Management of Neonatal Hepatic Hemangiomas: A Single-Center Experience Focused on Challenging Cases.

Background: Management of hepatic hemangioma (HH) in infancy ranges from close monitoring to surgical resection. We analyzed the clinical characteristics and outcomes of HH according to its treatment options, with particular focus on challenging cases. Methods: Data of patients diagnosed with HHs in their first year of life and followed up for at least 1 year were retrospectively reviewed and divided into treatment and observation groups. Serial imaging results, serum alpha-fetoprotein (AFP) levels, medications, and clinical outcomes were compared. The detailed clinical progress in the treatment group was reviewed separately. Results: A total of 87 patients (75 in the observation group and 12 in the treatment group) were included. The median HH size at the initial diagnosis and the maximum size were significantly larger in the treatment group than the observation group (2.2 [0.5-10.3] cm vs. 1.0 [0.4-4.0] cm and 2.1 [0.7-13.2] vs. 1.1 [0.4-4.0], respectively; all p < 0.05]. The median initial and last serum AFP levels were significantly higher in the treatment group than in the observation group (76,818.7 vs. 627.2 and 98.4 vs. 8.7, respectively; all p < 0.05). Serum AFP levels in both groups rapidly declined during the first 3 months of life and were almost undetectable after 6 months. Among the challenging cases, a large (14 × 10 × 6.5 cm sized) focal HH was successfully treated using stepwise medical-to-surgical treatment. Conclusions: Patients with large HH and mild symptoms can be treated using stepwise pharmacotherapy. More aggressive surgical treatment of tumors unresponsive to initial pharmacotherapy may help shorten the treatment period and improve outcomes.

Long-term outcomes of very low birth weight infants with intraventricular hemorrhage: a nationwide population study from 2011 to 2019.

BACKGROUND: Advancements in neonatal care have increased preterm infant survival but paradoxically raised intraventricular hemorrhage (IVH) rates. This study explores IVH prevalence and long-term outcomes of very low birth weight (VLBW) infants in Korea over a decade. METHODS: Using Korean National Health Insurance data (NHIS, 2010-2019), we identified 3372 VLBW infants with IVH among 4,129,808 live births. Health-related claims data, encompassing diagnostic codes, diagnostic test costs, and administered procedures were sourced from the NHIS database. The results of the developmental assessments  are categorized into four groups based on standard deviation (SD) scores. Neonatal characteristics and complications were compared among the groups. Logistic regression models were employed to identify significant changes in the incidence of complications and to calculate odds ratios with corresponding 95% confidence intervals for each risk factor associated with mortality and morbidity in IVH. Long-term growth and development were compared between the two groups (years 2010-2013 and 2014-2017). RESULTS: IVH prevalence was 12% in VLBW and 16% in extremely low birth weight (ELBW) infants. Over the past decade, IVH rates increased significantly in ELBW infants (P = 0.0113), while mortality decreased (P = 0.0225). Major improvements in certain neurodevelopmental outcomes and reductions in early morbidities have been observed among VLBW infants with IVH. Ten percent of the population received surgical treatments such as external ventricular drainage (EVD) or a ventriculoperitoneal (VP) shunt, with the choice of treatment methods remaining consistent over time. The IVH with surgical intervention group exhibited higher incidences of delayed development, cerebral palsy, seizure disorder, and growth failure (height, weight, and head circumference) up to 72 months of age (P < 0.0001). Surgical treatments were also significantly associated with abnormal developmental screening test results. CONCLUSIONS: The neurodevelopmental outcomes of infants with IVH, especially those subjected to surgical treatments, continue to be a matter of concern. It is imperative to prioritize specialized care for patients receiving surgical treatments and closely monitor their growth and development after discharge to improve developmental prognosis. Supplementary file2 (MP4 77987 kb).

Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

BACKGROUND: The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. PURPOSE: This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. METHODS: This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. RESULTS: A total 150 children (66 females) aged 7.7 years (6.4-9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%-75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC

Aesthetic doctors' perception and attitudes toward tolerance in botulinum toxin.

