Improved therapeutic approach for spinal muscular atrophy via ubiquitination-resistant survival motor neuron variant.

BACKGROUND: Zolgensma is a gene-replacement therapy that has led to a promising treatment for spinal muscular atrophy (SMA). However, clinical trials of Zolgensma have raised two major concerns: insufficient therapeutic effects and adverse events. In a recent clinical trial, 30% of patients failed to achieve motor milestones despite pre-symptomatic treatment. In addition, more than 20% of patients showed hepatotoxicity due to excessive virus dosage, even after the administration of an immunosuppressant. Here, we aimed to test whether a ubiquitination-resistant variant of survival motor neuron (SMN), SMNK186R, has improved therapeutic effects for SMA compared with wild-type SMN (SMNWT). METHODS: A severe SMA mouse model, SMA type 1.5 (Smn-/-; SMN2+/+; SMN∆7+/-) mice, was used to compare the differences in therapeutic efficacy between AAV9-SMNWT and AAV9-SMNK186R. All animals were injected within Postnatal Day (P) 1 through a facial vein or cerebral ventricle. RESULTS: AAV9-SMNK186R-treated mice showed increased lifespan, body weight, motor neuron number, muscle weight and functional improvement in motor functions as compared with AAV9-SMNWT-treated mice. Lifespan increased by more than 10-fold in AAV9-SMNK186R-treated mice (144.8 ± 26.11 days) as compared with AAV9-SMNWT-treated mice (26.8 ± 1.41 days). AAV9-SMNK186R-treated mice showed an ascending weight pattern, unlike AAV9-SMNWT-treated mice, which only gained weight until P20 up to 5 g on average. Several motor function tests showed the improved therapeutic efficacy of SMNK186R. In the negative geotaxis test, AAV9-SMNK186R-treated mice turned their bodies in an upward direction successfully, unlike AAV9-SMNWT-treated mice, which failed to turn upwards from around P23. Hind limb clasping phenotype was rarely observed in AAV9-SMNK186R-treated mice, unlike AAV9-SMNWT-treated mice that showed clasping phenotype for more than 20 out of 30 s. At this point, the number of motor neurons (1.5-fold) and the size of myofibers (2.1-fold) were significantly increased in AAV9-SMNK186R-treated mice compared with AAV9-SMNWT-treated mice without prominent neurotoxicity. AAV9-SMNK186R had fewer liver defects compared with AAV9-SMNWT, as judged by increased proliferation of hepatocytes (P < 0.0001) and insulin-like growth factor-1 production (P < 0.0001). Especially, low-dose AAV9-SMNK186R (nine-fold) also reduced clasping time compared with SMNWT. CONCLUSIONS: SMNK186R will provide improved therapeutic efficacy in patients with severe SMA with insufficient therapeutic efficacy. Low-dose treatment of SMA patients with AAV9-SMNK186R can reduce the adverse events of Zolgensma. Collectively, SMNK186R has value as a new treatment for SMA that improves treatment effectiveness and reduces adverse events simultaneously.

Usefulness of the BIG Score in Predicting Massive Transfusion and In-Hospital Death in Adult Trauma Patients.

The base deficit (B), international normalized ratio (I), and Glasgow coma scale (GCS) (BIG) score is useful in predicting mortality in pediatric trauma patients; however, studies on the use of BIG score in adult patients with trauma are sparse. In addition, studies on the correlation between the BIG score and massive transfusion (MT) have not yet been conducted. This study aimed to evaluate the predictive value of BIG score for mortality and the need for MT in adult trauma patients. This retrospective study used data collected between 2016 and 2020 at our hospital's trauma center and registry. The predictive value of BIG score was compared with that of the Injury Severity Score (ISS) and Revised Trauma Score (RTS). Logistic regression analysis was carried out to assess whether BIG score was an independent risk factor. Receiver operating characteristic (ROC) curve analysis was performed, and predictive values were evaluated by measuring the area under the ROC curve (AUROC). In total, 5,605 patients were included in this study. In logistic regression analysis, BIG score was independently associated with in-hospital mortality (odds ratio (OR): 1.1859; 95% confidence interval (CI): 1.1636-1.2086) and MT (OR: 1.0802; 95% CI: 1.0609-1.0999). The AUROCs of BIG score for in-hospital mortality and MT were 0.852 (0.842-0.861) and 0.848 (0.838-0.857), respectively. Contrastingly, the AUROCs of ISS and RTS for in-hospital mortality were 0.795 (0.784-0.805) and 0.859 (0.850-0.868), respectively. Moreover, AUROCs of ISS and RTS for MT were 0.812 (0.802-0.822) and 0.838 (0.828-0.848), respectively. The predictive value of BIG score for mortality and MT was significantly higher than that of the ISS. The BIG score also showed a better AUROC for predicting in-hospital mortality compared with RTS. In conclusion, the BIG score is a useful indicator for predicting mortality and the need for MT in adult trauma patients.

The Effect of Hypertension, Diabetes, and Hyperlipidemia on Medication Intake and Adherence: Analysis from Korean Health Panel Survey 2014-2017.

