Opicapone to Treat Early Wearing-off in Parkinson's Disease Patients: The Korean ADOPTION Trial.

BACKGROUND: Increasing levodopa (L-dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing-off symptoms in Parkinson's disease (PD) patients. OBJECTIVES: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing-off in PD patients. METHODS: ADOPTION was a randomized, parallel-group, open-label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L-dopa 100 mg (n = 81) (added to current L-dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society-Unified Parkinson's Disease Rating Scale and 8-item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. RESULTS: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L-dopa 100 mg (-62.1 vs. -16.7 minutes; P = 0.0015). Opicapone-treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L-dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. CONCLUSIONS: Opicapone 50 mg was more effective than an additional 100 mg L-dopa dose at decreasing off time in patients with PD and early wearing-off.

Spatiotemporal Analysis of Out-of-Hospital Cardiac Arrest Incidence and Survival Outcomes in Korea (2009-2021).

BACKGROUND: Out-of-hospital cardiac arrest is a major public health concern in Korea. Identifying spatiotemporal patterns of out-of-hospital cardiac arrest incidence and survival outcomes is crucial for effective resource allocation and targeted interventions. Thus, this study aimed to investigate the spatiotemporal epidemiology of out-of-hospital cardiac arrest in Korea, with a focus on identifying high-risk areas and populations and examining factors associated with prehospital outcomes. METHODS: We conducted this population-based observational study using data from the Korean out-of-hospital cardiac arrest registry from January 2009 to December 2021. Using a Bayesian spatiotemporal model based on the Integrated Nested Laplace Approximation, we calculated the standardized incidence ratio and assessed the relative risk to compare the spatial and temporal distributions over time. The primary outcome was out-of-hospital cardiac arrest incidence, and the secondary outcomes included prehospital return of spontaneous circulation, survival to hospital admission and discharge, and good neurological outcomes. RESULTS: Although the number of cases increased over time, the spatiotemporal analysis exhibited a discernible temporal pattern in the standardized incidence ratio of out-of-hospital cardiac arrest with a gradual decline over time (1.07; 95% credible interval [CrI], 1.04-1.09 in 2009 vs. 1.00; 95% CrI, 0.98-1.03 in 2021). The district-specific risk ratios of survival outcomes were more favorable in the metropolitan and major metropolitan areas. In particular, the neurological outcomes were significantly improved from relative risk 0.35 (0.31-0.39) in 2009 to 1.75 (1.65-1.86) in 2021. CONCLUSION: This study emphasized the significance of small-area analyses in identifying high-risk regions and populations using spatiotemporal analyses. These findings have implications for public health planning efforts to alleviate the burden of out-of-hospital cardiac arrest in Korea.

Association between out-of-hospital cardiac arrest quality indicator and prehospital management and clinical outcomes for major trauma.

INTRODUCTION: It is unclear whether emergency medical service (EMS) agencies with good out-of-hospital cardiac arrest (OHCA) quality indicators also perform well in treating other emergency conditions. We aimed to evaluate the association of an EMS agency's non-traumatic OHCA quality indicators with prehospital management processes and clinical outcomes of major trauma. METHODS: This retrospective cross-sectional study analyzed data from registers of nationwide, population-based OHCA (adult EMS-treated non-traumatic OHCA patients from 2017 to 2018) and major trauma (adult, EMS-treated, and injury severity score ≥16 trauma patients in 2018) in South Korea. We developed a prehospital ROSC prediction model to categorize EMS agencies into quartiles (Q1-Q4) based on the observed-to-expected (O/E) ROSC ratio for each EMS agency. We evaluated the national EMS protocol compliance of on-scene management according to O/E ROSC ratio quartile. The association between O/E ROSC ratio quartiles and trauma-related early mortality was determined in a multi-level logistic regression model by adjusted odds ratios (OR) and 95 % confidence intervals (95 % CI). RESULTS: Among 30,034 severe trauma patients, 4,836 were analyzed. Patients in Q4 showed the lowest early mortality rate (5.6 %, 5.5 %, 4.8 %, and 3.4 % in Q1, Q2, Q3, and Q4, respectively). In groups Q1 to Q4, increasing compliance with the national EMS on-scene management protocol (trauma center transport, basic airway management for patients with altered mentality, spinal motion restriction for patients with spinal injury, and intravenous access for patients with hypotension) was observed (p for trend <0.05). Multivariable multi-level logistic regression analysis showed significantly lower early mortality in Q4 than in Q1 (adjusted OR [95 % CI] 0.56 [0.35-0.91]). CONCLUSION: Major trauma patients managed by EMS agencies with high success rates in achieving prehospital ROSC in non-traumatic OHCA were more likely to receive protocol-based care and exhibited lower early mortality.

