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

Data handling and tabulation are a time-consuming job when writing appendices for clinical study reports. The authors have developed an automated appendix generation system (ARGUS) conforming to the CDISC/SDTM standard using SAS (version 9.3) and R (version 3.3.1: for PK plot generation). It consists of the one main program and three subprograms. The program runs to convert a database file into an appendix document with about 100 tables and plots in MS Word format within one min after pressing the submit button under common desktop environments. We found that tasks of constructing appendices for a typical 2×2 crossover design study that have taken our team about 8 days were completed within 6 or 7 hours using the ARGUS system.
Appendix* ; Clinical Study* ; Cross-Over Studies ; Writing

Time-series and case-crossover are two main study designs in environmental epidemiology. However, due to the differences in design principles and model construction between the two analyses, the results of the two analyses may not be consistent. Herein, we examined the short-term effect of cold spells on cardiovascular mortality in Nanjing using both time series and case-crossover analyses, aiming to provide a basis for the selection of appropriate research design in environmental epidemiology.
Humans ; Cross-Over Studies ; Time Factors

PURPOSE: The readiness assurance process (RAP) of team-based learning (TBL) is an important element that ensures that students come prepared to learn. However, the RAP can use a significant amount of class time which could otherwise be used for application exercises. The authors administered the TBL-associated RAP in class or individual readiness assurance tests (iRATs) at home to compare medical student performance and learning preference for physiology content. METHODS: Using cross-over study design, the first year medical student TBL teams were divided into two groups. One group was administered iRATs and group readiness assurance tests (gRATs) consisting of physiology questions during scheduled class time. The other group was administered the same iRAT questions at home, and did not complete a gRAT. To compare effectiveness of the two administration methods, both groups completed the same 12-question physiology assessment during dedicated class time. Four weeks later, the entire process was repeated, with each group administered the RAP using the opposite method. RESULTS: The performance on the physiology assessment after at-home administration of the iRAT was equivalent to performance after traditional in-class administration of the RAP. In addition, a majority of students preferred the at-home method of administration and reported that the at-home method was more effective in helping them learn course content. CONCLUSIONS: The at-home administration of the iRAT proved effective. The at-home administration method is a promising alternative to conventional iRATs and gRATs with the goal of preserving valuable in-class time for TBL application exercises.
Cross-Over Studies ; Cross-Sectional Studies ; Education, Medical ; Exercise ; Humans ; Learning* ; Physiology ; Students, Medical

BACKGROUND/OBJECTIVES: The purpose of this study was to examine whether plasma lipid profiles are affected differently by snack kinds with equal calorific values. SUBJECTS/METHODS: We compared a Korean traditional confectionery (dasik) with Western confectionery (cookie) in this regard. Controlled cross-over study consisted of two 3-week snack intake phases and for separating, a 2-week washout period (3–2–3) was carried out with 30 healthy women aged between 40-59 years old. Brown rice based Korean traditional confectionery and wheat flour based Western confectionery were used. The participants consumed either dasik or cookie every day for 3 weeks, providing 93 kcal a day. RESULTS: The total cholesterol (TC) in the dasik group had decreased significantly after 3 weeks (P < 0.05). Furthermore, in the dasik group, reduction in TC and low-density lipoprotein-cholesterol were greater than those in the cookie group (P < 0.05). CONCLUSIONS: Prioritizing functional snacks like dasik improves plasma lipid profiles; this may be useful information for individuals who cannot refrain from snacking.
Cholesterol ; Cross-Over Studies* ; Female ; Flour ; Humans ; Plasma* ; Snacks ; Triticum

BACKGROUND: Photodynamic therapy (PDT) in the treatment of warts is known to be a relatively effective and safe cure. However, the pain, which occurs during being exposed to a light source and after its exposure, is being reported to be the most frequent and serious limitation in this therapy. OBJECTIVE: The purpose of this study is to examine whether the level of pain can be lowered, by comparing EMLA(R), which is a topical anesthesia, with placebo, during topical ALA-PDT, and to try to compare the range and characteristics in pain. METHODS: Twenty two patients with common warts were treated with ALA-PDT twice in the interval of 4 weeks, and were divided into two groups by the random distribution table. The distribution was made so that the patients, who used EMLA(R) as the topical anesthesia given at the first visit, could use a placebo at the second visit, and so that the patients who used placebo at the first visit, could use EMLA(R) at the second visit. Thus, a randomized, double-blind, placebo-controlled crossover study was carried out. The pain was evaluated during the treatment, right after the treatment, and one day after the treatment by using Visual Analogue Scale (VAS). Also four different ranges of the pain and its six characteristics were evaluated. RESULTS: Of the 22 patients with common warts who underwent this study. 1 patient, was completely cured after the first visit, and did not participate further in the study. The data of the patients with complete recovery wasn't included in the final statistical analysis. As a result of the evaluation of pain, the mean VAS score that was measured during the treatment, right after the treatment, and one day after the treatment was measured to be a little lower in the case of applying EMLA(R) versus placebo, but a statistically significant difference was not observed. Regarding the degree of pain, regardless of applying EMLA(R), most patients felt painful locally on the surface, and the majority complained of burning and shooting pain. CONCLUSION: Dermatologists tend to routinely apply EMLA(R), prior to a procedure in order to decrease pain. However, as a result of this research, the routine use of EMLA(R) given at PDT is thought to be unreasonable.
Anesthesia ; Burns ; Cross-Over Studies ; Humans ; Light ; Photochemotherapy ; Triazenes ; Warts

