Safety and Effectiveness Analysis of Kivexa® (lamivudine/abacavir sulfate) in Human Immunodeficiency Virus Infected Korean Patients

BACKGROUND@#Lamivudine and abacavir sulfate are widely used nucleoside/tide reverse transcriptase inhibitors (NRTI) backbone agents, which are recommended in major international treatment guidelines. The fixed-dose combination of lamivudine and abacavir sulfate has been developed to contribute to low pill burden of antiretroviral therapy (ART) regimen and patient adherence. A mandatory post-marketing surveillance was conducted in Korea to monitor the safety of Kivexa (lamivudine 300 mg/abacavir 600 mg).@*MATERIALS AND METHODS@#An open label, multi-center, non-interventional post-marketing surveillance was conducted to monitor the safety of Kivexa from July 2011 to July 2017 in 23 hospitals in Korea. Subjects over 12 years old taking Kivexa per prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events during the study period. Secondary outcomes included the occurrence of adverse drug reaction, the occurrence of serious adverse events and the effectiveness of Kivexa.@*RESULTS@#A total of 600 patients from 23 hospitals were enrolled within the 6 years of study. The total observation period was 1,004 person-years. Three hundred and ten patients reported 674 adverse events. The incidence of upper respiratory infection (65 cases, 10.9%) was the highest, followed by diarrhea (20 cases, 3.3%), and nausea (18 cases, 3.0%). 109 subjects reported 71 events of adverse drug reactions, and the most common reaction was nausea in 2.33% of the subjects. Thirty-one subjects reported serious adverse events, none of them were considered drug related. From the total of 600 subjects, excluding 48 subjects who were ‘effectiveness unassessable’ by investigators, 552 patients were eligible for the subjective effectiveness analysis. 459 (83.2%) were evaluated as ‘improved’. Proportion of subjects whose human immunodeficiency virus-RNA is <50 copies/ml was 61.2% (309/505) at the beginning of observation and increased to 91.9% (464/505) at the end of study period.@*CONCLUSIONS@#The post-marketing surveillance showed the safety of Kivexa in HIV-1 patients in Korea. Ischemic cardiovascular events and hypersensitivity associated with Kivexa were few. There was no significant new safety information. This data may be helpful in implementing Kivexa and lamivudine/abacavir sulfate containing drugs in Korea.

An Open Label, Multi-Center, Non-Interventional Post-Marketing Surveillance to Monitor the Safety and Efficacy of ALTARGO® (Retapamulin) Administered in Korean Patients According to the Prescribing Information

BACKGROUND: With the approval of topical retapamulin ointment in 2011, it was officially required to conduct a post-marketing surveillance (PMS) study to obtain further data of its safety profile and effectiveness, in accordance with the requirement of the Korean Ministry of Food and Drug Safety (MFDS). OBJECTIVE: This study had prospectively designed to monitor safety and tolerability with the effectiveness of topical retapamulin in clinical practices. METHODS: Open label, multi-center, non-interventional observational study was done from May 2011 to October 2015. All subjects had bacterial skin infections of locally approved prescribing information accordingly. The study mainly focused on safety issues in the local target population (3,612 eligible subjects). And, drug effectiveness was also evaluated by physicians. RESULTS: The incidence of adverse events (AEs) and adverse drug reactions (ADRs) were 2.53% and 0.97%, respectively. In terms of the incidence of unexpected AEs and ADRs, 1.45% and 0.33%, and for the incidence of serious AEs, 0.28%, whereas no serious ADRs reported. And, the effectiveness of topical retapamulin rate was 96.1% (1,697 of total 1,765 subjects). CONCLUSION: Topical retapamulin is to be well-tolerated and effective in patients with bacterial skin infections of locally approved prescribing information.

