Background: The relationship between the quality of the diet and the adherence to the Mediterranean diet with the presence of persistent or recurrent depressive symptoms have been described. The objective of this study is to analyze the relationship between adherence to the Mediterranean diet and the intake of specific foods in primary care patients aged 45 to 75, having subclinical or major depression. The study also specifically analyzes this relationship in individuals suffering from chronic diseases. Methods: A cross-sectional descriptive study was conducted. 3062 subjects met the inclusion criteria from the EIRA study. Sociodemographic variables, clinical morbidity, depression symptomatology (PHQ-9) and adherence to Mediterranean diet (MEDAS) were collected. Results: Being female, younger, with a higher BMI, consuming more than 1 serving of red meat a day and drinking more than one carbonated or sugary drink daily, not consuming 3 servings of nuts a week and not eating 2 vegetables cooked in olive oil a week are predictors of having higher depressive symptomatology. Conclusions: Assessing the type of diet of patients presenting depressive symptoms and promoting adherence to a healthy diet is important, especially in patients with chronic diseases. However, depression is a very complex issue and the relationship between nutrition and depression must be further examined. Depression is considered to be the leading cause of disability worldwide, contributing to the overall global burden of morbidity and mortality. By 2030, it will most likely be the main contributor to morbidity . AccordiNumerous studies have described the relationship between obesity and depression , and betOne of the diet patterns that has been studied with regard to the prevention of depression is the Mediterranean diet ,19,32. IBasic research, for example, in experimental studies with rats, has revealed that the ongoing consumption of olive oil has neuroprotective effects, reducing behavioral alterations by acting on the metabolism of the serotonin and dopamine neurotransmitters. This supports its potential use as a therapeutic substance to treat depression and anxiety ,25. In eThe PREDIMED study, using a Spanish population sample, revealed that adherence to the Mediterranean diet was associated with an improved concentration of brain-derived neurotrophic factor (BDNF) in depressed patients ,38. SomeThe objective of this study is to analyze the relationship between adherence to the Mediterranean diet and the intake of specific foods  in primary care patients aged 45 to 75, having subclinical or major depression. The study also specifically analyzes this relationship in individuals suffering from chronic diseases.A cross-sectional descriptive study was conducted, as part of the EIRA study . This stThe participating population consisted of 3062 subjects meeting the following inclusion/exclusion criteria from the EIRA study:The following inclusion criteria were used: Individuals aged 45 to 75 years old, with two or more unhealthy behaviors  seen at the participating PHCs. In addition, they had to have an assigned doctor and nurse from the health center and their participation was voluntary. The exclusion criteria were: (1) individuals with serious, advanced illnesses, cognitive impairment, dependence, severe mental illness, participating in a home care program and with active or terminal cancer treatment, (2) individuals who would not be in Spain during the study period and (3) individuals who did not understand written and/or spoken Spanish.Study participants were recruited from 26 PHCs in seven of the 17 Spanish autonomous communities: Andalusia, Aragon, the Balearic Islands, the Basque Country, Castile and León, Catalonia and Galicia. Offering universal coverage with free access to all citizens, the Spanish health system is funded by public sources and depends predominantly on the public sector.This study’s sample size corresponds to that calculated for the EIRA study, which anticipated a difference in the percentage of individuals revealing a positive change of at least 8% between the two groups in one or more of the three behaviors. Assuming a 30% patient loss to follow-up, an alpha risk of 5%, a beta risk of 20% and an intra-cluster correlation of 0.01, it was considered necessary to study a minimum of 140 participants for each PHC, a total of 3640 individuals  . A totalParticipant selection was made amongst the subjects who attended the consultation of a family doctor or nurse at the participating PHCs for any reason and who met the inclusion criteria, considering age and gender quotas. The recruitment period was 12 months, beginning in January of 2017.The following variables were collected for this study:Sociodemographic variables: The variables of sex, age, place of birth, marital status , work activity  and educational level  were considered.The main variable is the intensity of the depressive symptomatology measured with the PHQ-9 questionnaire , using tClinical morbidity variables: data regarding