Blood and blood forming organs, Nervous system, Alimentary tract and metabolism, Musculo-skeletal system, and Other conditions including the respiratory system. In addition, 30 additives unrelated to the main ingredient were associated with genetic precautions. Conclusion This study showed that antineoplastic and immunomodulating agents accounted for half the drugs associated with pharmacogenetic information. For antitumor and immunomodulatory drugs, genomic tests were recommended depending on the indication; this was in contrast to genomic testing recommendations for non-antineoplastic medications. Genomic tests were rarely requested or recommended for non-antineoplastic medications because the relationships between genotype and efficacy among those drugs were relatively weak.