R2) were AP, latitude, AHN, AK and OM. Moreover, the interactions between latitude and longitude, AHN and AP, OM and AK have significant impact on Zn.Soil zinc (Zn) plays a crucial role in plant growth, but excessive accumulation in the environment may lead to air, water and soil pollution. It is affected by various chemical, environmental and spatial factors. Therefore, it is important to identify the factors influencing Zn content in the landscape. The main motivation for this study is to determine the suitability of a generalized additive model (GAM) to describe change in soil Zn content due to influencing factors. A total of 1497 soil nutrient samples were collected in Fangshan District, Beijing, China. Organic matter (OM), available phosphorus (AP), available potassium (AK), alkali-hydrolyzed nitrogen (AHN) and slowly available potassium (SAK) are considered. The relationship between Zn, nutrients and geographic location (latitude & longitude) is investigated using the GAM. More precisely, the Akaike information criterion (AIC) is used to select influencing factors on Zn content and cross-validated to avoid overfitting of the multivariate model. The results show that Zn content reaches its maximum at latitude 39.8°N and longitude 115.9°E. Zinc content increases as AP increases to 150 mg/kg. When OM content is greater than 90 g/kg, Zinc content decreases with an increase in OM content. Factors that affected Zn content, in descending order of significance derived from deviance explained and adjustment coefficient of determination (Adj. When a plant is short of Zn, the growth in the stem and bud is reduced, and normal growth will be significantly affected. Similarly, Zn is required in the photosynthesis cycle4. Nevertheless, various influencing factors can affect the accumulation of Zn. For example, geographic location  has influenced the distribution and content of vegetation, soil nutrients and heavy metals11. Moreover, a considerable number of interactions are taking place in the soil between physical and chemical properties, such as, organic matter (OM), soil reaction (pH), calcium carbonate (CaCO3) and essential macro and micronutrients 13.Zinc (Zn) in soil is one of the essential trace elements of plants14, Zn content prediction15, Zn pollution characteristics16, source analysis17 and potential ecological risk assessment18. Furthermore, spatial analysis and statistical methods, such as multivariate analysis21 have been used to analyze the relationships of nutrients and heavy metals on plant and soils. But the nonlinear relationship between soil nutrients and heavy metal elements in soils has not been identified. Moreover, the effect of interactions of influencing factors on variation of soil Zn content should be also figured out. The interactions have an important impact on the material circulation in the soil circle, and it is also important for maintaining the ecological balance of environmental materials and eliminating pollutants to soil, plants and even humans22. This aims to identify the interactions of geographical and physical factors that could affect Zn content in soil using a non-parametric model, such as generalized additive model (GAM).Previous studies investigating Zn in soils have mainly focused on the influence of Zn on plants25, financial research26, fishery survey27 and environmental and climate studies30, due to specific advantages32. For example, it can directly deal with the nonlinear relationship between response variables and multiple explanatory variables33, especially for analysis of large data sets34. Furthermore, GAM can be used to analyse interactions between influencing factors on the response variable37. Conversely, traditional statistical methods cannot perform well in addressing the complex nonlinear relationship39. In our study, soil Zn content (here after referred to as Zn) is taken as an example to study the relationship between soil heavy metals, nutrients and geographic location (latitude & longitude). In the GAM, Zn is used as the response variable, geographic location and five types of soil nutrients are used as the explanatory variables.GAM has been widely used in medical application37. It is found that most explanatory variables could pass the significance test at the P-value < 0.01 level, but most of the Pearson correlation coefficients (Rs) are less than 0.3  which increases with the increase in the number of independent variables are 0.16 and 0.2 for AP and longitude, respectively. The precision of model derived from each individual explanatory variable is low. Consequently, multiple variable interactions are considered for investigating their influences on Zn.The regression model with cubic splines is used to analyze the influences of each individual explanatory variable on Zn and corresponding fitting degree of the model Table . The resR2 = 0.4The variables are gradually added to the GAM, and the tests are carried out using the Akaike information criterion (AIC) score Table . It can R2 of 0.6 is an improvement on the model which does not have concurvity. The refitted GAM identifies the effect of the influencing factors on the changes in Zn content  and S(AK) are all close to or greater than 0.5 Table , suggestent Fig.  and the P-value < 0.01 level  demonstrates the impact of interactions on Zn . Conversely, Richardson et al.40 have shown that there is no correlation between site location and Zn content. The difference in results from ref.40 may be due to the specific geographic location and land use change in the study area. The Fangshan district is a mountainous region with manufacturing and agriculture as the prime land uses. Zinc content in soil in urban and industrial areas may be an order of magnitude greater than that in rural areas41. For example, Zn reaches its maximum at 115.8°E, 39.7°N  for the multivariate GAM but it does pass for the univariate GAM. This suggests there is a concave relationship between S(SAK) and S(AK).To explore the variation of Zn content in soil, the linearity of the influencing factors on Zinc were examined. On analysis of the EDFs of the smoothing functions from the univariate? GAM, it was identified that Zn content is affected by complex nonlinear influences. The univariate GAMs of Zn content in soil are able to estimate values for the significant influencing factors of latitude, longitude, OM, AHN, SAK, AP, AK. These factors are considered additive and hence a multivariate GAM was fitted, improving the goodness of fit over the univariate model. Nevertheless, SAK does not pass the significant test  is a link function, in this study, the log is used as a link function; i = 1, 2, …, 7) are the smooth functions of Xi, Xi  are the explanatory variables, and they are latitude, longitude, OM, AHN, AP, SAK, AK, respectively. It is a regression model that can define the relationships between the response variable and each explanatory variable through smooth functionsf, with two continuous derivatives, find one that minimize the penalized residual sum of squares.λ is the smoothing parameter. The smooth functions with cubic regression splines were used in our work. Cubic regression splines were constructed with piecewise cubic polynomials joined together at points called knots. The definition of cubic smoothing spline basis arises from the solution of the following optimization problem. Among all the functions 46. A Shapiro-Wilk test was employed to check the normality of Zn. Correlation coefficient (R) was used to check the correlation between variables. In general, when there is a definite collinearity relationship between the influencing factors in the model, the concurvity relationship must exist between these factors. The existence of concurvity in GAM would not only increase the variance of coefficients but also enlarge the standard deviation of coefficients. It can cause the narrowing of confidence interval. Hence, it is necessary to test whether model has concurvity. The concurvity test has three indicators: worst, observed and estimate k is the number of parameters in the model; L is the log likelihood; and n is the number of observations.A forward stepwise procedure was used to choose the most appropriate model removing each explanatory variable from the model, and then evaluating the AIC score. The smaller the score, the better the model fits. The AIC score is calculated as follows:The 95% confidence interval of the fitted values for Zn was obtained from bootstrapping. Additionally, the estimated degree of freedom (EDF) was used to determine whether the selected factors were nonlinearly associated with the response variables. In order to get a reliable and stable model, a cross-validation method was used to verify the model. We randomly selected 70% of the sampling data for modeling, and the remaining 30% was used as the test set.Using the GAM, we analyzed the relationship of Zn content between latitude, longitude, OM, AHN, AK, AP and SAK in Fangshan District, Beijing. Based on our analysis, we find that Zn content in soil is significantly affected by latitude, longitude, OM, AHN, AK, AP and interactions of OM, AP, longitude, AK with latitude. Thus, by fitting a GAM, the influence of interactions between factors affecting Zn content in soil can be quantitatively predicted and analyzed. In addition, to gain a greater understanding on influencing factors on Zn content in soil, other influencing factors (e.g. pH) need to be included in the GAM.


