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Background: The purpose of this study was to find out the relationship between appropriateness of antibiotic prescription and clinical outcomes in patients with community-acquired acute pyelonephritis (CA-APN). Methods: A multicenter prospective cohort study was performed in 8 Korean hospitals from September 2017 to August 2018. All hospitalized patients aged ≥19 years diagnosed with CA-APN at admission were recruited. Pregnant women and patients with insufficient data were excluded. In addition, patients with prolonged hospitalization due to medical problems that were not associated with APN treatment were excluded. The appropriateness of empirical and definitive antibiotics was divided into “optimal,” “suboptimal,” and “inappropriate,” and optimal and suboptimal were regarded as appropriate antibiotic use. The standard for the classification of empirical antibiotics was defined reflecting the Korean national guideline for the antibiotic use in urinary tract infection 2018. The standards for the classification of definitive antibiotics were defined according to the result of in vitro susceptibility tests of causative organisms. Clinical outcomes including clinical failure (mortality or recurrence) rate, hospitalization days, and medical costs were compared between patients who were prescribed antibiotics appropriately and those who were prescribed them inappropriately. Results: In total, 397 and 318 patients were eligible for the analysis of the appropriateness of empirical and definitive antibiotics, respectively. Of these, 10 (2.5%) and 18 (5.7%) were inappropriately prescribed empirical and definitive antibiotics, respectively, and 28 (8.8%) were prescribed either empirical or definitive antibiotics inappropriately. Patients who were prescribed empirical antibiotics appropriately showed a lower mortality rate (0 vs 10%; P = .025), shorter hospitalization days (9 vs 12.5 days; P = .014), and lower medical costs (US$2,333 vs US$4,531; P = .007) compared to those who were prescribed empirical antibiotics “inappropriately.” In comparison, we detected no significant differences in clinical outcomes between patients who were prescribed definitive antibiotics appropriately and those who were prescribed definitive antibiotics inappropriately. Patients who were prescribed both empirical and definitive antibiotics appropriately showed a lower clinical failure rate (0.3 vs 7.1%; P = .021) and shorter hospitalization days (9 vs 10.5 days; P = .041) compared to those who were prescribed either empirical or definitive antibiotics inappropriately. Conclusions: Appropriate use of antibiotics leads patients with CA-APN to better clinical outcomes including fewer hospitalization days and lower medical costs.
The explosive outbreak of COVID-19 led to a shortage of medical resources, including isolation rooms in hospitals, healthcare workers (HCWs) and personal protective equipment. Here, we constructed a new model, non-contact community treatment centres to monitor and quarantine asymptomatic and mildly symptomatic COVID-19 patients who recorded their own vital signs using a smartphone application. This new model in Korea is useful to overcome shortages of medical resources and to minimise the risk of infection transmission to HCWs.
Mycoplasma pneumoniae is a main pathogen causing community-acquired pneumonia in children and young adults. Since the emergence of macrolide-resistant M. pneumoniae in the early 2000s in Japan, it has been increasingly reported worldwide as a growing problem in treatment for children. With increasing macrolide-resistant M. pneumoniae and limited data regarding its characterization and molecular analysis, we investigated the dominant M. pneumoniae strains during the recent outbreak in South Korea, and evaluated if there was an association between a specific type and macrolide resistance. Between October 2014 and December 2016 in South Korea, 249 respiratory specimens obtained from patients with confirmed M. pneumoniae pneumonia were genotyped the P1 adhesin gene, and the mutations associated with resistance (A2063G and A2064G) were tested by sequencing the targeted domain V regions of the 23S ribosomal RNA gene. Results revealed that M. pneumoniae type 1 were predominant, which was strongly associated with macrolide-resistance during the whole study period. This is the first study assessing whether M. pneumoniae subtype is related to macrolide resistance during the outbreak of M. pneumoniae.
Recent hospital fire incidents in South Korea have heightened the importance of patient evacuation. Moving patients from an intensive care unit (ICU) or emergency department (ED) setting is a challenge due to the complexity of moving acutely unwell patients who are reliant on invasive monitoring and organ support. Despite the importance of patient evacuation, the readiness of ICU and ED for urgent evacuation has not been assessed.
To enhance the readiness and competencies of workers from ICU and ED in the evacuation of patients during a simulated tabletop fire exercise.