if the subjects had another chronic disease were collected (yes/no). The following were considered: cardiovascular diseases , dementia, COPD, connective tissue disease, mild liver disease, diabetes, chronic kidney disease, cancer (in treatment and non-treatment), AIDS and osteoporosis. Weight, size, abdominal perimeter and BMI were also collected and established with the Charlson Comorbidity Index (CCI)  of the pAdherence to the Mediterranean diet: This variable was evaluated through the Mediterranean Diet Adherence Screener (MEDAS) test, which is a validated instrument for the rapid estimation of the patient’s adherence to the Mediterranean diet. Its usefulness in clinical practice has been recognized . The MEDEvaluators received specific face-to-face training to ensure the standardization of data collection.t-test or Chi-square test. To analyze the relationship between the PHQ-9 score and the sociodemographic variables and adherence to the Mediterranean diet , a correlation between the quantitative variables was performed using the Pearson Correlation Coefficient, and a comparison group analysis was performed for the qualitative variables using the Student’s t-test. Finally, a multiple linear regression was performed, controlling for the influence of the various independent variables [Given the large sample size, parametric tests were deemed appropriate, since in large samples, even when data distribution is not normal, the statistics tend to be normal . First, ariables . The eduariables  to obtaiData from the questionnaire were statistically analyzed using the SPSS v.25  and AMOSThe phase III protocol of the EIRA study was approved by the Clinical Research Ethics Committee (CREC) of the Primary Care Research Institute (IDIAP) Jordi Gol of Barcelona and the CREC of each of the seven participating autonomous communities. The study was performed in accordance with the national and international standards of the Helsinki and Tokyo Declarations. To be included in the study, patients had to provide their signed informed consent.p-value < 0.001). It is also worth noting that participants suffering from chronic diseases were older (59.79 (SD: 7.98) vs. 55.39 (SD: 7.52), p-value < 0.001) and had a lower educational level. A higher percentage of these individuals were retired or had a permanent disability and had a higher BMI. As for adherence to the Mediterranean diet, a higher percentage of women displayed a good adherence , with a higher MEDAS questionnaire score (men: 6.57 (SD: 2.01) vs. women: 6.92 (SD: 1.93), p-value < 0.001).Of the 3062 subjects participating in the study, 45.1% were men and 54.9% were women, with an average age of 58.03 (SD: 8.10). As seen in p-value < 0.001), as well as younger people in the sample . The overall sample revealed a significant relationship between a higher BMI and a higher score on the PHQ-9 , but this relationship does not appear when independently analyzing individuals either with or without chronic diseases. Those following a proper Mediterranean diet had significantly less depressive symptomatology  (4.01 (SD 4.56) vs. 4.68 (SD 5.09), p-value = 0.003) and this result was also confirmed for the female sex and individuals without any chronic disease. A higher score obtained in the MEDAS questionnaire has been significantly related to a lower presence of depressive symptomatology . On the other hand, regarding the depressive symptomatology, it was found that individuals who usually cook with olive oil (4.49 (SD: 4.97) vs. 5.23 (SD: 5.29), p-value = 0.036), consume 3 or more servings of nuts a week (4.19 (SD: 4.68) vs. 4.68 (SD: 5.11), p-value = 0.014), eat less than one serving of red meat a day (4.30 (SD: 4.98) vs. 5.01 (SD: 5.01), p-value < 0.001), drink 7 glasses of wine a week (3.96 (SD: 4.56) vs. 4.71 (SD: 5.10), p-value < 0.001), or less than one carbonated or sugary drink a day (4.35 (SD: 4.78) vs. 5.09 (SD: 5.51), p-value < 0.001) have a less depressive symptomatology. This association has also been found for the female sex, except for wine consumption. Unexpectedly, it was found that consumption of two or more servings of vegetables a day is significantly related to increased depressive symptomatology (4.90 (SD: 5.02) vs. 4.44 (SD: 4.99), p-value = 0.029). This relationship has also been found for individuals with chronic diseases and those consuming 3 or more pieces of fruit a day.As for the multivariate analysis, p-value = 0.051). Our results confirm past evidence that suggests that the severity of depression and current depression diagnosis are associated with an unhealthy dietary intake and poorer dietary quality, a higher intake of sweets and fast-food/savory snacks and a lower Mediterranean diet score [This study aims to examine the relationship between adherence to the Mediterranean diet and the intake of specific foods  in patients with subclinical or major depression in primary care. It also specifically analyzes this relationship in individuals with chronic diseases. The bivariate analysis reveals that individuals with