Safety and Efficacy of Ziagen (Abacavir Sulfate) in HIV-Infected Korean Patients

BACKGROUND: Abacavir is a widely-used nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) infection. Mandatory postmarketing surveillance was conducted in Korea to monitor the safety and evaluate the effectiveness of Ziagen® (abacavir sulfate 300 mg; ViiV Healthcare, Middlesex, UK). MATERIALS AND METHODS: An open-label, multi-center, non-interventional postmarketing surveillance study was conducted from June 2010 to June 2016 to monitor the safety and effectiveness of Ziagen across 12 hospitals in Korea. Subjects older than 18 years taking Ziagen according to prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events after Ziagen administration. Secondary outcomes included the occurrence of adverse drug reactions, occurrence of serious adverse events, and effectiveness of Ziagen administration. RESULTS: A total of 669 patients were enrolled in this study, with a total observation period of 1047.8 person-years. Of these, 90.7% of patients were male. The mean age of patients was 45.8±11.9 years. One-hundred ninety-six (29.3%) patients reported 315 adverse events, and four patients reported seven serious adverse events, without any fatal events. There was one potential case of an abacavir hypersensitivity reaction. Among the 97 adverse drug reactions that were reported from 75 patients, the most frequent adverse drug reactions included diarrhea (12 events), dyspepsia (10 events), and rash (9 events). No ischemic heart disease was observed. In the effectiveness analysis, 91% of patients achieved HIV-1 RNA under 50 copies/mL after 24 months of observation with abacavir administration. CONCLUSION: Our data showed the safety and effectiveness of Ziagen in a real-world setting. During the study period, Ziagen was well-tolerated, with one incident of a clinically suspected abacavir hypersensitivity reaction. The postmarketing surveillance of Ziagen did not highlight any new safety information. These data may be helpful in understanding abacavir and the HIV treatment practices in Korea.

Safety and Tolerability of the Dual 5-Alpha Reductase Inhibitor Dutasteride in the Treatment of Androgenetic Alopecia

BACKGROUND: After the approval of dutastride for androgenic alopecia (AGA) in 2009, Korean authority required a post-marketing surveillance to obtain further data on its safety profile. OBJECTIVE: The objective was to monitor adverse events (AEs) of dutasteride 0.5 mg in Korean AGA male patients in a clinical practice environment. METHODS: Open label, multi-center, non-interventional observational study was done from July 2009 to July 2013. AGA subjects (18~41 years of age) with no experience of dutasteride were enrolled. Dosage regimen was recommended according to the prescribing information. The incidences of any AEs, serious adverse events (SAEs), and adverse drug reactions (ADRs) were evaluated. Multiple logistic regression method was used to identify risk factors related to ADRs. Effectiveness was generally evaluated by physicians. RESULTS: During study period, 712 subjects were enrolled. The subjects of 29.3±6.0 years old exposed to dutasteride for 204.7±161.5 days. One hundred and ten (15.4%) of subjects reported 138 AEs. Four subjects (0.6%) reported 5 SAEs (right radius fracture, 2 events of chronic follicular tonsillitis, influenza infection, and acute appendicitis). Sixty-six subjects (9.3%) reported 80 ADRs. Most frequent ADRs were libido decreased (9 subjects, 1.3%), dyspepsia (8 subjects, 1.1%), impotence (7 subjects, 1.0%), and fatigue (5 subjects, 0.7%). Other interested ADRs were sexual function abnormality (4 subjects, 0.6%), gynecomastia (2 subjects, 0.3%), and ejaculation disorder (1 subject, 0.1%). Most subjects (78.6%) showed overall improvement after treatment of dutasteride in the effectiveness. CONCLUSION: Dutasteride 0.5 mg is to be well-tolerated in 18 to 41 years old AGA patients in a clinical practice environment.

Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized, Double-Blind, Placebo-Controlled Trial with Open-Label Extension

PURPOSE: The efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study. MATERIALS AND METHODS: Women aged 60 to 90 years with a T-score of <-2.5 and ≥-4.0 at the lumbar spine or total hip were randomized to a single 60 mg subcutaneous dose of denosumab or placebo for the 6-month double-blind phase. Eligible subjects entered the 6-month open-label extension phase and received a single dose of denosumab 60 mg. RESULTS: Baseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals. CONCLUSION: Denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women.