Seat belt use and cardiac arrest immediately after motor vehicle collision: Nationwide observational study.

Objective: Motor vehicle collisions (MVCs) are known to cause traumatic cardiac arrest; it is unclear whether seat belts prevent this. This study aimed to evaluate the association between seat belt use and immediate cardiac arrest in cases of MVCs. Method: This cross-sectional observational study used data from a nationwide EMS-based severe trauma registry in South Korea. The sample comprised adult patients with EMS-assessed severe trauma due to MVCs between 2018 and 2019. The primary, secondary, and tertiary outcomes were immediate cardiac arrest, in-hospital mortality, and death or severe disability, respectively. We calculated the adjusted odds ratios (AORs) of immediate cardiac arrest with seat belt use after adjusting for potential confounders. Results: Among the 8178 eligible patients, 6314 (77.2 %) and 1864 (29.5 %) were wearing and not wearing seat belts, respectively. Immediate cardiac arrest, mortality, and death/severe disability rates were higher in the "no seat belt use" group than in the "seat belt use" group (9.4 % vs. 4.0 %, 12.4 % vs. 6.2 %, 17.7 % vs. 9.9 %, respectively; p < 0.001). The former group was more likely to experience immediate cardiac arrest (AOR [95 %CI]: 3.29 [2.65-4.08]), in-hospital mortality (AOR [95 %CI]: 2.72 [2.26-3.27]), and death or severe disability (AOR [95 %CI]: 2.40 [2.05-2.80]). Conclusion: There was an association between wearing seat belts during MVCs and a reduced risk of immediate cardiac arrest.

Effects of Transport to Trauma Centers on Survival Outcomes Among Severe Trauma Patients in Korea: Nationwide Age-Stratified Analysis.

BACKGROUND: Previous studies showed that the prognosis for severe trauma patients is better after transport to trauma centers compared to non-trauma centers. However, the benefit from transport to trauma centers may differ according to age group. The aim of this study was to compare the effects of transport to trauma centers on survival outcomes in different age groups among severe trauma patients in Korea. METHODS: Cross-sectional study using Korean national emergency medical service (EMS) based severe trauma registry in 2018-2019 was conducted. EMS-treated trauma patients whose injury severity score was above or equal to 16, and who were not out-of-hospital cardiac arrest or death on arrival were included. Patients were classified into 3 groups: pediatrics (age < 19), working age (age 19-65), and elderly (age > 65). The primary outcome was in-hospital mortality. Multivariable logistic regression analysis was conducted to evaluate the effect of trauma center transport on outcome after adjusting of age, sex, comorbidity, mechanism of injury, Revised Trauma Score, and Injury Severity Score. All analysis was stratified according to the age group, and subgroup analysis for traumatic brain injury was also conducted. RESULTS: Overall, total of 10,511 patients were included in the study, and the number of patients in each age group were 488 in pediatrics, 6,812 in working age, and 3,211 in elderly, respectively. The adjusted odds ratio (95% confidence interval [CI]) of trauma center transport on in-hospital mortality from were 0.76 (95% CI, 0.43-1.32) in pediatrics, 0.78 (95% CI, 0.68-0.90) in working age, 0.71(95% CI, 0.60-0.85) in elderly, respectively. In subgroup analysis of traumatic brain injury, the benefit from trauma center transport was observed only in elderly group. CONCLUSION: We found out trauma centers showed better clinical outcomes for adult and elderly groups, excluding the pediatric group than non-trauma centers. Further research is warranted to evaluate and develop the response system for pediatric severe trauma patients in Korea.

Establishing the Korean Out-of-Hospital cardiac arrest registry (KOHCAR).