a higher PHQ-9 score had an inadequate diet and a lower adherence to the Mediterranean diet. This significant relationship has also been found for individuals without chronic diseases, although, for those with a chronic disease, the relationship was almost significant  in its onset and maintenance [The mechanisms involved may be linked to an enhanced production of BDNF, and therefore essential functions such as neuroplasticity, neuron survival and the growth and differentiation of new neurons and synapses ,55. A lintenance ,14,56,57ntenance ,60,61,62As for sex, a significant relationship has been found in both the bivariate and multivariate analyses, since being female is associated with having a more significant depressive symptomatology. This result is coincidental and has been confirmed in numerous studies ,64,65. RIt has also been confirmed that individuals with chronic diseases present more significant depressive symptomatology, coinciding with abundant literature ,4,5,6. HRegarding adherence to the Mediterranean diet worldwide, a recent study shows that Southern Mediterranean countries (in which Spain is included), have a higher adherence comparing with the worldwide mean. However, Mediterranean countries altogether scored a lower adherence to the Mediterranean diet comparing with the worldwide mean .When considering the intake of specific foods and their relationship with a lower presence of depressive symptomatology, the consumption of nuts, vegetables (cooked in sauce) and the use of olive oil are of special relevance in the bivariate and multivariate analyses. In addition, a higher consumption of sugary drinks and red meats has been found to be related to a higher presence of depressive symptomatology.Nuts and olive oil  are rich in “polyunsaturated fatty acids” (PUFA), which are essential fatty acids. These fatty acids have a proven relevance in terms of depression disorder. The main brain PUFAs formed from these essential fatty acids are docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), derived from omega-3 alpha-linolenic fatty acid, and docosatetraenoic acid (DTA), derived from omega-6 linoleic acid. Studies in depressed patients have shown that their DHA levels in adipose tissue were significantly lower than those of non-depressed patients, up to −34.6%. Moreover, maintaining adequate levels of DHA has been found to be inversely related to depression ,73,74. DSimilar to vegetables and fruits, nuts also provide vitamins and minerals, mainly B vitamins, zinc and selenium. Mental health and well-being have been improved by increasing the consumption of fresh fruits and vegetables, which provide flavonols  ,78,79.Regarding B vitamins, vitamin B12 deficiency has been linked to depression . VitaminOther nutrients, such as zinc, are associated with lower levels of this disorder . Zinc suSelenium is another essential micronutrient whose deficit has been linked to the development of major depression in women; the prevalence of which has been found to be over two times that of women with an adequate intake . The recEven though fruits also provide vitamins and minerals, our study has found that individuals with chronic diseases who consume 3 or more pieces of fruit a day have a higher PHQ-9 score. This may be explained by the fact that the MEDAS questionnaire does not discriminate between types of fruits consumed. Studies have confirmed that eating an apple a day has positive effects on mood , but othEven though the alcohol-depression relationship is well established in the literature and recent studies have associated multiple alcohol-related dietary habits  with depression , in thisOn the other hand, analyses carried out in all population groups show that the consumption of red meat is related to a higher presence of depressive symptomatology. Even though red meat also contains vitamins and minerals with a positive effect on mood, an excessive consumption has been found to be a risk factor for depression . Meat riAn excessive consumption of sugary drinks has also been shown to be related with more significant depressive symptomatology. Sugars have been shown to impact very negatively on brain proteins, mainly on neutrophins, which are known to play a relevant role in depression since they protect the brain against oxidative stress and promote the growth of new brain cells .This study has strengths as well as limitations. Among its strengths, the sample stands out, for both its size and its origin. Furthermore, this study analyses the depressive symptomatology with regard to adherence to the Mediterranean diet and the intake of specific foods, providing evidence for both nutrients from food and the Mediterranean diet’s food synergy. The study’s design may be considered a limitation since cross-sectional methodology does not establish causality relationships. Furthermore, having such a large sample implies that significant differences can be obtained without translating into large differences at the clinical level. However, these results may clarify aspects of