Objective: The coronavirus disease 2019 (COVID-19) pandemic has posed a major threat to pregnant women's mental health. This study aimed to characterize the patterns of perceived stress in pregnant Chinese women during the COVID-19 pandemic, to examine the profile differences on anxiety and resilience, and to investigate whether the differences in these profiles on anxiety were mediated by resilience.Methods: From February 28, 2020 to April 26, 2020, a sample of 2,116 pregnant Chinese women who participated in online crisis interventions completed an online self-reporting questionnaire assessing their demographic characteristics, perceived stress, resilience, and anxiety.Results: Latent profile analysis (LPA) on two stress dimensions [perceived helplessness (HEL) and perceived self-efficacy (SEL)] indicated four perceived stress profiles: adaptive (33.7% of the sample), resistant (44.6%), insensitive (19.1%), and sensitive (2.6%). The women with both adaptive and insensitive profiles had the lowest levels of anxiety, whereas those with the resistant profile had the lowest levels of resilience. Multicategorical mediation analysis showed that resilience partially mediated the differences in the pregnant women's anxiety between the adaptive/insensitive and resistant profile.Conclusion: This study showed the heterogeneity in the perceived stress patterns of pregnant women during the COVID-19 pandemic, revealing the internal mechanisms of pregnant women's anxiety using a person-centered approach, and provided initial evidence guiding the development of differentiated stress interventions to alleviate pregnant women's anxiety during the pandemic. Since late December 2019, a novel coronavirus disease 2019 (COVID-19) has spread rapidly in China and between countries, with high morbidity and mortality rates. It was declared as a global pandemic by the WHO on March 11, 2020. Emerging evidence from around the world suggests that pregnant women during the COVID-19 pandemic are experiencing elevated anxiety  groups individuals into latent classes or profiles or subgroups according to the correlations on continuous variables. The LPA results reveal a typical co-occurrence of HEL and SEL among subgroups, which makes it possible to identify the patterns of pregnant women's perceived stress during the COVID-19 pandemic. This understanding can then be used to recognize the group to which each pregnant woman belongs and in turn to guide appropriate intervention efforts aimed at each group's unique needs rather than the target variables.A few studies have explored the profiles of perceived stress  among pregnant women during the COVID-19 pandemic. Pregnant women with high resilience showed lower levels of psychological distress during the COVID-19 pandemic  there may be perceived stress profiles reflecting different combinations of HEL and SEL. We employed an exploratory approach and therefore made no hypothesis about the number of perceived stress profiles. (2) There were significant differences in anxiety and resilience among the different stress profiles. Profiles with lower HEL have lower levels of anxiety and higher levels of resilience. (3) Resilience would mediate the effect of stress profile differences on anxiety. That is, the differences in anxiety between a profile with lower HEL and other profiles could be explained by the former group's higher resilience.n = 7). Pregnant women participated voluntarily in this study and provided an informed consent between February 28, 2020 and April 26, 2020. Ethics approval for the study was obtained from the Institutional Review Board of Institute of Psychology, Chinese Academy of Sciences.This study is part of a WeChat psychological crisis intervention program initiated by the Institute of Psychology, Chinese Academy of Sciences, that aimed to help pregnant Chinese women cope with stress during the COVID-19 pandemic. Pregnant women who attended regular examinations at medical institutions in Wuhan, Beijing, Lanzhou, and other cities of China were recruited to scan the QR code generated by an online survey platform to complete the survey. The inclusion criteria were at all stages of pregnancy, more than 18 years old, being able to read and write in Chinese and no infection with COVID-19. Pregnant women with a history of mental illness were excluded from the study  was used to assess persons' perceptions of situations in their life in terms of uncontrollability, unpredictability, and overload  was applied to assess the adaptability to stress  was used to measure the severity of anxiety symptoms, with a four-point Likert scale response ranging from 0  to 3 . GAD-7 was initially developed for screening the generalized anxiety disorder (GAD) and assessing the severity of symptoms in a primary care patient sample  lower comparative values of the Akaike information criteria (AIC), the Bayesian information (BIC), and the adjusted BIC (ABIC) values, as well as higher values of entropy with numbers closer to 1; (2) a significant Lo-Mendell-Rubin likelihood ratio test (LMR LR) and the Vuong-Lo-Mendell-Rubin test (VLMR). Third, after determining the best class solution, univariate ANOVAs and 2/df ≤ 5.000, comparative fit index (CFI), Tucker–Lewis index (TLI) ≥ 0.900, standardized root mean square residual (SRMR) ≤ 0.080, and root mean square error of approximation (RMSEA) ≤ 0.080 . Among the participants, 22.7% were in the first trimester, 23.8% in the second trimester, and 53.5% in the third trimester. The majority of participants were married (98.2%) and of Han nationality (95.8%). In terms of geography, 38.5% were from Beijing, 32.7% were from Hubei , 25.6% were from Gansu, 2.4% were from Hebei, and 0.8% were from the other provinces in China. Regarding their education levels, 11% had completed graduate studies or above, 44.1% had completed university, 28.7% had completed junior college, and 16.2% had completed senior high school or less. In terms of economic status, 12.6% of the participants' annual family income exceeded 300,000 RMB, and 31.24% of the participants' annual family income was <80,000 RMB. A total of 17.63% of the sample reported to have pregnancy complications.p < 0.001) but not related to SEL (p > 0.05). Resilience was negatively associated with HEL, SEL, and anxiety (p < 0.001).Means, SDs, and correlations for all of the variables are presented in p for LMR LR and VLMR. The five-profile model had significant values of p for LMR LR and VLMR, and lower AIC, BIC, and ABIC values than the four-profile model, but the downtrend of AIC, BIC, and ABIC became slow, and the entropy was less than that of the four-profile model. In addition, considering the simplicity and relative distinguishability of the model, we chose the four-profile solution as the final model.The fit indices of the six LPA models are reported in The differences in resilience and anxiety among the four profiles were examined by using ANOVAs. The adaptive profile had the highest resilience. The insensitive and sensitive profile had middle-level resilience. The resistant profile had the lowest resilience. The profiles also differed overall in terms of anxiety. The sensitive profile had the highest anxiety. The resistant profile had middle-level anxiety. The adaptive and insensitive profiles had the least amount of anxiety .2/df = 4.16, CFI = 0.985, TLI = 0.980, RMSEA = 0.039 , SRMR = 0.019.Three dummy variables  were created by using indicator coding to represent the four stress profiles. The resistant profile served as a reference group and was assigned a score of “0” across all variables. The adaptive, insensitive, and sensitive profiles were coded as “100,” “010,” and “001,” respectively. Adding the pregnant women's age, gestational age, number of births, and physical disease as covariates, these dummy variables were then entered into the SEM to test whether the differences in anxiety between the adaptive/insensitive/sensitive and resistant profiles were due to the differences in resilience and resilience's subsequent effect on anxiety. Compared with the resistant profile, the relative direct and indirect effects for the other profiles were calculated. The significance of each relative indirect path was tested by using the bootstrapping method . The mediation model was fitted ideally with χvia resilience , while the relative direct effect of D1 and D2 on anxiety was significant . The results suggested that compared with the resistant profile, the adaptive profile and insensitive profile led to significantly lower levels of anxiety via higher levels of resilience. The examination of the proportion of relative mediation effects showed that 23.6% (adaptive profile) and 7.3% (insensitive profile) of the relative total effect on anxiety were mediated by resilience. Meanwhile, the CIs spanned zero, indicating that the relative indirect effects of D3  on anxiety via resilience were not significant. The relative direct effect of D3 on anxiety was significant .According to Hayes and Preacher , a1, a2,We found that the perceived stress among pregnant women during the COVID-19 pandemic could be classified into four profiles: adaptive (low HEL/low SEL), resistant (high HEL/moderate SEL), insensitive (low HEL/high SEL), and sensitive (very high HEL/low SEL), which differed from one another in terms of anxiety and resilience. The differences in the pregnant women's anxiety between the adaptive/insensitive and resistant stress profiles could be explained by the former groups' higher resilience.The resistant stress profile occurs most frequently among pregnant women. This finding is partly in accordance with some previous research findings. For example, Lee et al.  reportedDiagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, In general, the pregnant women with a sensitive profile had the highest levels of anxiety, followed by the pregnant women with a resistant profile, an insensitive profile, and an adaptive profile. This suggested that a higher HEL is associated with an increased risk of anxiety. This finding is partly in line with a previous study; that is, only HEL is related to psychiatric symptoms between HEL and SEL for women (Martin et al., via higher levels of resilience, which is also partly consistent with past dimension-approach research results (Anyan and Hjemdal, An important finding of this research was that the effects of the differences between adaptive/insensitive and resistant profiles on anxiety were partially mediated by resilience. Compared with the resistant stress profile, the adaptive and insensitive stress profile led to significantly lower levels of anxiety The study found that although women with a sensitive profile had a higher level of anxiety than women with a resistant profile, resilience did not mediate the effect of the difference on anxiety between the sensitive stress profile and the resistant stress profile. One possible reason may be that the sensitive profile had a very high HEL, which can directly lead to anxiety and need not be mediated by resilience. A possible effect of heightened stress sensitivity on affective disorder onset and susceptibility has been supported by previous studies Bale, . AnotherTo our knowledge, this is the first study to apply LPA to identify the patterns of pregnant women's perceived stress during the COVID-19 pandemic and to examine the effect of resilience on the association between the perceived stress profiles and anxiety from a person-centered approach. However, this study has some limitations that need to be addressed. First, this was a cross-sectional study, and there was an absence of a pre-pandemic control group, which prevented us from reaching any causal conclusions about the association of perceived stress with anxiety. Future research should conduct longitudinal studies to identify causal relationships. Second, a self-reported data collection method might affect the validity of the data. Future research should combine multiple methods, such as brain imaging and molecular biological techniques, to collect data. Meanwhile, qualitative interviews or focused group discussions could have added more value to the study by exploring the causes of pregnant women's anxiety and how they cope with it. Third, although our study was based on two important dimensions of perceived stress, it might not fully encompass the stress that the pregnant women experienced. Fourth, GAD-7 was originally designed for screening for GAD and