Objective: Numerous studies have proved the importance of Evidence-Based Medicine (EBM) in daily clinical practice, however, clinicians’ attitudes play an important role in determining its implementation. The objective of this study was to investigate Chinese clinical physicians’ perception of and attitude towards EBM and their Evidence-Based Practice (EBP) as well as the barriers towards EBP. Methods: Using a cross-sectional design, self-response questionnaires were distributed to clinical physicians  across three tertiary hospitals in Wuhan, China. Results: In total, 131 out of 195 (67.2%) physicians completed and returned the questionnaire. A total of 64.9% of the physicians either knew moderately or a lot about EBM. The mean score of physicians’ attitude toward EBM was 2.35 ± 0.35, and that of their EBP skill/ competency was 1.51 ± 0.56 . In total, 76.0% of physicians often or sometimes applied EBM in routine daily practice. The largest barrier preventing implementation was the varying individual differences in diseases (61.0%), followed by a lack of investment from the hospital/department (39.8%), and a lack of patient cooperation (37.4%). Chinese physicians in tertiary hospitals possessed expressed positive attitudes towards EBM; however, they only retained a moderate level of clinical evidence competency. Both an individual factor  and organizational factors  had an effect on physicians’ attitudes and their EBP skills. Management and organizational efforts, in addition to time dedicated for EBP projects could help reduce barriers that prevent EBP. Evidence-based medicine (EBM) is considered to be the careful and meticulous use of up-to-date evidence in the decision-making process regarding individual patient care, whereas evidence-based practice (EBP) integrates individual clinical expertise with the best available clinical evidence obtained from systematic research . Since tth center of the International Cochrane Collaboration in 1999. EBM then spread rapidly across China through the introduction of Clinical Epidemiology and EBM as compulsory curricula in medical universities, as well as through the launch of academic journals such as the Chinese Journal of Evidence-Based Medicine (2001),the Journal of Evidence-Based Medicine (2001), the Chinese Journal of Evidence-Based Pediatrics (2006), the Chinese Journal of Evidence-Based Cardiovascular Medicine (2008), and through the establishment of professional institutions and academic organizations, such as the Chinese Medical Doctors Association’s Evidence-Based Medicine Committee (2003) and the Ministry of Education’s Virtual Research Center of Evidence-based Medicine (2004) [The official introduction of EBM into China can be traced back to the year 1996, when The Chinese Cochrane Center (The Center) was established. The Center was approved by China’s former Health Ministry in 1997 and became the 14e (2004) ,18.Although an increasing number of empirical studies on physicians’ knowledge, perception, attitude, competency, and practice of EBM in clinical practice settings have been witnessed in recent years, the relationship between knowledge/attitude and behavior has not been fully explored. Most empirical studies have been conducted in developed countries and few studies have been carried out in developing countries; additionally, very little English literature focuses on Chinese physicians . In thisThis study employed a cross-sectional survey design. The 2013 China Health Statistical Yearbook reported that there were 2,138,836 medical practitioners in China, 1,297,078 of whom were working in hospitals, with 74.1%  of them in general hospitals and 1.4%  in TCM-WM  hospitals. Based on the above data and a convenience sampling method, three tertiary public hospitals in the city of Wuhan located in Central China were chosen. Hospital A is a general and teaching hospital, Hospital B is a TCM-WM and teaching hospital, and Hospital C is a general and non-teaching hospital. Tertiary public hospitals were chosen because they are the highest-level hospital in China’s medical delivery system. Physicians in these hospitals are more likely to be highly trained and more educated compared to those in secondary and primary hospitals. The target population was hospital physicians and resident physicians, however, refresher physicians were excluded. Subjects from each hospital were recruited mainly from two departments . Hospital administrators and/or the directors of the departments distributed the questionnaires to physicians. Completed questionnaires were recovered by the distributor and checked by the researchers for quality of data collection. The contact telephone number of one of the researchers was included in the cover letter with the questionnaires in case the physicians needed to ask questions about the study. In total, 195 questionnaires were sent out to physicians and 131 completed questionnaires were returned. Demographic data are presented in Based on the definitions of EBM and EBP and relevant references such as McColl (1998) , Heiwe eStatistical analyses were performed using IBM, SPSS version 13.0 . Descriptive statistics were used to examine the frequencies of the respondents’ demographics, as well as the physicians’ opinions about EBM and EBP. Univariate and multivariate analyses analyzed the factors influencing physicians’ knowledge of, and attitudes towards EBM, as well as their skills/competency. Linear regression models were used to identify the factors that affected physicians’ attitudes towards EBM and their EBP skills/competence. Logistic regression models were used to identify the factors with a significant effect on physicians’ knowledge of EBM and the implementation of EBP.In total, 131 out of 195 (67.2%) physicians completed and returned the questionnaire. However, the questionnaire was incompletely filled. Most (58.0%) physicians knew moderately about EBM, while only 2.3% of them knew nothing about EBM. Physicians learned about EBM through a variety of channels. The main channel through which physicians learned about EBM was continuing education (61.8%), followed by school education (54.2%) and hardcopy journals (51.9%), see p = 0.006), specialty , and the number of working hours per week  still had a significant association with physicians’ attitudes, which explained 13.2% of physicians’ attitudes towards EBM . The univariate linear regression investigating attitudes towards EBM found gender, specialty, number of hours worked per week, hospital’s scientific research requirement, and a physician’s personal interest in scientific research to be statistically significant predictors. However, when those variables were entered into a multivariate linear regression model, only physicians’ personal interest in scientific research  and academic research (78.5%), followed by a teaching demand (22.3%), and hospital arrangement (8.5%).Among gender, educational background, specialty, attitude, the hospital’s requirement and personal interest, attitude, educational background and a hospital’s research requirement accounted for 22.9% of the physicians’ skills/competence . This study indicates that 17.7% and 58.5% of physicians, respectively, often and sometimes applied EBM in routine daily practice, and that 22.3% and 1.5% of physicians, respectively, rarely and never applied. Specialty and EBP skills/competency explained the 26.3% of physicians who implemented EBP . As for the barriers towards the implementation of EBP , 61.0% oWe believe that our investigation is an important effort to assess Chinese clinical physicians’ perception of, and attitudes towards EBM and their behaviors related to EBP, as well as the barriers that impede EBP. Firstly, Chinese physicians in this study possessed moderate levels of EBM knowledge and positive attitudes towards EBM, which is at a similar level to that of their counterparts in Britain, Germany , France The establishment of the Chinese Cochrane Center in 1996 was a symbol of the official introduction of EBM into China. After that, a new development model integrating discipline, platform, echelon and popularity  was adopAs expected, here was no strong collision between evidence-based medicine and traditional Chinese medicine or perhaps EBM was only blocked at the individual level of traditional Chinese medicine, owing to the top-down policy path in China. On the contrary, EBM has also burgeoned in the field of traditional Chinese medicine, with the evidence-based Medicine Center of Chinese Traditional Medicine being established  in 2019.In fact, EBM has been disseminated throughout China during the last two decades. Support from the Chinese government and its relevant departments, such as China’s former Health Ministry, the National Ministry of Education, and the National Natural Science Foundation , may havHowever, although physicians had positive attitudes towards EBM, their clinical evidence competence was just at a moderate level, and the actual execution of EBP was not as frequent as expected. This continues to be an abstract field, which, although recognized as important, is not always used in daily clinical practice . There eOur results reveal that physicians’ attitudes towards EBM could be influenced by both an individual factor (interest in scientific research) and an organizational factor (workload). Interest, as an intrinsic motivation and its creation and maintenance is an important tool during learning and instruction . It can In addition, we found that physicians’ EBP skills/competence could be influenced by both an individual factor (attitudes) and an organizational factor . The relationship between attitudes and skills has also been found among registered nurses in China . At the This study shows that physicians’ EBP competence affected their implementation of EBP, which is consistent with the findings of a study in the USA  that theLastly, time is usually the foremost-cited barrier to the implementation of EBP in many studies ,16,33,34This study has several limitations. First, we used a small convenience sample that focused on one city in China. A total of 32% of physicians did not complete the questionnaire; we could not identify how many of them were a missing sample and how many of them were EBM-minded. Secondly, since Chinese physicians in different types of hospitals  in various cities may respond differently, the results were representative of physicians in tertiary hospitals, not representative of physicians in secondary and primary hospitals. Thirdly, we concentrated on individuals and the hospital level. Further studies are needed to explore patients’ perception of, and attitudes towards EBM, which can influence the design of EBM education and the implementation of EBP.Overall, this study shows that Chinese physicians possessed expressed positive attitudes towards EBM; however, they only retained a moderate level of clinical evidence competency. Both an individual factor  and organizational factors  had an effect on physicians’ attitudes and EBP skills. The first three barriers preventing EBP were the varying individual differences in diseases, a lack of investment from the hospital/department, and a lack of patient cooperation. It is important to develop national clinical guidelines of high quality and routinely incorporate them into EBP. Management and organizational efforts in addition to time dedicated for EBP projects could help reduce barriers that prevent EBP.


The government management in the EU and non-EU countries should be strengthened to reduce the air pollutant and carbon dioxide emissions and raise energy transformation to the clean energy in renewable energy and improve health efficiencies in medical and health care field.There is a close and important relationship between environmental pollution and public health, and environmental pollution has an important impact on the public health. This study employed the two-stage meta-frontier dynamic network data envelopment analysis (TMDN-DEA) model to explore the environment pollution effects from energy consumption on the mortality of children and adult, tuberculosis rate, survival rate and health expenditure efficiencies in 28 EU countries and 53 non-EU countries from 2010 to 2014. We calculated the overall efficiency scores and the technology gap ratios of each EU and non-EU countries and the efficiencies of input and output variables in the production and health stage. The average overall efficiencies each year in EU countries are higher than in the non-EU countries. But EU countries have higher energy efficiency than non-EU countries, and non-EU countries have higher health efficiency than EU countries. The health expenditure efficiencies in the EU countries are obviously lower than those in non-EU countries. The renewable energy efficiencies are obviously higher than the non-renewable energy efficiencies; PM2.5 efficiencies are obviously higher than the CO The European Union (EU) is an important intergovernmental economic union and produced 21.54% GDP of the world in 2018 [The other countries also attach great importance to energy efficiency and environmental issues. As early as 1997, the United Nations Framework Convention on Climate Change adopted the Kyoto Protocol at the third Conference of States Parties. In November 2017, the 23rd Conference of the Parties to the United Nations Framework Convention on Climate Change was held in Bonn, Germany. The conference formulated the implementation guidelines for the Paris Agreement. The main content includes controlling the global temperature to within 2 degrees Celsius before the industrial revolution and reducing greenhouse gas emissions in stages. There are some input-output relationship and influence mechanism among energy, environment pollution, and health, as shown in the Based on such influence and transmission mechanism, this study employed a two-stage meta-frontier dynamic network data envelopment analysis (TMDN-DEA) model to explore the environment pollution effects from energy consumption on the mortality of children and adult, tuberculosis rate, survival rate and health expenditure efficiencies in EU and non-EU countries. This research analyzes the energy and health efficiencies in EU and non-EU countries. The first stage is the production stage and we can learn the