Population pharmacokinetic analysis and modeling procedures typically require estimates of both population and individual pharmacokinetic parameters. However, only some of these parameters are contained in models and only parameters in the model can be estimated. In this paper, we introduce a new R package, PKconverter, to calculate pharmacokinetic parameters using the relationships among them. After fitting the model, other parameters can be calculated from the functional relationship among the parameters. PKconverter provides the functions to calculate whole parameters along with a Shiny application for converting the parameters. With this package, it is also possible to calculate the standard errors of the other parameters that are not in the model and estimate individual parameters simultaneously.
Drug Packaging ; Pharmaceutical Preparations ; Models, Biological ; Computer Simulation ; Software

We report a 13-year-old girl with Graves disease, who showed an increased level of serum creatine kinase (CK) accompanied by myalgia after methimazole (MMI) treatment. This patient developed muscular pain two weeks after MMI administration, along with increased CK levels. The level of thyroid hormone was within the normal range when she showed increased CK levels. After the MMI dose was decreased and levo-thyroxine was added, serum CK levels decreased to normal and the myalgia improved. The pathophysiologic mechanism of this effect has not yet been elucidated. An acute relatively hypothyroid state occurs secondary to antithyroid drug (ATD) administration in chronic hyperthyroidism, which may cause changes in the CK levels. In this report, we present a rare pediatric case, along with a literature review of similar cases. In the initial state of MMI treatment, myalgia should be detected and when it occurs, CK levels should be measured. The clinical strategy of monitoring CK levels with the aim of normalizing thyroid hormones is helpful in case of the development of adverse reactions, such as myalgia, during ATD treatment for Graves disease in children.
Adolescent* ; Antithyroid Agents ; Child ; Creatine Kinase* ; Female ; Graves Disease* ; Humans ; Hyperthyroidism ; Methimazole* ; Myalgia ; Reference Values ; Thyroid Gland ; Thyroid Hormones

OBJECTIVE: Assessment of health-related quality of life in patients with rheumatoid arthritis (RA) has become important in health research. Health economists have used linear regression equations to mathematically transform changes in HAQ scores into EQ5D data, which can be used to calculate quality adjusted life years (QALYs). We aimed to examine whether a given approach is justified. METHODS: A total of 223 patients with RA were recruited from the Hospital for Rheumatic Diseases at Hanyang University. They completed the HAQ and EQ5D and a correlation analysis was performed between the two instruments. We compared HAQ and EQ5D score changes for patients who completed the EQ5D and HAQ at first and second visits (n=159). Predicted EQ5D was estimated from the HAQ using the calculating method of Bansnack et al. The mean difference between the predicted EQ5D from the HAQ and observed health utility score at the first visit and change during the study were tested by the paired t-test. RESULTS: In the cross-sectional study, EQ5D scores were moderately inversely correlated with HAQ (r=-0.716, p<0.001). However, the predicted EQ5D from the HAQ was significantly different from the observed EQ5D (p=0.001; 95% confidence interval [CI] 0.020~0.079). The change in EQ5D was also inversely correlated with the change in the HAQ (r=-0.615, p<0.001), and change in the predicted EQ5D scores corresponded well with changes in observed health utility scores (p=0.155; 95% CI (-0.0873~0.0140). CONCLUSION: Changes in predicted EQ5D corresponded with observer changes in EQ5D, suggesting that it may be better to use predicted EQ5D form HAQ to identify change in the quality of life.
Arthritis, Rheumatoid ; Cross-Sectional Studies ; Humans ; Linear Models ; Mitoxantrone ; Quality of Life ; Quality-Adjusted Life Years ; Surveys and Questionnaires ; Rheumatic Diseases