assessing the severity of symptoms in a clinical sample (Spitzer et al., via resilience. Thus, our results offer a reasonable basis for further developing resilience-specific crisis interventions that would be more targeted and thus increase their effectiveness. For example, it could help pregnant women to develop meaningful connections with family or friends and perceive increased social support to improve their resilience and reduce their anxiety.Despite the limitations, our findings might have important implications for medical staff to develop more effective crisis intervention programs to alleviate pregnant women's anxiety during a period of crisis. Pregnant women with different HEL/SEL patterns might have different levels of anxiety, which suggests differentiated clinical psychological nursing and interventions to balance the needs of all pregnant women. We encourage future anxiety interventions of pregnant women aimed at managing stress from a specific person-centered mode. Pregnant women in the adaptive group have low levels of HEL and SEL, which can help them deal with crises. For these pregnant women, additional psychological interventions are not needed. For pregnant women in the insensitive group, the main goal is to increase their perceptions of coping ability, i.e., general self-efficacy, through health education emphasizing high performance accomplishments, vicarious experiences, verbal persuasion, etc. Bandura, . PregnanThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Institutional Review Board of Institute of Psychology, Chinese Academy of Sciences. The patients/participants provided their written informed consent to participate in this study.ZLu, FS, and ZLi: study design, critical revision of the manuscript, and approval of the final version for publication. ZLu, YS, JY, and YZ: analysis and interpretation of data. ZLu and YS: drafting of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Then, we assessed the independent predictors of DKA occurrence in T1DM patients in an uninfected state. The diagnostic performance of variables was determined by receiver operating characteristic curve analysis. Serum NLR of T1DM patients is significantly higher than that of normal controls, and if DKA occurs, NLR increases further and increases with the severity of DKA. In addition to diastolic blood pressure, blood urea nitrogen, glycated hemoglobin (HbA1c), and WBC, NLR was also independently associated with DKA in T1DM patients with an uninfected state . Furthermore, the diagnosis analysis showed that except for NLR and WBC, the area under the curve (AUC) of indicators with a statistical difference in patients with and without DKA were 0.747 for DKA diagnosis, and after the addition of NLR and WBC, the AUC was 0.806. The increased NLR level represents a low-cost and highly accessible predictor for DKA in T1DM patients with an uninfected state. The addition of inflammation indicators can play a statistically significant role in the prediction model of the DKA occurrence.The role of inflammation has been identified in the pathogenesis of diabetic ketoacidosis (DKA). The neutrophil/lymphocyte ratio (NLR) and white blood cells (WBC) can be used to predict a systemic inflammatory response. Changes in NLR and WBC levels have never been explored in type 1 diabetes mellitus (T1DM) patients with DKA and an uninfected state. This retrospective study included a total of 644 participants. NLR and WBC were measured in the control group ( Therefore, early detection and treatment of DKA are beneficial to the prognosis of diabetic patients . If the The most common cause of DKA is infection. In addition, some patients with T1DM may develop DKA and other acute diabetic complications due to irregular use of insulin or the induction of diseases such as infection ,4. TheseThe neutrophil/lymphocyte ratio (NLR) and white blood cells (WBC) can be used to predict a systemic inflammatory response. The NLR, a new marker of the systemic inflammatory response, integrates the information of neutrophils and lymphocytes. Furthermore, it is easy to obtain NLR and is less affected by physiological factors and specimen treatment . Recent Despite our knowledge about increased inflammation in the context of DKA, the data about the relationship between DKA and NLR, a simple and economical index, are lacking in this population. Changes in NLR and WBC levels have never been explored in T1DM patients with DKA and an uninfected state. Therefore, the aim of this study was to depict the difference in NLR and WBC levels in T1DM patients with DKA and non-DKA in an uninfected state and determine the DKA diagnostic performance of NLR and WBC.22.1n = 316) and T1DM patients with mild-DKA (n = 92), severe-DKA (n = 52) and non-DKA (n = 184) groups. The normal control inclusion criteria were as follows: a healthy person with no physiological, physical, or psychologic abnormalities; Mild-DKA group: T1DM patients with ketosis and an uninfected state; Severe-DKA group: T1DM patients with ketoacidosis and an uninfected state; Non-DKA group: T1DM patients in an uninfected state without ketosis or ketoacidosis. Subjects with serious cardiovascular diseases, such as acute myocardial infarction, cachexia, immune disease, hepatic dysfunction, renal dysfunction (creatinine-based eGFR <90 mL/min/1.73 m2), infection, inflammation, or treatment with anti-inflammatory drugs, pregnancy, taking aspirin or statins, were excluded from this study.This retrospective study included a total of 644 participants. We first selected 328 T1DM patients hospitalized in Shandong Provincial Hospital affiliated to Shandong University  and Weihai Municipal Hospital  from January 2008 to January 2020. With age, sex, and examination time-matched for T1DM participants, we then collected 316 healthy controls from our database of the Health Examination Center. According to the onset characteristics, fasting blood glucose, islet autoantibodies, serum C-peptide, ketone bodies, and blood gas analysis results , the indInformed consent: Informed consent from each patient and healthy control was not required due to the retrospective study design and the use of anonymized data.Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of Shandong Provincial Hospital affiliated to Shandong University.2.2The authors retrieved all data from previous hospital records of patients and healthy controls admitted to Shandong Provincial Hospital affiliated to Shandong University and Weihai Municipal Hospital; physical examination and extraction and analysis of blood were performed by other experts when patients and healthy controls were admitted to the hospital. After fasting overnight, venous blood was collected. An automatic biochemistry analyzer  was used to analyze aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), blood urea nitrogen (BUN), creatinine (CREA), total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and uric acid (UA). Glycated hemoglobin (HbA1c) was determined using high-performance liquid chromatography (HPLC) with a hemoglobin A1c analyzer . WBC and NLR were analyzed on a blood cell analyzer . NLR = neutrophil count/lymphocyte count.2.3p < 0.05 in single-factor analysis. Notably, we performed collinearity diagnostics of the variables included in the logistic regression analysis. To address the problem of multicollinearity in the multiple linear regression analysis, we used a stepwise model to exclude variables with a minimal explanation of the dependent variable from the combination of multiple collinearities of independent variables. The independent variables included in the logistic regression model are not significantly collinearity. The diagnostic performance of the variables was determined by receiver operating characteristic (ROC) curve analysis. All p values were two-tailed, and p values less than 0.05 were considered statistically significant. SPSS version 24.0  was used for all parametric tests.The Kolmogorov–Smirnov test was used to test the normality of all parameters prior to performing parametric tests. Normally distributed continuous data are represented as the mean ± SD, while nonnormally distributed continuous parameters are represented as the medians with interquartile ranges. Categorical variables are expressed as percentages. To analyze differences between the four groups, data with a normal distribution were tested by one-way ANOVA, and skewed variables were tested by the Kruskal–Wallis H-test. Categorical variables were tested by the Chi-square test. Pearson, Spearman, and partial correlation analyses were used to determine factors that affect NLR and WBC levels. Then, the association between NLR or WBC levels and the occurrence of DKA in T1DM patients were assessed by logistic regression analysis of factors with 33.1n = 316) and T1DM patients in an uninfected state with non-DKA (n = 184), mild-DKA (n = 92), and severe-DKA (n = 52) groups  vs 5.66 (IQR: 4.71–6.93), p = 0.002, respectively).We first analyzed the differences in clinical indicators of the normal control group  groups . Non-DKA) groups . Next, w) groups . RegardiIn addition, there were no differences in gender, AST, or ALT levels between the four groups.Our findings indicated that serum NLR and the WBC level of T1DM patients is significantly higher than that of normal controls, and if DKA occurs, the NLR and the WBC level increase further and increase with the severity of DKA.3.2r = 0.367; p <0.001). To avoid the influence of age and duration of diabetes on NLR levels and eliminate potential confounding factors, we adjusted for age and duration of diabetes. After adjustment, CREA, HbA1c, and WBC positively correlated between NLR  and ALB negatively correlated with NLR , whereas the other positive or negative correlations above were no longer significant.The correlations between NLR and clinical parameters in patients with T1DM are shown in Considering the strong correlation between WBC and NLR, we assessed factors associated with WBC and found that WBC was positively correlated with NLR, HbA1c, TC, TGs, LDL-c, and UA and negatively correlated with ALB after adjustment for age and duration of diabetes .3.3Similarly, due to the strong correlation between WBC and NLR, we included WBC and NLR into the multiple logistic regression model, respectively. 3.4Furthermore, the diagnosis analysis showed that except for NLR and WBC, the area under the curve (AUC) of indicators with the statistical difference in patients with and without DKA were 0.747 for DKA diagnosis, and after the addition of NLR and WBC, the AUC was 0.806 . The add4The current study investigated NLR and WBC levels in normal people and in T1DM patients with non-DKA, mild-DKA, and severe-DKA in an uninfected state. Intriguingly, we found that serum NLR and the WBC level of T1DM patients is significantly higher than that of normal controls, and if DKA occurs, the NLR and WBC level increase further and increase with the severity of DKA. The increased serum NLR and WBC levels were independently associated with the occurrence of DKA in T1DM patients in an uninfected state, and the addition of NLR and WBC can play a statistically significant role in the prediction model of the occurrence of DKA. To the best of our knowledge, we have not seen any report describing the NLR levels in T1DM patients with DKA and an uninfected state.There is increasing evidence that easily obtainable laboratory biomarkers can have a predictive role and be used for diagnosis and outcome prediction in various medical conditions. NLR, a relatively inexpensive marker of inflammation, has recently been explored as a predictor of mortality in patients who undergo percutaneous coronary intervention and can aid in the risk stratification and prognosis of patients diagnosed with acute coronary syndromes . Moreovep <0.001). In addition to the explanation that T1DM is a chronic inflammatory disease and NLR reflects the state of systemic inflammation, we suspected that the increase of NLR in T1DM patients may also be related to poor blood glucose regulation. Sefil et al. [As is well known, both T1DM and type 2 diabetes mellitus (T2DM) are considered to be systemic inflammatory states ,30. Studl et al. . found tl et al. , and lyml et al. . In the l et al. . NonetheFurthermore, T1DM patients with DKA and an uninfected state had significantly higher serum NLR and WBC levels than those in the non-DKA group, and NLR and WBC levels increased with the severity