A tabletop simulation exercise was developed by the Center for Disaster Relief, Training, and Research referencing the fire evacuation manual developed by the hospital’s ICU and ED. The scenario consisted of evacuating patients horizontally and vertically from each department. The participants’ actions were assessed using a checklist. A debriefing was completed after the exercise to discuss the gaps observed. A post-survey questionnaire was used to evaluate the exercise and assess the perception changes of the participants. All pre-to-post differences within subjects were analyzed with paired t-tests.
A total of 22 and 29 people participated in the exercise from ICU and ED, respectively. Knowledge and confidence improved post-exercise for both ICU and ED scenarios (p<0.05). Course satisfaction was 7.9 and 8.7, respectively for ICU and ED exercise. Correct performance rates for ICU and ED were 59% and 58%, respectively. Common gaps noted for both ICU and ED were wearing protective masks, patient hand-over communication, and preparation for resources.
There need to be exercises to recognize system gaps in place for hospital fire evacuation preparedness. Tabletop simulation exercises are ideal tools for this purpose. Although this was a short 90-minute exercise, this increased familiarity with the evacuation plan, tested the plan, and allowed for identification of gaps.
South Korea experienced Middle East Respiratory Syndrome (MERS) outbreak in 2015. To mitigate the threat posed by MERS, the Ministry of Health and Center for Disease Control designated hospitals to be responsible for managing any suspected or confirmed infectious patient. These hospitals receive mandatory training in managing infectious patients, but many of the trainings lack practical skills practice and pandemic preparedness exercise.
To develop and evaluate a training course designed to train healthcare providers from designated hospitals to enhance their competencies in managing emerging infectious diseases and potential outbreaks.
A two-day course was developed by the Center for Disaster Relief, Training, and Research in collaboration with the Korea Health Promotion Institute using Kern’s 6-step approach. The course consisted of didactic lectures, technical skills training, tabletop simulation, and scenario-based simulation. Table-top simulation exercises consisted of cases involving a single infectious patient detected in the outpatient clinic and outbreak in the emergency department. Scenario-based simulation exercises involved managing a critically ill infectious patient in an isolated ward. A post-survey questionnaire was used to evaluate the course and assess the perception changes of the participants. All pre-to-post differences within subjects were analyzed with paired t-tests.
A total of 121 healthcare providers participated in three separate courses. The competencies for pandemic preparedness knowledge, skills, and attitude improved from pre- to post-course. The differences were all statistically significant (p<0.05). Overall course satisfaction in average for expectation, time, delivery method, and contents were 9.5, 9.2, 9.4, and 9.2, respectively.
There needs to be tests and exercises to recognize gaps of systems in place for pandemic preparedness. Simulation exercises are ideal tools for this purpose. Although this was only a two-day intensive course, this increased familiarity with workflows, tested the coordination of workflows between different disciplines and allowed the identification of gaps.
OBJECTIVES/SPECIFIC AIMS: One of the driving mechanisms of cancer progression is the reprogramming of metabolic pathways in intermediary metabolism. Cancers increase their energy expenditure by increasing ATP production for utilization in anabolic pathways to increase production of proteins, nucleic acids and lipids. The Warburg effect, where cancer cells predominantly use aerobic glycolysis rather than oxidative phosphorylation to produce ATP, was long thought to be the main initiating pathway in increasing tumor burden. However, compelling new evidence shows that there exists metabolic heterogeneity among and within tumors. Mitochondrial respiration often plays a major role in tumor progression, as many different cancers contain a subpopulation of slow-cycling tumor-initiating cells that are multidrug-resistant and dependent on oxidative phosphorylation. These cells represent a target for cancer therapy. In this study, we identification a novel endogenous regulator of mitochondrial respiration, retinoic acid receptor responder 1 (RARRES1). METHODS/STUDY POPULATION: We assessed the metabolic phenotype of RARRES1-depleted normal epithelial cells through metabolomics, a flux analyzer and blotting for phosphorylation of AMP kinase, a major regulator of energy homeostasis. We further examined mitochondrial energetics by staining the mitochondria with TMRM and Mito-Tracker. We then analyzed the apoptotic phenotype of epithelial cells with depletion of RARRES1 with fluorescence-activated cell sorting analysis of annexin V-staining. RESULTS/ANTICIPATED RESULTS: Remarkably, fluorescence-activated cell sorting analysis of annexin V-stained epithelial cells with depletion of RARRES1 were resistant to all studied modes of cell death, implying an effect on a fundamental cell process. By using proteomics, metabolomics, cellular and molecular analyses, our data show that RARRES1 regulates mitochondrial membrane potential and subsequently alters 1-carbon metabolism by modulating the function of the mitochondrial voltage-dependent anion channel. We believe this is the first example of a tumor suppressor protein that functions to directly regulate mitochondrial energetics. Using an extracellular flux analyzer, our data also show that depletion of RARRES1 causes an increase in mitochondrial respiration and ATP production, thus enhancing biosynthetic pathways that drive the pathogenicity and survival of cancer. The metabolic and anti-apoptotic phenotype of RARRES1-depleted cells was reversed by treatment of metformin, a mitochondrial inhibitor. DISCUSSION/SIGNIFICANCE OF IMPACT: These data lay the foundation for metabo-therapy of the many tumor types that exhibit RARRES1 depletion and may have the added benefit of targeting drug-resistant tumor-initiating cells.