Background: The Korean out-of-hospital cardiac arrest registry (KOHCAR) serves as the basis for a chain of survival monitoring and quality improvement programs for out-of-hospital cardiac arrest (OHCA). This study describes the development history and current status of KOHCAR. Methods/design: The KOHCAR, initiated in 2008, is a population-based OHCA registry that captures all emergency medical service (EMS)-assessed OHCA cases, regardless of etiology. The KOHCAR represents complete nationwide data and aligns with South Korea's comprehensive plan for cardiovascular disease, which has a legal basis. The KOHCAR is a collaboration between the National Fire Agency (NFA) and the Korea Disease Control and Prevention Agency (KDCA). The NFA identifies OHCA patients and provides prehospital information after integrating various EMS records, whereas the KDCA collects hospital information and clinical outcomes through a medical record review. Comprehensive Utstein variables, including patient and arrest characteristics, prehospital and hospital management, and survival outcomes, were collected. Discussion: The KOHCAR has significantly contributed to improving OHCA survival rates in South Korea; however, the COVID-19 pandemic has posed challenge. To address the post-pandemic survival rate decline, there is a need to enhance data utilization, expand data sources, and tailor communication with diverse stakeholders.

Association between Case Volumes of Extracorporeal Life Support and Clinical Outcome in Out-of-Hospital Cardiac Arrest.

AIM: Extracorporeal life support (ECLS) for out-of-hospital cardiac arrest (OHCA) is increasing. There is little evidence identifying the association between hospital ECLS case volumes and outcomes in different populations receiving ECLS or conventional cardiopulmonary resuscitation (CPR). The goal of this investigation was to identify the association between ECLS case volumes and clinical outcomes of OHCA patients. METHODS: This cross-sectional observational study used the National OHCA Registry for adult OHCA cases in Seoul, Korea between January 2015 and December 2019. If the ECLS volume during the study period was >20, the institution was defined as a high-volume ECLS center. Others were defined as low-volume ECLS centers. Outcomes were good neurologic recovery (cerebral performance category 1 or 2) and survival to discharge. We performed multivariate logistic regression and interaction analyses to assess the association between case volume and clinical outcome. RESULTS: Of the 17,248 OHCA cases, 3,731 were transported to high-volume centers. Among the patients who underwent ECLS, those at high-volume centers had a higher neurologic recovery rate than those at low-volume centers (17.0% vs. 12.0%), and the adjusted OR for good neurologic recovery was 2.22 (95% confidence interval (CI): 1.15-4.28) in high-volume centers compared to low-volume centers. For patients who received conventional CPR, high-volume centers also showed higher survival-to-discharge rates (adjusted OR of 1.16, 95%CI: 1.01-1.34). CONCLUSIONS: High-volume ECLS centers showed better neurological recovery in patients who underwent ECLS. High-volume centers also had better survival-to-discharge rates than low-volume centers for patients not receiving ECLS.

Effect of first epinephrine administration time on cerebral perfusion pressure and cortical cerebral blood flow in a porcine cardiac arrest model.

OBJECTIVE: The optimal time for epinephrine administration and its effects on cerebral blood flow (CBF) and microcirculation remain controversial. This study aimed to assess the effect of the first administration of epinephrine on cerebral perfusion pressure (CePP) and cortical CBF in porcine cardiac arrest model. METHODS: After 4 min of untreated ventricular fibrillation, eight of 24 swine were randomly assigned to the early, intermediate, and late groups. In each group, epinephrine was administered intravenously at 5, 10, and 15 min after cardiac arrest induction. CePP was calculated as the difference between the mean arterial pressure and intracranial pressure. Cortical CBF was measured using a laser Doppler flow probe. The outcomes were CePP and cortical CBF measured continuously during cardiopulmonary resuscitation (CPR). Mean CePP and cortical CBF were compared using analysis of variance and a linear mixed model. RESULTS: The mean CePP was significantly different between the groups at 6-11 min after cardiac arrest induction. The mean CePP in the early group was significantly higher than that in the intermediate group at 8-10 min and that in the late group at 6-9 min and 10-11 min. The mean cortical CBF was significantly different between the groups at 9-11 min. The mean cortical CBF was significantly higher in the early group than in the intermediate and late group at 9-10 min. CONCLUSION: Early administration of epinephrine was associated with improved CePP and cortical CBF compared to intermediate or late administration during the early period of CPR.

Apoptosis/Necroptosis Inducing Thiazole-Containing Artificial Polypeptide for Immunogenic Cell Death of Cancer.