of DKA. In addition, the increased serum NLR and WBC levels were independent predictors of the occurrence of DKA in T1DM patients with an uninfected state, and the addition of inflammation indicators can play a statistically significant gain in the prediction model of the occurrence of DKA. We have a few possible explanations for these findings. First, neutrophils are involved in the body’s inflammatory response, while lymphocytes as the inflammatory regulator can protect endothelial cells and reduce the inflammatory response. The ratio of neutrophils and lymphocytes reflects the balance between the inflammatory activator and the inflammatory regulator. The higher the NLR, the more severe the inflammatory response . The uniThe death of DKA patients due to delayed diagnosis and lack of reasonable treatment is still common. Therefore, analyzing the risk factors for DKA in T1DM patients with an uninfected state is of great significance for early prevention, early diagnosis, and treatment. In addition to NLR, WBC and HbA1c were also independent predictors of DKA occurrence in T1DM patients in an uninfected state. Poor blood glucose control indicates severe metabolic disorders and severe insulin deficiency in the body. Consistent with other studies ,45, a hiInterestingly, we found that serum NLR was positively correlated with SBP and DBP in T1DM patients with an uninfected state before adjusting for age and duration of diabetes . The relIt is incontestable that this study has many limitations. First, only one measurement of neutrophil and lymphocyte count and one calculation of NLR were carried out in the analysis. There was no monitoring of the dynamic trend of NLR. Second, selection bias may arise because our data are only from one hospital. Additionally, the sample size was small, and we look forward to future verification in large samples and multicenter studies. Third, our data came from a retrospective study. To fully understand the role of NLR in T1DM patients with DKA and an uninfected state, basic large-scale prospective studies should be conducted.5In summary, our study demonstrates that NLR and WBC levels increased in T1DM patients with DKA and an uninfected state and increased with DKA severity. NLR and WBC levels can be used as a simple and economical predictor for DKA occurrence in T1DM patients in an uninfected state. When DKA occurs, there may be a severe inflammatory reaction. In addition to lowering blood glucose, anti-inflammatory drugs are expected to relieve the internal environment disorder to a certain extent.


The objective of this study was to directly compare the ability of commonly used early warning scores (EWS) for early identification and prediction of sepsis in the general ward setting. For general ward patients at a large, academic medical center between early-2012 and mid-2018, common EWS and patient acuity scoring systems were calculated from electronic health records (EHR) data for patients that both met and did not meet Sepsis-3 criteria. For identification of sepsis at index time, National Early Warning Score 2 (NEWS 2) had the highest performance  followed NEWS, Modified Early Warning Score, and quick Sequential Organ Failure Assessment (qSOFA). Using validated thresholds, NEWS 2 also had the highest recall (0.758 [95% CI: 0.736–0.778]) but qSOFA had the highest specificity (0.950 [95% CI: 0.948–0.952]), positive predictive value (0.184 [95% CI: 0.169–0.198]), and F1 score (0.236 [95% CI: 0.220–0.253]). While NEWS 2 outperformed all other compared EWS and patient acuity scores, due to the low prevalence of sepsis, all scoring systems were prone to false positives , thus leaving room for more computationally advanced approaches. Sepsis is a syndrome caused by an infection resulting in organ dysfunction and high rates of death, is implicated in nearly half of all inpatient deaths, and is the costliest inpatient condition in the United States. Early recognition and treatment are critical to the management of septic patients. As a result, over time, researchers have developed numerous early warning scores that use clinical measurements such as vital signs and lab results to generate a value that is indicative of the severity of illness and is predictive of clinical deterioration. Increasingly, these scores have been used as screening tools for sepsis management. To understand the comparative performance of these early warning scores in the general ward setting, electronic health records data were used to calculate the scores. Of the compared scores, the National Early Warning Score (NEWS 2) outperformed the rest. However, partially due to the low prevalence of sepsis in the general ward, even NEWS 2 was prone to false positives, highlighting the potential for improvement using more advanced computational methods. The previously used Systemic Inflammatory Response Syndrome (SIRS) criteria which graded the host’s response to an inflammatory insult were easy to use at the bedside, but nearly half of all inpatients met these criteria during their hospitalization.,One emerging approach to sepsis screening is to implement early warning scores (EWS), such as the Modified Early Warning Score (MEWS), the National Early Warning Score (NEWS), or its successor, the NEWS 2.All patients ≥18 years of age admitted to Washington University in St. Louis/Barnes-Jewish Hospital between January 1, 2012 and June 1, 2018 were eligible for inclusion. Patients were excluded if discharged < 12 h after sepsis onset, total length of stay was < 48 h, surgery was performed in the preceding 72 h, < 1 set of vital signs were recorded in the 24-h preceding index time, or if < 1 set of common labs results (creatinine and white blood cell count) were recorded in the 24-h preceding index time. Patients were excluded if sepsis was present on admission or if admission service was hospice, psychiatry, or obstetrics and gynecology due to the highly variable rates of physiologic data collection. Patients were also excluded if they no encounter billing code, vital sign, laboratory, service, room, or medication data to indicate a complete hospitalization. To ensure temporal similitude between cohorts, patient encounters <12 h or >14 days in duration were excluded. Electronic health record (EHR) data were extracted from the Research Data Core at Washington University in St. Louis School of Medicine. This project was approved with a waiver of informed consent by the Washington University in St. Louis Institutional Review Board (IRB#201804121).Sepsis was defined according to the Sepsis-3 consensus statement as suspicion of infection  were equivalent .,,,,,The SIRS, MEWS, NEWS, NEWS 2, qSOFA, Sequential Organ Failure Assessment (SOFA), and Acute Physiology And Chronic Health Evaluation (APACHE II) scores were calculated every hour from 12-h prior to index time to 12 h after index time.U test or χ2 test for numeric and categorical variables, respectively, where P < .01 was considered significant. Performance metrics such as the area under the receiver operating characteristic curve (AUROC) and area under the precision recall curves (AUPRC) were reported as the median and 95% confidence interval determined through 1000 sample bootstrap.Patient characteristics and outcomes were compared between the sepsis and nonsepsis cohorts using the two-sided Mann-Whitney P < .01) and more likely to be white . Sepsis patients also had significantly higher Elixhauser comorbidity scores , APACHE II scores at the time of sepsis onset , longer lengths of stay , and higher rates of in-hospital mortality .In total, 45 776 patients met inclusion criteria and 1496 (3.3%) met sepsis criteria . CompareFor the discrimination of sepsis versus nonsepsis, performance of NEWS was nearly identical to that of NEWS 2, both of which were superior to all other EWS . As expeAt index time, NEWS 2 had the highest AUROC and AUPRC , which were superior to those of other EWS . For theIn this large retrospective analysis of EWS performance on sepsis discrimination in the general ward setting, patients who met Sepsis-3 criteria were older and had more medical comorbidities compared to other patients in the general ward. This sepsis cohort also had a higher level of acuity, length of stay, and rates of in-hospital mortality .Among the compared EWS and patient acuity scoring systems, NEWS 2 had the highest discriminatory capability throughout the assessed time points, including at the time of onset , Table 2The relatively poor performance of SOFA and APACHE II likely reflects the lower rate of vital sign and laboratory data collection available to patients on the hospital floor, as these tools were originally designed for the ICU setting and as patient acuity scores, not EWS. Such scores relying on infrequently measured variables  appear to translate poorly to the general ward setting, as would be expected.,,As seen in Studies comparing EWS are heterogeneous in their experimental design, especially in identifying the time-at-risk interval from which measurements are gathered for the control population. Methods include the usage of random time intervals, full encounters, or the first 24 h of admission.While none of the compared EWS were used for the study population during the study period, a locally developed sepsis alert tool was used during the study period.Surprisingly, the update from NEWS to NEWS 2 had a nearly unnoticeable impact on the performance. Many of the changes described in the report, however, address concerns not directly relating to the score calculations, but to the usage of the score.The limitations of this study are as follows: first, this is a single-center study at a large academic medical center and its patient population and culture-of-practice may preclude widespread generalization. Second, the retrospective nature of this study may yield EWS performance metrics different from those obtained from a prospective trial. Third, the choice of sepsis definition used may have resulted in biased performance metrics of EWS, especially for qSOFA which is used in the Sepsis-3 consensus definition. Fourth, this study evaluates only sepsis that developed on the general ward within 14 days of hospitalization and does not include patients with surgery within 72 h. Further evaluation of EWS in these specific populations may provide additional insight into their utility as a sepsis surveillance tool. Fifth, mental status—a variable used in all scores except SIRS—was not available as a discrete element during the study period and was assumed normal consistent with prior reports.In this large, retrospective, single-center study with 45 776 unique encounters, sepsis occurred in 3.3% of all hospital admissions, yielding a longer length of hospitalization and a higher rate of in-hospital mortality. EWS and patient acuity scores—APACHE II, qSOFA, MEWS, NEWS, NEWS 2, and SOFA—had low discriminative ability for sepsis, leaving room for more computationally advanced approaches.Journal of the American Medical Informatics Association online.S.C.Y., performed the data analysis, generated the figures and tables and contributed significantly to the crafting of the manuscript. N.S., contributed to the conceptualization of the project and assisted in data analysis of the EWS performance metrics. K.B., contributed to the conceptualization of this project and analyzed the clinical data. A.G., contributed to the conceptualization of the project and assisted in data analysis of the EWS performance metrics. A.M.L., analyzed and interpreted the data regarding EWS performance. M.H.K., contributed to the conceptualization of the project and assisted in data analysis of the EWS performance. P.R.O.P., played a significant role in the conceptualization of this project and analyzed and interpreted the data regarding EWS performance. A.P.M., contributed to the conceptualization of the project, assisted in clinical data and EWS performance metric review and drafted the manuscript. All authors read and approved the final manuscript.Marin H. Kollef is a consultant for Pfizer and Merck. The rest have no conflicts of interest to disclose.This study was approved with a waiver of consent by the Intuitional Review Board from Washington University in St. Louis prior to the commencement of this study (IRB#201804121).The datasets analyzed during the current study are not publicly available due to privacy concerns.ooab062_Supplementary_DataClick here for additional data file.