Background: Hypertension, diabetes, and hyperlipidemia are common chronic diseases in South Korea, and medication is a key factor in managing these diseases and preventing disease advancement to multimorbidity. This study aimed to evaluate the effect of chronic disease on medication intake and adherence among Koreans. Methods: This study was conducted utilizing data collected from 5,529 individuals that participated in the Korea Health Panel Survey (KHPS) in 2014-2017. The dependent variables were medication intake and adherence, and independent variables included socioeconomic status and the type of chronic disease. The differences in the medication intake and medication adherence by sociodemographic variables and the type of chronic disease were analyzed by chi-square test. The effect of hypertension, diabetes, and hyperlipidemia on medication intake and adherence was analyzed via multiple logistic regression using SAS statistical software. Results: The rate of medication intake and adherence were significantly different among patients with hypertension, diabetes, and hyperlipidemia, especially lower in patients with hyperlipidemia compared to those with hypertension and diabetes. In multiple logistic regression analysis, the probability of medication intake increased in female gender, older age, medical aid, medication adherence was higher in married, lower educational level and lower household income. Compared to hyperlipidemia, patients with hypertension and diabetes had more likely to take medication as prescribed. Conclusion: The importance of considering the type of chronic disease in developing and implementing public health programs aiming for improved medication adherence. Targeting better medication intake and adherence for each chronic disease could be a valuable policy strategy to effectively manage chronic diseases as well as prevent their complications.

Regional differences in health screening participation between before and during COVID-19 pandemic.

BACKGROUND: Health screening is a preventive and cost-effective public health strategy for early detection of diseases. However, the COVID-19 pandemic has decreased health screening participation. The aim of this study was to examine regional differences in health screening participation between before and during COVID-19 pandemic and vulnerabilities of health screening participation in the regional context. METHODS: Administrative data from 229 districts consisting of 16 provinces in South Korea and health screening participation rate of each district collected in 2019 and 2020 were included in the study. Data were then analyzed via descriptive statistics and geographically weighted regression (GWR). RESULTS: This study revealed that health screening participation rates decreased in all districts during COVID-19. Regional vulnerabilities contributing to a further reduction in health screening participation rate included COVID-19 concerns, the population of those aged 65+ years and the disabled, lower education level, lower access to healthcare, and the prevalence of chronic disease. GWR analysis showed that different vulnerable factors had different degrees of influence on differences in health screening participation rate. CONCLUSIONS: These findings could enhance our understanding of decreased health screening participation due to COVID-19 and suggest that regional vulnerabilities should be considered stringent public health strategies after COVID-19.

Awareness of, attitudes towards, and practices of health information management professionals in South Korea relating to privacy of personal health information.

Background: While information and communication technology has continued to advance, privacy of personal health information (PHI) has remained a challenge for health information management (HIM) professionals. Objective: This study aims to examine the awareness, attitude and practice relating to PHI privacy among HIM professionals in South Korea. Method: A survey questionnaire was developed for the study based on critical appraisal of relevant literature and expert consensus. It was completed by a sample of 312 respondents who were members of the Korean Health Information Management Association, over the age of 21, and worked in a healthcare organisation. Demographic data and questionnaire items (assessed on a 5-point Likert-type scale) were analysed using descriptive statistics, t-tests and ANOVA. Results: Mean scores and SDs for awareness, attitude and practice related to PHI privacy were calculated: 4.21 (0.60) for awareness, 4.17 (0.60) for attitude and 4.31 (0.63) for practice. Significant positive correlations were found between awareness and attitude scores (r = 0.765, p < 0.01); awareness and practice scores (r = 0.585; p < 0.01); and attitude and action scores (r = 0.672; p < 0.01). HIM professionals' awareness, attitude, and practice towards PHI privacy differed significantly according to age, level of education, years of HIM experience, type of employment, main task, number of completed privacy education activities within the previous 3 years and whether or not they had signed a pledge of confidentiality on PHI. More highly-educated, full-time employed respondents, those who had completed a greater number of privacy education activities and had more experience as HIM professionals, achieved higher scores on awareness, attitude and practice than did other respondents. These differences were all statistically significant (p < 0.01). Conclusion: Although causality cannot be inferred from results of this study, findings suggest that there is a relationship between PHI being a core responsibility of HIM professionals and their subsequent awareness, attitude and practice to ensure its privacy and confidentiality. To improve privacy practice, educational efforts should be prioritised and supported at all levels, including national, organisational, individual, and by professional HIM associations.

Notch1 and Notch2 Signaling Exclusively but Cooperatively Maintain Fetal Myogenic Progenitors.

Myogenic progenitors (MPs) generate myocytes that fuse to form myofibers during skeletal muscle development while maintaining the progenitor pool, which is crucial for generating sufficient muscle. Notch signaling has been known to reserve a population of embryonic MPs during primary myogenesis by promoting cell cycle exit and suppressing premature differentiation. However, the roles of individual Notch receptors (Notch1-4) during embryonic/fetal myogenesis are still elusive. In this study, we found that Notch1 and Notch2, which exhibit the highest structural similarity among Notch receptors, maintain the MP population by distinct mechanisms: Notch1 induces cell cycle exit and Notch2 suppresses premature differentiation. Moreover, genetic and cell culture studies showed that Notch1 and Notch2 signaling in MPs are distinctively activated by interacting with Notch ligand-expressing myofibers and MP-lineage cells, respectively. These results suggest that through different activation modes, Notch1 and Notch2 distinctively and cooperatively maintain MP population during fetal myogenesis for proper muscle development.