Little is known about longitudinal changes of the first twin presentation in twin gestations. This is a retrospective cohort study including 411 women who were admitted consecutively and delivered live-born twins at 36 weeks of gestation or more. Longitudinal assessment of the first twin presentation was conducted during gestation and at birth in all cases. Gestational age at antenatal assessment was divided into two intervals: early-third trimester (28–31 weeks) and mid-third trimester (32–35 weeks). Fetal presentation was categorized as vertex or non-vertex. We analyzed change of fetal presentation between antepartum intervals and birth. First twin presentation at early-third trimester had the same presentation at birth in 87.6% (360/411) of the study population. In this ‘no change’ group, vertex presentation was seen in 95.6% (283/296) and non-vertex was seen in 67.0% (77/115) of cases. In total, 96.1% (395/411) of the study population maintained their presentation between mid-third trimester and birth. Vertex presentation was seen in 98.4% (310/315) and non-vertex was seen in 88.5% (85/96) of cases. When comparing vertex with non-vertex, vertex presentation during third trimester was a more reliable predictor of presentation at birth (p < .001). The only factor that contributed significantly to spontaneous version of the first twin during mid-third trimester and birth was a lower birth weight of the first twin compared with the second twin. In conclusion, first twin presentation with vertex during third trimester is not likely to change into non-vertex at birth. We concluded that vertex presentation in twin gestations at early- and mid-third trimester is very predictable. In contrast, a non-vertex first twin presentation is relatively unstable.
OBJECTIVES/SPECIFIC AIMS: The goal of this study is to examine bioenergetic phenotype of retinoic acid receptor responder 1 (RARRES1)-depleted epithelial cells and to facilitate the discovery of personalized metabo-therapeutics in the context of cancers characterized with loss of or low expression of RARRES1. METHODS/STUDY POPULATION: Anoikis assay and annexinV labeling were used to assess drug resistance and apoptotic phenotype in RARRES1-depleted epithelial cells. Metabolomics, AMP kinase activity, mito-tracker, and extracellular flux assays were used to examine the bioenergetic profile of RARRES1-depleted epithelial cells. Extracellular flux assays were used to assess the phenotype of RARRES1-depleted epithelial cells treated with or without metformin. RESULTS/ANTICIPATED RESULTS: RARRES1 is a major regulator of mitochondrial function. Its depletion in tumors induces an oxidative phosphorylation dependent phenotype and subsequently increases ATP abundance in the cell, enhances anabolic pathways and increases survival. Treatment with FDA approved mitochondrial respiration inhibitor, metformin, reversed the metabolic phenotype of RARRES1 depleted-epithelial cells. Metformin could be the ideal therapeutics to reduce tumor burden in cancers with loss of or low expression of RARRES1. DISCUSSION/SIGNIFICANCE OF IMPACT: Bioenergetic dynamics are emerging as a basis for understanding the pathology of cancer. The malignancy progresses as its metabolic pattern and mitochondrial respiration become more dysfunctional. The regulatory pathways of bioenergetic dynamics are currently poorly understood, and the characterization of proteins implicated in those processes must be assessed. One understudied protein and tumor suppressor is RARRES1. RARRES1 is induced by retinoic acid (a major metabolic regulator) and functions as a putative carboxypeptidase inhibitor. Understanding the connection between this carboxypeptidase inhibitor and intermediary metabolism will enlighten our understanding of the bioenergetic profile of cells and facilitate the discovery of personalized metabo-therapeutics in the context of cancer.