BACKGROUND: Botulinum toxin is a crucial therapeutic tool with broad indications in both cosmetic and medical fields. However, the expanding cosmetic use and increased dosages of botulinum toxin have raised concerns about resistance, making it essential to study the awareness and management practices among healthcare professionals. METHODS: A survey was conducted among clinical physicians using botulinum toxin. The study investigated their experiences, awareness, and management practices related to toxin resistance. Real-time mobile app-based surveys were administered to clinicians attending the 45th International Academic Conference of the Korean Academy of Laser and Dermatology (KALDAT) on December 3, 2023. RESULTS: Among 3140 participants, 673 clinical physicians completed the survey. Of these, 363 clinicians (53.9%) reported experiencing botulinum toxin resistance. Regarding the resistance rate, 59.4% indicated less than 1%, 36% reported approximately 1%-25%, and 95.4% reported less than 25%. Efforts to prevent resistance included maintaining intervals of over 3 months (54.8%), using products with lower resistance potential (47.0%), employing minimal effective doses (28.2%), and minimizing re-administration (14.9%). CONCLUSION: In the South Korean aesthetic medicine community, a majority of clinical physician's report encountering botulinum toxin resistance. Given the potential loss of various benefits associated with resistance, there is a need to establish appropriate guidelines based on mechanistic studies and current status assessments. Educating clinicians on applicable guidelines is crucial.

Pharmacokinetic Modeling of Bepotastine for Determination of Optimal Dosage Regimen in Pediatric Patients with Allergic Rhinitis or Urticaria.

Bepotastine, a second-generation antihistamine for allergic rhinitis and urticaria, is widely used in all age groups but lacks appropriate dosing guidelines for pediatric patients, leading to off-label prescriptions. We conducted this study to propose an optimal dosing regimen for pediatric patients based on population pharmacokinetic (popPK) and physiologically based pharmacokinetic (PBPK) models using data from two previous trials. A popPK model was built using NONMEM software. A one-compartment model with first-order absorption and absorption lag time described our data well, with body weight incorporated as the only covariate. A PBPK model was developed using PK-Sim software version 10, and the model well predicted the drug concentrations obtained from pediatric patients. Furthermore, the final PBPK model showed good concordance with the known properties of bepotastine. Appropriate pediatric doses for different weight and age groups were proposed based on the simulations. Discrepancies in recommended doses from the two models were likely due to the incorporation of age-dependent physiological factors in the PBPK model. In conclusion, our study is the first to suggest an optimal oral dosing regimen of bepotastine in pediatric patients using both approaches. This is expected to foster safer and more productive use of the drug.

Assessment of Pharmacokinetic Effects of Herbal Medicines on Escitalopram.

Purpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb-antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant. Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype. Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan- 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang-1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san-1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang-1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups. Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram.

Population pharmacokinetic-pharmacodynamic modeling of clopidogrel for dose regimen optimization based on CYP2C19 phenotypes: A proof of concept study.

Clopidogrel is an antiplatelet drug used to reduce the risk of acute coronary syndrome and stroke. It is converted by CYP2C19 to its active metabolite; therefore, poor metabolizers (PMs) of CYP2C19 exhibit diminished antiplatelet effects. Herein, we conducted a proof-of-concept study for using population pharmacokinetic-pharmacodynamic (PK-PD) modeling to recommend a personalized clopidogrel dosing regimen for individuals with varying CYP2C19 phenotypes and baseline P2Y12 reaction unit (PRU) levels. Data from a prospective phase I clinical trial involving 36 healthy male participants were used to develop the population PK-PD model predicting the concentrations of clopidogrel, clopidogrel H4, and clopidogrel carboxylic acid, and linking clopidogrel H4 concentrations to changes in PRU levels. A two-compartment model effectively described the PKs of both clopidogrel and clopidogrel carboxylic acid, and a one-compartment model of those of clopidogrel H4. The CYP2C19 phenotype was identified as a significant covariate influencing the metabolic conversion of the parent drug to its metabolites. A PD submodel of clopidogrel H4 that stimulated the fractional turnover rate of PRU levels showed the best performance. Monte Carlo simulations suggested that PMs require three to four times higher doses than extensive metabolizers to reach the target PRU level. Individuals within the top 20th percentile of baseline PRU levels were shown to require 2.5-3 times higher doses than those in the bottom 20th percentile. We successfully developed a population PK-PD model for clopidogrel considering the impact of CYP2C19 phenotypes and baseline PRU levels. Further studies are necessary to confirm actual dosing recommendations for clopidogrel.