energy efficiencies from this stage. The second stage is the health treatment stage and we can learn the health efficiencies from this stage. This study has two main contributions. First, energy, environment, and health are included in one model to comprehensively explore energy and health efficiency of EU countries and non-EU countries taking comparative analysis. Second, this study divides the energy into the renewable energy and the non-renewable energy and divides the mortality rate into children’s mortality rate and adult’s mortality rate.The remainder of this article is organized as follows: the second section gives the literature review, the third section introduces the research model and method, the fourth section gives the empirical study results, and the fifth section presents the conclusions and implications.There have been many studies on energy environment and health issues, mainly from two independent directions of environment and health. The first area has been focusing on energy and environmental efficiency analyses. The second area is about the impact on human health from environmental pollution.Energy and environmental topics have long been analyzed by many scholars from the perspectives of economy, energy, pollution, and governance. With regard to the importance of energy and environmental issues, many scholars have also done a lot of research on this topic. Among them, some scholars use the data envelopment analysis (DEA) method to study the energy efficiency ,12,13,14X) caused by acid rain in the United States Clean Air Act (CAA). This study found that the environmental law is effective for the emission control of SO2 and NOX produced by coal-fired power plants in the United States. Liou and Wu [2 emissions control scale efficiency for utilization in developing countries. Choi et al. [2 emission performance index (MNMCPI) indicator to analyze the changes in China’s carbon dioxide emission efficiency and its driving force. The empirical results showed that the average annual growth rate of CO2 emissions from China’s provincial industrial sector was 5.53% from 1998 to 2011. The average carbon dioxide emissions of the industrial sector in the eastern, central, and western regions decreased in turn, and the annual growth rate of MNMCPI’s efficiency (EC) indicators increased. The rate was 2.297%, and the carbon dioxide emission efficiency change (EC) in 21 provinces showed an upward trend. Wang et al. [Sueyoshi and Mika  proposedu and Wu  used thei et al.  used thei et al.  used SBMi et al.  used thei et al.  believedi et al.  collecteg et al.  exploredg et al.  exploredg et al.  analyzedg et al.  used theg et al.  studied g et al.  used VARg et al.  summarizg et al.  also stu2 emissions. Dumana and Kasman [2 emissions can significantly harm population health. Fischer et al. [2 in the Netherlands over 30 years of age is associated with increased mortality. Yang et al. [3 increased in the blood. There was a significant relationship between the increase in eosinophil count, and the clinical decline in healthy lung function and the increase in inflammatory markers in French residents with short-term exposure to air pollution. Carlton et al. [2 concentrations in schools and households for each child. Among the 2630 children, the prevalence of asthma was currently 14.9%. According to estimates, there was an impact between exposure to outdoor NO2 and adverse respiratory health on the children in Australia. Roberts et al. [There are also many studies to take European countries as research objects on energy environment and health issues. Bampatsou et al.  used thed Kasman  used thed Kasman  used thed Kasman  found EUd Kasman  used botd Kasman  estimated Kasman  identifid Kasman  examinedd Kasman  evaluated Kasman  found thd Kasman  exploredr et al.  exploredg et al.  studied g et al.  exploredg et al.  used theg et al.  exploredn et al.  assessedn et al.  used then et al.  used linn et al.  studied n et al.  exploredn et al.  studied s et al.  exploreds et al.  explored2, SO2, and NOX emissions in some countries or in various provinces/states in some one countries. Their research yielded essentially the same results that energy and environmental efficiencies is low, especially for developing area. The studies on the energy and environmental efficiency in EU countries focus on the efficiency of nuclear energy, the energy efficiency of European livestock industry, the efficiency differences among EU countries , the GHG emissions (El) and the agricultural efficiency. We can learn from their research that the first 15 countries in EU had greater efficiency and energy and environmental efficiency, still have potential to reduce carbon dioxide emissions and so on to improve the energy and environmental efficiency in EU. The studies on the impact of exposure to environmental pollution on human health mainly focus on the developing countries. For example, China and BRICS countries. Studies have shown that increased PM2.5, PM10, CO2, and SO2 emissions can significantly harm population health.The studies on the energy and environmental efficiency focus on the many objects, such as fossil fuel consumption, COBased on the above literature analysis, this paper makes the following research hypotheses:Hypothesis 1.The average overall efficiency of EU countries is higher than that of non-EU countries.Hypothesis 2.The overall energy efficiency of EU countries is higher than that of non-EU countries.Hypothesis 3.The overall health efficiency of EU countries is higher than that of non-EU countries.Hypothesis 4.In each of the energy efficiencies, EU countries are higher than non-EU countries.Hypothesis 5.In each of the health efficiencies, EU countries are higher than non-EU countries.We used TMDN-DEA model to analyze the energy and health efficiencies. TMDN-DEA model in this paper is developed based on SBM dynamic DEA with meta-frontier (MF) and dynamic group boundary model including two stages.Farrell  measuredTone and Tsutsui  proposedSince this study considers undesirable output and regional differences in the dynamic network SBM model, we can modify Tone and Tsutsui’s  dynamic Suppose there are Set Inputs and OutputsLinkstj(kh)t ∈R+ZCarryoversN) are composed of decision units of g groups (N = 1N + 2N + ….+ gN) because of different management types, environments, and resources, and xij and yrj represent respectively the i-th input , the r-th final output r  in the j-th unit . Under the mate boundary, the decision unit k can choose the final output weight that is most favorable to its maximum value, so the efficiency of the decision unit k under the common boundary can be solved by the following linear programming procedure.Assuming that all manufacturers (t and t + 1 Equation (1) represents the connection equation between term Therefore, we can know the overall technical efficiency (OTE) value of all DMUs under the common boundary model with Equation (2).Assuming that the manufacturer is divided into g groups of decision units, the DMU under each group boundary will choose the most favorable final output weight. Therefore, the efficiency of the DMU under the group boundary will be solved by the following equation:Since the meta-frontier model contains g groups, the technical efficiency of the meta-frontier (MFE) will be less than the technical efficiency of the group frontier (GFE). The ratio value, called the technology gap ratio (TGR), is shown as:2 efficiency, and PM2.5 efficiency. In our study, “I” represents area and “t” represents time. The eleven efficiency models are defined in the following:We follow Hu and Wang’s  total-faIf the target labor, non-renewable energy efficiency, renewable energy efficiency, and health expenditure input equals the actual input, then the labor, non-renewable energy efficiency, renewable energy efficiency, and health expenditure efficiencies equal 1, indicating overall efficiency. If the target labor, non-renewable energy efficiency, renewable energy efficiency, and health expenditure input is less than the actual input, then the labor, non-renewable energy efficiency, renewable energy efficiency, and health expenditure efficiencies are less than 1, indicating overall inefficiency.2, and PM2.5 undesirable outputs equal the actual undesirable outputs, then tuberculosis rate efficiency, mortality rate of children efficiency, mortality rate of adult efficiency, CO2, and PM2.5 efficiencies equal 1, indicating overall efficiency. If the target tuberculosis rate efficiency, mortality rate of children efficiency, mortality rate of adult efficiency, CO2, and AQI undesirable outputs are less than the actual undesirable outputs, then the tuberculosis rate efficiency, mortality rate of children efficiency, mortality rate of adult efficiency, CO2, and PM2.5 efficiencies are less than 1, indicating overall inefficiency. If the target tuberculosis rate efficiency, mortality rate of children efficiency, mortality rate of adult efficiency, COIf the target GDP and survival rate of 65-years-old desirable output is equal to the actual GDP and survival rate of 65-years-old desirable output, then the GDP and survival rate of 65-years-old efficiency equals 1, indicating overall efficiency. If the actual GDP and survival rate of 65-years-old desirable output is less than the target GDP desirable output, then the GDP and survival rate of 65-years-old efficiency is less than 1, indicating overall inefficiency. This study compares the energy efficiency and healthy efficiency in EU and non-EU countries from 2010 to 2014. The diseases data are extracted from Global Tuberculosis Control Report   and the In our study, the variables in each stage are showed in the The first Stage: Production StageInput Variables:Labor: The numbers of employees in each country by the end of each year. Unit: Million person. Renewable energy: Renewable energy consumption in each country every year. Unit: Mega Joule.Non-renewable energy: Non-renewable energy consumption in each country each year. Unit: Mega Joule.Output Variables:GDP (desirable output): GDP in each country each year. Unit: billion dollars at current price.The Second Stage: the Health Treatment StageInput Variables:Healthy Expenditure: Total annual health expenditure in each country. Unit: billion dollars.Output Variables:Mortality rate of children (undesirable output): Mortality rate of children that is less than 5 years old in each country each year. Unit: percent.Mortality rate of the aged (undesirable output): Mortality rate of the aged that is more than 65 years old in each country each year. Unit: percent.Survival rate (desirable output): Survival rate is that of 65 years old in each country each year. Unit: percent.2 and PM2.5 in the air will reduce people’s immunity to pulmonary tuberculosis, thus increasing the incidence of pulmonary tuberculosis. Tuberculosis rate is that in each country each year. Unit: ‱.Tuberculosis rate (undesirable output): Excessive content of COLink Production Stage and the Health Treatment Stage Variables2: CO2 emissions in each country each year. Unit: million ton.COPM2.5: The content of PM2.5 in the air in each country each year. Unit: Micrograms per cubic meter.Carry Over Production Stage and the Health Treatment Stage VariableFixed assets: Capital stock of each country is calculated by fixed assets investment in each country by the end of each year. Unit: Billion dollars.Before the empirical study, this paper has carried out isotonicity test to justify the selection of variables. The minimum values of most variables are nearly 0 and they are not very clear in the picture. The minimum values of PM2.5, mortality rate of children and adults declined from 2010 to 2014. The minimum values of labor and survival rate of 65 years old were not change too much from 2010 to 2014.The maximum values of labor and survival rate of 65 years old were not changed too much from 2010 to 2014. The maximum and average values of CO2, non-renewable energy, tuberculosis rate, mortality rate of children and adults declined from 2010 to 2014. The maximum and average values of capital, GDP, renewable energy, and health expenditure increased from 2010 to 2014.The average values of labor, capital, renewable energy, non-renewable energy, and GDP were not change too much from 2010 to 2014. The average values of PM2.5, survival rate of 65 years old, tuberculosis rate, mortality rate of children and adults declined from 2010 to 2014. The average values of health expenditure increased from 2010 to 2014.The minimum values of PM2.5 decreased a little and that of mortality rate of children and adults were not change too much from 2010 to 2014. But the minimum value of survival rate of 65 years old increased significantly from 2010 to 2014.2, non-renewable energy, capital, GDP, renewable energy, and health expenditure increased from 2010 to 2014. The maximum values of labor and survival rate of 65 years old were not change from 2010 to 2014.The maximum values of tuberculosis rate, mortality rate of children and adults declined from 2010 to 2014. The maximum values of COThe overall efficiencies in each EU country from 2010 to 2014 are showed in the Bulgaria, Hungary, Poland, and Romania’s efficiencies of each year were below 0.2 from 2010 to 2014 and Czech’s overall efficiency was also below 0.2, and the efficiencies of Austria, Croatia, Latvia, Lithuania, and Slovak were between 0.2 to 0.3. These countries are all local in the east Europe. Except Malta, Cyprus, and Sweden; there are Finland, Greece, Italy, Luxembourg, Netherlands, and Sweden where efficiencies were over 0.5. Therefore, there were 9 countries where efficiencies were over 0.5 and 10 countries where efficiencies were below 0.3 in EU countries of 28.In the non-EU countries of 53, there are 6 countries where overall efficiencies were 1 in all four years, as showed in the Australia, Canada, Korea, New Zealand, Switzerland, United Arab Emirates total efficiencies were above 0.6 and those countries are developing countries. Albania, Cambodia, Cuba, Nepal, Norway, Iraq, Israel’s total efficiencies were between 0.5 to 0.6. Therefore, there were 19 countries where efficiencies were over 0.5 in non-EU countries of 53.India, Vietnam, South Africa, and Ukraine’s efficiencies were below 0.1 from 2010 to 2014. Those