The structural complexity of crossover studies for bioequivalence test confuses analysts and leaves them a hard choice among various programs. Our study reviews PROC GLM and PROC MIXED in SAS and compares widely used SAS codes for crossover studies. PROC MIXED based on REML is more recommended since it provides best linear unbiased estimator of the random between-subject effects and its variance. Our study also considers the covariance structure within subject over period which most PK/PD studies and crossover studies ignore. The QT interval data after the administration of moxifloxacin for a fixed time point are analyzed for the comparison of representative SAS codes for crossover studies.
Cross-Over Studies* ; Therapeutic Equivalency

PURPOSE: This study was performed to obtain baseline information about the occupational and environmental medicine(OEM) residency programs in Korea. METHODS: We surveyed 39 residents for the present training condition, satisfaction, vision of OEM, the condition and satisfaction after residency programs by self- administered questionnaire. RESULTS: Residents want to get appropriate clinical and practical training to be a medical director in a factory or specialist of the occupational medicine based at a hospital. They report, however, that current system for OEM residency training program is not appropriate. The curricula, duration of the each curriculum, level of training hospital or institute need to be reconsidered. CONCLUSIONS: We need to develop more systematic residency program with support from government and OEM society.
Curriculum ; Education ; Environmental Medicine* ; Humans ; Internship and Residency* ; Korea* ; Occupational Medicine ; Physician Executives ; Specialization ; Surveys and Questionnaires

BACKGROUND: With increasing use of medical radiologic procedures, wearing proper protector should be emphasized to reduce occupational radiation exposures. This research describes the rates of lead apron wearing for radiation protection and assessed occupational factors related to wearing rates for various types of healthcare professionals. METHODS: We conducted a self-administered questionnaire survey through a website, on-site visits, fax, and mail. Of the 13,489 participants, 8858 workers who could not completely separate themselves from radiological procedure areas. Their general characteristics (sex and age), work history (job title, duration of employment, and hospital type), and practices (frequency of radiation procedures, ability to completely separate from radiation, and frequency of wearing protective lead aprons) were examined. RESULTS: The mean rate of lead apron wearing during radiologic procedures was 48.0 %. The rate was different according to sex (male: 52.9 %, female: 39.6 %), hospital type (general hospital: 63.0 %, hospital: 51.3 %, clinic: 35.6 %, dental hospital/clinic: 13.3 %, public health center: 22.8 %), and job title (radiologic technologist: 50.3 %, doctor: 70.3 %, dentist/dental hygienist: 15.0 %, nurse/nursing assistant: 64.5 %) (p < 0.001). By logistic regression analysis stratified by job title, use of lead aprons by radiologic technologists and nurses/nursing assistants was associated with hospital type and exposure frequency score. For doctors, apron wearing was associated with employment duration. For dentists/dental hygienists, apron wearing was associated with the exposure frequency score. CONCLUSIONS: To improve working environments for healthcare professionals exposed to radiation, it is necessary to consider related factors, such as job title, duration of employment, and hospital type, when utilizing a planning and management system to prevent radiation-related health problems.
Delivery of Health Care* ; Employment ; Female ; Humans ; Logistic Models ; Postal Service ; Public Health ; Radiation Protection

BACKGROUND: Levodropropizine is non-opioid agent whose peripheral antitussive action may result from its modulation of sensory neuropeptide levels. Currently, levodropropizine 60 mg is taken three-times daily. A controlled release formulation of levodropropizine (levodropropizine CR) 90 mg was developed, which can be taken twice daily. The aim of this study was to evaluate the safety and pharmacokinetic characteristics after multiple oral administrations of levodropropizine CR 90 mg tablets in healthy male volunteers. METHODS: A randomized, open-label, cross-over study was conducted in 24 healthy male volunteers. Each subject received levodropropizine syrup 60 mg three times daily or levodropropizine CR 90 mg twice daily for 3 days. Blood samples for pharmacokinetic analysis were collected pre-dose and up to 24 hours on day 4. Pharmacokinetic analysis was conducted by non-compartmental method. Safety assessments including monitoring adverse events, laboratory tests, vital signs, physical examinations and ECGs were performed throughout the study. RESULTS: A total of 20 male volunteers completed the study. The maximum steady-state plasma concentration (Css,max) of levodropropizine syrup and levodropropizine CR were 313.28 ng/mL and 285.31 ng/mL and time to reach Css,max (Tmax,ss) were 0.48 hr and 0.88 hr, respectively. The area under the concentration-time curve to the last measured concentration of two groups were 2345.36 hr x ng/mL and 2553.81 hr x ng/mL, respectively. There was no serious adverse event. CONCLUSION: Levodropropizine CR 90 mg tablet was safe and well-tolerated when administered twice daily for 3 days. No statistically significant differences were seen in Css,max and AUCss,24hr between the two formulations. This study provided pharmacokinetic evidences that the twice-daily dosing regimen of levodropropizine 90 mg may substitute the conventional 3-times-daily regimen of levodropropizine 60 mg.
Administration, Oral ; Cross-Over Studies ; Electrocardiography ; Humans ; Male* ; Methods ; Neuropeptides ; Pharmacokinetics* ; Physical Examination ; Plasma ; Tablets ; Vital Signs

