Earticle

Background: Sevelamer is associated with reduced complications of chronic kidney disease-mineral bone disorder (CKD-MBD) resulted from hyperphosphatemia, which may contribute mortality, in CKD patients with dialysis. So far clinical outcomes of sevelamer on mortality and risk of cardiovascular mortality related to CKD-MBD are debating. Purpose of this study was to evaluate the effectiveness of sevelamer HCl on mortality of secondary hyperparathyroidism (SHPT), risk of cardiovascular mortality and, frequency of osteopathy in end stage renal disease (ESRD) patients with dialysis. Methods: We retrospectively reviewed the electronic medical records of 536 patients with ESRD, who were admitted for moderate to severe SHPT, for 36 months. 75 patients who met inclusion criteria were evaluated for the efficacy of sevelamer (mean serum iPTH = 487.5 pg/mL). Results: Sevelamer intervention was not associated with increased three-year survival time compared with non-sevelamers group [average survival month: 30.4 months in sevelamer group, 26.8 months in non-sevelamer group, p = 0.463]. Sevelamer intervention was not associated with significant mortality benefit and cardiovascular mortality benefit as compared to non-sevelamer group [sevelamer group: non-sevelamer group, all-cause mortality (iPTH > 600 pg/mL): 14.3% (1/34): 20% (1/41) p = 0.962, OR = 0.935, 95% CI, 0.058-14.98, heart disease mortality: 6.67% (2/30): 0% (0/32) p = 0.138]. Sevelamer was not associated with significantly lower cumulative incidence of osteopathy compared to non-sevelamer group (sevelamer group: non-sevelamer group, 5.9% (2/34):9.8% (4/41); p = 0.538; OR = 0.578; 95% CI, 0.099-3.367). Conclusion: Sevelamer was not associated with decreased all-cause mortality and risk of cardiovascular mortality compared to non-sevelamer group in ESRD patients with SHPT.

Background: Depression is the leading cause of lowering the quality of life of cancer patients and lung cancer is the most likely to cause depression. It is necessary to find out depression-related factors in lung cancer patients. Methods: The study was a retrospective cohort study using medical records, and was a non-equivalent comparison group design. It involved patients diagnosed of lung cancer at the Konkuk University Medical Center from January to December 2012. Between antidepressants prescription group and non prescription group, socio-demographic factors, clinical factors, treatment-related factors and other factors were analyzed statistically. Results: Antidepressant prescription group consisted of 23 people and non-prescription group of 206 people. Prescription rate of quetiapine was the highest 47.8% (11/23), followed by escitalopram (43.5%, 10/23), amitriptyline and trazodone (30.4%, 7/23). The prescription group was prescribed with an average of 1.9 antidepressants. Antidepressants were prescribed after average of 248 days from lung cancer diagnosis and prescription period per patient was average 177.5 days. According to the result of univariate logistic regression analysis between 2 groups, factors such as number of outpatient visit, number of admission, days of hospitalization, sleep disorder, and comorbidity were found to be statistically significant (p < 0.05). However, According multivariate logistic regression analysis showed that number of admission, days of hospitalization and sleep disorder were statistically significant (p < 0.05) excluding comorbidity. Conclusion: About 10% of lung cancer patients had received a prescription for antidepressants after lung cancer diagnosis. A sleep disorder, number of hospitalization and length of stay were identified as factors influencing the prescribing antidepressants.

Background: Azithromycin has broad spectrum and is effective to treat several bacterial respiratory tract infection. It is also relatively safe and tolerable to pediatric patient. Careful use of azithromycin is also required for the prescribers because it could cause cardiovascular toxicity (QTc prolongation) and ototoxicity. There has been no study on duration of azithromycin use in pediatric patients in Korea. Methods: The outpatient sample data on the azithromycin prescription was obtained from Korean health insurance review and assessment service. The characteristics of azithromycin prescription were analyzed with two different years (2011 and 2014). Results: Total 4,215 cases were analyzed. The azithromycin was prescribed the most frequently in the children (73.2% in 2011 and 62.5% in 2014) and for the condition of bronchopneumonia (28.7% in 2011 and 21.7% in 2014) in both years. The duration of prescribed for azithromycin has significantly different between 2011 and 2014. In 2014, 94.3% of prescription were indicated less than 5 days, but 86.6% were in 2011. Acute bronchiolitis and bronchopneumonia prescriptions more longer duration of treatment compared with acute bronchitis and others. Conclusion: The pattern of prescribing azithromycin has been changed for the treatment of several infectious diseases in pediatric patients. The rate of appropriate duration of azithromycin treatment has increased.