Factors associated with the response to postnatal dexamethasone use in very low birthweight infants: a nationwide cohort study.

BACKGROUND: Dexamethasone is widely used as a systemic corticosteroid to treat and prevent bronchopulmonary dysplasia (BPD) in preterm infants. We evaluated the current epidemiology of dexamethasone use to prevent BPD and analyse the factors associated with the response to dexamethasone in very low birthweight infants using a nationwide database. METHODS: We included very low birthweight infants born between January 2013 and December 2020 with a gestational age of 23-31 weeks using data from the Korean Neonatal Network registry. Patients were grouped based on their dexamethasone use into 'Dex' or 'No Dex' groups. Clinical variables and data were collected, and the annual trends of dexamethasone use and the proportion of patients who received dexamethasone according to gestational age were analysed. Respiratory outcomes were compared between the groups. Univariate and multivariate analyses were performed to analyse factors associated with the response to dexamethasone in BPD. RESULTS: Of 11 261 eligible infants, 2313 (20.5%) received dexamethasone, and 1714 (74.1%) of them were diagnosed with moderate-to-severe BPD. The 8-year annual prevalence of dexamethasone use was 17.7-22.3%. The 'Dex' group had more moderate-to-severe BPD, more frequent invasive ventilation use at a postmenstrual age of 36 weeks and longer ventilator duration. Birth weight, 5-minute APGAR score, pulmonary hypertension within the first 28 days, surgical treatment of patent ductus arteriosus, medical treatment of patent ductus arteriosus, pathological chorioamnionitis, hydrocortisone or budesonide use, surgical management of necrotising enterocolitis and fungal sepsis were associated with BPD after dexamethasone use. CONCLUSIONS: Approximately 20.5% of preterm infants received dexamethasone, and the frequency increased as gestational age decreased. Poor response to dexamethasone was associated with antenatal and postnatal inflammation, low birth weight and early pulmonary hypertension.

Prediction of Postnatal Growth Failure in Very Low Birth Weight Infants Using a Machine Learning Model.

Accurate prediction of postnatal growth failure (PGF) can be beneficial for early intervention and prevention. We aimed to develop a machine learning model to predict PGF at discharge among very low birth weight (VLBW) infants using extreme gradient boosting. A total of 729 VLBW infants, born between 2013 and 2017 in four hospitals, were included. PGF was defined as a decrease in z-score between birth and discharge that was greater than 1.28. Feature selection and addition were performed to improve the accuracy of prediction at four different time points, including 0, 7, 14, and 28 days after birth. A total of 12 features with high contribution at all time points by feature importance were decided upon, and good performance was shown as an area under the receiver operating characteristic curve (AUROC) of 0.78 at 7 days. After adding weight change to the 12 features-which included sex, gestational age, birth weight, small for gestational age, maternal hypertension, respiratory distress syndrome, duration of invasive ventilation, duration of non-invasive ventilation, patent ductus arteriosus, sepsis, use of parenteral nutrition, and reach at full enteral nutrition-the AUROC at 7 days after birth was shown as 0.84. Our prediction model for PGF performed well at early detection. Its potential clinical application as a supplemental tool could be helpful for reducing PGF and improving child health.

Growth and developmental outcomes of infants with hypoxic ischemic encephalopathy.