17α-hydroxylase deficiency is a rare cause of congenital adrenal hyperplasia and is characterized by primary amenorrhea, delayed puberty and hypertension. Although 17α-hydroxylase deficiency mimics mineralocorticoid-induced hypertension, impaired sexual development can aid in the differential diagnosis of this disease. A 32-year-old woman, who had a history of testicular feminization syndrome, presented with hypertension. Her aldosterone level was elevated whereas plasma renin activity was reduced, and her computed tomography scan showed a left adrenal adenoma, which was thought to be an aldosterone producing adenoma. A left adrenalectomy was performed to treat hypertension; however, the condition did not improve. The hormonal tests revealed high levels of plasma progesterone, mineralocorticoid and adrenocorticotropic hormone, and low levels of 17a hydroxyprogesterone, cortisol and sex hormones. The patient was diagnosed with 17α-hydroxylase deficiency and commenced on prednisolone, which controlled hypertension. Here, we report a case of 17α-hydroxylase deficiency mimicking hyperaldosteronism via aldosterone-producing adrenal adenoma.
Adenoma* ; Adrenal Hyperplasia, Congenital ; Adrenalectomy ; Adrenocortical Adenoma ; Adrenocorticotropic Hormone ; Adult ; Aldosterone ; Amenorrhea ; Androgen-Insensitivity Syndrome ; Diagnosis, Differential ; Female ; Gonadal Steroid Hormones ; Humans ; Hydrocortisone ; Hyperaldosteronism* ; Hypertension ; Male ; Plasma ; Prednisolone ; Progesterone ; Puberty, Delayed ; Renin ; Sexual Development

PURPOSE: We aimed to compare the detection of breast cancer using full-field digital mammography (FFDM), FFDM with computer-aided detection (FFDM+CAD), ultrasound (US), and FFDM+CAD plus US (FFDM+CAD+US), and to investigate the factors affecting cancer detection. METHODS: In this retrospective study conducted from 2008 to 2012, 48,251 women underwent FFDM and US for cancer screening. One hundred seventy-one breast cancers were detected: 115 invasive cancers and 56 carcinomas in situ. Two radiologists evaluated the imaging findings of FFDM, FFDM+CAD, and US, based on the Breast Imaging Reporting and Data System lexicon of the American College of Radiology by consensus. We reviewed the clinical and the pathological data to investigate factors affecting cancer detection. We statistically used generalized estimation equations with a logit link to compare the cancer detectability of different imaging modalities. To compare the various factors affecting detection versus nondetection, we used Wilcoxon rank sum, chi-square, or Fisher exact test. RESULTS: The detectability of breast cancer by US (96.5%) or FFDM+CAD+US (100%) was superior to that of FFDM (87.1%) (p=0.019 or p<0.001, respectively) or FFDM+ CAD (88.3%) (p=0.050 or p<0.001, respectively). However, cancer detectability was not significantly different between FFDM versus FFDM+CAD (p=1.000) and US alone versus FFDM+CAD+US (p=0.126). The tumor size influenced cancer detectability by all imaging modalities (p<0.050). In FFDM and FFDM+CAD, the nondetecting group consisted of younger patients and patients with a denser breast composition (p<0.050). In breast US, carcinoma in situ was more frequent in the nondetecting group (p=0.014). CONCLUSION: For breast cancer screening, breast US alone is satisfactory for all age groups, although FFDM+ CAD+US is the perfect screening method. Patient age, breast composition, and pathological tumor size and type may influence cancer detection during screening.
Breast Neoplasms* ; Breast* ; Carcinoma in Situ ; Consensus ; Diagnosis, Computer-Assisted ; Early Detection of Cancer ; Female ; Humans ; Information Systems ; Mammography* ; Mass Screening* ; Methods ; Retrospective Studies ; Ultrasonography* ; Ultrasonography, Mammary

Tooth wear is gradually increasing with increasing life expectancy. In particular, it is important to establish a treatment plan in the early stages so that it does not proceed to moderate or severe wear stages. It is essential to diagnose tooth wear accurately in order to plan a treatment for it. There are many risk factors including age, diet, and drugs which affects tooth wear. For the diagnosis of a tooth wear, appropriate index and evaluation method should be used. There were various tooth wear indices such as TWI, Lussi index, BEWE, and TWES. The evaluation method includes clinical examination, dental cast examination and clinical photographs. Recently, a 3D scanner is being used to assess tooth wear. The risk factors, tooth wear evaluation system, the methods of measuring tooth wear, and related literature were reviewed. The strengths and weaknesses of each index and evaluation methods were compared to derive a proper way to diagnose tooth wear.
Diagnosis ; Diet ; Life Expectancy ; Methods ; Risk Factors ; Tooth Wear ; Tooth

PURPOSE: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. MATERIALS AND METHODS: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. RESULTS: There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. CONCLUSION: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.
Biomarkers ; Capecitabine ; Chemotherapy, Adjuvant ; Classification ; Disease-Free Survival ; Drug Therapy ; Herpesvirus 4, Human ; Humans ; In Situ Hybridization ; Microsatellite Instability ; Microsatellite Repeats ; Multivariate Analysis ; Prognosis ; RNA ; Stomach Neoplasms