Development of Flexible Ion-Selective Electrodes for Saliva Sodium Detection

Saliva can be used for health monitoring with non-invasive wearable systems. Such devices, including electrochemical sensors, may provide a safe, fast, and cost-efficient way of detecting target ions. Although salivary ions are known to reflect those in blood, no available clinical device can detect essential ions directly from saliva. Here, we introduce an all-solid-state, flexible film sensor that allows highly accurate detection of sodium levels in saliva, comparable to those in blood. The wireless film sensor system can successfully measure sodium ions from a small volume of infants' saliva (<400 µL), demonstrating its potential as a continuous health monitor. This study includes the structural characterization and error analysis of a carbon/elastomer-based ion-selective electrode and a reference electrode to confirm the signal reliability. The sensor, composed of a pair of the electrodes, shows good sensitivity (58.9 mV/decade) and selectivity (log K = -2.68 for potassium), along with a broad detection range of 5 × 10-5 ≈ 1 M with a low detection limit of 4.27 × 10-5 M. The simultaneous comparison between the film sensor and a commercial electrochemical sensor demonstrates the accuracy of the flexible sensor and a positive correlation in saliva-to-blood sodium levels. Collectively, the presented study shows the potential of the wireless ion-selective sensor system for a non-invasive, early disease diagnosis with saliva.ope

Population pharmacokinetics and dose optimization of vancomycin in neonates

The pharmacokinetics of vancomycin vary among neonates, and we aimed to conduct population pharmacokinetic analysis to determine the optimal dosage of vancomycin in Korean neonates. From a retrospective chart review, neonates treated with vancomycin from 2008 to 2017 in a neonatal intensive care unit (NICU) were included. Vancomycin concentrations were collected based on therapeutic drug monitoring, and other patient characteristics were gathered through electronic medical records. We applied nonlinear mixed-effect modeling to build the population pharmacokinetic model. One- and two-compartment models with first-order elimination were evaluated as potential structural pharmacokinetic models. Allometric and isometric scaling was applied to standardize pharmacokinetic parameters for clearance and volume of distribution, respectively, using fixed powers (0.75 and 1, respectively, for clearance and volume). The predictive performance of the final model was developed, and dosing strategies were explored using Monte Carlo simulations with AUC0-24 targets 400-600. The patient cohort included 207 neonates, and 900 vancomycin concentrations were analyzed. Only 37.4% of the analyzed concentrations were within trough concentrations 5-15 µg/mL. A one-compartment model with first-order elimination best described the vancomycin pharmacokinetics in neonates. Postmenstrual age (PMA) and creatinine clearance (CLcr) affected the clearance of vancomycin, and model evaluation confirmed the robustness of the final model. Population pharmacokinetic modeling and dose optimization of vancomycin in Korean neonates showed that vancomycin clearance was related to PMA and CLcr, as well as body weight. A higher dosage regimen than the typical recommendation is suggested.ope

A 6-year safety surveillance of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in South Korea.

In 2010, Korea introduced 10-valent pneumococcal conjugate vaccine for children aged 6 weeks to 5 years against invasive disease caused by Streptococcus pneumoniae serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F and cross-reactive 19A. The aim of this 6-year real-world study of 646 healthy Korean children from 16 centers vaccinated in routine practice is to monitor vaccine safety, as per Ministry of Food and Drug Safety regulations. Around 50% had a past or existing medical condition, 19.3% an existing condition and 7.6% received concomitant medication). Total of 489 recorded adverse events (AEs) were reported in 274 infants; 86% were mild and the rest moderate, only three were reported as serious. Most AEs (97.8%) were not related to vaccination; one case of injection-site swelling and of fever was related, two cases of fever were probably related, five cases of fever and one case each of diarrhea and coughing were possibly related. None of the serious AEs were related to vaccination. Of 11 adverse drug reactions (ADRs) in 10 subjects, none were serious. Overall, 263 subjects (40.7%) received medication (mainly antibiotics or antipyretics) for the treatment of an AE, of which 6 subjects were treated for an ADR. There was no difference in the incidence of AEs according to age, sex or concomitant vaccination. Subjects with an existing medical condition had significantly more AEs than those without any conditions (p = 0.03), but no differences regarding ADRs. Four-dose vaccination with PHiD-CV appears to have a clinically-acceptable safety profile for Korean children. ClinicalTrials.gov identifier: NCT01248988.ope

Surfactant lavage therapy for meconium aspiration syndrome: a systematic review and meta-analysis