countries’ efficiencies were the lowest. Brazil, Bangladesh, Belarus, Chile, China, Colombia, Iran, Morocco, Kazakhstan, Kenya, Malaysia, Mexico, Peru, Philippines, Thailand, Tunisia, and Turkey’s efficiencies were below 0.2 in most or all year from 2010 to 2014. Algeria, Argentina, Cameroon, Costa Rica, Pakistan, and Sri Lanka’s total efficiencies were between 0.2 to 0.3. Therefore, there were 27 countries where efficiencies were below 0.3 in non-EU countries of 53.The overall efficiencies in non-EU countries were worse than those in EU countries. There are half countries where overall efficiencies were below 0.3 but that is one-third of the EU countries. We can also prove this from the average value of overall efficiencies in EU and non-EU countries. The average values of overall efficiencies are higher in EU countries than that in non-EU countries each year from 2010 to 2014. This basically proves the hypothesis:”H1: The average overall efficiency of EU countries is higher than that of non-EU countries.”From the view of each stage, the overall efficiencies of EU and non-EU countries have different performance. Because there are too many countries in EU and non-EU, we use the average values of the overall efficiencies of EU and non-EU countries to compare the difference between EU and non-EU countries. We can see the results in the But the average overall efficiencies of EU countries are lower than those of non-EU countries each year from 2010 to 2014 in the second stage . The average overall efficiencies of EU countries are below 0.27 except 0.3382 in 2010 from 2010 to 2014 in the second stage, but those of EU countries are above 0.34 for each year from 2010 to 2014. Therefore, the healthy efficiencies in EU countries is lower than non-EU countries and there is much more space to improve the healthy efficiencies in EU countries.Meanwhile, the average overall efficiencies of EU and non-EU countries each year in the second stage are all lower than those in the first stage, especially for EU countries. Thus, there are much more spaces to improve for the healthy efficiencies than for the energy efficiencies in EU countries and non-EU countries. This proves that the hypothesis “H3: The overall health efficiency of EU countries is higher than that of non-EU countries” is not true.We can learn the technical efficiency of the group frontier for EU and non-EU countries from the technology gap ratio (TGR) of EU and non-EU countries from 2010 to 2014, as showed in The explanation for this phenomenon is mainly due to the TGRs of EU countries in the second stage was lower significantly than non-EU countries from 2011 to 2014. The TGRs of EU countries in the second stage were all below 0.48, but those of non-EU countries were above 0.84 each year from 2010 to 2014. However, in the first phase, the TGRs of EU countries were higher than those of non-EU countries. Thus, EU countries have a bigger gap between group frontier (GF) and meta-frontier (MF) in the healthy treatment stage, and the TGRs of non-EU countries were very close and high in the production stage and the healthy treatment stages from 2011 to 2014.2 efficiencies of EU countries were all higher than ones of non-EU countries from 2010 to 2014. The gap of renewable energy, PM2.5 and CO2 efficiencies between EU countries and non-EU countries were more significant. There are much more space for the non-EU countries to improve the energy efficiencies of inputs and outputs. This basically proves the hypothesis: ”H4: In each of the energy efficiencies, EU countries are higher than non-EU countries.”We can learn the energy efficiencies for the inputs and outputs from the production stage in EU countries and non-EU countries. As the 2 efficiencies for EU countries and non-EU countries.Meanwhile, the renewable energy efficiencies were obviously higher than the non-renewable energy efficiencies and PM2.5 efficiencies were obviously higher than the COWe can learn the health efficiencies for the inputs and outputs from the health treatment stage in EU countries and non-EU countries. From the Because the health expenditure efficiencies are very low and there is different performance between the children and the adult mortality rate, we analyzed in detail the specific situation of health efficiencies of each EU and non-EU country. The results are showed in the In the EU countries see , there aThere are 7 countries where children’s mortality rate efficiencies were 1 in all five years and they are Cyprus, Estonia, Finland, Lithuania, Latvia, Slovenia, and Malta. The children’s mortality rate efficiency in Slovak was at the least and it was 0.5693. Another countries’ children’s mortality rate efficiencies were above 0.62 in EU. There are 3 countries where adult’s mortality rate efficiencies were 1 in all five years and they are Cyprus, Italy, and Malta. There are 6 countries where adult’s mortality rate efficiencies were above 0.8 in all five years and they are Bulgaria, Germany, Spain, Luxembourg, Netherlands, and Sweden. The adult’s mortality rate efficiencies in Estonia, Hungary, and Lithuania were lower than the ones of other countries and they were 0.3787,0.3218, 0.2700 respectively.In the non-EU countries see , there aThere are 12 countries where the mortality rate of children efficiencies was 1 in all five years and they are Albania, United Arab, Belarus, Brunei, Iceland, Japan, Cambodia, Korea, Nepal, Saudi Arabia, Singapore, and USA. There are still other 8 countries where children’s mortality rate efficiencies were above 0.8. But there are 15 countries where children’s mortality rate efficiencies were below 0.56 in all five years and the least value is 0.2742 in Brazil. But children’s mortality rate efficiencies were all above 0.56 in EU countries each year. There are 11 countries where adult’s mortality rate efficiencies were 1 in all five years and they are Albania, United Arab, Brunei, Canada, China, Iceland, Japan, Nepal, Saudi Arabia, Singapore, and USA. There are still other 10 countries where adult’s mortality rate efficiencies were above 0.8 in all five years. There are 5 countries where adult’s mortality rate efficiencies were below 0.4 in all five years and they are Belarus, Botswana, Colombia, Kazakhstan, and Philippines in non-EU countries of 53 and they were 0.2221, 0.3831, 0.3381, 0.2346, 0.3576 respectively. Relatively speaking, there are 3 countries where adult’s mortality rate efficiencies were below 0.4 in EU countries of 28. 2, labor, GDP, tuberculosis rate, children’s mortality rate, adult’s mortality rate, health expenditure efficiencies, and survival rate efficiencies. Finally, we have a generalization of the results of the study. First, the average overall efficiencies in EU countries were higher than in non-EU countries. Second, EU countries have higher energy efficiencies than non-EU countries and non-EU countries have higher health efficiencies than EU countries. Third, the renewable energy efficiencies were higher than the non-renewable energy efficiencies. The detail conclusions from analysis are as follows.This study focuses on the energy efficiencies and health efficiencies in 28 EU countries and 53 non-EU countries from 2010 to 2014. Using a TMDN-DEA model, we calculate the overall efficiencies score and the technology gap ratios of each EU and non-EU countries from 2010 to 2014 in each and total stages. The first stage is production stage and the second stage is health treatment stage. Then we also calculate the efficiencies for the inputs and outputs of the production and health stage in EU countries and non-EU countries, including the non-renewable energy, renewable energy, PM2.5, COAverage overall efficiencies each year in EU countries were higher than in non-EU countries from 2010 to 2014. An overall efficiency of 1 in all four years was achieved by Malta which are EU countries and Brunei, Japan, Iceland, Saudi Arabia, Singapore, and United States which are non-EU countries.These countries where average overall efficiencies are lower in EU are all located in the east Europe, for example, Bulgaria, Hungary, Poland, Czech, Romania, Austria, Croatia, Latvia, Lithuania, and Slovak. The countries where average overall efficiencies are lower in non-EU are developing countries. For example, India, Vietnam, South Africa, Ukraine Brazil, Bangladesh, Belarus, Chile, China, Colombia, Iran, Morocco, Kazakhstan, Kenya, Malaysia, Mexico, Peru, Philippines, Thailand, Tunisia, and Turkey.EU countries have higher energy efficiencies than non-EU countries and non-EU countries have higher health efficiencies than EU countries. The average overall efficiencies of EU countries are higher than those of non-EU countries each year from 2010 to 2014 in the first stage (production stage). But the average overall efficiencies of EU countries are lower than those of non-EU countries each year from 2010 to 2014 in the second stage .There is much more space to improve the healthy efficiencies for the countries in EU. The average overall efficiencies in the second stage are all lower than those in the first stage both for EU countries and for non-EU countries each year, especially it is obviously for EU countries.EU countries have a bigger gap between group frontier (GF) and meta-frontier (MF) in the healthy treatment stage. Although the TGRs of EU countries were higher than the ones of non-EU countries in the first stage, the TGRs of EU countries were too low than the non-EU countries. Thus, the technical efficiency of the group frontier of non-EU countries is higher than EU countries.2 efficiencies for EU countries and non-EU countries. But there is much more space for the non-EU countries to improve the energy efficiencies of inputs and outputs.The renewable energy efficiencies were higher obviously than the non-renewable energy efficiencies and PM2.5 efficiencies were higher obviously than the COThere is much more space for the non-EU countries to improve the tuberculosis rate efficiencies and children’s mortality rate efficiencies, and there are much more space for the EU countries to improve the health expenditure efficiencies and the adult’s mortality rate efficiencies.The children’s mortality rate efficiencies were higher than the adult’s mortality rate efficiencies for EU countries and non-EU countries. There are 19 countries where the children’s mortality rate efficiencies were 1, but there are 14 countries where the children’s mortality rate efficiencies were 1 in all five years.The health expenditure efficiencies in the EU countries are obviously lower than those in non-EU countries. In the non-EU, there are 9 countries where health expenditure efficiencies were 1, but there are 2 countries in EU. There are 13 countries where health expenditure efficiencies were below 0.1 in the non-EU countries, but there are 11 countries in EU. Most of countries where the health expenditure efficiencies were below 0.1 in the EU countries are high welfare countries, for example, Belgium, Denmark, France, UK, Iceland, Netherlands, Spain, and Portugal.In theory, this paper has enough literature to prove the significance and value of our research. First of all, we applicate a modified meta dynamic network model with a production stage to analysis renewable and non-renewable energy efficiency. Second, we have a second health treatment stage to focus on health expenditure and the impact on survival rate of 65 years old, children’s and adults’ mortality rate in EU countries and non-EU countries. Through the conclusion of this paper, this paper puts forward the following practical and positive suggestions for the EU and non-EU countries.As we known from conclusions, the non-renewable energy efficiencies are much lower than the renewable energy efficiencies in the EU and non-EU countries. The government management in the EU and non-EU countries should be strengthened to reduce air pollutant and carbon dioxide emissions which are from the consumption of the non-renewable energy. Moreover, EU-ETS should play a greater role. The price of emission right has affected the production decision of enterprises. If enterprises do not take emission reduction measures, they need to bear more cost of emission reduction. This is conducive to the transformation of energy consumption of enterprises to renewable energy.Because the efficiencies of renewable energy are higher than ones of non-renewable, so it is more inclined to use renewable energy, especially clean energy in renewable energy, such as solar energy, wind energy, and so on. Further attention should be given to raise energy transformation to the clean energy in renewable energy. At the same time, the efficiency improvement of renewable energy is to improve the efficiency of energy management. The efficiency improvement of energy transmission and distribution management will enhance the utilization efficiency of new energy. EU countries and non-EU countries should encourage the application of new technologies in new energy development and energy management efficiency improvement.Because of the differences of the health efficiencies are serious among the non-EU countries and the health efficiencies in developing countries are lower than ones of developed countries. These developing countries should concentrate more on the health expenditure. Health expenditure is the basic social security. Non-EU governments should consider establishing corresponding laws and regulations to protect health expenditure.As we known from conclusions, the health expenditure efficiency of EU countries is even much lower than non-EU countries. Meanwhile, most of these EU countries are the high-welfare countries. These high-welfare countries in Western Europe should consider how to make full use of medical resources and improve medical efficiency. The government of high welfare countries should actively encourage new medical technology to improve health efficiency while ensuring health expenditure.The health efficiencies are low in the EU and non-EU countries, health expenditure efficiency should be improved. Especially in EU countries, there are too much space to reduce their adult’s mortality rate. The prompt of health efficiency not only depends on the improvement of technology, but also the management efficiency of government in health expenditure.