Prediction of Severe Injury in Bicycle Rider Accidents: A Multicenter Observational Study.

Introduction: This study aimed to establish a predictive model that includes physiological parameters and identify independent risk factors for severe injuries in bicycle rider accidents. Methods: This was a multicenter observational study. For four years, we included patients with bicycle rider injuries in the Emergency Department-Based Injury In-depth Surveillance database. In this study, we regarded ICD admission or in-hospital mortality as parameters of severe trauma. Univariate and multivariate logistic regression analyses were performed to assess risk factors for severe trauma. A receiver operating characteristic (ROC) curve was generated to evaluate the performance of the regression model. Results: This study included 19,842 patients, of whom 1,202 (6.05%) had severe trauma. In multivariate regression analysis, male sex, older age, alcohol use, motor vehicle opponent, load state (general and crosswalk), blood pressure, heart rate, respiratory rate, and Glasgow Coma Scale were the independent factors for predicting severe trauma. In the ROC analysis, the area under the ROC curve for predicting severe trauma was 0.848 (95% confidence interval: 0.830-0.867). Conclusion: We identified independent risk factors for severe trauma in bicycle rider accidents and believe that physiologic parameters contribute to enhancing prediction ability.

Factors Associated with Chronic Disease and Health Care Utilization Among Young Adults in South Korea.

Hypertension, diabetes, and hyperlipidemia have become prevalent in young adults. Health care utilization is a key factor in managing early onset chronic diseases. This study aimed to examine the factors affecting health care utilization among young South Korean adults with a single chronic disease. From the Korea Health Panel Survey data collected between 2014 and 2017, young adults who were 30-49 years old and diagnosed with a single chronic condition (hypertension, diabetes, or hyperlipidemia) were included in this study (n = 993). The factors affecting health care utilization were analyzed through multiple logistic regression. The health care utilization rate of the 40-49 and 30-39-year age groups was 84.2% and 71.1%, respectively, and it was significantly higher in the healthy behavior group, who had no smoking and drinking habits and joined in physical activities. Among the chronic diseases, hyperlipidemia obtained the lowest health care utilization rate (62.8%). From the multiple logistic regression analysis, medication intake was likely to increase in the older, unemployed, and healthy behavior groups. Patients with hypertension and diabetes were more likely to use health care services than those with hyperlipidemia. Given the rising prevalence of chronic diseases among young adults, these findings may be helpful in implementing new public health approaches for this type of population by encouraging proper health care utilization.

COVID-19: Protecting Health-Care Workers in South Korea.

OBJECTIVES: Health-care workers (HCWs) are vulnerable to the risk of coronavirus disease 2019 (COVID-19) infections, and the safety of HCWs is important in situations where a prolonged COVID-19 is expected. METHODS: HCWs were recently put in great danger around the globe; as of December 21, there were 306 confirmed cases in HCWs in South Korea, representing 0.60% of the total 50,591 confirmed cases nationally. RESULTS: After experiencing Middle East respiratory syndrome (MERS), South Korea has put a range of infection prevention and control (IPC) measures with long-term perspectives in place, including the use of personal protective equipment (PPE), HCW's infection status tracing, visitor control, and a variety of supports from both national and local public health authorities. CONCLUSIONS: This article introduces the infection status of HCWs and IPC measures currently taken in South Korea, emphasizing the collaborative and long-term IPC efforts for ensuring the safety of HCWs.

Analysis of information security management systems at 5 domestic hospitals with more than 500 beds.

OBJECTIVES: The information security management systems (ISMS) of 5 hospitals with more than 500 beds were evaluated with regards to the level of information security, management, and physical and technical aspects so that we might make recommendations on information security and security countermeasures which meet both international standards and the needs of individual hospitals. METHODS: The ISMS check-list derived from international/domestic standards was distributed to each hospital to complete and the staff of each hospital was interviewed. Information Security Indicator and Information Security Values were used to estimate the present security levels and evaluate the application of each hospital's current system. RESULTS: With regard to the moderate clause of the ISMS, the hospitals were determined to be in compliance. The most vulnerable clause was asset management, in particular, information asset classification guidelines. The clauses of information security incident management and business continuity management were deemed necessary for the establishment of successful ISMS. CONCLUSIONS: The level of current ISMS in the hospitals evaluated was determined to be insufficient. Establishment of adequate ISMS is necessary to ensure patient privacy and the safe use of medical records for various purposes. Implementation of ISMS which meet international standards with a long-term and comprehensive perspective is of prime importance. To reflect the requirements of the varied interests of medical staff, consumers, and institutions, the establishment of political support is essential to create suitable hospital ISMS.