Contrast-enhanced MR (CE-MR) imaging is often required to improve lesion detection and characterization and to increase diagnostic confidence. This study aimed to evaluate the safety and effectiveness, as well as the use pattern, of the macrocyclic gadolinium-based contrast agent Clariscan in real-world clinical practice in Korea.  This was a prospective, multicenter, observational study of patients undergoing CE-MR as part of routine clinical care at 6 university hospitals in Korea. Effectiveness was evaluated by determining diagnostic confidence and image quality; safety evaluation included the adverse event (AE) expression rate. Subgroup analyses were conducted by body regions of diagnosis  and in pediatric patients (aged ≤7 years).  From October 2019 to September 2020, 1,376 subjects were included in the study. The mean volume of Clariscan used was 0.26 mL/kg (0.13 mmol/kg). In the overall study population and in each subgroup, diagnostic confidence increased after contrast enhancement with Clariscan. Overall, image quality was excellent in 72.5% of subjects and good-to-adequate in 27.2%. Clariscan was well tolerated (14 AEs occurred in 10 subjects); all AEs were of mild severity. Subgroup analyses showed that the mean dose of Clariscan used was ≥0.1 mmol/kg for nervous system-related diagnoses  and ≤0.1 mmol/kg for musculoskeletal and pediatric-related diagnoses. All musculoskeletal and pediatric examinations were provided with a smaller package of 5 mL Clariscan. By body region of MR examination, the most common region was the nervous system in 69.0%, musculoskeletal system in 13.6%, and reproductive system in 4.9%.  This study confirmed the use pattern of Clariscan and its excellent effectiveness and safety in the real-world clinical environment in Korea. The small-dose package indicated the possibility of increasing the convenience and efficiency of drug use. Contrast-enhanced magnetic resonance (CE-MR) imaging is often required to improve lesion detection and characterization and to increase confidence in diagnosis . GadoterThis prospective, multicenter, observational study was approved by the Institutional Review Boards of the participating centers. Written informed consent was obtained from patients.The study included a total of 1,376 subjects who were administered Clariscan  for MRI at 6 sites in Korea between Oct. 2019 and Sep. 2020.Clariscan was administered in accordance with the guidelines and procedures of the individual participating institutions. Individuals of all ages were considered in this study. The exclusion of patients was based on the institution's criteria of contraindication of GBCA and the recommendation guidelines.For demographic characteristics, gender, age, height, weight, body mass index (BMI), and type of referral were collected. For clinical characteristics, volume of contrast, use of automatic injector, field strength of MRI, previous imaging examinations, allergies, renal replacement, concomitant medications, and comorbidities were examined. Diagnosis of MR included provisional diagnosis and putative diagnosis. Body regions of MR examinations were classified by system organ class (SOC).Effectiveness assessment was based on image quality and diagnostic confidence reported by local radiologists. Image quality for MRI and/or MRA images were assessed on a 4-point Likert scale: 1, poor, inadequate/blurring of the arterial segment; 2, fair, partial/inadequate arterial enhancement for confident diagnosis; 3, good, adequate arterial enhancement for confident diagnosis; and 4, excellent, excellent arterial enhancement for highly confident diagnosis. Diagnostic confidence was assessed using the most representative lesion for each patient. Before reviewing the CE-MR image, the radiologist was asked to document their level of confidence in making a diagnosis for the patient, with 5 categories each of 20% as a whole number between 0% and 100% based only on the nonenhanced image. After reading the CE-MR scan results, the radiologist was then asked to document their diagnostic confidence, using the same 5 categories each of 20% as a whole number between 0% and 100%. Results were used to calculate the change in diagnostic confidence by the local radiologist, before/after Clariscan use.For safety assessment, the incidence of adverse events (AEs) occurring up to 7 days from Clariscan administration along with the number of subjects with AEs and number of events was presented. AEs were standardized by SOC and preferred term (PT) according to MedDRA. Status of radiological examinations including Clariscan at each site and satisfaction of the medical staff with Clariscan were collected as site information.The primary study objective was to assess the pattern of use of Clariscan in MRI centers in Korea; the secondary objective was to evaluate the effectiveness and safety profile of Clariscan in real-life settings. To assess study objectives in specific populations, subgroup analyses were also conducted in patients who underwent MRI examination of the nervous system, musculoskeletal system, others, and pediatric patients (aged ≤7 years).N) and frequency (%) were presented as categorical variables. Demographic and clinical characteristics, body regions of MR examinations, quality of images, diagnostic confidence, and AEs were summarized by descriptive statistics. The incidence of AEs was presented with a 95% confidence interval. All analyses were performed using R version 3.5.1. software.Generally, summary statistics  were presented as continuous variables, and the number of subjects , pediatric patients , musculoskeletal system (N = 148), and others (N = 143). Demographic and clinical characteristics of patients in the subgroups are shown in Supplementary Effectiveness, safety, and use patterns were also analyzed in the following subgroups: nervous system  in the nervous system, pediatric, musculoskeletal system, and others subgroups, respectively . By bodyp < 0.0001; musculoskeletal system: p=0.0026) (Supplementary p < 0.0001)  and the nervous system group (n = 4), while the 5 delayed AEs were reported in the musculoskeletal system and connective tissue disorders group (n = 3) and others group (n = 2). By SOC and PT, skin and subcutaneous tissue disorders  were most commonly observed in each subgroup, with the exception of the pediatric group (no cases).By time of onset of all 14 AEs, the 9 immediate AEs were observed in the pediatric group  mainly for contrast enhancement in the examination of nervous system disorders and cancer. In the overall study population, an increase in diagnostic confidence was observed with Clariscan—the proportion of subjects with ≥60% diagnostic confidence was 73.3% before Clariscan use versus 99.4% after contrast enhancement with Clariscan. The quality of images was most commonly assessed by radiologists as “excellent contrast-enhancement” in 72.5% of subjects. Consistent with the results of the present study, a 2015 review of previous studies that evaluated the safety and efficacy of gadoteric acid also showed a high level of improvement in diagnosis upon the use of gadoteric acid, with good or excellent image quality reported in 95 to 100% of cases  mmol/kg . The stuIn a prospective, observational study of gadoterate meglumine in 35,499 patients (SECURE), the incidence of AEs was reported to be 0.1% . In a Gep < 0.0001).Based on these real-world results, Clariscan is considered to be effective and safe for use as an MRI contrast. Unlike conventional agents that are supplied in mid to large volumes of ≥10 mL, Clariscan is supplied in a small 5 mL package. Hence, it is notable that, in the subgroup analyses, a smaller volume of Clariscan was used in pediatric patients and those with musculoskeletal and connective tissue disorders in routine clinical practice compared with doses normally used for other diseases in adults. Higher mean doses of Clariscan used in the subgroup of patients with nervous system disorders reflect a large number of brain CE-MR images. In pediatric patients, the lower mean volume of Clariscan was associated with a statistically significant increase in diagnostic confidence: ≥60% diagnostic confidence was evident in 2.0% of patients before Clariscan use, increasing to 99.0% after Clariscan use (The study is limited in that it employed descriptive statistics only. However, the study is considered meaningful because it is the first prospective study conducted in Korea on the use patterns, effectiveness, and safety of Clariscan in routine clinical settings. An additional strength of this study is the classification and evaluation of Clariscan use in children, which highlights the need to further study the use of GBCAs in special populations such as infants and children.This study identified use patterns of Clariscan and confirmed the favorable effectiveness and safety profiles of Clariscan in routine clinical settings in Korea. In a noncomparative comparison with previous studies, no notable differences were observed between Clariscan and conventional agents in terms of effectiveness and safety. Furthermore, the study indicated the potential for the small-volume package of Clariscan to contribute to increased convenience and effectiveness in drug use.