During the past decade, carbapenemase-producing Enterobacteriaceae (CPE) has emerged and spread across the world.1 The major carbapenemase enzymes currently being reported are KPC, NDM-1, VIM, IMP, and OXA.2 Because carbapenemase can be effectively transmitted via mobile genetic elements, and current therapeutic options for CPE infections are extremely limited, CPE may be one of the most serious contemporary threats to public health. However, very little is known about the characteristics of CPE carriage during hospitalization. The aims of this study were to investigate the clearance rate of CPE carriage and determine the number of consecutive negative cultures required to confirm CPE clearance. We also examined CPE transmission among hospitalized patients.
Infect. Control Hosp. Epidemiol. 2015;36(11):1361–1362
Genetic factors have been suggested to be one of the determinants of the variation of left ventricular (LV) structure and function. However, the heritability range of LV structure varies across studies and the influence of genetics on LV function is not well established, especially in Asian populations. Study subjects were 1,642 healthy Korean adults from 426 families, consisting of 298 pairs of monozygotic twins, 62 pairs of dizygotic twins, one set of triplets, 567 siblings, and 354 parents. LV structure and function were measured by M-mode and 2D echocardiography, and conventional and tissue Doppler imaging (TDI). Pairwise intra-class correlations for various familial relationships and heritability were estimated for LV structure and function. The heritability of LV mass, LV ejection fraction (LVEF), left atrial volume index, the ratio between early and late diastolic velocity of mitral inflow (E/A ratio), and the ratio between early diastolic velocity of mitral inflow and early diastolic mitral annular velocities (E/Ea ratio) was 0.44, 0.27, 0.44, 0.25, and 0.33, respectively. Bivariate genetic analysis showed that LV structural and functional traits had significant genetic correlations with cardiovascular risk factors. Additive genetic correlation (ρG) of LV mass with body mass index, systolic blood pressure, and high density lipoprotein cholesterol were 0.49, 0.42, and -0.15 respectively. LVEF (ρG = 0.33) and left atrial volume index (ρG = 0.24) also had a significant genetic correlation with systolic blood pressure. These findings support the theory that genetic factors have significant influence on these traits and necessitate further work to identify the specific genes involved.
Cognitive impairments are common in Parkinson’s disease (PD). Despite its clinical importance, the development of dementia is still difficult to predict. In this study, we investigated the possible associations between non-motor symptoms and the risk of developing dementia within a 2-year observation period in PD.
A total of 80 patients with PD participated in this study. Nonmotor symptoms (the Nonmotor Symptoms Questionnaire), PD status (Unified Parkinson’s Disease Rating Scale), depression (Geriatric d Depression Scale or Montgomery-Asberg Depression Scale), stereopsis and severity of nonmotor symptoms (Non-motor symptoms scale) were assessed. Global cognitive function (Mini-Mental State Examination) were evaluated at baseline and 2 years later.
Presence of depression, vivid dreaming, REM sleep behavior disorders, hyposmia, abnormal stereopsis, non-smoking and postural instability/ gait disturbance phenotype were associated with a significantly more rapid decline of Mini-Mental State Examination. Logistic regression analyses demonstrated that depression (odds ratio=13.895), abnormal stereopsis (odds ratio=10.729), vivid dreaming (odds ratio=4.16), REM sleep behavior disorders (odds ratio=5.353) and hyposmia (odds ratio=4.911) were significant independent predictors of dementia risk within 2 years. Postural instability/ gait disturbance phenotype and age >62 years were also independent predictors of dementia risk (odd ratio=38.333, odds ratio=10.625).
We suggest that depression, vivid dreaming, REM sleep behavior disorders, hyposmia and abnormal stereopsis are closely associated with cognitive decline, and that presence of these nonmotor symptoms predict the subsequent development of Parkinson’s disease dementia.
few studies have addressed the association between the characteristics of ischemic lesions detected by diffusion-weighted imaging (dWi) and the clinical outcome in patients with hyperacute posterior circulation ischemic stroke. this study demonstrates a relationship between the findings assessed by dWi and the outcome in patients with hyperacute posterior circulation ischemic stroke.
We reviewed data from 118 patients who had posterior circulation ischemic stroke within six hours from the onset of their symptoms. the clinical outcome included early neurological deterioration (end) and a favorable outcome at three months after the onset of symptoms. using dWi, the lesion volume and the number and location of injured anatomical regions were analyzed to evaluate whether the results correlated with the clinical outcome measures.
the number of injured anatomical regions assessed by dWi was associated with the initial and delayed neurological status. Both the total volume and the number of injured anatomical regions associated with end and a favorable outcome. analysis of the location of the injured regions determined that only a pontine lesion independently associated with end. interestingly, four out of five patients who underwent decompressive craniectomy exhibited a large infarction volume but minor symptoms.
in patients with hyperacute posterior circulation ischemic strokes, the lesions assessed by dWi were associated with the clinical outcome, regardless of the initial neurological status. dWi is an effective initial imaging tool for assessing the extent of lesions and clinical outcomes in patients with hyperacute posterior circulation ischemic stroke.