Background: Kawasaki disease (KD) may be associated with infection of unknown pathogen(s). For predicting of the etiology of KD, we evaluated epidemiological characteristics in KD, common infectious diseases and immune-mediated diseases in childhood.Methods: We respectively, reviewed the data of patients with KD, influenza, aseptic meningitis, exanthem subitum (ES), Mycoplasma pneumoniae (MP) pneumonia, acute pyelonephritis (APN), Henoch-Schönlein purpura (HSP), acute poststreptococcal glomerulonephritis (APSGN), and childhood asthma. We compared and interpreted epidemiological data across the groups.Results: In age distribution, KD, APN, and ES showed a similar pattern in that majority of patients were infants or young children, and other diseases showed a relatively even age-distribution which had a peak age, mainly 5–6 years, with bell-shape patterns. In annual-case pattern, there were epidemic years in aseptic meningitis and MP pneumonia, and the fluctuated annual cases were seen in other diseases. The trends of decreasing cases were seen in APSGN, HSP, and childhood asthma in recent years. In seasonal frequency, influenza or aseptic meningitis occurred in mainly winter or summer season, respectively. HSP and APSGN cases had less in summer, and KD, APN, and ES showed relatively even occurrence throughout a year without significant seasonal variations.Conclusions: Our results suggest that KD agents may be associated with normal flora that are influenced by environmental changes, since pathogens of APN and ES could be regarded as normal flora that originate from the host itself or ubiquitously existing human reservoirs. Kawasaki disease (KD) disease was a novel disease that appeared in East Asian countries in the order of Japan, South Korea, Taiwan, and China with a 5–10 year time-gap . After tThe clinical manifestations of Kawasaki disease share similarities in some aspects of viral diseases, bacterial diseases, or infection-related immune mediated diseases such as systemic juvenile idiopathic rheumatoid arthritis or acute rheumatic fever (ARF). However, extensive studies searching for the etiologic agent(s) have turned up as failures until the present time . Common In this study, to predict the etiology of KD, we evaluated and compared epidemiological characteristics between KD and common infectious diseases or immune-mediated diseases in children. After evaluating epidemiological parameters focused on age distribution, annual-case pattern and monthly-case pattern, we found that the epidemiological profiles in KD were similar to those in acute pyelonephritis (APN) or exanthema subitum (ES). We discussed the implications of these findings in KD epidemiology in Korea.Mycoplasma pneumoniae (MP) pneumonia, influenza, aseptic meningitis, APN, ES, acute poststreptococcal glomerulonephritis (APSGN), HSP, childhood asthma (or recurrent wheezing episode), and KD. As an exception, the subjects diagnosed with influenza in this study were selected from outpatients who were positive for influenza in rapid diagnostic testing during the winter of influenza seasons. The diagnosis or selection criteria in each disease were referenced from other publications (The subjects of this study were collected from the patients (0–15 years of age) who were admitted at The Catholic University of Korea Daejeon St. Mary's Hospital from January 1987 to December 2016. We evaluated the epidemiological characteristics of patients diagnosed with ications –20. AlthThe written informed consents were obtained from the parents/caregivers of all children for the medical records to be used in this study at time of admission. The study was approved by the Institutional Review Board of The Catholic University of Korea Daejeon St. Mary's Hospital (DC18RESI0100).n = 779)  [ (n = 320) (n = 429), and as for infection-related immune diseases, APSGN  (n = 515) (unpublished observation) and childhood asthma (or recurrent wheezing episode)  (n = 942)  [, 14, unp= 2,201) , APN (20 n = 99) , HSP 19n = 384) , and KD n = 384 ,n = 942) .The male-to-female (M:F) ratio, mean age, and peak ages are shown in Male predominance was observed in all the diseases except ES (0.95:1), but the M:F ratios were somewhat different across the diseases. The highest M:F ratio was seen in APSGN (2.3:1), and the lower M:F ratios were seen in ES, MP pneumonia and influenza , and KD showed 1.7:1 ratio in this series. The lowest mean age was noted in order of ES (mean 1 year of age), APN (1.5 years), and KD (2.2 years) and the higher mean age was noted in APSGN (8.3 years) and HSP (6.5 years). In age distribution, KD, APN, and ES showed a similar pattern in that the majority of patients were infants and young children (0–4 years), and after this age period the prevalence decreased dramatically. There were only a few patients >3 years of age in ES and a few patients >5 years in KD, however there was relatively an even distribution with female predominance after >2 years in APN. A bell-shape distribution pattern with a peak prevalence, mainly in the 4–6 years age range was observed in other diseases, however peak ages were slightly different across the diseases . There wCyclic epidemics caused by possibly new strains of pathogens, such as macrolide-resistant strains were noted in MP pneumonia and in aseptic meningitis caused by mainly enteroviruses; all had similar patterns with nationwide epidemics or outbreaks in Korea , 15. InfA higher number of cases were seen in the fall and winter in MP pneumonia. Aseptic meningitis was noted mainly during the summer whereas influenza mainly during winter and early spring seasons. There was a trend showing a lower number of cases in the summer in HSP, and a higher number of cases in the winter for APSGN. A higher number of cases were seen during the fall and spring for childhood asthma. Although KD affected more patients during summer than any other season in this series, KD had no difference in seasonal variation according to the definition of the seasonality. Also, no seasonality was seen in APN and ES .E. coli or Streptococcus pneumoniae, could be categorized as endogenous pathogens. It is well-known that a newly introduced disease by an exogenous pathogen has affected all aged persons in a population and spread to other populations in relatively a short-time period of time after its first emergence. Over time, infected persons and groups have immunity to the pathogens, and young children and infants would remain susceptible, especially during cyclic epidemic viral infections. Accordingly, epidemiologic characteristics of infectious diseases or infection-related diseases in the populations at a given time may differ.It is hypothesized that KD may have an etiologic agent(s), although many studies searching for the etiology of KD have failed. Etiologic agents in infectious diseases originate from an external source and invade into the host. However, at present time, they could be classified as exogenous pathogens and the endogenous pathogens; the former is generally accepted as agents that are newly introduced to humans from other animal species or other places, whereas the latter originates from the host in the forms of normal flora  or those becoming a normal flora from initially being an exogenous pathogen. For examples, measles in immune-innocent populations in the past and acquired immunodeficiency syndrome (AIDS) were caused by new external pathogens. On the other hand, the pathogens causing APN or acute otitis media, such as In the present study, we found that epidemiological characteristics in KD were most similar to those in APN or ES among the 8 evaluated diseases. In age distribution, these 3 diseases had an age predilection in infancy and young children; 79.7% of patients in APN, 95.8% in ES, and 50.1% in KD were 0–1 years of age, and 87.5% of patients in APN, near 100% in ES, and 91.7% in KD were 0–4 years of age. In the view of epidemiological and clinical aspects, an infected infant with pathogens from these diseases are difficult to disperse the pathogens to other infants. Other diseases showed a relatively even age-distribution throughout childhood, though peak ages were slightly different across the diseases. This suggests that younger children may have less chance on exposure to the pathogens and older children and young adult groups may have immunity or tolerability to the pathogens causing the diseases.E. coli or other uropathogens such as Klebsiella spp., Proteus spp., and Enterococcus spp., and they may originate from the intestinal commensals in the host. It is possible that after colonization of a strain of E. coli or other uropathoegns transferred from other persons, the pathogens invade into the host on occasional events and elicit immune reactions , substances from injured host cells, and those from activated immune cells are produced. When these diverse substances spread from the focus into systemic circulation, clinical manifestations such as fever, tissue cell injury and/or bacteremia begin to occur, and the host immune system may respond to the substances. The majority of patients infected with APN pathogens may be asymptomatic and their disease are self-limited if systemic spread did not occur and the substances in the focus were controlled as a localized inflammation . On the Based on the data from epidemiological and clinical studies of KD, the pathogenesis of KD could be explained as follows. Along with economic growth and westernization in East Asian countries in order of Japan, South Korea, Taiwan, and China, a species in normal flora (microbiota) in people may be affected by environmental changes such as improved hygiene or increased consumption of westernized foods including red meats , 11. TheThis retrospective study has some limitations. Epidemiological data observed in a single hospital may not match the nationwide data. However, we found that outbreaks of infectious diseases such as MP pneumonia, influenza, and aseptic meningitis in our city had occurred concurrently with nationwide epidemics. Demographic and some epidemiologic characteristics of KD, APN, APSGN, HSP, childhood asthma, and possibly ES were similar to the data in published papers in Korea (data not shown).In conclusion, epidemiological characteristics of KD were similar to APN or ES in age distribution, annual case pattern, and seasonal variations. The pathogens of APN and ES could be regarded as one species of normal flora, since they may have originated from the host itself or ubiquitously existing human reservoirs. KD may also be associated with a species in the normal flora that may be influenced by environmental changes.The written informed consents were obtained from the parents/caregivers of all children for the medical records to be used in this study at time of admission. The study was approved by the Institutional Review Board of The Catholic University of Korea Daejeon St. Mary's Hospital (DC18RESI0100).K-YL designed the study, collected data, contributed to interpretation of results, and drafted the manuscript. J-WR contributed to data collection and drafted the initial manuscript. HK and J-WH contributed to data collection and revised the manuscript. All authors have read and approved submission of the final version of the manuscript.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.


