Sex, age, and species differences of perfluorooctanoic acid modeled by flow- versus permeability-limited physiologically-based pharmacokinetic models.

This study aimed to investigate sex, age, and species differences of perfluorooctanoic acid (PFOA) using physiologically-based pharmacokinetic (PBPK) models in rats and humans. PBPK models were generally developed as either flow- or permeability-limited models. The flow-limited model is cost-effective and allows for human PK prediction through simple allometric scaling, while the permeability-limited model can incorporate detailed information on the disposition process through in vitro-in vivo extrapolation (IVIVE). PFOA was administered via oral or intravenous administration with 5 mg/kg in male and female rats of different ages and the data was used to develop the PBPK models. Our results showed that both models successfully captured sex differences in rats, while only the flow-limited model with male rats and the permeability-limited model with both male and female rats provided comparable predictions in the human clinical study. More than the flow-limited model, the permeability-limited model effectively explained sex differences in rats and species differences through IVIVE. Additionally, the ontogeny-based mechanistic description of PFOA disposition enabled the interpretation of age- and sex-dependent pharmacokinetics. Although the flow-limited PBPK model lacked mechanistic interpretability compared to the permeability-limited model, it demonstrated reliable human prediction through simple allometric scaling. In conclusion, the permeability PBPK model could interpret age, sex, and species differences and it could improve the accuracy of human prediction.

Continuous renal replacement therapy increased plasma cholinesterase activity in a case of acute organophosphate poisoning.

Extracorporeal removal of organophosphate from blood has been proposed, but the efficacy of hemodialysis and hemoperfusion has not been established. We report a case of organophosphate poisoning in which continuous renal replacement therapy (CRRT) was applied with conventional indications and was found to increase plasma cholinesterase levels by hemodiafiltration. A 73-year-old male was found unconscious at home and was brought to the emergency department by ambulance. An empty bottle of Supracide insecticide, of which the active ingredient is methidathion, was found beside him. CRRT was initiated because he showed signs of oliguria and acidosis with an unstable hemodynamic condition. Although his condition improved temporarily after CRRT initiation, it subsequently deteriorated, and he died despite maximal supportive effort. His prefilter plasma cholinesterase levels remained at <200 U/L for 3 days, while his postfilter levels were 358 U/L 1 hour after CRRT initiation and they were 689 U/L 18 hours later. Our case suggests that CRRT might play a role in treating organophosphate poisoning by possibly eliminating organophosphate.

Future and Development Direction of Digital Healthcare.

OBJECTIVES: Digital healthcare is expected to play a pivotal role in patient-centered healthcare. It empowers patients by informing, communicating, and motivating them. However, a pragmatic evaluation of the present status of digital healthcare has not been presented; therefore, we aimed to examine the status of digital healthcare in Korea. METHODS: This article discusses digital healthcare, examples of assessment in Korea and other countries, the implications of past examples, and future directions for development. RESULTS: Over the years, various clinical studies have used clinical evidence to assess the feasibility of digital healthcare. If feasible, it is actually clinically effective. If it is effective, can it be commercialized at an acceptable cost? These questions have been investigated in various evidence-based studies. In addition, great efforts are being made to secure ample evidence to assess various aspects of digital healthcare, such as safety, quality, end-user experience, and equity. CONCLUSIONS: Digital healthcare requires a deep understanding of both the technical and medical aspects. To strengthen the competence of the medical aspect, medical staff, patients, and the government must work together with continuous interest in this goal.

User Experience of Mobile Personal Health Records for the Emergency Department: Mixed Methods Study.

