No abstract available.
Down Syndrome* ; Leukemia, Megakaryoblastic, Acute*

Background: Carvedilol is a beta-adrenergic receptor antagonist primarily metabolized by cytochromes P450 (CYP) 2D6. This study established a carvedilol population pharmacokinetic (PK)–pharmacodynamic (PD) model to describe the effects of CYP2D6 genetic polymorphisms on the inter-individual variability of PK and PD. Methods: The PK–PD model was developed from a clinical study conducted on 21 healthy subjects divided into three CYP2D6 phenotype groups, with six subjects in the extensive metabolizer (EM, *1/*1, *1/*2), seven in the intermediate metabolizer-1 (IM-1, *1/*10, *2/*10), and eight in the intermediate metabolizer-2 (IM-2, *10/*10) groups. The PK–PD model was sequentially developed, and the isoproterenol-induced heart rate changes were used to establish the PD model. A direct effect response and inhibitory E max model were used to develop a carvedilol PK–PD model. Results: The carvedilol PK was well described by a two-compartment model with zeroorder absorption, lag time, and first-order elimination. The carvedilol clearance in the CYP2D6*10/*10 group decreased by 32.8% compared with the other groups. The inhibitory concentration of carvedilol estimated from the final PK–PD model was 16.5 ng/mL regardless of the CYP2D6 phenotype. Conclusion The PK–PD model revealed that the CYP2D6 genetic polymorphisms were contributed to the inter-individual variability of carvedilol PK, but not PD.

An adaptive design is a clinical trial design that allows for modification of a structured plan in a clinical trial based on data accumulated during pre-planned interim analyses. This flexible approach to clinical trial design improves the success rate of clinical trials while reducing time, cost, and sample size compared to conventional methods. The purpose of this study is to identify the current status of adaptive design and present key considerations for planning an appropriate adaptive design based on specific circumstances. We searched for clinical trials conducted between January 2006 to July 2021 in the Clinical Trials Registry (ClinicalTrials.gov) using keywords specified in the Food and Drug Administration Adaptive Design Clinical Trial Guidelines. In order to analyze the adaptive designs used in selected cases, we classified the results according to the phase of the clinical trial, type of indication, and the specific adaptation method employed. A total of 267 clinical trials were identified on ClinicalTrials.gov. Among them, 236 clinical trials actually applied adaptive designs and were classified according to phase, indication types, and adaptation methods. Adaptive designs were most frequently used in phase 2 clinical trials and oncology research. The most commonly used adaptation method was the adaptive treatment selection design. In the case of coronavirus disease 2019, the most frequently used designs were adaptive platform design and seamless design. Through this study, we expect to provide valuable insights and considerations for the implementation of adaptive design clinical trials in different diseases and stages.

Coproporphyrin (CP)-I and CP-III are the markers of organic anion-transporting polypeptides’ (OATPs) activities, and they are porphyrin metabolites that originate from heme synthesis.Furthermore, CP-I and CP-III, which are OATP1B endogenous metabolites, have gradually attracted the attention of scientists and researchers in recent years. Previous studies have also observed CP-I and CP-III levels as clinical biomarkers for predicting OATP1B inhibition in drug–drug interaction studies. To establish an accurate ultra-high performance liquid chromatography–mass spectrometry method for the quantitation of CP-I and CP-III, we reviewed previous methodological publications and applied them to a clinical pharmacology study using a human urine matrix. We used 13.25 M formic acid as a working solution for internal standards (CP-I 15 N 4 and CP-III d8 ) to avoid isobaric interference. The calibration curve showed good linearity in the range of 1–100 ng/mL, with a correlation coefficient (R 2 ) higher than 0.996 in each validation batch. Both the between-run and within-run assays achieved good precision and accuracy, and we found that both CP-I and CP-III were stable in the prestudy validation. The method exhibited suitable dilution integrity, allowing for the re-analysis of samples with concentrations exceeding the upper limit of quantification through dilution.Overall, the application of the described method in a clinical study revealed that it can be utilized effectively to monitor drug–drug interactions mediated by OATP1B.