Immunogenic cell death (ICD) has emerged as a promising approach to cancer immunotherapy. During ICD, cancer cell death and the release of damage-associated molecular pattern (DAMP) signals occur simultaneously. Increased production of reactive oxygen species (ROS) and severe endoplasmic reticulum stress are necessary for enhanced ICD. Furthermore, the levels of ROS and reduced glutathione (GSH) are involved in various cell death mechanisms. The thiazole ring structure has gained considerable interest as a functional moiety for anticancer agents. This study designed and synthesized a positively charged cell-penetrating polypeptide with a thiazole functional moiety (NS). The NS internalizes into the cancer cells through direct penetration and endo-lysosomal escape. The NS induces mitochondrial depolarization and ER stress in a concentration-dependent manner, leading to a significant ROS production and GSH depletion. Consequently, the ICD of cancer cells is activated, resulting in the release of DAMP signals. Furthermore, NS causes a shift in the cell death pathway from apoptosis to necroptosis as the concentration increases. In this study, we confirmed the possibility of NS as a promising ICD inducer that can be used while varying the concentration according to the cancer type.

Family history, socioeconomic factors, comorbidities, health behaviors, and the risk of sudden cardiac arrest.

Genetic, environment, and behaviour factors have a role in causing sudden cardiac arrest (SCA). We aimed to determine the strength of the association between various risk factors and SCA incidence. We conducted a multicentre case-control study at 17 hospitals in Korea from September 2017 to December 2020. The cases included out-of-hospital cardiac arrest aged 19-79 years with presumed cardiac aetiology. Community-based controls were recruited at a 1:1 ratio after matching for age, sex, and urban residence level. Multivariable conditional logistic regression analysis was conducted. Among the 1016 cases and 1731 controls, 948 cases and 948 controls were analysed. A parental history of SCA, low educational level, own heart disease, current smoking, and non-regular exercise were associated with SCA incidence (Adjusted odds ratio [95% confidence interval]: 2.51 [1.48-4.28] for parental history of SCA, 1.37 [1.38-2.25] for low edication level, 3.77 [2.38-5.90] for non-coronary artery heart disease, 4.47 [2.84-7.03] for coronary artery disease, 1.39 [1.08-1.79] for current smoking, and 4.06 [3.29-5.02] for non-regular exercise). Various risk factors related to genetics, environment, and behaviour were independently associated with the incidence of SCA. Establishing individualised SCA prevention strategies in addition to general prevention strategies is warranted.

Feasibility of Isokinetic Training to Modify Coupling of Upper Limb Muscle Synergy Activation in Stroke-affected Upper Limb.

Abnormal intermuscular coordination in stroke-affected upper limbs contributes to motor deficits after stroke. In particular, abnormalities in the activation of upper limb muscle synergies after stroke were demonstrated for endpoint force control during isokinetic exercises. This study aimed to investigate the feasibility of isokinetic training to alter these abnormal synergy activations and improve motor control. Muscle synergies and Wolf Motor Function Test Functional Ability Scale (WMFT-FAS) score were compared before and after three weeks of electromyography-based training. The proposed training changed the synergy activation and improved the WMFT-FAS score in a chronic stroke survivor while preserving the muscle weights of the synergies.Clinical Relevance- This study presents the feasibility of neuromuscular training to modify the activation of upper limb muscle synergies against stroke-specific patterns of intermuscular coordination and improve WMFT-FAS score.

Expanding the repertoire of intermuscular coordination patterns and modulating intermuscular connectivity in stroke-affected upper extremity through electromyogram-guided training: a pilot study.