BACKGROUND: Personal health records (PHRs) can be useful in the emergency department, as they provide patient information in an accurate and timely manner and enable it to be used actively. This has an effect on patients' health outcomes and patient experience. Despite the importance of PHRs in emergencies, there are only a few studies related to PHRs in emergencies that evaluate patient experience. OBJECTIVE: This study aims to introduce the novel mobile PHR (mPHR) platform to emergency environments and assess user experience. METHODS: The study was conducted from October 2019 to November 2019. In total, 1000 patients or carers in the emergency departments of 3 hospitals were provided an application-based service called FirstER, which was developed to collect and utilize medical information for patients in the emergency department. This study was performed as a mixed methods study. After using FirstER, we investigated its usability and conducted a survey on the experience of obtaining medical information with a legacy system and with FirstER. Additionally, we interviewed 24 patients to gain insight into their experiences regarding medical information using FirstER. For the quantitative analysis, the survey results were analyzed using descriptive statistics (mean and standard deviation). For the qualitative analysis, we determined the keywords and their frequencies from each survey question and interview question. RESULTS: In total, 1000 participants, consisting of both patients and carers, were recruited in this study. Their mean age was 41.4 (SD 13.3) years. We ascertained participants' satisfaction with FirstER and their mPHR needs through a survey and an in-depth interview. With the current system, participants were not well aware of their health conditions and medical information, and they were passive in the use of their medical information and treatment. However, they wanted their medical information for several reasons, such as information sharing and managing their health conditions. FirstER provided participants with their needed information and an easy way to access it. The mean System Usability Scale (SUS) value was 67.1 (SD 13.8), which was considered very near to acceptable. CONCLUSIONS: This study is the first to implement mPHRs in the emergency department of large tertiary hospitals in the Republic of Korea. FirstER was found to enhance user experience in emergencies, as it provided necessary medical information and proper user experience. Moreover, the average SUS was 67.1, which means that participants found FirstER to be very near to acceptable. This is very encouraging in that FirstER was developed within a very short time, and it was a pilot study. TRIAL REGISTRATION: Clinicaltrials.gov NCT04180618; https://clinicaltrials.gov/ct2/show/NCT04180618.

Association between Full Electronic Medical Record System Adoption and Drug Use: Antibiotics and Polypharmacy.

OBJECTIVES: We investigated associations between full Electronic Medical Record (EMR) system adoption and drug use in healthcare organizations (HCOs) to explore whether EMR system features such as electronic prescribing, medicines reconciliation, and decision support, might be related to drug use by using the relevant nation-wide data. METHODS: The study design was cross-sectional. Survey data of the level of adoption of EMR systems were collected for the Organization for Economic Co-operation and Development benchmarking information and communication technologies (ICT) study between November 2013 and January 2014, in Korea. Survey respondents were hospital chief information officers and medical practitioners in primary care clinics. From the national health insurance administrative dataset, two outcomes, the rate of antibiotic prescription and polypharmacy with ≥6 drugs, were extracted. RESULTS: We found that full EMR adoption showed a 16.1% lower antibiotic drug prescription than partial adoption including paper-based medical charts in the hospital only (p = 0.041). Between EMR adoption status and polypharmacy prescription, only those clinics which fully adopted EMR showed significant associations with higher polypharmacy prescriptions (36.9%, p = 0.001). CONCLUSIONS: The findings suggested that there might be some confounding effects present and sophisticated ICT may provide some benefits to the quality of care even with some mixed results. Although a negative relationship between full EMR system adoption and antibiotic drug use was only significant in hospitals, EMR system functions searching drugs or listing specific patients might facilitate antibiotic drug use reduction. Positive relationships between full EMR system adoption and polypharmacy rate in general hospitals and clinics, but not hospitals, require further research.

Spiral mouthpiece design in a dry powder inhaler to improve aerosolization.