Vitamin D Repletion in Korean Postmenopausal Women with Osteoporosis

PURPOSE: Up to 71% of South Korean postmenopausal women have vitamin D deficiency {serum 25-hydroxyvitamin D [25(OH) D] level <50 nmol/L}. Data on vitamin D supplementation was collected during the screening phase of an efficacy/safety study of denosumab in Korean postmenopausal women with osteoporosis. This report describes the effect of vitamin D supplementation on repletion to 25(OH)D levels ≥50 nmol/L in Korean postmenopausal women with osteoporosis. MATERIALS AND METHODS: Vitamin D levels of Korean postmenopausal women (60-90 years old) were measured by extracting 25(OH)D2 and 25(OH)D3 from serum samples via protein precipitation and using liquid chromatography with tandem mass spectrometry detection. Calibration curves were constructed from the mass chromatograms to obtain total vitamin D levels. Subjects with serum 25(OH)D levels <50 nmol/L were supplemented with 1000 IU of vitamin D tablets during the 2.5-month-long screening period. Dose, frequency, and duration were determined by the investigator. If repletion was achieved (≥50 nmol/L) on retest, subjects were eligible to be rescreened for study entry. RESULTS: Of 371 subjects screened, 191 (52%) required vitamin D supplementation, and 88% (168 of 191) were successfully repleted. More than half of the subjects (58%) who were successfully repleted received doses of 2000 IU daily. The mean time to successful repletion was 31 days (standard deviation 8.4 days; range 11-48 days). CONCLUSION: Supplementation with daily median doses of 2000 IU vitamin D successfully repleted 88% of Korean postmenopausal women with osteoporosis within 48 days to a serum vitamin D level of 50 nmol/L.

Changing Clinical Characteristics according to Insulin Resistance and Insulin Secretion in Newly Diagnosed Type 2 Diabetic Patients in Korea

BACKGROUND: The role of increased insulin resistance in the pathogenesis of type 2 diabetes has been emphasized in Asian populations. Thus, we evaluated the proportion of insulin resistance and the insulin secretory capacity in patients with early phase type 2 diabetes in Korea. METHODS: We performed a cross-sectional analysis of 1,314 drug-naive patients with newly diagnosed diabetes from primary care clinics nationwide. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index to measure insulin resistance, which was defined as a HOMA-IR > or =2.5. Insulin secretory defects were classified based on fasting plasma C-peptide levels: severe ( or =1.7 ng/mL). RESULTS: The mean body mass index (BMI) was 25.2 kg/m2; 77% of patients had BMIs >23.0 kg/m2. Up to 50% of patients had central obesity based on their waist circumference (> or =90 cm in men and 85 cm in women), and 70.6% had metabolic syndrome. Overall, 59.5% of subjects had insulin resistance, and 20.2% demonstrated a moderate to severe insulin secretory defect. Among those with insulin resistance, a high proportion of subjects (79.0%) had a mild or no insulin secretory defect. Only 2.6% of the men and 1.9% of the women had both insulin resistance and a moderate to severe insulin secretory defect. CONCLUSION: In this study, patients with early phase type 2 diabetes demonstrated increased insulin resistance, but preserved insulin secretion, with a high prevalence of obesity and metabolic syndrome.

Influence of Insurance Benefit Criteria on the Administration Rate of Osteoporosis Drugs in Postmenopausal Females