Abnormal intermuscular coordination is a major stroke-induced functional motor impairment in the upper extremity (UE). Previous studies have computationally identified the abnormalities in the intermuscular coordination in the stroke-affected UE and their negative impacts on motor outputs. Therefore, targeting the aberrant muscle synergies has the potential as an effective approach for stroke rehabilitation. Recently, we verified the modifiability of the naturally expressed muscle synergies of young able-bodied adults in UE through an electromyographic (EMG) signal-guided exercise protocol. This study tested if an EMG-guided exercise will induce new muscle synergies, alter the associated intermuscular connectivity, and improve UE motor outcome in stroke-affected UE with moderate-to-severe motor impairment. The study used the six-week isometric EMG signal-guided exercise protocol that focused on independently activating two specific muscles, the biceps and brachioradialis, to develop new muscle activation groups. The study found that both the stroke and age-matched, able-bodied groups were able to develop new muscle coordination patterns through the exercise while habitual muscle activation was still available, which led to improvements in the motor control of the trained arm. In addition, the results provided preliminary evidence of increased intermuscular connectivity between targeted muscles in the beta-band frequencies for stroke patients after training, suggesting a modulation of the common neural drive. These findings suggest that our isometric exercise protocol has the potential to improve stroke survivors' performance of UE in their activities in daily lives (ADLs) and, ultimately, their quality of life through expanding their repertoire of intermuscular coordination.Clinical Relevance- This study shows the feasibility of expanding the intermuscular coordination pattern in stroke-affected UE through an isometric EMG-guided exercise which positively affects task performance and intermuscular connectivity.

Relevance of Upper Limb Muscle Synergies to Dynamic Force Generation: Perspectives on Rehabilitation of Impaired Intermuscular Coordination in Stroke.

This study investigated the impact of stroke on the control of upper limb endpoint force during isokinetic exercise, a dynamic force-generating task, and its association with stroke-affected muscle synergies. Three-dimensional upper limb endpoint force and electromyography of shoulder and elbow muscles were collected from sixteen chronic stroke survivors and eight neurologically intact adults. Participants were instructed to control the endpoint force direction during three-dimensional isokinetic upper limb movements. The endpoint force control performance was quantitatively evaluated in terms of the coupling between forces in orthogonal directions and the complexity of the endpoint force. Upper limb muscle synergies were compared between participants with varying levels of endpoint force coupling. The stroke survivors generating greater force abnormality than the others exhibited interdependent activation profiles of shoulder- and elbow-related muscle synergies to a greater extent. Based on the relevance of synergy activation to endpoint force control, this study proposes isokinetic training to correct the abnormal synergy activation patterns post-stroke. Several ideas for implementing effective training for stroke-affected synergy activation are discussed.

The Impact of the COVID-19 Outbreak on Emergency Medical Service: An Analysis of Patient Transportations and Time Intervals.

BACKGROUND: This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on the Emergency Medical Service (EMS) system in South Korea. The study focused on the differences in EMS time intervals following the COVID-19 outbreak, particularly for patients with fever. METHODS: A retrospective analysis of EMS patient transportation data from 2017 to 2022 was conducted using the national EMS database. RESULTS: Starting from the year 2020, coinciding with the COVID-19 outbreak, all EMS time intervals experienced an increase. For the years 2017 to 2022, the mean response time interval values were 8.6, 8.6, 8.6, 10.2, 12.8, and 11.4 minutes, and the mean scene time interval values were 7.1, 7.2, 7.4, 9.0, 9.8, and 10.9 minutes. The mean transport time interval (TTI) values were 12.1, 12.3, 12.4, 14.2, 16.9, and 16.2 minutes, and the mean turnaround time interval values were 27.6, 27.9, 28.7, 35.2, 42.0, and 43.1 minutes. Fever (≥ 37.5°C) patients experienced more pronounced prolongations in EMS time intervals compared to non-fever patients and had a higher probability of being non-transported. The mean differences in TTI between fever and non-fever patients were 0.8, 0.8, 0.8, 4.3, 4.8, and 3.2 minutes, respectively, from 2017 to 2022. Furthermore, the odds ratios for fever patients being transported to the emergency department were 2.7, 2.9, 2.8, 1.1, 0.8, and 0.7, respectively, from 2017 to 2022. CONCLUSION: The study findings highlight the significant impact of the COVID-19 outbreak on the EMS system and emphasize the importance of ongoing monitoring to evaluate the burden on the EMS system.

Developing new intermuscular coordination patterns through an electromyographic signal-guided training in the upper extremity.