This study presents the effect of a spiral mouthpiece design in a carrier-based dry powder inhalation on particle aerosol characteristics. Two kinds of mouthpieces, with spiral and non-spiral shaped flow channels, were fabricated by 3D-printing; particle image velocimetry and Anderson cascade impactor were performed to evaluate the drug aerosol characteristics. The obtained experimental results were in agreement with the simulation results of the computational fluid dynamics analysis. The spiral channel created a strong swirl motion of the air flow emitted from the mouthpiece exit, which produced angular momentum rather than the axial flow velocity in the forward direction. This is beneficial in terms of liberating the micronized drug particles from the carrier surface, and leads to more effective delivery of these drug particles to the peripheral target regions of the respiratory system. The spiral device could produce drug particles with significantly smaller mass median aerodynamic diameters and higher fine particle fraction than the non-spiral device.

Electrocardiogram Sampling Frequency Range Acceptable for Heart Rate Variability Analysis.

OBJECTIVES: Heart rate variability (HRV) has gained recognition as a noninvasive marker of autonomic activity. HRV is considered a promising tool in various clinical scenarios. The optimal electrocardiogram (ECG) sampling frequency required to ensure sufficient precision of R-R intervals for HRV analysis has not yet been determined. Here, we aimed to determine the acceptable ECG sampling frequency range by analyzing ECG signals from patients who visited an emergency department with the chief complaint of acute intoxication or overdose. METHODS: The study included 83 adult patients who visited an emergency department with the chief complaint of acute poisoning. The original 1,000-Hz ECG signals were down-sampled to 500-, 250-, 100-, and 50-Hz sampling frequencies with linear interpolation. R-R interval data were analyzed for time-domain, frequency-domain, and nonlinear HRV parameters. Parameters derived from the data on down-sampled frequencies were compared with those derived from the data on 1,000-Hz signals, and Lin's concordance correlation coefficients were calculated. RESULTS: Down-sampling to 500 or 250 Hz resulted in excellent concordance. Signals down-sampled to 100 Hz produced acceptable results for time-domain analysis and Poincaré plots, but not for frequency-domain analysis. Down-sampling to 50 Hz proved to be unacceptable for both time- and frequency-domain analyses. At 50 Hz, the root-mean-squared successive differences and the power of high frequency tended to have high values and random errors. CONCLUSIONS: A 250-Hz sampling frequency would be acceptable for HRV analysis. When frequency-domain analysis is not required, a 100-Hz sampling frequency would also be acceptable.

The Prevalence and Risk Factors of Atopic Dermatitis and Clinical Characteristics according to Disease Onset in 19-Year-Old Korean Male Subjects.

BACKGROUND: The natural course of atopic dermatitis (AD) in infancy, childhood, and adolescence is not yet completely known. OBJECTIVE: To investigate the prevalence and risk factors of atopic dermatits among 19-year-old Korean male subjects. METHODS: All 19-year-old Korean males must undergo medical examination for conscription. We precisely evaluated the prevalence of AD in three Korean provinces using the information from this physical checkup. AD was diagnosed by experienced dermatologists according to the Hanifin and Rajka criteria. The disease severity was assessed by the scoring of atopic dermatitis (SCORAD) index. In order to investigate the risk factors for AD, a questionnaire was administered to all subjects regarding parental atopic history, geographical characteristics of past habitation, past economic status, number of siblings, parental occupation, etc. RESULTS: The point prevalence in the Korean provinces ranged from 1.15% to 1.44%. In multivariable analysis, a parental history of AD was a significant risk factor in all 3 disease-onset groups (infancy, childhood, and adolescent onset). In the infancy-onset group, low economic status was also a significant risk factor for AD. The SCORAD index was significantly higher in AD subjects with early onset and those living in small-sized habitations. Moreover, erythema, edema, lichenification, dryness of skin, and sleep loss appeared to be more severe in early-onset cases. CONCLUSION: The younger the age of disease onset, the more severe the clinical outcomes in 19-year-old male subjects. In addition, active AD treatment at younger ages might affect the prevalence and the severity of AD in adulthood.

Histologic analyses on the response of the skin to 1,927-nm fractional thulium fiber laser treatment.