Plasma ionized calcium (Ca2+) concentrations are tightly regulated in the body and maintained within a narrow range; thus it is challenging to quantify calcium absorption under normal physiologic conditions. This study aimed to develop a mechanistic model for the parathyroid hormone (PTH) response after calcium intake and indirectly compare the difference in oral calcium absorption from PTH responses. PTH and Ca2+ concentrations were collected from 24 subjects from a clinical trial performed to evaluate the safety and calcium absorption of Geumjin Thermal Water in comparison with calcium carbonate tablets in healthy subjects. Indirect response models (NONMEM Ver. 7.2.0) were fitted to observed Ca2+ and PTH data, respectively, in a manner that absorbed but unobserved Ca2+ inhibits the secretion of PTH. Without notable changes in Ca2+ levels, PTH responses were modeled and used as a marker for the extent of calcium absorption.
Absorption ; Calcium Carbonate ; Calcium* ; Parathyroid Hormone* ; Plasma ; Tablets ; Water

PURPOSE: The aim of this retrospective study was to identify the reliable long term prognostic factors in patients with stage II/III breast cancer who were treated with an adjuvant extension of neoadjuvant chemotherapy (NC). METHODS: Women under the age of 70-years, with previously untreated clinical stage II and III breast cancer, were treated with NC, which was comprised of three cycles of FEC (5-FU, epirubicin, and cyclophosphamide every 3 weeks) or MMM (methotrexate, mitoxantrone, and mitomycin-C every 3 weeks) with an adjuvant extension of three cycles of the same regimen. RESULTS: Cumulative 10-years disease-free survival (DFS) was 87.3% for patients with a good response and 55.5% for patients with no response (p=0.032); 92.9% for node negative patients, 75.0% for 1-3 positive nodes, 50.0% for 4-9 positive nodes and no survival for 10 or more positive nodes (p<0.001). Cumulative 10-years overall survival (OS) was 89.1% for patients with good response and 55.5% for patients with no response (p=0.024); 95.2% for node negative patients, 80.0% for 1-3 positive nodes, 50.0% for 4-9 positive nodes and no survival for 10 or more positive nodes (p<0.001). No significant difference was observed in DFS and OS between the FEC and MMM treated groups. CONCLUSION: Based on a review of data with a long follow-up, only the clinical response to NC and the absolute number of metastatic axillary lymph node identified at surgical staging were independent predictors of both DFS and OS in patients with stage II/III breast cancer patients treated with adjuvant extension of NC.
Breast ; Breast Neoplasms ; Cohort Studies ; Cyclophosphamide ; Disease-Free Survival ; Epirubicin ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; Mitomycin ; Mitoxantrone ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies

BACKGROUND: Epoxy resin compounds are one of the common causes of occupational allergic contact dermatitis. In Korea, most cases of allergic contact dermatitis from epoxy resin compounds have been caused by the epoxy resin itself. We report a rare case of allergic contact dermatitis which was caused by epichlorohydrin, an ingredient of epoxy resin and 2,4,6-tris-(dimethylaminomethyl)phenol (tris-DMP), a kind of hardeners. CASE REPORT: A 43-year-old man, who had worked at the epoxy resin glue manufacturing factory since 1999, presented with mild and intermittent erythematous papules and rashes on his face, neck, trunk, and both arms. He was dealing with epoxy resin, epichlorohydrin, bisphenol A and hardeners. After a new hardener was added in August 2008, his skin lesions worsened from what he had experienced in the past. A skin patch test was performed to identify the causative chemicals of the skin lesion. Epichlorohydrin and tris-DMP elicited positive reactions after 48 hours and increased after 96 hours. CONCLUSION: This case confirmed occupational allergic contact dermatitis caused by epichlorohydrin and tris-DMP, an ingredient of epoxy resin and a hardener, respectively.
Adhesives ; Adult ; Arm ; Benzhydryl Compounds ; Dermatitis, Allergic Contact ; Epichlorohydrin ; Exanthema ; Humans ; Korea ; Neck ; Patch Tests ; Phenols ; Skin