BACKGROUND: Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully established. OBJECTIVE: To investigate the effects of surfactant lavage therapy for MAS by a systematic meta-analysis. METHODS: Relevant studies were identified by database searches in MEDLINE (from 1950), EMBASE (from 1980), and CENTRAL, up to June 2010, and by additional hand searches. Meta-analyses were separately conducted for randomized controlled trials (RCTs) and non-randomized controlled studies (NRSs). Risk of bias was assessed and clinical as well as statistical heterogeneities were also investigated in explaining the potential bias. RESULTS: Two RCTs (87 patients) and eight NRSs (178 patients) were identified. From the results of the meta-analysis of RCTs, surfactant lavage significantly decreased death or the need for extracorporeal membrane oxygenation (RR 0.34, 95% CI 0.11, 0.99). An interventional benefit was indicated for other outcomes, although it was not statistically significant based only on the two RCTs. Results from the analysis of outcomes from NRSs are consistent with those from RCTs and demonstrated a beneficial effect, which could be considered as supporting evidence. CONCLUSIONS: Lung lavage with diluted surfactant appeared to improve the clinical outcome in infants with MAS. Given that less than 100 infants were included in the two RCTs, the findings of this study may still be regarded as insufficient evidence. Further research will be needed to confirm the benefit as well as to refine the lavage technique.ope

The predictors for the non-compliance to follow-up among very low birth weight infants in the Korean neonatal network.

The critical need to emphasize preterm infant follow-up after neonatal intensive care unit (NICU) discharge assures early identification of and intervention for neurodevelopmental disability. The aims of this study were to observe the follow-up rates in high-risk follow-up clinics, and analyze factors associated with non-compliance to follow-up among very low birth weight (VLBW) infants. The data was prospectively collected for 3063 VLBW infants between January 2013 and December 2014 from 57 Korean neonatal network (KNN) centers at a corrected age of 18-24 months. Correlations among demographic data, clinical variables, and neonatal intensive care unit (NICU) volume (divided into 4 quartiles) with the occurrence of non-compliance were analyzed. The overall follow-up rate at the corrected age of 18-24 month was 65.4%. The follow-up rates were inversely related to birth weight and gestational age. Apgar score, hospital stay, maternal age, and maternal education were significantly different between the compliance and non-compliance groups. The follow-up rate was higher for mothers with chorioamnionitis, abnormal amniotic fluid, multiple pregnancy, and in vitro fertilization. Infants with respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus ligation, periventricular leukomalacia, and retinopathy of prematurity were more common in the compliance group. Follow-up rates showed significant differences according to NICU volume. Using multivariate logistic regression, high birth weight, low NICU volume, siblings, foreign maternal nationality and high 5 min APGAR scores were significant independent factors associated with the non-compliance of VLBW infants for follow-up at 18-24 months of age. This is the first nation-wide analysis of follow-up for VLBW infants in Korea. Understanding factors associated with failure of compliance could help improve the long-term follow-up rates and neurodevelopmental outcomes through early intervention.ope

Barriers to and enablers of kangaroo mother care

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The burden of illness for meconium aspiration syndrome and cost prediction related to surfactant therapy for meconium aspiration syndrome in Korea

Meconium aspiration syndrome (MAS) is an important cause of respiratory distress in neonates. Surfactant therapy has been used to improve oxygenation for infants with MAS recently. The object of this study is to estimate the number of candidates for surfactant use in MAS and the cost for surfactant, and to analyze its cost-effectiveness in Korea. Using Korean Health Insurance Review and Assessment Service reimbursement data, the number of neonates with a diagnosis of MAS receiving mechanical ventilation was counted. The annual cost for surfactant use was calculated using the number of patients receiving mechanical ventilation for at least three days who were considered potential candidates for surfactant use. The cost-effectiveness was evaluated using the effectiveness data from a previous meta-analysis. Infants with a diagnosis of MAS receiving mechanical ventilation were 0.92 per 1,000 live births annually. Among them, 55% were potential candidates for surfactant use. The expected annual cost for surfactant was 990 million Korean won and 500 million Korean won and the number needed to treat was 14.3 and 6.7 in surfactant bolus therapy and surfactant lavage therapy, respectively. Sixty-four million won was estimated as the cost to prevent one infant death by surfactant bolus therapy and 15 million won by surfactant lavage therapy. The surfactant therapy for MAS is presently not covered by the Korean national health insurance and its application to MAS is limited because of the high financial burden to the patients' family. This study's results could help healthcare decision makers establish a policy in the future.ope