BACKGROUND: Preventive measures need to be implemented to lower the incidence of osteoporotic fractures. Osteoporotic fractures increase morbidity and mortality as well as impose a socioeconomic burden; however, current research is limited to the administration rates of osteoporosis drugs for Korean postmenopausal females. METHODS: This study represents a nationwide, observational, and cross-sectional survey that investigates the administration rates of osteoporosis drugs based upon a bone mineral density (BMD) test performed on Korean postmenopausal patients who visited outpatient orthopedic clinics. BMD test results were examined in postmenopausal female patients (50 to 80 years of age); subsequently, the patients were classified into an osteoporosis group, osteopenia group, and normal group. The administration rates of osteoporosis drugs and bisphosphonates were then analyzed. The osteoporosis group was subdivided into a T-score less than -3.0 group and a T-score between -3.0 and -2.5 group that were separately analyzed. RESULTS: Based on the lumbar spine BMD, the rate of administration of osteoporosis drugs in the osteoporosis group was 42.1%, which was significantly higher compared to the osteopenia group or normal group. A significantly low bone mineral density was observed in patients who were administered bisphosphonates. Based on the lumbar spine BMD, the administration rate of osteoporosis drugs in the group with a T-score between -3.0 and -2.5 (34.2%) was significantly lower than the group with a T-score less that -3.0 (46.2%). The bisphosphonate administration rate was also significantly low; however, the administration rate for osteoporosis drugs was significantly lower than that of the osteopenia group. CONCLUSIONS: Only about 40% of Korean postmenopausal female patients with osteoporosis were administered osteoporosis drugs. The administration rate in patients with a T-score between -3.0 and -2.5 was particularly low and active treatment to prevent osteoporotic fractures is required in this group.

A Validation Study for the Korean Version of Chronic Obstructive Pulmonary Disease Assessment Test (CAT) / 결핵및호흡기질환

BACKGROUND: Health status measure is not only important for clinical research studies but also for clinical practices of chronic obstructive pulmonary disease (COPD) patients. The objective of this study is to evaluate the validity of the Korean Version of COPD Assessment Test (CAT) in primary care clinics as well as in referral hospitals. METHODS: Smokers or ex-smokers, aged 40 years or older, with a smoking history of >10 pack-years; and a COPD diagnosis in the past 6 months or more, were recruited from 4 primary care clinics and 2 referral hospitals. Demographic, medical, and spirometry data was collected from patients who completed the CAT and St. George Respiratory Questionnaire (SGRQ), and had their dyspnea been assessed. The primary endpoint was the correlation between of the Korean version of CAT with SGRQ in patients with COPD. RESULTS: A total 100 patients were enrolled. The mean age and smoking amounts were 69.2+/-8.4 years and 40.6+/-22.3 pack-years, respectively. Sixty-seven percent of the patients reported at least one exacerbation in the past year. The mean CAT score was 16.9+/-8.0. The internal consistency assessed by Cronbach's alpha was 0.85. The CAT score was positively correlated with the SGRQ score (r=0.76, p<0.0001) and each component of SGRQ: symptoms, activity and impacts; r=0.68, r=0.61, and r=0.72, respectively (all p<0.0001). These positive correlations were preserved in the different groups (r=0.86, p<0.0001 in primary care clinic group; r=0.69, p<0.0001 in hospital group). The CAT score was also positively correlated to the Medical Research Council dyspnoea scale (r=0.46, p<0.0001). CONCLUSION: The Korean version of CAT had good internal consistency and showed good correlations with SGRQ. It can be used for assessing the impacts of COPD on the patient's health including primary care setting.

Post-marketing Surveillance of the Safety of Dutasteride Prescribed to Korean Patients with Benign Prostate Hyperplasia

BACKGROUND: Dutasteride is an inhibitor of both types I and II 5 alpha-reductase and was approved in Korea in April 2004. This post-marketing surveillance was to assess the safety of dutasteride in Korean patients with benign prostate hyperplasia in real life and to elucidate the risk factors related adverse events. METHODS: From December 2004 to January 2010, 3,977 patients were enrolled by 184 urologists. According to post-marketing surveillance regulation, patients were enrolled consecutively. Patients administered dutasteride at least once were included in safety assessment. The incidences of any adverse events and serious adverse events were evaluated. Multiple logistic regression method was used to identify risk factors related to adverse events. RESULTS: The safety assessment included 3,870 patients with the mean age of 67.3 years. The incidence of adverse events was 3.8 %. The most frequent adverse event was impotence (75 cases, 1.9 %), libido decrease (49 cases, 1.3 %), ejaculation disorder (30 cases, 0.8 %), and gynecomastia (5 cases, 0.1 %). The incidence of unexpected adverse events was 0.5 % and cerebral infarction, lung cancer, pulmonary embolism, and diarrhea were reported as serious adverse events. CONCLUSION: In this survey, impotence was the most frequently reported adverse events. Dutasteride was well tolerated in Korean patients with benign prostate hyperplasia. These results updated the safety information and would provide important additional information for prescribers.