Despite advances in obstetric care, hypoxic ischemic encephalopathy (HIE) remains a significant disease burden. We determined the national trends of HIE prevalence, therapeutic hypothermia (TH) use, mortality, and outcomes from 2012 to 2019. This study included term infants diagnosed with HIE between 2012 and 2019 from the National Health Insurance Service database. The prevalence of HIE was 2.4 per 1000 births without significant change during the period. TH was performed in approximately 6.7% of infants with HIE, and the annual variation ranged from 2.4 to 12.5%. The mortality among all term infants with HIE was 4.6%. The mortality rate among infants with HIE and TH significantly declined from 40 to 16.9% during the eight years. Infants with TH had higher mortality, increased use of inhaled nitric oxide, and more invasive ventilator use, indicating greater disease severity in the TH group. Infants with TH also showed significantly poorer outcomes, including delayed development, cerebral palsy, sensorineural hearing loss, and seizure, compared to infants without TH (p < 0.0001). With the increasing application of TH, mortality and developmental outcomes among infants with HIE have been improving in the past eight years in Korea. Further efforts to improve outcomes should be needed.

Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium-glucose cotransporter-2 inhibitor, with phentermine in healthy subjects.

BACKGROUND: DWP16001, a sodium-glucose cotransporter-2 inhibitor, has shown promise for improving blood glucose control and facilitating weight loss. Co-administration with phentermine could enhance these effects. So, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of DWP16001 and phentermine. METHODS: We conducted a randomized, open-label, 3-treatment, 6-sequence, 3-period crossover study involving 24 healthy adults. Participants received either DWP16001 (2 mg), phentermine (37.5 mg), or a combination of both once daily for 7 days. Blood samples, urine samples, and body weights were collected to evaluate the PK and PD. RESULTS: The PK of the combination was found to be similar to that of the monotherapy. The geometric mean ratio (GMR) of Cmax,ss, and AUCtau,ss were 0.98 and 1.00, respectively, for DWP16001, and 1.01 and 0.94, respectively, for phentermine. Co-administration did not significantly affect the 24-hour urinary glucose excretion compared to DWP16001 monotherapy, and the GMR was 0.90. Participants tended to experience greater weight loss in the combination therapy group, and all demonstrated good tolerance. CONCLUSIONS: Our findings indicate that there were no significant interactions during co-administration. These results suggest that the combination of DWP16001 and phentermine may be safe and effective for the treatment of obesity and diabetes. CLINICAL TRIAL REGISTRATION: NCT05321732.

Development of Photo-Polymerization-Type 3D Printer for High-Viscosity Ceramic Resin Using CNN-Based Surface Defect Detection.

Due to the high hardness and brittleness of ceramic materials, conventional cutting methods result in poor quality and machining difficulties. Additive manufacturing has also been tried in various ways, but it has many limitations. This study aims to propose a system to monitor surface defects that occur during the printing process based on high-viscosity composite resin that maximizes ceramic powder content in real time using image processing and convolutional neural network (CNN) algorithms. To do so, defects mainly observed on the surface were classified into four types by form: pore, minor, critical, and error, and the effect of each defect on the printed structure was tested. In order to improve the classification efficiency and accuracy of normal and defective states, preprocessing of images obtained based on cropping, dimensionality reduction, and RGB pixel standardization was performed. After training and testing the preprocessed images based on the DenseNet algorithm, a high classification accuracy of 98% was obtained. Additionally, for pore and minor defects, experiments confirmed that the defect surfaces can be improved through the reblading process. Therefore, this study presented a defect detection system as well as a feedback system for process modifications based on classified defects.

The impact of non-pharmaceutical interventions on premature births during the COVID-19 pandemic: a nationwide observational study in Korea.