The control group consisted of healthy children and adolescents, strictly matched for gender and age in a 1:1 case-control manner. More than half of the examined children (n = 26) followed a GFD. CD children had significantly higher mean values of the fat free mass , and total body water , and lower mean values of the fat mass . Children who were on a GFD presented slightly higher, but not statistically significant, mean values of FM and FFM, than children who did not follow dietary recommendations . After minimum one year of a GFD, CD children showed significantly higher values of FFM [kg] (p = 0.001), muscle mass (MM) [kg] (p < 0.001), TBW [L] (p < 0.001) and body cell mass (BCM) [kg] (p < 0.001). Furthermore, CD children who were on a GFD presented a significantly higher increase in weight (p = 0.034) and body mass index (BMI) (p = 0.021). The children adhering to a GFD demonstrate a tendency towards higher indices of selected body composition components.The primary and proven therapy, in cases of celiac disease (CD), is a rigorous gluten-free diet (GFD). However, there are reports of its negative effects in the form of nutritional deficiencies, obesity, and adverse changes in body composition. The study aimed to assess the impact of a GFD on the body composition of children with CD. In a case-controlled study ( Celiac disease (CD) is a diet-dependent disease and one of the most common food intolerances in Europe posing significant health-related problems . The disCD is a life-long autoimmune enteropathy due to gluten sensitivity . In CD pIn practice, body composition assessment can be based on measurements of skin fold thickness, and methods of bioelectrical impedance (BIA) and dual-energy X-ray absorptiometry (DXA) ,20,21. CThe study was approved by the institutional Bioethics Committee at the University of Rzeszów (Resolution No. 5/02/2012) and by all appropriate administrative bodies. The study was conducted in accordance with ethical standards laid down in an appropriate version of the Declaration of Helsinki and in Polish national regulations. The study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria.The study involved 41 children and adolescents  with celiac disease receiving inpatient treatment at the Clinical Department of Pediatrics with the Pediatric Neurology Unit, at the Clinical Regional Hospital No. 2 in Rzeszów. The study group consisted of patients with newly diagnosed CD and subjects at different stages of treatment.The inclusion criteria were as follows: diagnosed celiac disease, age 4 to 18 years, no other autoimmune or chronic diseases affecting height, weight or nutritional status, as well as written informed consent, signed by parents or legal guardians, and by the adolescents over 16 years of age.The control group consisted of the same number of children and adolescents attending primary, middle, and secondary schools in urban and rural areas. Inclusion criteria were the same as for the study group with the exception for CD diagnosis. The healthy participants and those with CD were strictly matched for age (the nearest birth date) and gender in a 1:1 case-control manner. Detailed information concerning the children with CD, namely the diagnosis, the course and treatment of the disease, and comorbidities, was retrieved from their medical records. In addition, laboratory tests  and endoscopy were performed to ensure CD diagnosis and to assess the intestinal mucosa status at the time of the diagnosis according to the Marsh scale, modified by Oberhuber . These aAll the adolescents were assessed for height and weight, and their body mass index (BMI) was calculated. Subsequently, BIA was performed with AKERN BIA-101 analyser  to examine their body composition and nutritional status. The measurements were performed between 7:00 a.m. and noon, on an empty stomach, in the supine position, with abducted upper (30°) and lower (45°) limbs, following at least a 5-min rest.A tetrapolar electrode arrangement was applied with the contralateral recording mode. The amplitude of the measured current was 800 μA, sinusoidal, 50 kHz. To ensure the results were reliable and reproducible, two measurements were performed, one after another. Disposable electrodes were placed on the dorsal surface of the right arm (above the wrist) and the right leg (on the ankle). All measurements were performed according to guidelines described by other authors ,26,27. D2 test. If the conditions for application of parametric tests were fulfilled, it was possible to use the t-test for independent samples, one-way analysis of variance (ANOVA) or Pearson’s correlation. A p-value below 0.05 was considered statistically significant.Statistical analysis was performed using the Statistical Software for the Social Sciences SPSS Statistics 20 . For this purpose, parametric and non-parametric tests of significance were applied. Normality of the distributions of the quantitative variables was verified with the Kolmogorov–Smirnov test. Homogeneity of variances was then examined with the Levene’s test, and equivalence of variables distributions was verified using the χBody composition parameters were significantly different between the CD and control groups. CD children had significantly higher mean values of the fat-free mass and total body water, and lower mean values of the fat mass .Among children with CD participants who were non-compliant to GFD presented apparently lower mean values of FM (kg) and also FM% and FFM%, than children who did follow dietary recommendations, but the difference did not reach the level of statistical significance .In a subset of 22 children and adolescents with CD, we performed a follow-up examination after a mean of 17.2 months. In this analysis children with CD demonstrated, as could be expected, significant weight, height and (borderline) BMI gain higher values of fat free mass, muscle mass, total body water (extracellular and intracellular), body cell mass and body cell mass index, while fat mass in kg did not increase significantly. None of these parameters expressed as a percentage of body composition has changed significantly during follow-up .Children and adolescents with CD who were non-compliant to GFD presented lower weight increase, and fall in BMI which was significantly different compared to group compliant to GFD. In addition, fat mass decreased, but the difference with participants who followed GFD did not achieve the level of statistical significance .In the present case-controlled study, we observed that selected body composition parameters  and nutritional indicators (body mass index and body cell mass index) in children with CD are significantly different than in healthy controls. Reports related to changes in body composition, in adults and in children, both at the stage of diagnosis and during treatment, are limited and ambiguous. They depend on a number of variables, such as the age at the time of diagnosis, the disease progression, duration of impairments associated with malabsorption syndrome, methods of body composition assessment, as well as the degree of compliance to dietary guidelines.p = 0.007 and p = 0.015, respectively), and higher mean percentage values of the FFM (p = 0.015), and TBW (p = 0.012). Our results provide evidence that children with CD have lower energy reserves reflected as a lower total body fat mass, which may result in reduced immunity, a potential higher risk of malnutrition and faster dynamics of body components changes due to existing malnutrition. Furthermore, our results show, that children who were at baseline compliant to GFD presented apparently higher, but not statistically significant, mean values of FM and FFM (both in kg and in %), than children who did not follow dietary recommendations. The described differences in body composition components were close to the level of statistical significance despite the relatively low number of children in each group. After mean 17.2 months of follow-up, children with CD, as could be expected, demonstrated a significant increase of FFM, MM, TBW, BCM, and BCMI expressed in kg or L. However, the percentage of body mass components did not change significantly. Within this group children who did not follow strictly GFD presented lower weight gain and even decrease in BMI which was significantly different compared to the children compliant to GFD . In addition, changes in fat mass tended to be different between compliant and non-compliant groups, which did not achieve statistical significance due to a very small number of children in each group. This indicates lower energy reserves and increased the potential risk of malnutrition in case of exacerbation of the disease in children not following GFD. Some studies report no significant changes in the specific components of body composition after a GFD is introduced [The results of the present study showed that children with CD had significantly lower mean values of the FM expressed both in kg and as percentage of body mass  was not done in all the children, we were not able to analyze the association of these variables with body composition components. Searching for such relationships would be an intriguing implication for further research. We also did not perform serology markers assessment at the follow-up visit. It would be interesting to analyze its relationship with compliance to GFD.Given the controversies related to changes in anthropometric indices and body composition observed in individuals following a GFD, this problem unquestionably requires further study. It would be of extreme importance to conduct a long-term assessment of the effects produced by a GFD on body composition, beginning from childhood, when patients receive CD diagnosis until they reach adulthood. It would then be easier to eliminate small fluctuations in the components of body composition associated with age and the level of gluten cross-contamination in foods, and consequently to obtain reliable results.The children with celiac disease differ significantly in body composition compared to healthy comparators. Participants adhering to a gluten-free diet presented a trend towards higher indices of selected body composition components. To assess the predictive and prognostic value of these findings, further prospective, longer-lasting studies, including a higher number of participants are required in this population.