BACKGROUND: Muscle synergies, computationally identified intermuscular coordination patterns, have been utilized to characterize neuromuscular control and learning in humans. However, it is unclear whether it is possible to alter the existing muscle synergies or develop new ones in an intended way through a relatively short-term motor exercise in adulthood. This study aimed to test the feasibility of expanding the repertoire of intermuscular coordination patterns through an isometric, electromyographic (EMG) signal-guided exercise in the upper extremity (UE) of neurologically intact individuals. METHODS: 10 participants were trained for six weeks to induce independent control of activating a pair of elbow flexor muscles that tended to be naturally co-activated in force generation. An untrained isometric force generation task was performed to assess the effect of the training on the intermuscular coordination of the trained UE. We applied a non-negative matrix factorization on the EMG signals recorded from 12 major UE muscles during the assessment to identify the muscle synergies. In addition, the performance of training tasks and the characteristics of individual muscles' activity in both time and frequency domains were quantified as the training outcomes. RESULTS: Typically, in two weeks of the training, participants could use newly developed muscle synergies when requested to perform new, untrained motor tasks by activating their UE muscles in the trained way. Meanwhile, their habitually expressed muscle synergies, the synergistic muscle activation groups that were used before the training, were conserved throughout the entire training period. The number of muscle synergies activated for the task performance remained the same. As the new muscle synergies were developed, the neuromotor control of the trained muscles reflected in the metrics, such as the ratio between the targeted muscles, number of matched targets, and task completion time, was improved. CONCLUSION: These findings suggest that our protocol can increase the repertoire of readily available muscle synergies and improve motor control by developing the activation of new muscle coordination patterns in healthy adults within a relatively short period. Furthermore, the study shows the potential of the isometric EMG-guided protocol as a neurorehabilitation tool for aiming motor deficits induced by abnormal intermuscular coordination after neurological disorders. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service (CRiS) of the Korea National Institute of Health (KCT0005803) on 1/22/2021.

Prehospital National Early Warning Score as a predictor of massive transfusion in adult trauma patients.

BACKGROUND: Previous studies have shown that an elevated prehospital National Early Warning Score (preNEWS) is associated with increased levels of adverse outcomes in patients with trauma. However, whether preNEWS is a predictor of massive transfusion (MT) in patients with trauma is currently unknown. This study investigated the accuracy of preNEWS in predicting MT and hospital mortality among trauma patients. METHODS: We analyzed adult trauma patients who were treated and transported by emergency medical services (EMS) between January 2018 and December 2019. The main exposure was the preNEWS calculated for the scene. The primary outcome was the predictive ability for MT, and the secondary outcome was 24 h mortality. We compared the prognostic performance of preNEWS with the shock index, modified shock index, and reverse shock index, and reverse shock index multiplied by Glasgow Coma Scale in the prehospital setting. RESULTS: In total, 41,852 patients were included, and 1456 (3.5%) received MT. preNEWS showed the highest area under the receiver operating characteristic (AUROC) curve for predicting MT (0.8504; 95% confidence interval [CI], 0.840-0.860) and 24 h mortality (AUROC 0.873; 95% CI, 0.863-0.883). The sensitivity of preNEWS for MT was 0.755, and the specificity of preNEWS for MT was 0.793. All indicies had a high negative predictive value and low positive predictive value. CONCLUSION: preNEWS is a useful, rapid predictor for MT and 24 h mortality. Calculation of preNEWS would be helpful for making the decision at the scene such as transfer straightforward to trauma center and advanced treatment.

A simple scoring rule to predict survival to discharge after out of hospital cardiac arrest at the time of ED arrival.

BACKGROUND: It is important to be able to predict the chance of survival to hospital discharge upon ED arrival in order to determine whether to continue or terminate resuscitation efforts after out of hospital cardiac arrest. This study was conducted to develop and validate a simple scoring rule that could predict survival to hospital discharge at the time of ED arrival. METHODS: This was a multicenter retrospective cohort study based on a nationwide registry (Korean Cardiac Arrest Research Consortium) of out of hospital cardiac arrest (OHCA). The study included adult OHCA patients older than 18 years old, who visited one of 33 tertiary hospitals in South Korea from September 1st, 2015 to June 30th, 2020. Among 12,321 screened, 5471 patients were deemed suitable for analysis after exclusion. Pre-hospital ROSC, pre-hospital witness, shockable rhythm, initial pH, and age were selected as the independent variables. The dependent variable was set to be the survival to hospital discharge. Multivariable logistic regression (LR) was performed, and the beta-coefficients were rounded to the nearest integer to formulate the scoring rule. Several machine learning algorithms including the random forest classifier (RF), support vector machine (SVM), and K-nearest neighbor classifier (K-NN) were also trained via 5-fold cross-validation over a pre-specified grid, and validated on the test data. The prediction performances and the calibration curves of each model were obtained. Pre-processing of the registry was done using R, model training & optimization using Python. RESULTS: A total of 5471 patients were included in the analysis. The AUROC of the scoring rule over the test data was 0.7620 (0.7311-0.7929). The AUROCs of the machine learning classifiers (LR, SVM, k-NN, RF) were 0.8126 (0.7748-0.8505), 0.7920 (0.7512-0.8329), 0.6783 (0.6236-0.7329), and 0.7879 (0.7465-0.8294), respectively. CONCLUSION: A simple scoring rule consisting of five, binary variables could aid in the prediction of the survival to hospital discharge at the time of ED arrival, showing comparable results to conventional machine learning classifiers.