Background: Non-pharmaceutical interventions (NPIs), such as social distancing and hand washing, have been associated with a decline in the preterm birth rate worldwide. We aimed to evaluate whether the preterm birth rate in Korea during the coronavirus disease 2019 lockdown has changed compared to that in previous years. Method: A birth registry from the Korea Statistical Information Service, which is a nationwide official database, was used to include all births claimed to have occurred between 2011 and 2020. Newborns with gestational age (GA) less than 22 weeks and birth weight less than 220 g were excluded. The pre-NPI period was designated as January 2011 to January 2020, and the NPI period was defined as February 2020 to December 2020. We assessed the effect of NPI on the incidence of prematurity per 100 births using an interrupted time-series quasi-experimental design and implementing an autoregressive integrated moving average (ARIMA) model. Results: From 2011 to 2020, a total of 3,931,974 live births were registered, among which 11,416 were excluded. Consequently, the final study population included 3,920,558 live births (both singleton and multiple births) among which 275,009 (7.0%) were preterm. The preterm birth rate was significantly higher during the NPI period (8.68%) compared to that in the pre-NPI period (6.92%) (P < 0.001). The ARIMA model showed that in all singleton and multiple births, except those in July (observed 9.24, expected 8.54, [95% prediction interval {PI} 8.13-8.96], percent difference 7.81%), September (observed 7.89, expected 8.35, [95% PI 7.93-8.76], percent difference -5.66%), and December (observed 9.90, expected 9.40, [95% PI 8.98-9.82], percent difference 5.2%), most observed values were within the 95% PI of the expected values and showed an increasing trend. Conclusion: In this nationwide observational study, the trend in premature birth rate did not significantly change due to NPI implementation in Korea, as it had been increasing since 2011. The trend of Korea's birth rate appears to be unaffected by the implementation of NPIs; however, further studies with a longer follow-up period are needed.

Pharmacokinetic and pharmacodynamic drug-drug interactions between evogliptin and empagliflozin or dapagliflozin in healthy male volunteers.

Evogliptin (EV) is a novel dipeptidyl peptidase-4 inhibitor (DPP4i) for glycemic control in patients with type 2 diabetes mellitus (T2DM). This study evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between EV and sodium glucose cotransporter-2 inhibitors (SGLT2i) in healthy volunteers since combination therapy of DPP4i and SGLT2i has been considered as an effective option for T2DM treatment. A randomized, open-label, multiple-dose, two-arm, three-period, three treatments, two-sequence crossover study was conducted in healthy Korean volunteers. In arm 1, subjects were administered 5 mg of EV once daily for 7 days, 25 mg of empagliflozin (EP) once daily for 5 days, and the combination once daily for 5 days (EV + EP). In arm 2, subjects were administered 5 mg of EV once daily for 7 days, 10 mg of dapagliflozin (DP) once daily for 5 days, and the combination once daily for 5 days (EV + DP). Serial blood samples were collected for PK analysis, and oral glucose tolerance tests were conducted for PD analysis. In each arm, a total of 18 subjects completed the study. All adverse events (AEs) were mild with no serious AEs. The geometric mean ratio and confidence interval of the main PK parameters (maximum concentration of the drug in plasma at steady state and area under the plasma drug concentration-time curve within a dosing interval at a steady state) between EV and either EP or DP alone were not significantly altered by co-administration. Administration of EV + EP or EV + DP did not result in significant PD changes, as determined by the glucose-lowering effect. Administration of EV + EP or EV + DP had no significant effects on the PK profiles of each drug. All treatments were well-tolerated.

The effects of long-term cumulative HbA1c exposure on the development and onset time of dementia in the patients with type 2 diabetes mellitus: Hospital based retrospective study (2005-2021).

AIMS: We examined cumulative effects of long-term glycemic exposure in patients with type 2 diabetes mellitus (T2DM) on the development of dementia. METHODS: The study involved 20,487 records of patients with T2DM identified in the electronic medical record at Severance Hospital, Korea. Cumulative HbA1c (AUCHbA1c) and mean HbA1c over time (HbA1cavg) as measures of long-term glycemic exposure were compared for the development of dementia and the time to dementia. RESULTS: AUCHbA1c and HbA1cavg were significantly higher in patients who later developed dementia than in those who did not (AUCHbA1c: 56.2 ± 26.4 vs. 52.1 ± 26.1 %Year; HbA1cavg: 7.3 ± 1.0 vs. 7.0 ± 1.0%). Odds ratio of dementia increased when HbA1cavg was 7.2% (55 mmol/mol) or above, and when AUCHbA1c was 42 %Year (e.g., HbA1c 7.0% maintained for 6 years) or above. Among those who developed dementia, as HbA1cavg increased, the time to dementia onset decreased (ß = -380.6 days, 95% confidence interval [CI]: -416.2 to -345.0). CONCLUSIONS: Our results indicate poorly controlled T2DM was associated with an increased risk of developing dementia, as measured by AUCHbA1c and HbA1cavg. Higher cumulative glycemic exposure may lead to developing dementia in a shorter time.