Lignocellulosic biomass fractionation is typically performed using methods that are somehow harsh to the environment, such as in the case of kraft pulping. In recent years, the development of new sustainable and environmentally friendly alternatives has grown significantly. Among the developed systems, bio-based solvents emerge as promising alternatives for biomass processing. Therefore, in the present work, the bio-based and renewable chemicals, levulinic acid (LA) and formic acid (FA), were combined to fractionate lignocellulosic waste  and isolate lignin. Different parameters, such as LA:FA ratio, temperature, and extraction time, were optimized to boost the yield and purity of extracted lignin. The LA:FA ratio was found to be crucial regarding the superior lignin extraction from the waste biomass. Moreover, the increase in temperature and extraction time enhances the amount of extracted residue but compromises the lignin purity and reduces its molecular weight. The electron microscopy images revealed that biomass samples suffer significant structural and morphological changes, which further suggests the suitability of the newly developed bio-fractionation process. The same was concluded by the FTIR analysis, in which no remaining lignin was detected in the cellulose-rich fraction. Overall, the novel combination of bio-sourced FA and LA has shown to be a very promising system for lignin extraction with high purity from biomass waste, thus contributing to extend the opportunities of lignin manipulation and valorization into novel added-value biomaterials. Lignocellulosic biomass valorization for potential use in the production of biochemicals, biofuels, biomaterials, and other added-value products, represents an important opportunity to reduce and valorize agroforest residues ,2. In thNumerous physical, thermal and chemical pre-treatments and their combinations have been developed to boost biomass fractionation and isolation ,14. ThesAs an environmentally benign and green solvent, water is most always preferred and has been extensively utilized for biomass fractionation and chemical production . HoweverRecent studies demonstrate the suitability of eutectic solvents and ionic liquids for biomass fractionation ,23,24,25Despite the recent efforts to improve lignin isolation and purification, it is clear that the vast majority of lignin is still obtained as a low-quality byproduct from pulping industries. To continue boosting the lignin-based materials and chemicals expansion towards novel advanced and demanding applications, superior fractionation strategies are required to improve lignin quality and its selective extraction. Therefore, in this work, using a closed reactor, capable of handling high pressures, a novel binary mixture composed of LA and FA is suggested as an efficient medium for lignocellulosic biomass fractionation. LA has been identified as a sustainable platform and building block for many valuable chemicals . This acThe fractionation suitability of this novel binary system was studied, and the extraction conditions, such as the LA:FA ratio, temperature, and extraction times, were optimized to maximize the lignin yield and purity. The extracted lignin was further characterized by Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).Pinus pinaster Ait.) sawdust was kindly supplied by the Portuguese company Valco–Madeiras e Derivados, S.A . The sawdust was initially sieved (mesh size of 20) and oven dried at 105 °C. LA  was purchased from Acros Organics and FA  was purchased from CARLO ERBA. Lactic acid  and glacial acetic acid  were acquired from VWR Chemicals, while sulphuric acid (72%) was obtained from Chem-lab NV (MW = 98.08 g/mol and a density of 1.63 g/mL). De-ionized water was used for the preparation of all solutions. Dichloromethane (DCM) was purchased from Sigma-Aldrich and the 4-nitroanisol was acquired from Dagma. Microcrystalline cellulose Avicel PH-101, with an average particle size of 50 mm and degree of polymerization of ca. 260, was acquired from Sigma Aldrich. For the intrinsic measurements and molecular weight (MW) estimation of lignin, n,n-dimethylformamide (DMF) (≥99.8%) ACS Reagent, was used. Maritime pine , previously dried in an oven at 105 °C, was weighed and transferred to a metallic cylindric reactor, able to support high pressure. The reactor was filled with the solvent up to its maximum capacity (10 ml) and the vessel was properly closed. The reactor was placed in an oven, at the desired temperature  and time . After the end of the extraction, the vessel was carefully opened and the extracted lignin content estimated, as described below. Extraction yields were calculated as the average of extracted residue in duplicate and total lignin recovery was determined based on the residue yield and lignin content . Statistical analysis was performed using one-way ANOVA (α = 0.05) to evaluate significant differences between the extraction yields. The lignin content extracted by the solvent was estimated using the standard LAP-004 protocol from the National Renewable Energy Laboratory (NREL) . In brieη] can be related to the MW of the polymer by the semi-empirical Mark–Houwink equation =KMwK = 2.51 ). The limax was determined for the probe in each solvent. The solvatochromic π* parameter was determined using the equation [The solvatochromic probe 4-nitroanisol was used to estimate the Kamlet–Taft parameter π* (polarizability index). A stock solution of the dye in DCM was prepared to a concentration of 4 mM. The dye stock solution was added to the solvents understudy to a final concentration of 0.1 mM, which enables to obtain the absorbance values within the required measurable range, and DCM was removed by evaporation at room temperature. The absorption spectra of the solvatochromic probe were recorded from 250 nm to 500 nm in a quartz cell with a 10 mm path length, using a Shimadzu UV/VIS spectrometer UV-1700 at 1 nm stepwise. The wavelength at maximum absorption νequation .π*= . Secondary electron mode, an acceleration voltage of 1 kV and a working distance of 9 mm, were selected as the operational conditions. Uncoated samples were deposited directly on the carbon tape. −1 range with a resolution of 4 cm−1 and 64 scans.FTIR-ATR spectra of the different samples were obtained on a JASCO FT/IR-4200 spectrometer  using a MKII Golden Gate accessory. The spectra were recorded in the 500–4000 cmThe raw lignocellulosic material used in this work was pinewood sawdust and its lignin content was initially estimated to be 27.36 ± 7.93%, which is in agreement with the literature ,34,35.v/v)  and temperature  on the extraction yield, by systematically varying these two parameters for a fixed LA:FA solvent ratio of 1:1 (v/v) . Two striking observations can be made from the analysis of Similarly, to other biomass residues, the pinewood sawdust consists not only of lignin but also of cellulose, hemicellulose, pectins, sugars and other minor compounds ,37. OfteAs it can be observed in Similarly to the purity of the lignin, the MW is also influenced by the extraction time and temperature . The incLignin is almost colorless in wood, while industrial lignin presents color due to the appearance of different chromophores during the extraction process. Lignin mainly includes quinoids, catechols, aromatic ketones, stilbenes, conjugated carbonyls with phenolics and metal complexes that are able to modify its coloration . In addiThe LA:FA ratio was also analyzed  regardinAll tested ratios induce enhanced lignin purity from ca. 62 to 83%, considerably above the 56% obtained for FA alone. Regarding the extraction yield, it remains fairly constant (around 29%) when the FA content in the solvent mixture varies between 50 to 90%. The highest extraction yields around 40%) are obtained for the 7:3 and 6:4 ratios (LA:FA); however, the purity was compromised. Lignin with a lower MW is obtained when solely using FA as the extraction solvent. The lignin depolymerization strongly depends on the FA/LA ratio and, therefore, depending on the intended application, it is possible to obtain lignins with different MW without the need of using other depolymerization processes [% are obtOverall, data suggests that a balance between the two acids is favorable for the pine sawdust fractionation, where enhanced extraction yields can be obtained with reasonable specificity, thus avoiding other expensive and complicated pre-treatments. Moreover, these two solvents appear to have different roles during the lignin extraction process but, when combined, their synergy results in a more efficient fragmentation; as a smaller molecule, FA is capable of penetrating into the sawdust structure and destabilize it, while LA seems to establish preferential interactions with lignin, via its extra ketone groups. The effect of using other monocarboxylic acids in combination with LA on the extraction efficiency was also assessed. The results show a clear dependence of the extraction yield with the acid being used in combination with LA; lower extraction yields were obtained for the binary solvent systems in the following order: LA:FA > LA:lactic acid > LA:acetic acid a. The soData suggests that the lignin extraction is favored when using acidic solvents with higher π* values; LA and FA have the highest polarization indexes and, when combined to form a binary solvent system, were found more effective than LA:lactic acid or LA:acetic acid. These results are in accordance with our previous work where it was demonstrated that LA and formic acids have a similar and superior dissolution efficiency for “model” lignin (kraft lignin) and also the highest π* values, in comparison to other carboxylic acids . A similScanning electron microscopy was used to observe the microscopic morphological features of pine sawdust, before and after fractionation with a solvent ratio mixture of 6:4 (LA:FA) at different extractions times and temperatures . The staFTIR spectroscopy can provide reliable insights on structural and chemical features of lignocellulosic materials . Therefo−1 region while the OH and CH vibration modes are detected in the 3800–2700 cm−1 region [−1 is mostly attributed to the stretching of the C=C bonds, part of the aromatic skeletal of lignin molecules. Furthermore, the C=O stretching conjugated to the aromatic ring bending mode is assigned to the band at ca. 1720–1660 cm−1. Finally, the bands at 1490 and 1510 cm−1 can be assigned to the vibration modes of the aromatic rings in lignin [The characteristic fingerprints from functional groups of carbohydrates and lignin appear in the 1800–1200 cm1 region . The vibn lignin . The preEnvironmentally benign and selective methods for biomass fractionation, enabling the isolation and valorization of the different fractions, such as cellulose, hemicellulose, and lignin, have been targeted in much recent research. In this work, a novel binary solvent composed of bio-sourced and renewable FA and LA was developed and successfully applied to fractionate pine sawdust waste biomass. In comparison with the individual solvent systems, the appropriate tuning of temperature, extraction time and LA: FA ratio, allows the extraction of lignin with high yield and purity. Generally, higher temperatures and extraction times led to better results. Apart from the time–temperature balance, the solvent nature was sought for, further envisioning the industrial translation of the developed method. This study further suggests that LA has a good affinity with lignin, also proven by the higher MW obtained for lignin extracted solely with LA compared with the lignin extracted with only FA. Both the electron microscopy and FTIR data support the enhanced lignin extraction performance by the novel binary LA:FA mixtures developed. This eco-friendly and sustainable approach is potentially very interesting for future lignin valorization into novel biomaterials of added-value.