depression, since it is a complex pathology both in its ethology and in treatment. Another study limitation is the instrument used, which, although quick and easy-to-administer and very useful in measuring adherence to the Mediterranean diet, does not permit discrimination between types of fish, fruit, etc. Therefore, it is impossible to differentiate the type of food consumed and the nutrients found. Moreover, the MEDAS questionnaire does not consider eating behavior but rather, it only measures the quantity and frequency of food consumption. In addition, we measure depression with the PHQ-9, and we base the differences in the severity of depression on its numerical resultAdherence to the Mediterranean diet and the resulting consumption of nuts, vegetables and olive oil has been found to relate to a lower presence of depressive symptomatology. On the other hand, a poorer adherence to the Mediterranean diet and an excessive consumption of sugary drinks and red meats has been related to higher depressive symptomatology. Assessing the dietary pattern of patients presenting depressive symptoms and chronic diseases and promoting adherence to a healthy diet could be important, as well as assessing the depressive symptoms or chronic conditions of people with unhealthy dietary patterns. However, depression is a very complex issue and the relationship between nutrition and depression must be further examined to obtain additional scientific evidence.


Background: Job burnout (JB) has become a prevalent emotional and psychological syndrome across diverse contexts, especially in the face of the COVID-19 pandemic. This study aimed to examine the relationship between perceived organizational support (POS), job satisfaction (JS), self-efficacy (SE), and JB, alongside their mechanism of interplay. Methods: We took 210 Chinese academic journal editors as the research participants and designed a moderated mediation model to examine the posited construct. All the data were gathered online and analyzed with the statistical software SPSS and SmartPLS. Results: The participants comprised 117 women (55.71%) and 93 men (44.29%). There were significant differences among observed variables in age, experience, and title. POS had a significant negative predictive effect on JB . JS mediated the relationship between POS and JB . SE moderated the association between JS and JB  but did not function as a moderator in the relationship between POS and JS . Conclusions: POS, JS, and SE were crucial determinants of JB among Chinese academic journal editors. Targeted interventions should be initiated to diminish editors’ feelings of being unappreciated, inefficient, dissatisfied, and unaccomplished at work. Burnout, widely characterized by three related, but empirically distinct, components—exhaustion, depersonalization, and reduced professional efficacy ,2—is an POS refers to employees’ perceptions of the extent that their contributions are appreciated and their wellbeing is cared for by their organization . SeveralAdditionally, some theoretical and empirical studies have identified the interrelationship between those predictors of JB. According to social exchange theory e.g., ,21), POS, POS21])As part of a typical public service industry, academic journal editing is a stressful profession that involves numerous articles in print  alongsidThese previous studies have greatly enriched our understanding of people’s experiences with JB and its antecedents. However, these representative determinants affecting JB have not yet been integrated into a synthetic model that can identify individual and organizational factors. Specifically, little attention has been paid to the interaction between POS, JS, SE, and JB. More importantly, with the continuous spread of the COVID-19 pandemic and its restrictions, psychological problems, including burnout, have been further exacerbated ,37,38,39Hypotheses 1 (H1).POS negatively predicts JB.Hypotheses 2 (H2).JS mediates the association between POS and JB.Hypotheses 3 (H3).SE moderates the mediating impact of JS on the link between POS and JB.The purpose of this study was to measure the predictive effects of POS, JS, and SE on JB, and explore the mechanisms at play among Chinese academic journal editors in the context of the COVID-19 outbreak. This study will add value to the theoretical literature on burnout constructs by assessing the complex relationship between JB and its correlations in a sample composed of Chinese academic journal editors. The following hypotheses were assumed:The complete hypothesized model is presented in All participants were recruited online via each author’s social media  due to the social-distancing restrictions under the COVID-19 pandemic. We first incorporated these four measures into a single file and then input the measures into the Wenjuanxing Online Survey Software, known as Chinese Qualtrics, so that participants could fill out the survey at any time and in any place. After the participants had completed the questionnaire, we examined the validity