Effect of Pharmacist-Led Intervention in Elderly Patients through a Comprehensive Medication Reconciliation: A Randomized Clinical Trial.

PURPOSE: Polypharmacy can cause drug-related problems, such as potentially inappropriate medication (PIM) use and medication regimen complexity in the elderly. This study aimed to investigate the feasibility and effectiveness of a collaborative medication review and comprehensive medication reconciliation intervention by a pharmacist and hospitalist for older patients. MATERIALS AND METHODS: This comprehensive medication reconciliation study was designed as a prospective, open-label, randomized clinical trial with patients aged 65 years or older from July to December 2020. Comprehensive medication reconciliation comprised medication reviews based on the PIM criteria. The discharge of medication was simplified to reduce regimen complexity. The primary outcome was the difference in adverse drug events (ADEs) throughout hospitalization and 30 days after discharge. Changes in regimen complexity were evaluated using the Korean version of the medication regimen complexity index (MRCI-K). RESULTS: Of the 32 patients, 34.4% (n=11/32) reported ADEs before discharge, and 19.2% (n=5/26) ADEs were reported at the 30-day phone call. No ADEs were reported in the intervention group, whereas five events were reported in the control group (p=0.039) on the 30-day phone call. The mean acceptance rate of medication reconciliation was 83%. The mean decreases of MRCI-K between at the admission and the discharge were 6.2 vs. 2.4, although it was not significant (p=0.159). CONCLUSION: As a result, we identified the effect of pharmacist-led interventions using comprehensive medication reconciliation, including the criteria of the PIMs and the MRCI-K, and the differences in ADEs between the intervention and control groups at the 30-day follow-up after discharge in elderly patients. TRIAL REGISTRATION: (Clinical trial number: KCT0005994).

Evaluation of pharmacokinetic interactions between lobeglitazone, empagliflozin, and metformin in healthy subjects.

Concomitant administration of lobeglitazone, empagliflozin, and metformin is expected to enhance blood glucose-lowering effects and improve medication compliance in patients with diabetes mellitus. In this study, we investigated the pharmacokinetic (PK) interactions and safety of lobeglitazone and co-administered empagliflozin and metformin, which are approved agents used in clinical settings. Two randomized, open-label, multiple-dose, 2-treatment, 2-period, 2-sequence crossover clinical trials (parts 1 and 2) were conducted independently. In part 1, lobeglitazone monotherapy or lobeglitazone, empagliflozin, and metformin triple therapy was administered for 5 days. In part 2, empagliflozin and metformin dual therapy or the abovementioned triple therapy were administered for 5 days. Serial blood samples were collected up to 24 hours after the last dose in each period for PK evaluation. The primary PK parameters (AUCtau,ss, Cmax,ss) of treatment regimens in each study part were calculated and compared. For lobeglitazone, the geometric mean ratios (GMRs) with 90% confidence intervals (CI) for triple therapy over monotherapy were 1.08 (1.03-1.14) for Cmax,ss and 0.98 (0.90-1.07) for AUCtau,ss. For empagliflozin, the GMRs and 90% CIs for triple therapy over dual therapy were 0.87 (0.78-0.97) for Cmax,ss and 0.97 (0.93-1.00) for AUCtau,ss. For metformin, the GMRs and 90% CIs for triple therapy over dual therapy were 1.06 (0.95-1.17) for Cmax,ss and 1.04 (0.97-1.12) for AUCtau,ss. All reported adverse events were mild. The triple therapy consisting of lobeglitazone, empagliflozin, and metformin did not show any clinically relevant drug interactions in relation to the PKs and safety of each drug substance. Trial Registration: ClinicalTrials.gov Identifier: NCT04334213.

Fabrication of 3D Printed Ceramic Part Using Photo-Polymerization Process.