Radotinib Decreases Prion Propagation and Prolongs Survival Times in Models of Prion Disease.

The conversion of cellular prion protein (PrPC) into pathogenic prion isoforms (PrPSc) and the mutation of PRNP are definite causes of prion diseases. Unfortunately, without exception, prion diseases are untreatable and fatal neurodegenerative disorders; therefore, one area of research focuses on identifying medicines that can delay the progression of these diseases. According to the concept of drug repositioning, we investigated the efficacy of the c-Abl tyrosine kinase inhibitor radotinib, which is a drug that is approved for the treatment of chronic myeloid leukemia, in the treatment of disease progression in prion models, including prion-infected cell models, Tga20 and hamster cerebellar slice culture models, and 263K scrapie-infected hamster models. Radotinib inhibited PrPSc deposition in neuronal ZW13-2 cells that were infected with the 22L or 139A scrapie strains and in cerebellar slice cultures that were infected with the 22L or 263K scrapie strains. Interestingly, hamsters that were intraperitoneally injected with the 263K scrapie strain and intragastrically treated with radotinib (100 mg/kg) exhibited prolonged survival times (159 ± 28.6 days) compared to nontreated hamsters (135 ± 9.9 days) as well as reduced PrPSc deposition and ameliorated pathology. However, intraperitoneal injection of radotinib exerted a smaller effect on the survival rate of the hamsters. Additionally, we found that different concentrations of radotinib (60, 100, and 200 mg/kg) had similar effects on survival time, but this effect was not observed after treatment with a low dose (30 mg/kg) of radotinib. Interestingly, when radotinib was administered 4 or 8 weeks after prion inoculation, the treated hamsters survived longer than the vehicle-treated hamsters. Additionally, a pharmacokinetic assay revealed that radotinib effectively crossed the blood-brain barrier. Based on our findings, we suggest that radotinib is a new candidate anti-prion drug that could possibly be used to treat prion diseases and promote the remission of symptoms.

Impact of emergency medical service with advanced life support training for adults with out-of-hospital cardiac arrest in the Republic of Korea: A retrospective multicenter study.

Prehospital advanced life support (ALS) has been offered in many countries for patients experiencing out-of-hospital cardiac arrest (OHCA); however, its effectiveness remains unclear. This study aimed to determine the impact of emergency medical service (EMS) with ALS training as a nationwide pilot project for adults with OHCA in the Republic of Korea. This retrospective multicenter observational study was conducted between July 2019 and December 2020 using the Korean Cardiac Arrest Research Consortium registry. The patients were categorized into an intervention group that received EMS with ALS training and a control group that did not receive EMS with ALS training. Conditional logistic regression analysis was performed using matched data to compare clinical outcomes between the two groups. Compared with the control group, the intervention group had a lower rate of supraglottic airway usage (60.5% vs. 75.6%) and a higher rate of undergoing endotracheal intubation (21.7% vs. 6.1%, P < 0.001). In addition, the intervention group was administered more intravenous epinephrine (59.8% vs. 14.2%, P < 0.001) and used mechanical chest compression devices more frequently in prehospital settings than the control group (59.0% vs. 23.8%, P < 0.001). Based on the results of multivariable conditional logistic regression analysis, survival to hospital discharge (odds ratio: 0.48, 95% confidence interval: 0.27-0.87) of the intervention group was significantly lower than that of the control group; however, good neurological outcome was not significantly different between the two groups. In this study, survival to hospital discharge was worse in patients with OHCA who received EMS with ALS training than in those who did not.