BACKGROUND: The histologic responses to varied parameters of 1,927-nm fractional thulium fiber laser treatment have not yet been sufficiently elucidated. OBJECTIVE: This study sought to evaluate histologic changes immediately after 1,927-nm fractional thulium fiber laser session at various parameters. METHODS: The dorsal skin of Yucatan mini-pig was treated with 1,927-nm fractional thulium fiber laser at varied parameters, with or without skin drying. The immediate histologic changes were evaluated to determine the effects of varying laser parameters on the width and the depth of treated zones. RESULTS: The increase in the level of pulse energy widened the area of epidermal changes in the low power level, but increased the dermal penetration depth in the high power level. As the pulse energy level increased, the increase in the power level under the given pulse energy level more evidently made dermal penetration deeper and the treatment area smaller. Skin drying did not show significant effects on epidermal changes, but evidently increased the depth of dermal denaturation under both high and low levels of pulse energy. CONCLUSION: These results may provide important information to establish treatment parameters of the 1,927-nm fractional thulium fiber laser for various skin conditions.

A pilot study for triple combination therapy with a low-fluence 1064 nm Q-switched Nd:YAG laser, hydroquinone cream and oral tranexamic acid for recalcitrant Riehl's Melanosis.

BACKGROUND: Riehl's melanosis presents as a diffuse gray-brown to black hyperpigmentation around face. The treatment of this disease is challenging and quite limited despite patients' excessive psychological stresses. OBJECTIVE: In this prospective pilot study, we evaluated the efficacy and safety for a novel combination therapy based on low-fluence Q-switched 1064 nm Nd:YAG laser, hydroquinone cream and oral tranexamic acid for recalcitrant Riehl's melanosis. METHODS: Totally eight patients with Riehl's melanosis who had failed improvements previously received multiple sessions (10-18 times) of combination treatment regimen. The primary endpoint was clinical score by the physician and the secondary endpoints were clinical score by the patients, instrumental analysis using melanin and erythema values, and histopathological score. RESULTS: Among eight patients, three received "Almost clear" grade, the other five patients received "Marked improvement" grade at final visits. No serious adverse events and post-treatment downtime was observed. Mean Melanin and Erythema Indexes also showed significant decreases compared with baseline. Histopathologic examination confirmed a significantly greater reduction of melanin content in melanophages. CONCLUSION: This combination method can be a viable option for Asian patients having Riehl's melanosis with high risk of post-inflammatory hyperpigmentation, maintaining low-dose laser irradiation.

Incidence of Adult In-Hospital Cardiac Arrest Using National Representative Patient Sample in Korea.

OBJECTIVES: This study analyzed the incidence and characteristics of in-hospital cardiac arrest (IHCA) in Korea based on a sample group of patients that is representative of the population. METHODS: The incidence of IHCA in adults was extracted from HIRA-NIS-2009, a sample of all patients using medical services in Korea. IHCA patients were analyzed according to gender, age, type of medical institute, and classification under the 6th revision of the Korean Standard Classification of Diseases (KCD-6). In addition, to assess the differences arising from the size of medical institutes, the IHCA incidence was analyzed in relation to the number of inpatient beds. RESULTS: Based on the sample data, the total incidence of IHCA in Korea was found to be 2.46 per 1,000 admissions (95% confidence interval [CI], 2.37-2.55). A higher incidence was found among men at 3.18 (95% CI, 3.03-3.33), compared to women at 1.84 (95% CI, 1.74-1.94). The incidence of IHCA was also higher in hospitals that had more than 600 inpatients beds at 5.40 (95% CI, 5.16-5.66) in comparison to those that had less than 600 inpatients beds at 4.09 (95% CI, 3.76-4.36) (p < 0.001). By primary disease, the incidence was the highest for infectious diseases. CONCLUSIONS: We demonstrated that the IHCA incidence based on gender, age, diagnostic group, and number of beds could be analyzed using the insurance claim data from a national representative sample.