of the data and confirmed that all data collected between March and June 2021 were of high quality. Ultimately, 210 Chinese academic journal editors were included in our study.POS was calculated by the Chinese version of the eight-item scale extracted by Settoon et al.  from theJB was gauged with the Chinese version of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) originally developed by Maslach et al.  and compJS was assessed with the Chinese version of the Minnesota Satisfaction Questionnaire Short Form (MSQ-SF), originally constructed by Weiss, Dawis, and England , consistSE was measured with the Chinese version of the General Self-efficacy Scale (GSES), comprising ten items that investigate people’s self-beliefs in difficulties or dilemmas ,52,53. RWe deployed SmartPLS 3.3.2, the most widely used partial least square (PLS) statistical analysis software, and the PROCESS macro in SPSS to analyze the data. As our study relied on self-reported measures, we first checked the common method variance (CMV) using Harman’s one-factor test . The outThis study was examined and authorized by the South China Normal University Academic Ethics Committee. The research ethics approval was attached to the explanatory statement, and a consent form was supplied to the participants.The participants comprised 117 women (55.71%) and 93 men (44.29%). The ages of 72.38% of participants ranged from 31 to 50 years old. Years of work experiences spanned 1–5 (20.5%), 6–10 (31.4%), 11–20 (31.9%), and above 20 (16.2%) years. The majority of the participants (74.76%) obtained post-graduate degrees . Participants with the titles of professor, associate professor, lecturer, and primary accounted for 12.9%, 36.2%, 39.0%, and 11.9% of the total, respectively. The work contracts of the participants were both long-term (70%) and fixed-term (30%). Over half the participants worked as full-time editors (54.8%), compared with the dual roles of teacher–editor (27.1%) and manager–editor (18.1%). The journals employing the participants were found to be affiliated with universities (58.1%), research institutes (20%), industries (11.4%), and academic associations (10.5%). More detailed demographical information about journal publication scopes, categories, and metrics is provided in p = 0.01). In terms of experience, participants with the least work experience gained the highest scores for POS and SE, and editors over 20 years old scored the highest for JS. Participants who had 6 to 10 years of work experiences obtained the highest scores for JB, but significant differences were observed only for the latter two variables (p = 0.05 and 0.01). Regarding title, participants with professor-level titles gained the highest scores for JS and SE, while those who were awarded a primary title scored the highest for POS and JB. However, the difference was only significant for SE (p = 0.04). There were no significant differences found for the other control variables.p < 0.01). JB was negatively significantly related with the other variables (p < 0.01). The two dimensions of JS both positively significantly predicted JS. All three dimensions of JB also positively significantly predicted JB, but low personal accomplishment was unrelated to emotional exhaustion and depersonalization. This result confirmed the suggestion that the professional efficacy subscale is weakly linked to the other two subscales and can be used separately  to ).Furthermore, we performed a simple slope to visualize the moderating effect of SE on the correlation between JS and JB. With the increase in SE, the predictive effect of JS on JB gradually declined . However, this indirect effect was not significant at the value of one standard deviation above the mean of the moderator . With an increase in the editors’ sense of SE, the indirect effect of POS on JB via JS was gradually weakened.As shown in In sum, the moderated mediation model was partly established. JS acted as a mediator in the link between POS and JB. Moreover, SE served as a moderator in the association between JS and JB but did not play a moderating role in the relationship between POS and JS.In this study, we examined the moderating role of SE in the mediating effect of JS on the relationship between POS and JB among Chinese academic journal editors in the face of COVID-19. Participants’ overall means were intermediate or above the midpoint of the scales, indicating that they were highly appreciated by their organizations, quite satisfied with their work conditions, and self-efficacious when achieving their tasks. However, the participants felt burned out due to repetitive work. These results are consistent with the finding that scientific journal editors had moderate degrees of satisfaction with their jobs and felt burnt out . The resFurthermore, the significant difference analysis revealed that 31–40-year-old employees with 6–10 years of work experience had higher levels of burnout than their peers, similar to the empirical findings of Reinardy . Except In addition, the results