Practice Patterns of Korean Urologists for Screening and Managing Prostate Cancer according to PSA Level

PURPOSE: There are still debates on the benefit of mass screening for prostate cancer (PCA) by prostate specific antigen (PSA) testing, and on systemized surveillance protocols according to PSA level. Furthermore, there is a paucity of literature on current practice patterns according to PSA level in the Korean urologic field. Here, we report the results of a nationwide, multicenter, retrospective chart-review study. MATERIALS AND METHODS: Overall 2122 Korean men (>40 years old, PSA >2.5 ng/mL) were included in our study (from 122 centers, in 2008). The primary endpoint was to analyze the rate of prostate biopsy according to PSA level. Secondary aims were to analyze the detection rate of PCA, the clinical features of patients, and the status of surveillance for PCA according to PSA level. RESULTS: The rate of prostate biopsy was 7.1%, 26.3%, 54.2%, and 64.3% according to PSA levels of 2.5-3.0, 3.0-4.0, 4.0-10.0, and >10.0 ng/mL, respectively, and the PCA detection rate was 16.0%, 22.2%, 20.2%, and 59.6%, respectively. At a PSA level >4.0 ng/mL, we found a lower incidence of prostate biopsy in local clinics than in general hospitals (21.6% vs. 66.2%, respectively). A significant proportion (16.6%) of patients exhibited high Gleason scores (> or =8) even in the group with low PSA values (2.5-4.0 ng/mL). CONCLUSION: We believe that the results from this nationwide study might provide an important database for the establishment of practical guidelines for the screening and management of PCA in Korean populations.

Post-marketing Surveillance of the Safety and Effectiveness of Rosiglitazone/Metformin in Korean Patients with Type 2 Diabetes

BACKGROUND: To evaluate the safety and effectiveness of rosiglitazone/metformin in patients with type 2 (non-insulin-dependent) diabetes. METHODS: A total of 982 patients were enrolled by 19 physicians from November 2003 to November 2010. Patients treated with rosiglitazone/metformin at least once, were included in safety assessment. The incidences of adverse events (AEs) and serious adverse events (SAEs) were estimated. The effectiveness of rosiglitazone/metformin was evaluated through change in fasting blood glucose (FBG), 2-hour postprandial glucose (2hr PPG), Hemoglobin A1c (HbA1c). RESULTS: Of the 982 patients, 713 patients with the mean age of 56.4 +/- 11.5 years were included in the safety assessment. A total of 130 AEs were reported from 110 patients (15.4 %). The most frequent AEs were upper respiratory infection (2.4 %), oedema (2.2 %), gastritis (1.3 %), and weight increase (1.1 %). The incidence of unexpected AEs was 5.9 % (42/713, 47 AEs). Three SAEs such as bacterial pneumonia, hyperglycaemia, chest pain were reported in 2 patients. As it is about effectiveness, patients showed statistically significant reductions after treatment of rosiglitazone/metformin in FBG, 2hr PPG, and HbA1c (P<0.001 by paired t-test, for all). CONCLUSION: Our data suggest that rosiglitazone/metformin is well tolerated and effective in Korean patients with type 2 (non-insulin-dependent) diabetes.

Post-marketing Surveillance of the Safety and Effectiveness of Rosiglitazone/Metformin in Korean Patients with Type 2 Diabetes