Objective: Until now, there is minimal number of research for overall domestic status of orphan drug use in Korea. The purpose of this study is to identify the list of orphan drugs available in Korea and to understand the status of orphan drug usage in tertiary Hospitals and rare incurable disease Hospital. Methods: We made domestic orphan drug lists based on available orphan drugs in Korea. Based on this lists, we conducted e-mail survey from August, 2014 to September, 2014 to identify domestic status of orphan drug usage including the availability and management of orphan drugs. Results: There are three hundred and eighteen orphan drugs (184 ingredients) registered in Ministry of Food and Drug Safety. Among the three hundred and eighteen orphan drugs, Two hundred and twenty-eight drugs (102 ingredients) were selected. Information on each item was collected and documented with generic and brand names, manufacturers, wholesalers, indications, FDA approval status and insurance coverage. Forty-three tertiary hospitals and thirty-two rare incurable hospitals responded to the survey questionnaire (57.3%). According to the survey result, the antineoplastics and immunomodulating agents group has the highest percentage (40%) usage in the hospital. Of fortythree tertiary hospitals, thirteen hospitals manage orphan drugs separately (30.2%). Based on the reply, most of the healthcare professionals commented the drug information related to efficacy and safety including medication counseling of orphan drugs is insufficient. Conclusion: Through this study we anticipate providing an understanding of orphan drug usage status in Korea. We found the limited resources to the information on orphan drugs and this information requires updating on a regular basis. This can be the basis for further studies about preparing drug information, educational resources for rare disease patients.

Objective: This study was to explore the association between having a usual source of care and adherence to medicines in patient with chronic diseases. Methods: The 2012 Korea Health Panel was used as a data source. We analyzed 4,418 respondents that were diagnosed with chronic diseases and utilized health care services. Non-adherence to medication, a dependent variable, was defined as “not taking the medicines that were prescribed for treating chronic disease” or “not following the direction for medication”. Whether having a usual source of care or not was used as a key independent variable, which was defined as having a regular site or a regular doctor for medical test, treatment, and consultation. Sex, age, education level, marital status, income, the type of health insurance, the number of chronic disease and CCI (Charlson Comorbidity Index) were included as covariates in the analysis. We conducted a multivariate logistic regression. Results: Totally, 30 percent of respondents reported to experience nonadherence to medication. Having a usual source of care was significantly associated with lower non-adherence to medication regardless its type, which is a regular doctor (OR=0.61, 95% CI=0.53-0.70) or a regular site (OR=0.67, 95% CI=0.58-0.78). Furthermore, having a usual source of care was associated with both of medication persistence (OR=0.66, 95% CI=0.54-0.81) and compliance (OR=0.65, 95% CI=0.56-0.76). Conclusion: Our results showed the possibility that usual source of care is able to conduct a positive role in improving adherence to medication with better management of chronic disease.

Objective: Online pharmacies were introduced in some countries such as United States of America or Canada. They can provide benefits to consumer because they can buy and take conveniently drugs without limitation of location or time. In Korea, online pharmacies are illegal and only pharmacists can sell drugs to consumers or patients. Therefore, we investigated the knowledge of online pharmacy and the possible problem in Korea to survey pharmacists. Methods: We developed questionnaire based on previous articles about online pharmacy and surveyed nation-wide pharmacists by mail or e-mail. The data was analyzed by SPSS and Microsoft Excel. P-values less than 0.05 were statistically significant. Results: 175 pharmacists involved in this study. About introduction of online pharmacies, 53.1% were opposition while 10.3% were approval and 36.6% were conditional. Although online pharmacies were introduced, 46.3% pharmacists do not have a plan to start online pharmacy. However, the approval and tends about starting online pharmacies were higher in younger pharmacists (20s, 30s) (p < 0.05). The criteria of permission about opening online pharmacies were 100% pharmacist license regardless of holding off-line pharmacy. 53.7% pharmacists responded education about taking medication is impossible. When online pharmacies are introduced, 65.1% pharmacists responded traditional pharmacies are affected negatively. Pharmacists concerned that the competition with large-sized distribution corporations, reduced reliance between pharmacists and patients, illegal transaction of counterfeit drugs, increased misuse of drugs. Conclusion: These results showed that Korea pharmacists have negative standard on online pharmacies. Therefore it is required to be more cautious before introducing online pharmacy and it need strict watching system and continuous education and study for safety after introducing online pharmacy.