Studies on the association between gastric cancer (GC) and the intake of soup-based dish groups , which are sodium-contributing foods, in Korea are insufficient, and the results of studies on the intake of pickled vegetables such as kimchi are inconsistent. This study aimed to determine the association between the incidence of GC and the daily intake of high-sodium dish groups  and whether these associations differ depending on behavioral risk factors for GC. In this case-control study, subjects aged 20–79 years were recruited from two hospitals between December 2002 and September 2006. A total of 440 cases and 485 controls were recruited, of which 307 pairs were matched and included for the analysis. In our results, a higher intake of noodles and dumplings was associated with a significantly increased incidence of GC. In the participants who consumed past or current alcohol, a higher intake of noodles and dumplings was associated with a significantly increased incidence of GC. Our results suggest that efforts to reduce the daily sodium intake from noodles and dumplings are needed to prevent and reduce the incidence of GC. Based on GLOBOCAN 2020 data, gastric cancer (GC) is the fifth most common cancer and fourth for mortality globally, with an estimated 769,000 deaths in 2020 . In partHelicobacter pylori (H. pylori) infections [Recently, a systematic review reported the following as risk factors for GC: diet, lifestyle, genetic predisposition, family history, treatment and medical conditions, and fections . The Worfections . In addifections ,7,8,9,10fections ,11. On tfections  or salt fections ,14 and Gfections , and eacfections . In addiAccording to Korea Health Statistics 2019, the daily intake of sodium is 3512.3 mg (aged ≥ 19 years) , which iIn addition, smoking and alcohol consumption are well-known behavioral risk factors for GC . AdditioTherefore, the primary goal of the present study was to determine the association between the incidence of GC and the daily intake in major dish groups that contribute to sodium intake. The secondary goal of this study was to evaluate whether the behavioral risk factors of GC  influence the association between the incidence of GC and the daily intake of major dish groups that contribute to sodium intake.Subjects aged 20–79 years were recruited from the Chungnam University Hospital and Hanyang University Guri Hospital between December 2002 and September 2006. Due to the slight change in the questionnaire items during the study period, the subjects were recruited in the following stages: 1st (December 2002 to August 2003) and 2nd (October 2003 and September 2006) stages. GC was histologically diagnosed based on the World Health Organization classification of tumors of the digestive system, as follows : a gastr2). We grouped the participants into four based on their BMI: “obese”, ≥25 kg/m2; “overweight”, 23.0–24.99 kg/m2; “normal weight”, 18.5–22.99 kg/m2; and “underweight”, ≤18.49 kg/m2. H. pylori infection was tested with the Campylobacter-like organism (CLO) test kit , a rapid urea degradation test. This test was performed when tissue collection was possible.The questionnaire included questions on sociodemographic characteristics , behavioral factors , disease status, family history, and dietary habits. Height and weight were collected from the medical records and questionnaires. Body mass index (BMI) was computed as weight in kilograms divided by height in meters squared (kg/mThe data on dietary factors were collected using a quantitative food frequency questionnaire (FFQ). The FFQs used for the 1st and 2nd stages had slightly different survey items and methods. For the first stage, the FFQ assessed 103 food or dish items, with an intake period (1–12 months) of 1 year, frequency of food consumption per month, week, or day, and average serving size. For the second stage, the FFQ comprised 116 food or dish items, frequency of food consumption with nine categories , and average serving size. Therefore, we extracted the common food items for the first stage based on the second stage. After that, the food intake or nutrient intake was calculated for each of the stages, divided into three quartiles, and merged. This was converted into daily intake by considering the intake period and frequency, and the intake of each of the investigated foods. All questionnaires were administered by a well-trained interviewer and investigated the frequency and amount of food consumed during 12 months of 3 years before the date of the interview to assess remote dietary intake. The total energy intake for each food was estimated using the Korean Foods and Nutrients Database . The disThe dietary questionnaire included items on salty taste preference, with a 5-point Likert scale: (1) not favored at all; (2) slightly not favored; (3) no opinion; (4) slightly favored; and (5) strongly favored. The five responses on the salty taste preferences were classified into three categories: (1) not favored at all and slightly not favored; (2) no opinion; and (3) slightly favored and strongly favored.t-test was used to analyze the continuous variables and the Chi-squared test was used for categorical variables. The continuous and categorical variables are presented as mean values ± standard deviation and numbers (percentages), respectively. Since there was a slight difference between the FFQs for the first and second stages, the tertiles of each dish group were applied according to each stage. The odds ratios (OR) and 95% confidence intervals (CI) for the GC risk were calculated across the tertiles for each high-sodium dish group using logistic regression after controlling for known risk factors. The lowest tertile of each high-sodium dish group was used as a reference. To test for trends, the median values of each tertile category of the high-sodium dish groups were used as continuous variables. We analyzed the OR for GC according to the salty food preference of the participants who answered “no opinion” as the reference group. Model I was adjusted for age (as a continuous variable) and sex. Model II was further adjusted for BMI , education level , family history (first-degree relatives) of GC , smoking status , alcohol consumption , total energy intake (as a continuous variable), and H. pylori infection . In addition, we conducted a stratified analysis according to the GC risk factors  for the fully adjusted model. During the stratification analysis, the stratified variables were excluded from the model. The current and past smokers were combined into the “ever smoked” group before analysis. Moreover, the current and past drinkers were combined into the “ever drank” group before analysis.The statistical analysis was performed using the SAS 9.4 version . To compare the general characteristics of the cases and controls, the Student’s p = 0.014). The control group had a higher proportion of participants with H. pylori infection (45.6%) than the case group (31.6%) (p < 0.001). The case group consumed significantly more total energy than the control group (p = 0.002).p for trend = 0.0005). For model II, the fully adjusted model, the highest tertile of intakes of noodles and dumplings showed a significantly higher incidence of GC than the lowest tertile . The daily intakes of soups and stews showed no significant differences related to the incidence of GC. In contrast, medium (the 2nd tertile) intake of pickled vegetables was associated with a tendency of a decrease in the incidence of GC .p for trend = 0.017), but this association was not significant among those who had never drunk. When stratified by smoking status, the highest tertile of the intakes of noodles and dumplings showed a tendency of an increase in the incidence of GC compared with the lowest tertile among the participants with past or current smokers in the fully adjusted model . This association was not significant in the participants who had never smoked.p for trend = 0.046). However, statistical significance was weakened in model II .In our study, a higher daily intake of noodles and dumplings was associated with a higher incidence of GC. When stratified by alcohol consumption in participants who were past or current alcohol drinkers, a higher daily intake of noodles and dumplings was associated with a significantly increased incidence of GC.Sodium is an essential element for homeostasis and physiological functioning in the body, but high sodium intake has been reported to cause health problems such as obesity , high blThe higher consumption of sodium by Koreans than by inhabitants of other countries may be attributed to the high intake of traditional pickled foods and soup-based diets ,20. The H. pylori infection, (2) damages the mucous cell layer surface, (3) increases the expression of inflammatory mediators such as cyclooxygenase-2 and inducible nitric oxide, and (4) upregulates cagA expression, which leads to inflammation, hypochlorhydria, and enhanced carcinogenesis [enolase 1) [Among the major dish groups with high sodium content, noodles and dumplings are among the most popular foods for Korean adults . In a stogenesis . Second,ogenesis , and canolase 1) . Ye et aolase 1) . Third, olase 1) ,45. In aolase 1) .The results of previous studies on pickled vegetables, such as kimchi, are inconsistent ,22,23. IIn our study, there was no association between the incidence of GC and daily intake of soups and stews. Only one study reported that high-stewed foods, such as soybean paste stew and hot pepper-soybean stew, may increase the risk of GC, although they did not report for the daily intake of stewed foods . In our H. pylori infection, we found that a higher intake of noodles and dumplings showed a tendency of increased risk of GC in participants with a family history of GC or with positive H. pylori infection (Smoking and alcohol consumption are well-known behavioral risk factors for GC . Additionfection . TherefoIn addition, several studies have reported an association between salty food preference and GC ,47. Kim H. pylori infection rate was found to be lower in cases than in the controls. This might be due to the fact that H. pylori detection rates can decrease with the progression of gastric atrophy and intestinal metaplasia [This study has several strengths. It was conducted based on the ranking of major dish groups that contribute to sodium intake in Koreans, and it confirmed the association between GC and the intake of noodles and dumplings, which has not been reported in other studies. In addition, to avoid information bias, interviews of all subjects were conducted without disclosing the disease status after endoscopic examination. In addition, to avoid misclassification bias, controls recruited from the same hospital during the same period were confirmed to have no gastric problems through gastroscopy. This study also has limitations. In our study, the cases were recruited from only two hospitals, the controls were also recruited from the patients who visited the hospital, and they may be less representative of the general population. In addition, the sample for the analysis was small because some cases and controls could not be matched by age, sex, or hospital. There was also a slight difference in the content of the FFQ survey for the first and second stages, and there may have been unintentional misclassification. In addition, we adjusted for various confounding factors in the statistical model; however, there may have been residual confounding effects. Moreover, in our study, the taplasia ,50. Regataplasia . HoweverOur study showed that the risk of GC increased with the high intake of noodles and dumplings among Koreans, especially in participants who were past or current drinkers. Therefore, in order to prevent and reduce GC, we suggest that Koreans need to reduce their broth intake when eating noodles, make practical efforts to consume as little salt as possible when eating food, and reduce the salt content of noodles themselves as a policy.