This study aimed to evaluate the oral switch (OS) stewardship intervention in the intensive care unit (ICU).This was a retrospective study with a convenience sample in two Brazilian ICUs from different hospitals in patients with sepsis receiving antibiotic therapy. The stewardship intervention included OS in patients diagnosed with sepsis when clinical stability was achieved. The primary outcome was overall mortality. Other variables evaluated were as follows: cost of antimicrobial treatment, daily costs of intensive care, acute kidney injury, and length of stay.p = 0.06). Length of stay in the ICU (p = 0.029) was shorter and acute kidney injury incidence (p = 0.032) and costs of antimicrobial therapy (p < 0.001) were lower in the OS group.There was no difference in mortality between the OS and non-OS groups (OS stewardship programs in the ICU may be considered a safe strategy. Switch therapy reduced the cost and shortened the length of stay in ICUs.The online version of this article (10.1186/s12879-019-4280-0) contains supplementary material, which is available to authorized users. An antimicrobial stewardship program can be defined as the set of actions performed in hospitals for the rational use of antibiotics; reduction of adverse events, dosage errors, and appearance of multiresistant bacteria; and shortening of length of hospital stay. The performance of the multiprofessional team implementing these programs, including clinical pharmacists, physicians and nurses, is associated with a reduction in in-hospital mortality rate . The vasManaged antimicrobial administration programs shorten the length of hospital stay and reduce costs associated with the use of these medications. Although the literature is consistent with the transition from IV to oral antibiotics in hospitalized patients, data on a similar approach in critically ill patients are inadequate . Some coThe switch from IV to oral route may have some benefits, such as early discharge, decreased risk of bacteremia, reduced use of venous access and incidence of thrombophlebitis, and reduced cost of treatment . For exaThis study aimed to evaluate the safety, mortality, and economic outcome of IV-to-oral antibiotic switch therapy in critical care units.This was a retrospective study with a convenience sample of critically ill patients with sepsis who received antibiotic therapy in two ICUs of different Brazilian hospitals from January 2016 to March 2018. Patient inclusion was performed at two hospitals in the city of Curitiba: a 207-bed public school hospital , whose ICU is a referral center for the care of patients with trauma, and a 210-bed hospital , with an ICU specializing in clinical and surgical care. The local ethics committee (Comitê de Ética em Pesquisa da Pontifícia Universidade Católica do Paraná) approved this study (committee’s reference number = 74844017800000020). No administrative permissions were required to access the raw data. The requirement of informed consent was waived by the institutional review board. The STROBE checklist is presented as Additional file The primary outcome was safety  in the IV-to-oral switch (OS) groups compared to the group of patients who did not switch to oral administration. The two groups were formed in accordance with the stewardship intervention decision described below and possibility of OS.The inclusion criteria were as follows: age > 18 years, admission to the ICU with the clinical diagnosis of sepsis or septic shock (in accordance with Sepsis-3 criteria), regular oral or enteral feeding at a flow rate > 40 mL/h, availability of a suitable oral dosage form for the prescribed medication, absorption and bioequivalence of the oral dosage form comparable with the parenteral pharmaceutical form, consent provided by the attending team, and at least 24 h of observed clinical improvement. Antimicrobial therapy was administered to all patients with a life expectancy of > 24 h and those for whom treatment was not considered futile. The sample size was determined by convenience.The exclusion criteria were as follows: fasting, diet intolerance or refusal to receive oral medications, refusal of the attending team or ICU, increased gastrointestinal bleeding, and absence of clinical improvement with IV treatment or worsening in the last 24 h prior to the multiprofessional visit.The stewardship program was initiated in both hospitals by the same team with the aim of promoting the rational use of antimicrobials, including dose adjustment, route of administration, and appropriate selection of treatment regimens. Thus, daily multiprofessional visits were conducted, which included evaluation by an infectious disease specialist, nurse, and clinical pharmacist, who reviewed the cases and suggested to the assistant and intensivist the possibility of changing the route of administration from IV to oral, after 24 h of clinical recovery. An application for consultation of institutional protocols and bioequivalence of medications was available. The attending physician and ICU attendant could modify the route of administration in the case of clinical worsening  at any moment by discussion using a mobile phone with the application WhatsApp, 24 h a day, 7 days per week .Staphylococcus aureus (MRSA) is suspected. The complete protocol of the hospital is detailed on the following website: www.atbhuc.goodbarber.com. The most common options for OS were amoxicillin (capsules or solution for nasogastric feeding), amoxicillin/clavulanate (capsules or solution for nasogastric feeding), ciprofloxacin (whole or crushed tablets), levofloxacin (whole or crushed tablets), doxycycline (capsules), sulfamethoxazole/trimethoprim (tablets or solution for nasogastric feeding), and metronidazole (whole or crushed tablets). The choice of oral therapy was defined during clinical visit according to the culture results, infection site, organ dysfunction, and possible side effects. OS is part of a more inclusive strategy, and the possible impact of other interventions, such as dose adjustment, infusion duration, antimicrobial combination, and drug interaction, on the evaluated switch cannot be separately analyzed.Formulary restriction was not used in this group of patients because all of them were included in the sepsis protocol of the hospital. In the sepsis protocol of both hospitals, antibiotic administration is promptly authorized without restriction. Briefly, for sepsis secondary to community pyelonephritis, pneumonia, intra-abdominal infection, and meningitis, ceftriaxone was the first option, including metronidazole for intra-abdominal infection. Cefepime was the first option for community infection in patients who recently used antibiotic or those admitted within < 5 days. For ventilator-associated pneumonia and most hospital infections, amikacin with levofloxacin was the most common option for treatment, in accordance with local epidemiology. Vancomycin is added if presence of methicillin-resistant Pseudomonas aeruginosa (14 days) [The decision on treatment duration is based on the clinical response and infection site. Generally, the duration of ventilator-associated pneumonia treatment is 4–6 days, with the exception of 14 days) . Intra-a14 days) , 11.The following clinical and laboratory data were assessed: sex, age, total days of IV antibiotic, total days of oral antibiotic, total days of mechanical ventilation, duration of hospital and ICU stay, vasoactive and inotropic drug use, renal function, transfusion of blood products, and outcome. The Acute Physiology and Chronic Health Evaluation (APACHE) II disease classification system scores were calculated in all patients. Sequential Organ Failure Assessment (SOFA) score was also assessed on admission day.Infection severity was classified according to Sepsis-3 criteria: sepsis  and septic shock  . Daily sDaily oral and IV antimicrobial costs were calculated in all patients in local currency . This was subsequently converted to United States dollars (US$), according to the official exchange values published by the Central Bank of Brazil, in the average of June 2018. The time of antimicrobial use, daily dose, indication, route of administration, and infection site were evaluated from admission in the ICU to discharge of the patient . AntimicAfter inclusion of the patient in the institutional sepsis protocol, culture-positive bacterial/fungal identification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry, and the antimicrobial profile was determined by the VITEK 2 instrument. All preliminary results of the cultures of the biological materials were sent to the multiprofessional team. Crude mortality rate was calculated, a hospital overall survival curve was constructed, and ICU discharge was evaluated, comparing IV and OS therapy.p < 0.05) indicated statistical significance. For the multivariate analysis, all variables with statistical significance in the univariate analysis (p < 0.05) were included in a binary logistic regression.Qualitative data were described as percentages, and quantitative data were described as arithmetic means or median values according to the distribution pattern. Standard deviation and 25 and 75% interquartile range (IQR) were the distribution variables for the mean and median, respectively. Risk factors associated with outcomes (death) were evaluated according to each variable, and distribution was determined using the Student’s t-test, Mann−Whitney, chi-square, or Fisher’s exact test. A difference of 5%  were constructed from the time of antibiotic initiation to the patient’s death or discharge. Overall mortality was included in the analysis, and 30-day mortality curves were constructed, and the Gehan−Breslow−Wilcoxon test was performed. All tests were performed using SPSS 23.A total of 1313 patients were admitted to the two ICUs during the study period, and 349 patients fulfilled the sepsis and inclusion criteria.n = 189, 54.3%), followed by abdominal infection  and urinary infection . The most prescribed antibiotics were cefepime , ceftriaxone , and aminoglycoside  , Escherichia coli , Enterobacter spp. , Klebsiella spp. , and P. aeruginosa   fulfilled the criteria for sepsis without shock, and 207 (59.2%) presented with septic shock. Respiratory infection was the most frequently observed infection (n = 111), the mean age of patients was 60.9 years , and 69% of patients were men. The mean length of ICU stay was 6.4 days . The mean duration of hospitalization was 15.7 days . The most prescribed antibiotics were quinolone , cefepime , and penicillin   and E. coli  , the mean age of patients was 62.98 years . The most prescribed antibiotics were vancomycin , ceftriaxone , and cefepime . The most prevalent bacteria were Enterobacter spp. , E. coli  and S. aureus  (Table p = 0.012) , and the probability of survival in 30 days (p = 0.026) was determined using the Kaplan−Meier survival curve  and SOFA score (p = 0.112), was similar in the two groups in the univariate analysis. However, after removal of confounding variables, a significant difference was noted in both groups (p = 0.003). The confounding variables were excluded with the binary logistic regression (backward steps), which presented p < 0.05 in the univariate analysis, but not statistically significant in the multivariable analysis. However, there was no difference in global mortality between groups (p = 0.06). The APACHE II score was categorized using the ideal binning from SPSS 23 according to mortality. Patients in the OS group with an APACHE II score ≥ 17 presented a higher probability of survival (p < 0.05) .The direct costs of treatment, antibiotics, workload, and consumables were lower in the OS group .The present study aimed to evaluate a stewardship intervention based on the conversion of IV therapy to oral therapy as soon as clinical improvement was observed. The main data showed that there was no difference in mortality between the OS and non-OS groups, which makes this strategy safe for use in critically ill patients. In this population, the costs of antimicrobial treatment and daily intensive care value were lower in the OS group, although the total cost of hospitalization was not statistically different (p = 0.063). The reduction was not significant due to sample power in the OS group.Antibiotics account for a considerable cost in hospital bills, accounting for almost 20% of drug costs in our ICUs. The usage policy is a controversial subject, since it varies among hospitals, due to epidemiological