BACKGROUND: To evaluate the safety and effectiveness of rosiglitazone/metformin in patients with type 2 (non-insulin-dependent) diabetes. METHODS: A total of 982 patients were enrolled by 19 physicians from November 2003 to November 2010. Patients treated with rosiglitazone/metformin at least once, were included in safety assessment. The incidences of adverse events (AEs) and serious adverse events (SAEs) were estimated. The effectiveness of rosiglitazone/metformin was evaluated through change in fasting blood glucose (FBG), 2-hour postprandial glucose (2hr PPG), Hemoglobin A1c (HbA1c). RESULTS: Of the 982 patients, 713 patients with the mean age of 56.4 +/- 11.5 years were included in the safety assessment. A total of 130 AEs were reported from 110 patients (15.4 %). The most frequent AEs were upper respiratory infection (2.4 %), oedema (2.2 %), gastritis (1.3 %), and weight increase (1.1 %). The incidence of unexpected AEs was 5.9 % (42/713, 47 AEs). Three SAEs such as bacterial pneumonia, hyperglycaemia, chest pain were reported in 2 patients. As it is about effectiveness, patients showed statistically significant reductions after treatment of rosiglitazone/metformin in FBG, 2hr PPG, and HbA1c (P<0.001 by paired t-test, for all). CONCLUSION: Our data suggest that rosiglitazone/metformin is well tolerated and effective in Korean patients with type 2 (non-insulin-dependent) diabetes.

The Clinical and Laboratory Characteristics of Patients with Chronic Hepatitis B Using Current or Past Antiviral Therapy in Korea: A Multi-Center, Nation-Wide, Cross-Sectional Epidemiologic Study

BACKGROUND/AIMS: The proper assessment of the current disease status of patients with chronic hepatitis B would be valuable for establishing optimal management strategies. METHODS: The clinical and laboratory characteristics of 2,954 patients with current or previous antiviral treatment (46.2+/-10.8 years, 69.7% male) enrolled from 46 referral hospitals and 129 local hospitals or clinics throughout Korea were analyzed. RESULTS: The disease status included chronic hepatitis, cirrhosis, and hepatocellular carcinoma in 79.9%, 16.4%, and 3.7% of the patients, respectively. The major mode of hepatitis B virus (HBV) infection was vertical transmission. The hepatitis C virus (HCV) co-infection rate was 1.5%; however, only 50.8% of patients were evaluated for HCV. The use of herbal or complementary medicines was reported in 33.5% of the patients. The majority of patients (97.6%) were treated with oral nucleoside/nucleotide analogues. Several characteristics were different between the patients treated at referral hospitals and local hospitals/clinics, including the disease state, choice of antiviral drug, and methods of HBV DNA measurement. CONCLUSIONS: This study provides a comprehensive picture of the clinical and laboratory characteristics of patients treated in Korea. Efforts to optimize management strategies are warranted.

Reasons for Investigators to Participate Industry Sponsored Clinical Trials

BACKGROUND: It is getting more difficult to involve appropriate investigators in clinical trials. Knowing what investigators want from sponsor initiated clinical trials would help industry cooperate with investigators more efficiently. This study aims to describe the incentives for investigators choosing to participate or not and perform well in sponsored clinical trials. METHODS: Investigators who have participated in GSK sponsored clinical trials were interviewed face-to-face or through e-mail using the standardized questionnaire. Investigators were asked to choose five items and determine the ranking or those five items. RESULTS: Questionnaires answered by 122 investigators were collected. The top three incentives were "Academic merit" (108, 88.5 %), "Expectation of treatment potentially helpful to patient" (101, 82.8 %), and "Access to new treatments" (92, 75.4 %). The disincentives and the factors affecting an investigator's performance were analyzed separately because of the different questionnaire between investigators for medicine and vaccine. Investigators for medicine choose as disincentives "Insufficient time" (43, 61.4 %), "Difficult protocol" (41, 58.6 %), and "Adverse event concerns" (41, 58.6 %). Vaccine investigators pointed out "Limited support staff" (41, 78.8 %), "Insufficient time" (40, 76.9 %), and "Difficult blood sampling" (333, 63.5 %) as disincentives. Factors adversely affecting an investigator's performance showed similar results to those of disincentives. CONCLUSION: Investigators focused on academic curiosity and patients and insufficient time mostly inhibits them from participating and performing clinical trials. Our results would help industry cooperate with investigators more efficiently, finally making companies perform clinical trials more effectively.