Objective: First-in-human dose estimation is an essential approach for successful clinical trials for drug development. In this study, we systematically compared first-in-human dose and human pharmacokinetic parameter estimation approaches. Methods: Firstin- human dose estimation approaches divided into similar drug comparison approaches, regulatory guidance based approaches, and pharmacokinetic based approaches. Human clearance, volume of distribution and bioavailability were classified for human pharmacokinetic parameter estimation approaches. Results: Similar drug comparison approaches is simple and appropriate me-too drug. Regulatory guidance based approaches is recommended from US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding no-observed-adverse-effect level (NOAEL) or minimum anticipated biological effect level (MABEL). Pharmacokinetic based approaches are 8 approaches for human clearance estimation, 5 approaches for human volume of distribution, and 4 approaches for human bioavailability. Conclusion: This study introduced and compared all methods for firstin- human dose estimation. It would be useful practically to estimate first-in-human dose for drug development.

Objective: A meta-analysis was performed to determine effect of ginseng on blood pressure. Methods: The databases of PubMed, Embase, Cochrane Library, RISS, DBpia, KISS, and Koreamed were searched for all published studies from inception to January 2016. The following terms were used: “ginseng”, “hypertension”, and “blood pressure”. Using the Review Manager 5, mean differences (MDs) were pooled to measure the effect of ginseng on blood pressure compared to that of placebo. Results: Eleven randomized controlled trials were included. In this meta-analysis, ginseng treatment significantly lowered systolic blood pressure (SBP) in a dose-independent way (MD: −1.99, p = 0.04). In subgroup analysis, 8-12 week consumption of ginseng achieved significantly greater reduction in SBP (MD: −3.14, p = 0.03), while single administration of ginseng failed to show BP-lowering effect. When ingested over 8-12 weeks, ginseng significantly lowered diastolic blood pressure (DBP) (MD: −1.96, p = 0.03). No significant association was found between ginseng dose and the magnitude of BP- lowering effect. However, a significant positive relationship was observed between baseline SBP level and the magnitude of SBP reduction (r = 0.848, p = 0.033). Such a relationship was not seen in DBP. Conclusion: Consumption of ginseng for 8-12 weeks achieved significant reductions in SBP and DBP in a dose-independent way. There was a significant positive relationship between baseline SBP level and the magnitude of SBP reduction.

Background: Ischemic heart disease is the most common type of heart disease and an important cause of death in Korea. Among marketed anti-anginal medications, molsidomine, nicorandil, and trimetazidine are approved in Korea with unique mechanism of actions. As these drugs are not approved by the US Food and Drug Administration, the access to the up-to-dated and comprehensive safety-related information has been less than optimal from drug information resources used by Korean pharmacists. Methods: A systematic review was conducted using Embase and Korean manuscripts to compile safety updates for these medications. Out of 418 articles from keyword searches, 52 studies were reviewed in full to compare adverse effects (AEs) with the approved package inserts (PI). Results: Molsidomine related adverse effects were mostly mild or moderate, but anxiety, palpitation, epigastric pain, and sexual potency reduction were additional AEs found from the review not listed in PI. Although PI has included ulceration in oral cavity and gastrointestinal tracts including anus by nicorandil, the Korea FDA recently recommended adding corneal, genital, and skin ulcers to the approved PI. Trimetazidine induced Parkinsonism, worsening of the symptoms for patients diagnosed with Parkinson's disease, gastrointestinal burning, and muscle cramps were additionally identified AEs not listed in PI for trimetazidine. Conclusion: Continuous evaluations of the safety profile of these agents are needed to balance the risks and benefits to provide evidence-based safety counseling to the patients. In addition, more focused efforts on spontaneous reporting are warranted by healthcare professionals to safeguard patients against AEs.

Background: There has been on increasing emphasis on the importance of monitoring the safety of participants in a clinical trial to protect patients and maintain the integrity of the trial. The independent data monitoring committee (IDMC) has become common component of randomized clinical trials in recent years. Methods: It is important to consider the implications of different approaches that are being used in various countries. IDMC guidelines in Korea, US, and Europe were reviewed and compared to provide the objective, composition and operation of IDMC in detail. Results: IDMC is a group of experts in related subject are as who perform interim data monitoring to make a recommendation to the sponsor or organizer regarding appropriateness of trial continuation and the need for modifications of the trial. Independence of IDMC is preferred in order to minimize influence of factors unrelated to scientific, medical and ethical considerations that should underlie decision-making. Conclusion: IDMC has become an increasingly important component of clinical trials in recent years. Practical operating procedures need to be developed considering the future regulatory status of data monitoring committees.