Moreover, the pain reduction following WI was statistically significant in the healthcare workers’ group (p = 0.005), but not in the other workers’ group. The participants on sick leave and the number of days of sick leave decreased in the WI group without statistical significance . Finally, LBP recurrence was significantly reduced in the WI group (p = 0.006). WI led to a significant improvement of clinical outcomes in a workers’ population affected by LBP.This systematic review and meta-analysis aimed to analyze the effects of workplace interventions (WI) on clinical outcomes related to low back pain (LBP) in a worker population, and to assess socio-economic parameters as participants on sick leave, days of sick leave, and return to work following WI. A systematic literature search was performed to select randomized clinical trials that investigated the effectiveness of WI on return to work, sick leave, and working capacity of workers affected by nonspecific LBP. Fourteen articles were included in the review and meta-analysis. The meta-analysis showed improvements in pain ( Non-specific low back pain (LBP) is a common worldwide disorder with a significant impact on productivity, work ability, and quality of life . Indeed,Therefore, the prevention of work absenteeism due to LBP recurrence has become a public and occupational health priority worldwide . The treNevertheless, our current knowledge of the real effectiveness of WI remains rather fragmented and, at the same time, the understanding of the key factors or best combination of WI for achieving significant prevention or reduction of work-related LBP is equally limited. For this reason, in this context, we performed this systematic review and meta-analysis in order to critically evaluate the effects of WI on LBP in workers. In detail, the primary aim was to analyze the effects on clinical and occupational outcomes related to LBP in workers after the implementation of specific WI programs. The secondary endpoint was to assess the impact of WI on socio-economic parameters as participants on sick leave, days of sick leave, and return to work.This study was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)  guidelinThe inclusion criteria were RCTs in the English language published in the last twenty years, which investigated the effectiveness of workplace interventions on return to work, sick leave, and the working capacity of workers affected by nonspecific LBP. The workplace interventions include technical interventions, physical exercise programs, behavioral training, educational programs, and participatory ergonomics. Exclusion criteria were represented by studies that enrolled patients with neurodegenerative diseases, previous spinal or brain surgery, or following spinal cord infections or injuries. We excluded studies that analyzed only physical or psychosocial activities as an intervention, and that only evaluated reducing sitting time as an outcome or the impact of a sit–stand workstation.A systematic literature search was executed using PubMed–Medline, Cochrane Central, Scopus, and Google Scholar. We used the following search strings: (“workplace” [MeSH Terms] or “workplace” [All Fields] or “workplaces” [All Fields] or “workplaces” [All Fields]) and  and (“low back pain” [MeSH Terms] or (“low” [All Fields] and “back” [All Fields] and “pain” [All Fields]) or “low back pain” [All Fields]). The reference lists of the included RCTs were detected to obtain further eligible studies. After removing duplicates, two independent investigators reviewers (G.P. and F.R.) checked the abstracts of potentially included studies. Any divergence was discussed with the third review author (G.V.). Finally, two review authors (G.P. and F.R.) read the full articles in order to select the included studies for this review and meta-analysis. Two independent reviewers (G.P. and F.R.) conducted data extraction. The following data were extracted from the included studies: Authors, year of publication, type of study, level of evidence, numbers of participants in study and control groups, age and sex of participants, types of workers, intervention in the experimental and in the control group, follow-up, and results. LBP, disability, fear-avoidance beliefs, quality of life, and work ability were assessed as outcomes in the included studies. Finally, participants on sick leave, days of sick leave, LBP recurrence, and return to work were compared between workplace intervention and control groups.The risk of bias of the included RCTs was evaluated by two authors (G.P. and F.R.) by the guideline for systematic reviews in the Cochrane Back and Neck Group . This to2 test. A fixed-effect model was adopted for low heterogeneity (I2 < 55%); otherwise, a random-effect model was involved. The statistical significance of the results was set at p < 0.05. A meta-analysis was performed using the Review Manager (RevMan) software Version 5.4.1 . Low back pain, disability, fear-avoidance beliefs, quality of life, and work ability between the experimental and the control groups were calculated as continuous outcomes. Instead, participants on sick leave, days of sick leave, LBP recurrence, and return to work were evaluated as dichotomous outcomes. The continuous data are presented as the standard mean difference (SMD) with 95% confidence intervals due to the adoption of diverse scores in the included studies. The outcomes expressed with negative mean values of SMD present a higher improvement with lower values. Dichotomous data are shown as odds ratio (OR) with 95% confidence intervals. For the calculation of the weight of the samples of the trials, for the days of sick leave, we used mean days of sick leave per participant as events and the total number of days of follow-up per participant as the total. A subgroup analysis was performed to evaluate LBP in healthcare workers and other kinds of workers. The heterogeneity was calculated using the IThe quality of the evidence and strength of recommendation of the selected outcomes were analyzed by the GRADE  assessment. Five elements  were assessed for each result and were categorized as not serious, serious, or very serious. The outcomes for RCTs received an initial ranking of high quality of evidence, which could be downgraded to moderate, low, or very low concerning the valuation of the five items.n = 9), not evaluating workplace interventions (n = 6), not specific for LBP (n = 4), patients with mental disorders (n = 3), validation of work rehabilitation program (n = 2), subgroup analysis of previous study (n = 2), and protocols of RCT (n = 2). Finally, 14 articles were included in the review and meta-analysis ; an educational program and ergonomic posture training sessions (six studies); a supervised intervention of exercise sessions of muscle strengthening, flexibility, segmental stabilization, and endurance training on the workplace (six studies); and behavioral counseling and cognitive-behavioral therapy for LBP or stress self-management (two studies). The mean follow-up was 11.3 months and ranged from 3 to 24 months. Clinical outcomes were diversified in the included studies. LBP was assessed in 10 studies, using the Visual Analogue scale (VAS) ,23,24,25Through the guideline for systematic reviews in the Cochrane Back and Neck Group, four studies (28.6%) were at low risk of bias (A), eight studies (57.1%) were judged at unclear risk of bias (B), and only two studies (14.3%) were at a high risk of bias (C) . Precisep = 0.004). Disability scores showed significant improvements for workplace interventions compared to controls . FABQ-W demonstrated lower fear-avoidance beliefs about work in workers who underwent WI compared to controls , but no significant differences (p = 0.32). FABQ-P showed a significant reduction of fear-avoidance beliefs about physical activity in the experimental group . Work ability presented improvements in favor of the intervention group , without significant differences (p = 0.31). Short-Form Health Survey results showed statistically significant improvements in quality of life for both the scales for the participants in the workplace intervention group . Finally, evaluating the clinical outcomes in totality, a significant difference was reported in favor of the workplace intervention group compared to the controls (p < 0.00001).The meta-analysis demonstrated the effectiveness of workplace interventions on LBP, disability, the Fear-Avoidance Beliefs Questionnaire for work and psychical activity, work ability, and quality of life compared to controls . Pain dep = 0.85) (p = 0.10) (p = 0.08) (p = 0.006)  but no significant differences ( = 0.85) . The num = 0.10) . Return  = 0.08) . Finally= 0.006) .p = 0.29). However, the pain reduction after WI was statistically significant in the healthcare workers’ group (p = 0.005), but no difference was reported in the other workers’ group  or moderate (FABQ-W and FABQ-P) quality of evidence and strength of recommendation at GRADE—except for work ability, which had a low quality of evidence—justifying a recommendation of workplace interventions in workers with LBP. On the other hand, GRADE reported a low quality of evidence for participants on sick leave and days of sick leave and very low quality for LBP recurrence. Finally, it should be noted that by the guideline for systematic reviews in the Cochrane Back and Neck Group, only two studies have been judged at a high risk of bias, showing an acceptable overall quality of the included studies. Almost all the studies showed a low risk of bias for random sequence generation and allocation concealment. However, in all studies, the risk of bias was high for blinding for patients and care providers, due to the impossibility to blind patients to the interventions that they were receiving. Instead, in all the trials, the outcomes were reported by assessors blinded to the group allocation.p < 0.4). Sowah et al. [In their review, Gobbo et al.  showed th et al.  evaluateh et al.  proved sh et al. , they diCertain limitations may hinder the interpretation of data. The limitations of this study are related to the heterogeneity in the population of workers of the included RCTs. Indeed, three studies ,22,25 diThe evaluation of findings provided by the studies included in this review clearly showed that different types of WI determine a beneficial effect both on clinical outcomes and socio-economic parameters related to LBP in workers. However, in consideration of the considerable heterogeneity  of the studies, trying to establish which is the best approach in terms of effectiveness in preventing LBP (and therefore in reducing its multiple negative effects) is a rather challenging task that can also lead to drawing conclusions that are not entirely correct. Indeed, in this regard, it should be taken into account that the degree of effectiveness of the different WI strategies may be affected by numerous factors such as the socio-demographic characteristics of the working population , the working activities carried out by employees, which determine a greater or lesser exposure to occupational risk factors for LBP , and the number and type of WI  . ConsequThis systematic review demonstrated that workplace interventions led to a significant improvement of clinical outcomes in a worker population affected by LBP. The meta-analysis showed strong evidence that WI improved LBP, disability, and quality of life in workers. However, a statistical increase in purely working parameters has not been described, testifying to the fact that despite the pain decreased, workers were still afraid to fully return to work. WI should be practiced in order to prevent and treat musculoskeletal symptoms, which could reduce the work ability and increase the number of sick leave days for the workers. However, workplace interventions standardized for specific works are needed, and the follow-up should be longer to evaluate the long-term effects of WI on clinical and working outcomes.