Association of TG2 from mast cells and chronic spontaneous urticaria pathogenesis.

BACKGROUND: Mast cells and their mediators play important roles in chronic spontaneous urticaria (CSU) pathogenesis. Transglutaminase 2 (TG2) is expressed in activated mast cells and contributes to airway inflammation in allergic asthma. OBJECTIVE: To investigate the role of TG2 in CSU. METHODS: Patients with CSU (n = 72) and healthy controls (n = 51) were evaluated. Skin biopsy specimens were obtained from 5 patients with CSU and 2 healthy controls. Cord blood-derived human mast cells and peripheral blood-derived human mast cells were activated with IgE. TG2 activity and inflammatory mediators, such as histamine, leukotriene C4, and cytokines, were measured in serum or supernatant from cultured mast cells by enzyme-linked immunosorbent assay. Colocalization of mast cells and TG2 was determined in skin tissues by immunofluorescence. RESULTS: TG2 activity was significantly higher in serum samples from patients with CSU than in serum samples from healthy controls (P < .001). Colocalization of mast cell surface marker c-kit and TG2 was significantly increased in the lesional skin of patients with CSU compared with that in healthy controls. The levels of histamine, leukotriene C4, tumor necrosis factor α, transforming growth factor ß, and interleukins 4, 5, and 6 were significantly higher in patients with CSU than in healthy controls (P < .001). Serum TG2 levels had positive correlations with each inflammatory mediator (P < .001). TG2 activity was increased in cord blood-derived human mast cells (CBMCs) and peripheral blood-derived human mast cells activated with IgE compared with those without activation (P < .05). CONCLUSION: Our findings suggest that TG2 expressed in and released from mast cells plays an important role in CSU pathogenesis.

Availability and use of public access defibrillators in Busan Metropolitan City, South Korea.

Out-of-hospital cardiac arrest (OHCA) is considered an important health issue worldwide, and early defibrillation is a key element for a favourable prognosis. In South Korea, public access defibrillation (PAD) programmes were initiated in 2007. However, the impact of PAD programmes on OHCA survival rates remains unclear. This study evaluated the deployment and maintenance status of public automatic external defibrillators (AED), including how frequently they were used, in Busan Metropolitan City, South Korea. Managers of possible AED sites were first contacted by telephone and asked to confirm the possession of an AED. AED suppliers were contacted for AED sales records to identify missing AED sites. AEDs located in ambulances and medical institutions were not included. Investigators visited confirmed AED sites and completed a checklist on AED maintenance and use. In total, 206 AEDs were located, indicative of an AED density of 0.268 AED/km(2) and a prevalence of 6.07 per 100,000 in Busan Metropolitan City. We found that public AEDs had been used for resuscitation only 15 times, an average rate of use of once every 26.3 years. Our results indicate that AEDs in Busan Metropolitan City are underused according to the guidelines, and several are in low-priority locations. We believe that AED deployment based on cardiac arrest statistics is important to optimise layperson AED training and utilisation.

Facial Psoriasis Log-based Area and Severity Index: A valid and reliable severity measurement method detecting improvement of facial psoriasis in clinical practice settings.