presented close links between POS, JS, SE, and JB among Chinese academic journal editors. The specific interrelationship between the four observed variables is discussed explicitly in the following subsections.The results indicated that POS had a significant negative correlation with all dimensions of JB and could significantly and negatively predict JB. This indicates that the higher the POS levels of Chinese academic journal editors, the lower their JB.This result is consistent with previous theoretical arguments ,86. AccoThe results confirmed that JS could act as a mediator between POS and JB among Chinese academic journal editors; that is, the impact of POS on JB could be partly direct and partly indirect, through JS.This result is congruent with the findings that the organizational support perceived by employees plays a critical role in predicting and promoting JS ,93. EmplThis result also agrees with the assumption of Maslach, Schaufeli, and Leiter  that a dAcademic journal editors experience an increased risk of stress in their profession due to deadlines, the need for a low rate of word inaccuracy, and ongoing updates to technology . This siHowever, it is worth noting that POS still had a significant direct effect on JB, which indicated that JS was only a partial mediator. Complete mediation can be established in theory but would be rare. Moreover, there may be other variables that were not considered in this study.This study also indicated that, in the indirect effect of POS on JB via JS, SE significantly moderated only the latter half of the relationship between JS and JB. The conditional effect outcome showed a transitional point along the continuum of the moderator between statistically significant and nonsignificant. Specifically, when Chinese academic journal editors’ sense of SE was low, the negatively predictive effect of JS on JB was strong; when the Chinese academic journal editors’ sense of SE was high, the negatively predictive effect of JS on JB was weakened.This result further confirmed the social cognitive theory ,100, whir = 0.32), this remarkable result could be explained by the social cognitive theory that proposes that, when employees lack confidence in their abilities to achieve their work aspirations or lack the desired opportunities and support needed to take responsibility and increase their dedication, those workers will feel unaccomplished and dissatisfied with their jobs. Therefore, despite the gap between the hypothesized model and the empirical path, organizations also need to focus on organizational-level intervention strategies, involving reducing workload [However, the present results do not completely support the JDR model, which proposes that POS influences JS through SE . Unlike workload , improviworkload , and ideWhile the reliability and validity issues of the model were verified in the current study, there are a few limitations that must be acknowledged. The first limitation is that the data were gathered by self-reporting. Therefore, causality and generalization in the results should be treated with caution. Nevertheless, the results suggest common scenarios among Chinese academic journal editor cohorts. The second limitation is that although the sample was deemed representative, the sample size was still small, constraining the generalizability of the findings. Further research is needed to enlarge the sample size and improve the statistical effect size post-COVID-19. The third limitation is that we did not consider controlled variables when validating the model, which may have resulted in statistical bias. Future work should incorporate more controlled variables, such as age, title, and work experience, which show differences in the levels of their constructs, to enhance the statistical power and model discrimination.This study aimed to design a moderated mediation model in which POS, JS, SE, and JB were tested among Chinese academic journal editors, drawing on social cognitive theory, social exchange theory, and the JDR model. The results revealed that POS is a critical antecedent when predicting JB and JS. The results also showed that JS partially mediated the impact of POS on JB. Although SE only moderated the relationship between JS and JB, the total moderating effect was significant. Notably, the moderating role of SE at the low level was stronger than that at a high level. This empirical result adds value to the current literature on employees’ emotional and psychological health in the academic publishing industry. This research also provides an informative insight into how to provide academic journal editors with their desired level of organizational support, accelerate their SE, and boost their satisfaction with their jobs in the face of the COVID-19 pandemic by offering more opportunities to develop their professional skills and more flexible career promotion options. This study could be further strengthened and generalized by amplifying the sample size and diversity to increase the effect size and decrease random errors.