Ceramics are high-strength and high-temperature resistant materials that are used in various functional parts. However, due to the high strength and brittleness properties, there are many difficulties in the fabrication of complex shapes. Therefore, there are many studies related to the fabrication of ceramic parts using 3D printing technology optimized for complex shapes. Among them, studies using photo-polymerization (PP) 3D printing technology with excellent dimensional accuracy and surface quality have received the most widespread attention. To secure the physical properties of sintered ceramic, the content and distribution of materials are important. This study suggests a novel 3D printing process based on a high-viscosity composite resin that maximizes the content of zirconia ceramics. For reliable printing, the developed 3D printers that can adjust the process environment were used. To minimize warpage and delamination, the divided micro square pattern images were irradiated in two separate intervals of 1.6 s each while maintaining the internal chamber temperature at 40 °C. This contributed to improved stability and density of the sintered structures. Ultimately, the ceramic parts with a Vickers hardness of 12.2 GPa and a relative density of over 95% were able to be fabricated based on a high-viscosity resin with 25,000 cps.

Effect of Rifampicin on the Pharmacokinetics of Evogliptin in Healthy Volunteers.

Purpose: Evogliptin (DA-1229) is a novel, potent, and selective dipeptidyl peptidase 4 (DPP-4) inhibitor for treating type 2 diabetes mellitus. This study investigates the effect of rifampicin on evogliptin pharmacokinetics. Patients and Methods: An open-label, crossover, one-sequence study was conducted on 12 healthy subjects. Reference baseline pharmacokinetic samples were collected on day 1 after the subjects were administered a single dose of 5 mg evogliptin. After a washout period, the subjects were administered 600 mg rifampicin once daily for 10 days, from days 8 to 17, for full induction of hepatic enzyme activity. On day 17, single doses of evogliptin (5 mg) were administered along with rifampicin (600 mg). The test pharmacokinetic samples were collected with a sampling schedule identical to that used for the reference. Results: Maximum concentration (Cmax) and area under the plasma drug concentration-time curve (AUC0-96h) of evogliptin with and without co-administration of rifampicin were compared. Reference and test Cmax and AUC0-96h values of evogliptin were 4.70 ng/mL vs 4.86 ng/mL and 153.97 ng∙h/mL vs 58.83 ng∙h/mL, respectively. All adverse events were mild in intensity and considered unrelated to evogliptin administration. Conclusion: Rifampicin decreased the AUC0-96h of evogliptin by 61.8% without significantly affecting Cmax. The mechanism underlying the decrease in AUC0-96h is thought to be the induction of cytochrome P450 (CYP), especially 3A, by rifampicin. The adverse events, none of which were serious, were not significantly altered by the concomitant administration of evogliptin and rifampicin. Nevertheless, it would be prudent that evogliptin dosing should be carefully considered when co-administered with CYP3A inducers.

Inappropriate Topical Antibiotics Use in Clean Dermatological Procedures in South Korea in 2018: A Nationwide Population-Based Cross-Sectional Study.

BACKGROUND: The use of topical antibiotics (TA) for prophylactic purposes after clean dermatologic procedures (CDP) is generally not recommended, and the prescription of TA needs to be individualized in consideration of each patient's situation and underlying disease. The aim of this study was to determine the proportion of patients who underwent CDP in outpatient settings and were prescribed TA inappropriately, as well as the factors that may affect the prescription of TA. METHODS: Outpatient visits coded for CDP were selected using claims data from the Health Insurance Review and Assessment Service in 2018. Of these, patients receiving TA prescriptions were classified as having inappropriate TA use, and the proportion was estimated through technical analysis. A logistic regression analysis was used to identify factors influencing inappropriate prescriptions. RESULTS: Data were analyzed using 423,651 visits, and TA was prescribed for approximately 1.9% of the visits. TA usage was higher among women (2.0%), 0-19 years of age (2.2%), medical aid (2.2%), clinic settings (2.4%), and metropolitan areas (2.0%). TA was prescribed more frequently in urology (8.6%), pediatrics (5.0%), and dermatology (4.2%) than in other specialties. CONCLUSION: The prescription rate of TA after CDP was 1.9% using the 1.4 million patient sample from the national health insurance claims data in Korea, which is equally weighted to represent 50 million people. Although the proportion of inappropriate TA prescriptions in Korea is lower than that in other nations, it cannot be overlooked because of the large number of cases. Efforts to improve quality are required to reduce the number of inappropriate prescriptions.