Post-Marketing Surveillance for the Safety and Effectiveness of Adefovir in Patients with Chronic Hepatitis B

BACKGROUND: To investigate the safety and effectiveness of adefovir in Korean patients with chronic hepatitis B, an observational study was carried out. METHODS: A total of 4,393 patients with chronic hepatitis B were enrolled from February 2004 to February 2010. For the safety assessment, investigators recorded the occurrence of observed and patient-reported adverse events (AEs) throughout the course of treatment. Antiviral effectiveness was assessed by measuring the degree of symptom improvement and the reduction of HBV DNA after 12 weeks of treatment. RESULTS: Of the 4,393 patients, 4,158 patients were evaluated for safety and 3,867 patients for effectiveness assessment. A total of 118 AEs were reported in 4,158 patients (1.8 %). The most frequent AE was hepatic failure (0.2 %) followed by coughing (0.2 %), hepatic neoplasm (0.2 %), abdominal pain (0.1 %), dyspepsia (0.1 %), nausea (0.1 %), flatulence (0.1 %), hepatic cirrhosis (0.1 %), asthenia (0.1 %), increase in sputum production (0.1 %), and varicose vein (0.1 %). The incidence of unexpected AEs was 0.9 %. Forty-nine cases of serious AE were reported in 32 patients but all of those were thought to be unrelated to adefovir according to physician's evaluations. The rate of subjects with well effectiveness was 96.2 %. CONCLUSION: Adefovir was clinically well tolerated and effective in treatment of chronic hepatitis B patients.

The Evaluation of the Efficacy and the Safety of Docetaxel in Korean Breast Cancer Patients: through Post-Authori- zation Survey to Fulfill the Registrative Requirement / 한국유방암학회지

PURPOSE: Post-authorization survey(PAS) is a useful tool for obtainting wider range of data on the safety and efficacy of new drugs following their approval, as they can detect uncommon, unreported adverse events(AEs), which enables more attention to be directed to the practioners. Especially, the limited number of patients in oncology trial cannot usually give the actual incidence of AEs. METHODS: Since Nov. 1998, when docetaxel gained Korean approval in the treatment of breast cancer, a PAS to investigate its safety profiles has been conducted targeting more than 600 patients over 4 calendar years. RESULTS: Case report forms from 626 out of 646 patients were assessable for safety and 444 for efficacy. The patient characteristics are: mean age, 48.1 years; male/female 4/622; Wt/Ht/BSA 57.9 kg/156.1 cm/1.56 m2 ; stage I-II/III/IV 109 (18.2%)/125 (20.8%)/366(61.0%). In 344 patients, 960 AEs were reported in severity of mild/moderate/severe in 6.7, 40.9 and 51.1 % of cases. From AE results, 36.0% needed dose reduction; 34.3% transient interruption of the cycle; and 1.3% permanent discontinuation of docetaxel. Thirty five serious AEs such as febrile neutropenia, alopecia, diarrhea, abdominal pain and headache were reported in 21 patients. Unexpected AEs such as skin ulcer, discoloration of skin, H. Zoster infection, ulticaria, facial flush, chest pain, hemoptysis, pneumonia, stridor, nasal bleeding, photophobia, haematuria, Cushing's syndrome, hyperglycemia and insomnia were reported regardless of any causal relationship. Factors affecting the development of AEs were age, stage, concomitant medication other than chemotherapeutic agents and the number of cycles treated. The efficacy was evaluable in 444 patients with overall response rate of 36.5% (CR/PR 6.3/30.2%). Factors affecting the efficacy were stage, concommitant medication other than chemotherapeutic agents and the number of treatment cycles. CONCLUSION: This post-authorization survey on the safety and efficacy of docetaxel in breast cancer offers oncology practice in the real world without subject selection as is the case in clinical trials, although it was performed to fulfill the registrative requirement of the Korean health authority with limited data. The efficacy and safety profile of docetaxel in breast cancer was no much different from those reported in clinical trials.