OBJECTIVE: The purpose of this study was to evaluate any improvement in the quality of abdominal CTs after the utilization of the nationally based accreditation program. MATERIALS AND METHODS: Approval was obtained from the Institutional Review Board, and informed consent was waived. We retrospectively analyzed 1,011 outside abdominal CTs, from 2003 to 2007. We evaluated images using a fill-up sheet form of the national accreditation program, and subjectively by grading for the overall CT image quality. CT scans were divided into two categories according to time periods; before and after the implementation of the accreditation program. We compared CT scans between two periods according to parameters pertaining to the evaluation of images. We determined whether there was a correlation between the results of a subjective assessment of the image quality and the evaluation scores of the clinical image. RESULTS: The following parameters were significantly different after the implementation of the accreditation program: identifying data, display parameters, scan length, spatial and contrast resolution, window width and level, optimal contrast enhancement, slice thickness, and total score. The remaining parameters were not significantly different between scans obtained from the two different periods: scan parameters, film quality, and artifacts. CONCLUSION: After performing the CT accreditation program, the quality of the outside abdominal CTs show marked improvement, especially for the parameters related to the scanning protocol.
*Accreditation ; Humans ; *Quality Improvement ; Radiography, Abdominal/*standards ; Republic of Korea ; Retrospective Studies ; Tomography, X-Ray Computed/*standards

OBJECTIVE: To evaluate whether there is a relationship between subjective parameters determined by a reviewer (spatial resolution, low contrast resolution, and artifacts) and objective parameters (the CT number of water, noise, and image uniformity) in CT phantom image evaluations. MATERIALS AND METHODS: We reviewed the CT results of phantom image evaluations conducted by Korean Institute for Accreditation of Medical Image (KIAMI) from May 2007 to June 2007. We compared the objective parameters against the pass or fail groups for the subjective parameters. We also evaluated whether there is a relationship between the artifact types and the other subjective parameters. RESULTS: The mean noise value was significantly higher in the fail groups for the subjective parameters compared to the pass groups (p = 0.006). Specifically, noise and low contrast resolution were found to have a statistically significant positive correlation (r = 0.183, p < 0.001). In the fail group for low contrast resolution, the failure due to artifacts was significantly higher than the pass group (p < 0.001). In contrast, no statistically significant differences were found for the mean CT number of water, noise, or image uniformity based on the types of artifacts. CONCLUSION: Subjective CT image parameters evaluated by a reviewer correlate with objectively measured parameters, especially noise. Therefore, a stricter noise standard might be able to improve the subjective parameters results, such as low contrast resolution.
Artifacts ; Korea ; *Phantoms, Imaging ; *Tomography, X-Ray Computed

Emerging concerns regarding the hazard from medical radiation including CT examinations has been suggested. The purpose of this study was to observe the longitudinal changes of CT radiation doses of various CT protocols and to estimate the long-term efforts of supervising radiologists to reduce medical radiation. Radiation dose data from 11 representative CT protocols were collected from 12 hospitals. Attending radiologists had collected CT radiation dose data in two time points, 2007 and 2010. They collected the volume CT dose index (CTDIvol) of each phase, number of phases, dose length product (DLP) of each phase, and types of scanned CT machines. From the collected data, total DLP and effective dose (ED) were calculated. CTDIvol, total DLP, and ED of 2007 and 2010 were compared according to CT protocols, CT machine type, and hospital. During the three years, CTDIvol had significantly decreased, except for dynamic CT of the liver. Total DLP and ED were significantly decreased in all 11 protocols. The decrement was more evident in newer CT scanners. However, there was substantial variability of changes of ED during the three years according to hospitals. Although there was variability according to protocols, machines, and hospital, CT radiation doses were decreased during the 3 years. This study showed the effects of decreased CT radiation dose by efforts of radiologists and medical society.
Abdomen/radiation effects ; Angiography ; Brain/radiation effects ; Female ; Hospitals ; Humans ; Liver/radiation effects ; Longitudinal Studies ; Male ; Middle Aged ; *Radiation Dosage ; *Tomography, X-Ray Computed/instrumentation

The current guidelines for therapeutic drug monitoring (TDM) of vancomycin suggest a target 24-hour area under the curve (AUC 0-24 ) of 400 to 600 mg*h/L for serious methicillinresistant Staphylococcus aureus infections. In this study, the predictabilities of acute kidney injury (AKI) of various TDM target parameters, target levels, and sampling methods were evaluated in patients who underwent TDM from January 2020 to December 2020. The AUC 0-24 and trough values were calculated by both one- and two-point sampling methods, and were evaluated for the predictability of AKI. Among the AUC 0-24 cutoff comparisons, the threshold value of 500 mg*h/L in the two sampling methods was statistically significant (P = 0.042) when evaluated for the predictability of AKI. Analysis by an receiver operating characteristic curve estimated an AUC 0-24 cutoff value of 563.45 mg*h/L as a predictor of AKI, and was proposed as the upper limit of TDM target.