The present study aimed to assess the adequacy of Ca intake and major food sources of Ca in Korean children and adolescents.
A cross-sectional study.
Data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2007–2010. We analysed the daily Ca intake, major food sources of Ca and the prevalence of inadequate Ca intake in the study population. Ca intake was categorized as inadequate when the participant's daily Ca intake was less than the Estimated Average Requirement.
The study population consisted of 7233 children and adolescents (3973 boys, 3260 girls; aged 1–18 years).
Mean Ca intake was 510·2 mg/d in boys and 431·7 mg/d in girls. Overall, 75·0 % of adolescents (boys 71·6 %, girls 79·1 %) had inadequate Ca intake. The prevalence of inadequate Ca intake increased significantly from toddlers (45–55 %) to adolescents (78–86 %) in both genders. The highest ranked food sources for Ca were dairy products (35·0 %), followed by vegetables (17·3 %), grains (11·3 %) and seafood (9·9 %). Ca intake from dairy products decreased significantly from 57 % in toddlers to 30 % in adolescents, while Ca intakes from other foods increased with age.
Inadequate Ca intake is highly prevalent and increased with age in Korean children and adolescents. It should be emphasized to encourage children and adolescents to eat more Ca-rich products to meet their Ca needs.
Cataract, defined as opacity of the lens in one or both eyes, is a major cause of blindness throughout the world, and not uncommon, particularly in the elderly population. However, congenital cataracts are rare and occur with a frequency of 30 cases in 100,000 births. About one-third of the cases fall into the group inherited without systemic abnormality. Importantly, congenital cataracts produce deprivation amblyopia, refractive amblyopia, and retinal detachment, leading to lifelong visual impairment. Successful management is dependent on early diagnosis and referral for surgery when indicated. Here we present a case of hereditary bilateral cataracts in a dizygotic twin detected on prenatal ultrasound examinations and postnatally confirmed as congenital cataracts associated with posterior lenticonus.
We investigated microstructures, compositional distributions, and electrical properties of dielectric CaCu3Ti4O12 (CCTO) thin films deposited on Pt/TiO2/SiO2/Si substrates from 700 to 800 °C by pulsed laser deposition. With increasing the deposition temperature from 700 to 750 °C, the dielectric constants (εr) of CCTO films were greatly enhanced from ∼300 to ∼2000 at 10 kHz, respectively. However, the εr values of CCTO films were gradually decreased above 750 °C, which was surely attributable to the formation of a TiO2-rich dead layer at the interface between CCTO and Pt electrode. Compositional analyses by Auger electron spectroscopy, energy dispersive spectroscopy, and electron energy loss spectroscopy revealed that the TiO2-rich dead layer became thicker because of severe Cu diffusion from CCTO films to Pt electrode. The leakage current behaviors of CCTO films are in good agreement with Poole–Frenkel conduction mechanism, where both the TiO2-rich dead layer and rutile TiO2 nanocrystalline particles are considered to play a role of charge trapping centers.
The effects of tannic acid (TA) supplementation (0·02 %, wt/wt) were compared with the effects of clofibrate (CF) supplementation (0·02 %, wt/wt) in apo E-deficient (apo E− / −) mice fed a AIN-76 semi-synthetic diet (normal diet) over 20 weeks. The mice were monitored for the modulation of hepatic mRNA expression and the activities of lipid-regulating enzymes. Both TA and CF supplementation lowered hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) activity and prevented atherosclerotic lesion formation in comparison with the control group. Hepatic carnitine palmitoyl transferase and β-oxidation activities were significantly higher in the TA and CF groups than in the control group. Both CF and TA supplementation resulted in significant decreases in hepatic HMGR mRNA levels in association with its enzyme activity. However, in contrast to CF supplementation, TA supplementation seemed to decrease the accumulation of hepatic lipids in the apo E− / − mice without increasing liver weight. These results suggest that the overall effect of TA is more desirable than CF for the alleviation of hepatic lipogenesis and atherogenesis in apo E− / − mice.
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