RT consisted of exercises using elastic tube bands, and BT consisted mainly of exercises performed using a variety of balance tools. Exercises were performed for 6 weeks, twice a day for 20 min, 5 days per week. Isokinetic eversion strength, Y-Balance test and hop tests, and foot and ankle outcome score (FAOS) were evaluated. Both RT and BT significantly improved strength and dynamic balance (p < 0.05). Compared to RT, BT also significantly improved the outcome of the crossover hop test (p = 0.008). The changes reflected group and time in pain (p = 0.022), sports (p = 0.027), and quality of life (p = 0.033) of FAOS were significantly greater in BT than RT. Ankle sprain is a commonly recurring sports injury. This study aimed to compare the rehabilitation effects of resistance and balance training programs in patients with recurrent ankle sprain. Patients with recurrent lateral ankle sprain completed a home-based rehabilitation program comprising resistance training (RT;  Ankle sprain occurs mainly on the lateral side due to inversion of the ankle, and is a common sports injury with a high recurrence rate . RecurrePatients with ankle sprains often require rehabilitation training. Typical symptoms after ankle injury include muscle weakness and loss of neuromuscular function; therefore, rehabilitation exercises are primarily focused on restoring strength and neuromuscular recovery ,7. In geOther studies compared the outcomes of participants treated with different rehabilitation methods. One study revealed that plyometric training was more effective than RT for patients with ankle sprain ; anotherDespite the importance of rehabilitation, it has been reported that many athletes do not receive systematic medical treatment after sustaining an ankle injury. In a study investigating CAI, only 63 of the 175 athletes evaluated received appropriate initial treatment following injury . MoreoveTherefore, this study was conducted to directly compare the efficacy of RT and BT for recurrent ankle sprain in non-professional athletes. The isokinetic eversion strength, dynamic balance, results of lower extremity functional hop tests, and outcomes of subjective questionnaire-based evaluation were evaluated in patients with recurrent ankle sprain. We hypothesized that both RT and BT are effective at improving dynamic balance and functional recovery, but that BT would achieve better outcomes than RT.A total of 54 patients were enrolled based on sample size calculations using the G*power software . The following statistical conditions were set as follows: effect size f = 0.25, α error = 0.05, and power (1-β err prob) = 0.95. Statistical analyses were performed using the F-test and two-way repeated-measures analysis of variance (ANOVA).Through treatment and consultation, we investigated the injury history including the site, mechanism, pain, injury frequency, and comorbid conditions of the patients. Physical examination was performed to determine skin discoloration, swelling, and tenderness. ROM was measured using a goniometer, and the anterior draw test was performed. Radiological examination was conducted to evaluate the gap between the fibula and talus, as well as to detect the presence of bone deformations, fractures, or loose bodies.Patients aged 20–39 years, admitted to a sports rehabilitation center with CAI or recurrent ankle sprain during sports activities from 2017 to 2018, were included. The participants were active individuals who engaged in recreational sports but were not professional athletes. Moreover, patients in the study had grades I to II anterior talofibular ligament or calcaneofibular ligament injury due to recurrent ankle sprains.On the basis of the information obtained from the consultation, we excluded the following patients: patients with bilateral injuries, ankle surgery history, visual analog scale (VAS) score ≥ 6, inversion and eversion ROM < 35° (as required for the isokinetic strength test), and those who could not stand on one leg ,18.n = 27) or BT (n = 27) groups. All participants provided informed consent, and the study complied with the Helsinki Declaration and was approved by an institutional ethics Review Board of the Gangneung-Wonju National University (GWNUIRB 2021-13).Participants were assigned a unique ID number and, depending on whether their ID number ended in an odd or even number, were assigned to either the RT  and body-weight exercises a. DifferTo maintain consistent exercise intensity, we instructed the participants to maintain the tube band’s placement at 30 cm from a fixed point on the ankle. The exercise focused on eversion and dorsiflexion on the anterolateral side and trained the peroneal and tibialis anterior muscles. Additionally, inversion and plantar flexion were performed together to strengthen the surrounding ankle. Participants were instructed to perform each exercise for 3–5 sets (20–30 repetitions per set). The exercise intensity was increased on the basis of the following: (1) tube band resistance, (2) increased number of repetitions and sets, and (3) speed. For RT using body weight, the participants performed heel raises, forefoot raises, and squats.The patient was instructed to remain as centered as possible by standing on one leg on a variety of unstable surface instruments, such as the TOGU DYNAAIR  or BOSU  b. AlternEversion ankle strength was evaluated using a CSMi  isokinetic test instrument. The test was conducted by referring to the manual and published literature presented by the equipment manufacturer ,21. The The test range was performed with the concentric contraction mode at 30–35° for ankle inversion and 25–30° for ankle eversion; the angular velocities were 30°/s and 120°/s. Each of the 4 maximum force exerted tests was performed, and the rest time between tests was set to 60 s. The examiners provided the start signal and instructions regarding repetitions; they also ensured that the patients maintained proper posture. The test was initiated in the eversion position; thereafter, the inversion force was exerted, followed by the eversion force to return to the start position. For a safe and accurate examination, a healthy ankle was first measured and then the injured foot was performed. In this study, only eversion was analyzed because the injured ligament due to the ankle sprain was located on the lateral side. The absolute value (Nm) and the relative value (Nm/body weight) were used in the analysis of the results.TM, Chatham, VA, USA) according to the recommended guidelines [A dynamic balance test was performed using the Y-Balance test (YBT) equipment , other symptoms (7 items), function in activities of daily living , function in sports and recreation (5 items), and quality of life (4 items). Five scales, with scores ranging from 0 to 4, were used to answer each question; 0 represented no symptoms at all, and 4 corresponded to extremity pain or difficulty. Both the section scores and the total score were calculated using the 100-point scale suggested by the FAOS, with 0 representing the worst symptoms and 100 corresponding to no symptoms ,25. The p < 0.05). The Mann–Whitney U test was conducted to compare the continuous variables such as the general characteristics, strength, results of YBT and hop tests, and FAOS between the groups. The Wilcoxon signed-rank test was performed to compare pre- and post-training intragroup differences in strength, YBT and hop test outcomes, and FAOS. A two-way repeated-measures ANOVA was performed to test the significance based on the 6-week training period and between the RT and BT groups. For categorical variables, the chi-squared test was applied. Statistical significance was set at p < 0.05.Statistical analyses were performed using SPSS 25.0 . For the tests, both the healthy and injured sides were examined; however, in this analysis, the results of only the injured side, obtained before and after the tests, were considered for intra- and inter-group comparisons. The Kolmogorov–Smirnov test was performed, and the results indicated that the data did not conform to a normal distribution (p = 0.036). The results of YBT improved significantly in the anterior, posterior medial, and posterior lateral directions with BT, but no significant improvement in posterior lateral directions was observed with RT. The differences according to training period and training group were significant for the total score (p = 0.002) and for the scores in the posterior medial (p < 0.001) and posterior lateral (p < 0.001) directions.p = 0.008), but not in single (p = 0.549), triple (p = 0.225), and 6-m timed hop tests (p = 0.233).p = 0.022), sports (p = 0.027), and quality of life (p = 0.033), but not significant different for the total score, symptoms, and ADL.Ankle sprain is a very common traumatic sports injury that occurs more frequently in physically active individuals ,26,27. AThe fundamental goal of rehabilitation exercises is to prevent recurrent injury and ensure safe engagement in sports and ADL . GeneralMany studies on rehabilitation exercise have been conducted to assess the effects of neuromuscular control, which is also termed BT or proprioception, and is a method of increasing the sensitivity of the muscles and nervous system ,13. TherThe effectiveness of BT in patients with ankle sprain has been demonstrated, with most studies reporting positive changes and effective preventing recurrence ,12,13,30The first major finding of this study was that the strength improvement was significant exhibited in the BT group as well as the RT group. These results were consistent with those reported by other studies ,34. O’DrThe second main finding of this study is the improvement of the RT group’s balance ability. Similar to this study, several studies have reported improvement in balance through RT ,39,40,41In this study, BT showed improvement in isokinetic eversion strength and all direction of YBT, whereas RT showed significant improvement in isokinetic eversion strength and directions except posterior lateral of YBT. Overall, BT was slightly more effective in improving strength and balance than RT. These results are similar to those reported by previous studies. Smith et al.  conducteThe YBT is a method used to measure dynamic balance. The star excursion balance test measures balance in eight directions, whereas the YBT measures it in three directions and has the advantage of being a simple exercise . SeveralHop tests are suitable for testing the function of the lower extremities in patients with ankle sprains and have been reported to have high validity and reliability ,49,50. TIn this study, the subjective condition of the ankle was evaluated using the FAOS questionnaire, which revealed the efficacy of both RT and BT. The results of this study also indicate that even though the two trainings are different, both are effective in alleviating patient discomfort. Similarly, De Ridder et al.  reportedThere are various methods of conservative treatment for ankle treatment, such as rehabilitation exercises, taping, braces, and manual therapy. These treatments have a positive effect, and it is difficult to determine which method is superior. Research that directly compares the different treatment methods is limited . A studyAlthough this study and others indicated the positive effects of BT, the effectiveness of a brace cannot be overlooked. The brace is a traditional conservative therapy and is worn until the lengthening of the lateral ligament is stabilized . When atA strength of this study is that home training was conducted for non-professional athletes who may otherwise have limited access to exercise and rehabilitation due to work obligations, distance, or cost. If it is inconvenient to visit a center and exercise, it becomes difficult to maintain a high participation rate. This study was conducted to identify an effective training method to recover function following repeated ankle injuries in persons who engage in recreational sports, and to test the effectiveness of home-based training.On the basis of these results, we recommend practical applications to rehabilitation experts as follows. First of all, the rehabilitation experts may be able to provide both or one program according to the patient’s needs and characteristics. If the patient is at high risk of falls, RT will be a safer and more effective program than BT. In addition, the tube band RT is recommended for patients who are suitable for exercise with a portable tool. However, rehabilitation experts should emphasize BT in order to help return-to-play for athletes or patients with high participation in sports and activity. Moreover, BT is recommended for people experiencing pain and low QoL due to recurrent ankle sprain.This study has some limitations. Although there is typically a high occurrence of ankle re-injury, this study did not specifically investigate the frequency of re-injury. Further research is necessary involving larger cohorts, including women, are therefore needed to answer this question. Moreover, it is necessary to assess the effectiveness of various trainings, including home and remote mobile programs. Moreover, previous studies have verified the usefulness of game-type exercises. Therefore, further studies evaluating the effectiveness of the game-type exercise programs applied to rehabilitation are required.In patients with ankle sprains, 6 weeks of RT and BT improved eversion strength, lower extremity hop function, and subjective assessment. Moreover, BT was more effective than RT in improving the dynamic balance, results of the crossover hop test, conferring pain relief, and return to sporting activities. Therefore, BT rather than RT should be emphasized to provide pain relief and restore function for the return to sporting activities.