Wireless, Flexible, Ion-Selective Electrode System for Selective and Repeatable Detection of Sodium

Wireless, flexible, ion-selective electrodes (ISEs) are of great interest in the development of wearable health monitors and clinical systems. Existing film-based electrochemical sensors, however, still have practical limitations due to poor electrical contact and material-interfacial leakage. Here, we introduce a wireless, flexible film-based system with a highly selective, stable, and reliable sodium sensor. A flexible and hydrophobic composite with carbon black and soft elastomer serves as an ion-to-electron transducer offering cost efficiency, design simplicity, and long-term stability. The sensor package demonstrates repeatable analysis of selective sodium detection in saliva with good sensitivity (56.1 mV/decade), stability (0.53 mV/h), and selectivity coefficient of sodium against potassium (-3.0). The film ISEs have an additional membrane coating that provides reinforced stability for the sensor upon mechanical bending. Collectively, the comprehensive study of materials, surface chemistry, and sensor design in this work shows the potential of the wireless flexible sensor system for low-profile wearable applications.ope

Blood Culture Proven Early Onset Sepsis and Late Onset Sepsis in Very-Low-Birth-Weight Infants in Korea

Neonatal sepsis remains one of the most important causes of death and co-morbidity in very-low-birth-weight (VLBW) infants. The aim of this study was to determine the current incidences of early-onset sepsis (EOS) and late-onset sepsis (LOS), the distribution of pathogens, and the impact of infection on co-morbidities in VLBW infants. We analyzed the data including sepsis episode from 2,386 VLBW infants enrolled in Korean Neonatal Network from January 2013 to June 2014. We defined EOS as a positive blood culture occurring between birth and 7 days of life and LOS after 7 days of life. Sepsis was found in 21.1% of VLBW infants. The risk of sepsis was inversely related to birth weight and gestational age. EOS was found in only 3.6% of VLBW infants, however the mortality rate was as high as 34.1%. EOS was associated with the increased odds for bronchopulmonary dysplasia and intraventricular hemorrhage. The vast majority of EOS was caused by Gram-positive organisms, particularly coagulase-negative staphylococci (30.6%). LOS developed in 19.4% of VLBW infants with a 16.1% mortality rate. Pathogens in LOS were dominated by coagulase-negative staphylococci (38.3%). Twenty-five percent and fifty percent of first LOS episode occurred after 12 days and 20 days from birth, respectively. Younger and smaller VLBW infants showed the earlier occurrence day for the 25% of first LOS episode. This study provides a recent nationwide epidemiology of sepsis in VLBW infants in Korea. Based on this study, successful strategies to reduce infections would improve survival and reduce morbidity.ope

Survey on the Status of Breastfeeding in Korean Medical Institution Workers

Background: Human breast milk is essential and provides irreplaceable nutrients for early humans. However, breastfeeding is not easy for various reasons in medical institution environments. Therefore, in order to improve the breastfeeding environment, we investigated the difficult reality of breastfeeding through questionnaire responses from medical institution workers. Methods: A survey was conducted among 179 medical institution workers with experience in childbirth within the last five years. The survey results of 175 people were analyzed, with incoherent answers excluded. Results: Of the 175 people surveyed, a total of 108 people (61.7%) worked during the day, and 33 people (18.9%) worked in three shifts. Among 133 mothers who stayed with their babies in the same nursing room, 111 (93.3%) kept breastfeeding for more than a month, but among those who stayed apart, only 10 (71.4%) continued breastfeeding for more than a month (P = 0.024). Ninety-five (88.0%) of daytime workers, 32 (94.1%) two-shift workers, and 33 (100%) three-shift workers continued breastfeeding for more than a month (P = 0.026). Workers in general hospitals tended to breastfeed for significantly longer than those that worked in tertiary hospitals (P = 0.003). A difference was also noted between occupation categories (P = 0.019), but a more significant difference was found in the comparison between nurses and doctors (P = 0.012). Longer breastfeeding periods were noted when mothers worked three shifts (P = 0.037). Depending on the period planned for breastfeeding prior to childbirth, the actual breastfeeding maintenance period after birth showed a significant difference (P = 0.002). Of 112 mothers who responded to the question regarding difficulties in breastfeeding after returning to work, 87 (77.7%) mentioned a lack of time caused by being busy at work, 82 (73.2%) mentioned the need for places and appropriate circumstances. Conclusion: In medical institutions, it is recommended that environmental improvements in medical institutions, the implementation of supporting policies, and the provision of specialized education on breastfeeding are necessary to promote breastfeeding.ope