In Vitro Activities of Gatifloxacin against Bacteria isolated from Respiratory Specimens of Patients of University Hospitals in Korea

BACKGROUND: Gatifloxacin, a new 8-methoxyquinolone, has a broad-spectrum activity with expanded potency against respiratory pathogens. In this study, we examined the in vitro activity of gatifloxacin and comparators against recently isolated bacteria from respiratory specimens of patients in Korean hospitals. METHODS: Forty-nine isolates were from respiratory specimens of patients with acute exacerbations of chronic lower respiratory infections in eight university hospitals and 108 isolates were from respiratory specimens from patients of Yonsei University Hospital. Minimum inhibitory concentrations (MICs) were determined by NCCLS agar dilution method. RESULTS: MIC90 of gatifloxacin for Streptococcus pneumoniae was 1 g/mL, which was 8-fold and 2-fold lower than those of ciprofloxacin and levofloxacin, respectively. All strains of Haemophilus in fluenzae and Moraxella (Branhamella) catarrhalis were inhibited by < or =0.06 g/mL and < or =0.25 g/mL of gatifloxacin, respectively, and were susceptible to all fluoroquinolones tested. MIC90 of gatifloxacin for Klebsiella pneumoniae was 0.06 g/mL, which was 2-fold lower than those of levofloxacin and moxifloxacin. CONCLUSION: Gatifloxacin is highly active against S. pneumoniae, H. influenzae and M. (B.) catarrhalis isolated from respiratory specimens of patients of university hospitals in Korea.

In Vitro Activities of Gatifloxacin against Bacteria isolated from Respiratory Specimens of Patients of University Hospitals in Korea

BACKGROUND: Gatifloxacin, a new 8-methoxyquinolone, has a broad-spectrum activity with expanded potency against respiratory pathogens. In this study, we examined the in vitro activity of gatifloxacin and comparators against recently isolated bacteria from respiratory specimens of patients in Korean hospitals. METHODS: Forty-nine isolates were from respiratory specimens of patients with acute exacerbations of chronic lower respiratory infections in eight university hospitals and 108 isolates were from respiratory specimens from patients of Yonsei University Hospital. Minimum inhibitory concentrations (MICs) were determined by NCCLS agar dilution method. RESULTS: MIC90 of gatifloxacin for Streptococcus pneumoniae was 1 g/mL, which was 8-fold and 2-fold lower than those of ciprofloxacin and levofloxacin, respectively. All strains of Haemophilus in fluenzae and Moraxella (Branhamella) catarrhalis were inhibited by < or =0.06 g/mL and < or =0.25 g/mL of gatifloxacin, respectively, and were susceptible to all fluoroquinolones tested. MIC90 of gatifloxacin for Klebsiella pneumoniae was 0.06 g/mL, which was 2-fold lower than those of levofloxacin and moxifloxacin. CONCLUSION: Gatifloxacin is highly active against S. pneumoniae, H. influenzae and M. (B.) catarrhalis isolated from respiratory specimens of patients of university hospitals in Korea.

Evaluation of the development of high risk low birth weight infants using bayley developmental test

Forty two high risk low birth weight infants who had been admitted in neonatal intensive care unit at Yongdong Severance Hospital from August 1987 to July 1990 and followed up in the high risk infants follow-up clinic were studied for evaluation of their development using the Bayley develop-mental test at the age of 9 month(corrected age). The results obtaincd were as follows: 1) Their Mental Developmental Index(MDI)and Psychomotor Developmental Index(PDD)were 99.4+/-12.8 and 101.8+/-16.6 MDI and PDI in birth weight 1000~1500 gm group were 95.3+/-9.8 and 99.3+/-14.3 and the indexes in birth weight 1500~2500gm group were 102.2+/-14.3 and 103.5+/-17.9. 2) There is no statistical significant relationship between the results of Bayley scales and birth weight, cranial ultrasonographic finding, APGAR score, ventilator care and neonatal seizure. However, the MDI was significantly lower in small for gestational age group than appropriate gestational age group. 3) The body weight, height and head circumference measured at the age of 9 month, at the same time when Baylcy developmcntal test was performed, were 45.0+/-29.6, 40.2+/-25.7 and 46.2+/-26.8percentile of Korean Pediatric Growth Standard(1985).