We compared the clinical performance of central 24-2(C-24-2 test) and central 30-2 full threshold test(C-30-2 test) in detecting glaucomatous visual field defect. Thirty glaucoma patients underwent automated perimetry were enrolled. One eye of each patient was examined with both C-24-2 test and C-30-2 test by a simple crossover design. MD, CPSD, SF, test time and number of question asked were compared using two tests. Whether the differences between two tests would be related to the order of test, the duration between two tests, patient's age, and the degree of visual field loss were performed. C-24-2 test showed 24.4% saving in test time(p<0.001), a lower number of question asked(p<0.001) as well as a increase of MD(0.68+/-1.43dB)(p=0.02). CPSD and SF showed no significant differences between two tests(p>0.05). The increase in MD in C-24-2 test was not related to patient`s age, order of tests, the duration between two tests and degree of visual field defect(p>0.05). In conclusion, C-24-2 test reduced test time and increased MD compared to C-30-2 test. It is suggested that the conventional C-30-2 test can be replaced with C-24-2 test without compromising the reliability and ability to detect localized defects.
Cross-Over Studies ; Glaucoma* ; Humans ; Visual Field Tests ; Visual Fields

OBJECTIVES: A stratified cross-over study was conducted to evaluate the effects of familiarity with computer on the performance of computerized neurobehavioral tests. Effects of keyboard type on the relationship between familiarity with computer and performance of computerized neurobehavioral tests were also examined. METHODS: We tested 70 persons classified into three groups according to degree of familiarity with computer: Group 1 was people with no computer competency, Group 2 had slight working experience on the computer, and Group 3 were highly competent and efficient on the computer. For each group, we executed 4 tests of the Korean version of the Swedish Performance Evaluation System (Simple Reaction Time, Addition, Symbol Digit, and Finger Tapping Speed). Three types of keyboard were applied for all three groups. Type 1 keyboard was a conventional layout with 106 keys. We removed the unused keys except for the 17 which were used in the test and remodeled the normal keyboard into Type 2 keyboard with 17 keys (10 numeric keys, 4 arrow keys, space bar, and both Ctrl keys). Type 3 keyboard with 11 keys consisted of 10 numeric keys and the space bar was newly developed for the computerized neurobehavioral performance test. RESULTS: It was found that Simple Reaction Time, Addition, and Finger Tapping Speed were not affected by familiarity with computer and type of keyboard. The mean reaction time of Symbol Digit adjusted by age and educational level with Type 1 keyboard was found to have significant difference among the three groups (F=3.347, p=0.041). The performance of Symbol Digit in Group 1 was found to be significantly lower than that in Group 2. The performances of Symbol Digit measured with Types 2 and 3 keyboards were not found to have significant differences among the three groups. In Groups 1 and 3, the performances of Symbol Digit measured with Type 1 keyboard were found to be significantly lower than those of other keyboards. CONCLUSIONS: According to the above results, Simple Reaction Time, Addition, and Finger Tapping Speed have high priority over other neurobehavioral tests for the workers having varying degrees of computer familiarity. It is also suggested that familiarity with computer and keyboard type needs to be considered in interpretation of the performance of Symbol Digit. We recommended executing the computerized neurobehavioral test with keyboards 2 or 3 to reduce the effect of computer familiarity.
Cross-Over Studies ; Fingers ; Humans ; Reaction Time ; Recognition (Psychology)*

BACKGROUND: Sustained-release theophylline, which is generally prescribed as a twice-daily equal-dose regimen, is one of the more common asthma treatments. the development of a sustained-release drug delivery technology that enables improved control of the theophylline blood levels represents a significant advancement in both the efficacy and safety of dosing. METHOD: A crossover study was conducted with 25 adult chronic asthmatic patients requiring daily bronchodilator therapy. The study group included thirteen males and twelve females with ages ranging from 19 to 71 years. The overall approach was to place the patients first on the twice-daily preparation(Etheophyl®) for 28 days at 8 AM and 8 PM, and measure the pulmonary function and theophylline level on the 28th day. the patients were subsequently switched to the once-daily preparation(Uniphyl®) in the same daily dose at 8 PM on the 29th day and the same parameters were measured on the 56th day. RESULTS: the mean serum levels of theophylline were 8.18±1.66µg/ml in the Etheophyl®-treated period and 8.00±1.75µg/ml in the Uniphyl®-treated period. In addition, the FEV1 showed 71.40±7.48 percent in the Etheophyl®-treated and 69.18±9.00 percent in the Uniphyl®-treated period. Thus there were no significant differences between the once-daily and twice-daily preparation. CONCLUSION: The results indicated little clinical differences between the two medication. The two drugs are equally effective in controlling asthma over the four weeks of treatment.
Adult ; Asthma* ; Cross-Over Studies ; Female ; Humans ; Male ; Theophylline

Aceclofenac is a non-steroidal anti-inflammatory drug (NSAIDs) for inflammatory diseases. In this report, we report a serious adverse event (AE) occurred during the phase I clinical trial for a new sustained-release (SR) formulation of aceclofenac. There was a serious adverse event (AE), agranulocytosis, induced by aceclofenac SR form. An open-labeled, repeated-doses, randomized, crossover study was conducted at Kyung Hee University Hospital and 26 Korean healthy male volunteers were enrolled. All subjects received both aceclofenac SR 200 mg once daily and aceclofenac IR 100 mg twice daily for 4 days with 11 days washout period. After 11 days washout period, one subject showed a serious decrease in the segment neutrophil (267/mm3) on a laboratory test prior to the reference drug administration in period 2. We first report a case of agranulocytosis, during a phase I clinical trial.
Agranulocytosis* ; Cross-Over Studies ; Humans ; Male ; Neutrophils ; Volunteers