SKL10406, triple monoamine reuptake inhibitor, is a novel antidepressant candidate. A PET study was performed to investigate the occupancies of serotonin and dopamine transporters (SERT and DAT) in human brain, and the relationship between SKL10406 concentration and SERT occupancy was assessed using pharmacokinetic-pharmacodynamic (PK-PD) modeling methods. Fifteen healthy volunteers were given SKL10406 100 mg/day for 6 days or 150 mg/day for 6 days after 100 mg/day for 4 days. Each subject underwent full PK sampling for SKL10406 and PET scans at predose, 4 h and 16 h after dosing at a steady state to investigate the occupancies of SERT and DAT using 11C-DASB and 11C-PE2I, respectively. Naive pooled method (NPM) and nonlinear mixed-effect methods (ME) including a direct ME (DME) and an effect compartmental ME (EME) were used (NONMEM Ver. 7.2). Six and five subjects completed the studies for SERT and DAT, respectively. The final estimates of Emax (53.4%) and EC50 (11.8 ng/mL) from DME were relatively lower than those from NPM (Emax, 74.1%; EC50, 36.8 ng/mL) and EME (Emax, 68.6%; EC50, 40.2 ng/mL). DAT occupancy results were not modeled because of lower occupancies. The results showed that the dosage regimens may be applied in patient studies. However, difference between estimation methods alerts that ME may not be a recommendable analysis tool for sparsely sampled PET scan data.
Brain ; Dopamine ; Healthy Volunteers ; Humans ; Positron-Emission Tomography ; Serotonin ; Serotonin Plasma Membrane Transport Proteins*

As prediction of rapidly aging society, bone health is considered increasingly important and received more attention than ever. Bone health is regulated by balancing between bone resorptive osteoclasts and bone formative osteoblasts. Disruption of balance between bone-resorbing osteoclasts and bone-forming osteoblasts results in bone disease. Natural products have recently received much attention as an alternative tool for the development of novel therapeutic strategy. Baicalein is reported it has anti-cancer, anti-inflammatory and antioxidant effects. Baicalein also has been known that it has both promotive effect on MC3T3-E1 cell line and inhibitory effect on RAW 264.7 cell line. However, the inhibitory mechanism of baicalein using bone marrow derived macrophages (BMMs) on osteoclast differentiation remains not clear. In this study, the suppressive mechanism by baicalein on osteoblast differentiation was evaluated. Bicalein inhibited receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation in BMMs in a dose dependent manner without any toxicity. Baicalein suppressed phosphorylation of protein kinaseB (Akt), c-Jun N-terminal kinases (JNK) and phosphoinositide-specific phospholipaseCgamma2 (PLCgamma2). Furthermore, Baicalein suppressed the induction of RANKL-induced c-Fos and Nuclear factor of activated T cell c1 (NFATc1), essential genes on osteoclastogenesis. In BMMs, Bicalein inhibited the mRNA expression of tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), cathepsinK, dendritic cell-specific transmembrane protein (DC-STAMP). Moreover, baicalein promoted differentiation of osteoblast on bone marrow stromal cells (BMSCs). Taken together, these results suggest that baicalein has a potential for treating bone lytic diseases, such as osteoporosis, periodontitis, and rheumatoid arthritis.
Acid Phosphatase ; Aging ; Antioxidants ; Arthritis, Rheumatoid ; Biological Products ; Bone Diseases ; Bone Marrow* ; Cell Line ; Genes, Essential ; Macrophages* ; Mesenchymal Stromal Cells ; Osteoblasts ; Osteoclasts* ; Osteoporosis ; Periodontitis ; Phospholipase C gamma ; Phosphorylation ; Phosphotransferases ; RANK Ligand ; RNA, Messenger

Statistical analysts engaged in typical clinical trials often have to confront a tight schedule to finish massive statistical analyses specified in a Standard Operation Procedure (SOP). Thus, statisticians or not, most analysts would want to reuse or slightly modify existing programs. Since even a slight misapplication of statistical methods or techniques can easily drive a whole conclusion to a wrong direction, analysts should arm themselves with well organized statistical concepts in advance. This paper will review basic statistical concepts related to typical clinical trials. The number of variables and their measurement scales determine an appropriate method. Since most of the explanatory variables in clinical trials are designed beforehand, the main statistics we review for clinical trials include univariate data analysis, design of experiments, and categorical data analysis. Especially, if the response variable is binary or observations collected from a subject are correlated, the analysts should pay special attention to selecting an appropriate method. McNemar's test and multiple McNemar's test are respectively recommended for comparisons of proportions between correlated two samples or proportions among correlated multi-samples.
Appointments and Schedules ; Arm ; Chi-Square Distribution ; Cross-Over Studies ; Statistics as Topic ; Weights and Measures