differences, and among units from the same hospital, because it must consider the specificity of each location . The totAn antimicrobial stewardship program improves antimicrobial use in ICUs, resulting in shorter therapy durations, lower resistance rates, and lower costs . StewardRebuck et al. showed that levofloxacin is well absorbed after oral administration in critically ill patients in the ICU . In our Even in critically ill patients with complicated abdominal infections, Solomkin et al. conducted the conversion of IV (imipenem) to oral therapy (quinolone). However, all benefits related to a shorter IV therapy treatment time, which would allow for earlier hospital discharge for some patients, and reduced drug and drug administration costs were unclear. Despite this fact, this study would support the efficacy of this approach, with low mortality rates  .Antibiotic stewardship programs are safe and cost-effective, an approach important particularly in developing countries . Our stuThe present study showed some limitations, such as the type of the study (retrospective), inclusion of only 2 hospitals, use of a narrow range of antimicrobials, and specific microbiological profiles. A relevant factor was that the antimicrobial agent sulfamethoxazole-trimethoprim was not compatible with enteral catheter administration, which limited the sample size. This is an important issue considering that sulfamethoxazole-trimethoprim is the main alternative drug in our institution due to the susceptibility profile. In contrast, the data related to costs and doses of antimicrobials were individualized and not estimated by the defined daily dose, which would provide more reliable data on the consumption of antimicrobials. The sample of patients subjected to OS has in itself different characteristics, generally of lower clinical severity and lesser bacteriological complexity. Some pharmacokinetic aspects can be different in oral administration, as they can be different in patients with sepsis. OS is part of the antimicrobial stewardship program; thus, it is impossible to attribute all influences of these interventions on the final results.Stewardship programs based on OS therapy in ICUs can be a safe intervention, thereby decreasing the cost and shortening the length of stay when well-defined criteria are employed and a clinical decision is reached. In developing countries, where limited resources and intensive care beds have a major impact on resource management, such a strategy can have a positive contribution. Randomized trials with a larger number of patients are required to clarify the large-scale impact of this strategy.Additional file 1: STROBE Statement—checklist of items that should be included in reports of observational studies. (DOC 78 kb)


Internet gaming disorder (IGD) is a new disease proposed by the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), and has been studied extensively in relation to depression and impulsivity. The relationship between resilience and disease has been found in a variety of addictive disorders, but studies on IGD are lacking. In this study, 71 IGD patients and 78 healthy controls (HCs) were recruited. Impulsivity, resilience, affects, and the degree of internet game addiction were measured using formal tools. The measured values were analyzed by mediation analysis to evaluate the mediating role of affects on resilience and impulsivity related to IGD symptoms. The IGD group showed higher impulsivity, lower resilience, lower positive affect, and higher negative affect than the HC group. The mediation analysis showed that a positive affect was a mediator between impulsivity and the severity of addiction in both groups. Negative affect mediated impulsivity/resilience and the severity of addiction only in the IGD group. Although the results of this study are based on a narrow category of subjects, who are young male adults around 25 years of age, the results suggest that positive affect can be strengthened to prevent the IGD illness, and that illness symptoms may be alleviated by reducing negative affect. Since the development of the internet, the internet has had many impacts on our society. One of them is an internet game. Since 2005, when the phenomenon related to Internet game addiction has been reported, and various countries have received varying degrees of attention . The DiaAmong the various psychiatric symptoms, impulsivity has been identified as a risk factor in many addictive disorders . ExcessiApproximately 15–25% of patients with IGD are known to have depression ,19,20. IHowever, the relationship between resilience, mood change, and impulsivity has not been clarified. Research on how resilience and impulsiveness affect IGD symptoms through the mediation of emotions is particularly insufficient. In this study, we investigated the difference in impulsiveness, resilience, and affect status between patients with IGD and healthy controls (HCs). We further investigate the role of affect status between impulsiveness as a risk factor and resilience as a protective factor in IGD. The hypothesis of this study is that resilience acts as a protective factor in IGD patients to reduce IGD symptoms through positive emotion, and impulsivity exacerbates IGD symptoms through negative emotions.A total of 150 young male adults participated in this study, 71 of which had been diagnosed with IGD (age = 25.56 ± 5.67 years), as well as 79 healthy controls (age = 25.57 ± 4.59 years). All patients were recruited from SMG-SNU Boramae Medical Center in Seoul, South Korea, from October 2014 to September 2018. The patients with IGD were diagnosed by a clinically experienced psychiatrist according to DSM-5 criteria. None of the participants had a history of significant head injury, seizure, intellectual disability (IQ ≥ 80), or psychotic or neurological disorders. Additionally, all participants were medication-naive. Participants who spent more than 4 h per day and 30 h per week playing internet games were included in the IGD group, in order to exclude milder cases of gaming problems . All parThe institutional review board of the SMG-SNU Boramae Medical Center approved the study protocol , which adhered to the principles of the Declaration of Helsinki. All participants understood the study procedure and provided written informed consent prior to participation.The severity of IGD was evaluated with Young’s internet addiction test (Y-IAT). In this study, we used a scale made by modifying IAT to assess the symptoms of IGD, which consisted of 20 items, each evaluated by 5 points ,29. The The Barratt impulsiveness scale (BIS-11) includes 11 items rated on a four-point scale. BIS-11 assesses the degree of impulsivity, and includes three subscales: cognitive, motor, and non-planning impulsiveness (Cronbach’s α = 0.72).The Connor-Davidson resilience scale (CD-RISC) is a 25-item, self-reporting instrument that uses a five-point response scale. The CD-RISC total score ranges from 0 to 100, with higher scores reflecting greater resilience (Cronbach’s α = 96).The positive and negative affect schedule (PANAS) consists of a two-factor structure of 10 questions regarding 10 positive and 10 negative affect types on a five-point Likert scale .t-test were performed to compare the demographic and clinical characteristics of the IGD and HC groups. Pearson’s correlation analysis was conducted to examine the relationships between IGD symptoms (Y-IAT), impulsivity (BIS-11), resilience (CD-RISC), and affect (PANAS). To examine whether the quality of affect mediates the relationship between impulsivity or resilience and IGD symptoms, we performed a serial mediation analysis using the SPSS PROCESS macro, version 2.16 (model 4), developed by Hayes. In particular, we conducted the analysis using the bootstrapping method. SPSS software version 21.0  was used for all data analyses. For all analyses, p values < 0.05 were considered to indicate statistical significance.A Chi-square test and t(1.706) = 8.64, p < 0.001), BIS-11 scores (t(0.001) = 5.22, p < 0.001), and negative scores on the PANAS (t(0.398) = 4.42, p < 0.001) were significantly higher in the IGD group than in the HC group, and the CD-RISC scores (t(2.972) = −5.32, p < 0.001) and positive scores on the PANAS (t(1.809) = −4.99, p < 0.001) were significantly lower in the IGD group than in the HC group , positive affect , and negative affect . However, there was a significant relationship between IGD symptoms and impulsivity only in the HC group . Impulsivity was not related to IGD symptoms in the IGD group, as shown in In both IGD and HC groups, IGD symptoms, as measured by Y-IAT, were significantly correlated with resilience (IGD: As shown in As shown in In this study, the IGD group showed higher impulsivity, lower resilience, lower positive emotions, and higher negative emotions than the HC group. A correlation analysis revealed that IGD symptoms were correlated with resilience, negative affect, or positive affect in both the IGD and HC groups. No correlation was detected between impulsivity and IGD symptoms in the IGD group, as opposed to the HC group, in which a significant correlation was detected. This association was analyzed by mediation analysis; the direct effects of resilience and IGD symptom severity were detected in the HC group, but not in IGD patients. In the IGD group, both negative and positive emotions mediated the relationship between impulsivity and addiction. The relationship between resilience and addiction was significantly mediated only by negative emotion. On the other hand, only positive emotions mediated the relationship between impulsivity and addiction in HC group. All of these results were obtained in young male adults.Positive affect served as a protective mediator between impulsivity and IGD symptoms in both groups. Positive affect plays a role in depression, and also affects the quality of life for cancer survivors, as well as the prognosis after lumbar surgery ,31,32. PThe differences in the direct effects of resilience between the HC and the IGD groups suggest that resilience directly protects against IGD symptoms in the HC group, but only has indirect effects on addiction symptoms through negative affect in the IGD group. In the disease condition, it may not be possible to see the direct effect of resilience, because there is no alternative strategy seen in it, as cognitive impairment arises after the disease sets in. Cognitive deficits are widely found in many addiction disorders, including IGD ,38. EspeCognitive impairment is affected not only by disease but also by negative affect. Many studies have shown a relationship between cognitive errors and negative emotions, such as depression, and the cognitive behavioral therapy for treating negative emotions has also been recognized as effective ,47,48. IThe final conclusions of this study suggest that IGD can be prevented by enhancing positive affect, and that addiction can be moderated by modulating negative affect after IGD. Indeed, previous studies have suggested that strengthening active coping among the various aspects of resilience may provide a key benefit in patients with psychiatric disorders . There aHowever, there are limitations to consider when interpreting our results. First, as this study was conducted in young male adults, it is not yet clear whether these results are consistent across all age groups or female groups with IGD. Many IGD studies have been conducted in adolescents, and school-age mental illnesses differ from adult-onset mental illnesses in clinical manifestations. A difference has been detected between the appetitive aspect and the compulsive aspect in adolescents and adults with addiction disease . In addiIn this study, the HC group showed a direct correlation between the degree of resilience and the severity of IGD symptoms, and only positive emotions mediated impulsivity and the severity of IGD symptoms. In the IGD group, the effects of impulsivity and resilience on the severity of addiction were mediated by negative affect, with no direct effects of resilience on the IGD. These results suggest that controlling emotions could help prevent disease and relieve symptoms. To confirm the results of the present study, future research should examine the effects of changes in emotions while taking drugs. The results also suggest that identifying the mediation effects of various factors associated with game addiction may be helpful in understanding the psychological etiology of a disease.