Facial psoriasis is often observed in moderate to severe degrees of psoriasis. While we previously demonstrated construct validity of the facial Psoriasis Log-based Area and Severity Index (fPLASI) system for the cross-sectional evaluation of facial psoriasis, its reliability and accuracy to detect clinical improvement has not been confirmed yet. The aim of this study is to analyze whether the fPLASI properly represents the range of improvement for facial psoriasis compared with the existing facial Psoriasis Area and Severity Index (fPASI) after receiving systemic treatments in clinical practice settings. The changing severity of facial psoriasis for 118 patients was calculated by the scales of fPASI and fPLASI between two time points after systemic treatments. Then, percentage changes (ΔfPASI and ΔfPLASI) were analyzed from the perspective of both the Physician's Global Assessment of effectiveness (PGA) and patients' Subjective Global Assessment (SGA). As a result, the distribution of the fPASI was more heavily clustered around the low score range compared with the fPLASI at both first and second visits. Linear regression analysis between ΔfPASI and ΔfPLASI shows that the correlation coefficient was 0.94, and ΔfPLASI represented greater percentage changes than ΔfPASI. Remarkably, degrees of clinical improvement measured by the PGA matched better with ΔfPLASI, while ΔfPASI underestimated clinical improvements compared with ΔfPLASI from treatment-responding groups by the PGA and SGA. In conclusion, the fPLASI represented clinical improvement of facial psoriasis with more sensitivity and reliability compared with the fPASI. Therefore, the PLASI system would be a viable severity measurement method for facial psoriasis in clinical practice.

Avoidance Behavior against Positive Allergens Detected with a Multiple Allergen Simultaneous Test Immunoblot Assay in Patients with Urticaria: Factors Associated with Avoidance Success/Failure.

BACKGROUND: Avoidance behavior against positive allergens detected by using multiple allergen simultaneous test (MAST)-immunoblot assay in patients with urticaria has been rarely reported. OBJECTIVE: We aimed to assess the avoidance behavior of patients with urticaria against positive allergens detected with a MAST. METHODS: One hundred and one urticaria patients who showed positivity to at least one allergen on a MAST completed a questionnaire regarding their test results. The avoidance behavior of the patients was evaluated, and relevant determining factors of avoidance success/failure were statistically assessed. RESULTS: We detected 144 different data (n=51, food allergens; n=17, pollen allergens; and n=76, aeroallergens) from 101 patients with urticaria. The avoidance failure rates were 33.3% for food allergens, 70.6% for pollen allergens, and 30.3% for aeroallergens. The pollen group showed a significantly higher avoidance failure rate than the food and aeroallergen groups (p<0.05). The patients with higher educational levels or more severe urticaria tended to successfully avoid allergens (p<0.05). The monthly household income level and patients' reliability to the test showed borderline correlations (p=0.057 and p=0.075, respectively). CONCLUSION: We believe that the results of this study could be helpful in predicting avoidance success or failure against allergens in patients with urticaria when clinicians conduct allergen-specific immunoglobulin E tests.

Application of Telemedicine System to Prehospital Medical Control.

OBJECTIVES: Although ambulance-based telemedicine has been reported to be safe and feasible, its clinical usefulness has not been well documented, and different prehospital management systems would yield different results. The authors evaluated the feasibility and usefulness of telemedicine-assisted direct medical control in the Korean emergency medical service system. METHODS: Twenty ambulances in the Busan area were equipped with a telemedicine system. Three-lead electrocardiogram, blood pressure, and pulse oximetry data from the patient and audiovisual input from the scene were transferred to a server. Consulting physicians used desktop computers and the internet to connect to the server. Both requesting emergency medical service (EMS) providers and consulting physicians were asked to fill out report forms and submit them for analysis. RESULTS: In the 41 cases in which telemedicine equipment was used, cellular phones were concomitantly used in 28 cases (68.35%) to compensate for the poor audio quality provided by the equipment. The EMS providers rated the video transmission quality with a 4-point average score (interquartile range [IQR] 2-5) on a 5-point scale, and they rated the biosignal transmission quality as 4 (IQR 3-5). The consulting physicians rated the video quality as 4 (IQR 2.5-4) and the biosignal quality as 4 (IQR 3-4). The physicians' ratings for usefulness for making diagnosis or treatment decisions did not differ significantly in relation to the method of communication used. CONCLUSIONS: Our study did not find any significant advantage of implementing telemedicine over the use of voice calls in delivering on-line medical control. More user-friendly, smaller devices with clear advantages over voice communication would be required before telemedicine can be successfully implemented in prehospital patient care.