Introduction: Monocyte to high-density lipoprotein (HDL) cholesterol ratio (MHR) has emerged as a novel marker of endothelial injury, inflammation, and oxidative stress. This study aimed to investigate the effect of MHR on primary nephrotic syndrome (NS) and its relationship with the severity of proteinuria.Methods: This study enrolled 161 patients newly diagnosed with primary NS and 100 healthy individuals. Demographic characteristics of the patients, primary NS diagnosis, basal laboratory parameters, the amount of 24-hour urinary protein excretion, and MHR were recorded. The groups were compared regarding these parameters.Results: MHR was significantly higher in patients with primary NS compared with the healthy group . There was no difference between the groups in terms of age and sex. The amount of protein in the 24-hour urine in patients with a diagnosis of primary NS was 6.91 ± 3.73 g/day. The correlation analysis showed a positive correlation between MHR and the amount of proteinuria  and creatinine level . The multivariate regression analysis found that the severity of proteinuria was independently correlated to MHR (p < 0.001). According to the receiver operating characteristic curve analysis, the optimal cut-off level for MHR in NS was 10.08 .Conclusion: Our study is the first to compare the severity of proteinuria and renal functions with MHR in patients with primary NS. We believe that MHR can be used as a biomarker to determine inflammation, endothelial injury, and the level of oxidative stress, and may be useful to predict prognosis in patients with primary NS. Nephrotic syndrome (NS) is a disorder that causes proteinuria as a result of increased permeability of the glomerular filtration membrane . Its patResearchers all over the world have focused on discovering reproducible, simple, fast, and low-cost biomarkers to evaluate endothelial dysfunction and to determine inflammatory status and oxidative stress. Various cytokines are released in response to endothelial dysfunction, inflammation, and increased oxidative stress. Monocytes are the first cells that are activated in this process. Therefore, they are of critical importance for inflammation. Activated monocytes are transformed into macrophages. These monocytes and macrophages phagocytes oxidize low-density lipoprotein (LDL) cholesterol molecules and form foam cells, thereby inducing the release of pro-inflammatory and pro-oxidant cytokines. High-density lipoprotein (HDL) cholesterol, on the other hand, reduces monocyte activation and protects endothelium against the detrimental effects of oxidized LDL cholesterol particles. Moreover, HDL prevents the expression of adhesion molecules and causes nitric oxide release, and induces vasodilation. Due to these properties, it has anti-inflammatory and anti-oxidant properties. An increased count of pro-inflammatory monocytes and a reduced level of anti-inflammatory HDL cholesterol have been considered novel markers of inflammation. As a result of these studies, the monocyte to HDL cholesterol ratio (MHR) has emerged as a novel marker for determining endothelial injury, inflammation, and oxidative stress -12.Although the relationship of MHR, a new biomarker, and many diseases where chronic inflammation is involved has been evaluated, no study related to primary NS has been performed. In the present study, we aimed to investigate the influence of MHR on primary NS and its relationship with the severity of proteinuria.This study was conducted with a total of 261 subjects. The study population consisted of newly diagnosed primary NS patients of both sexes older than 18 years of age, who presented to the nephrology and internal medicine outpatient clinics between January 2017 and December 2020, and healthy controls. A total of 161 patients with newly diagnosed primary NS and 100 healthy subjects were enrolled. Patients who were under the age of 18 years, who had secondary NS, active infection, chronic inflammatory disease, definitive or suspected malignancy, hematological disorders, or treated hyperlipidemia were excluded. The control group consisted of healthy individuals free of any documented disease, who presented to the internal medicine outpatient clinic; the NS group was composed of patients with newly diagnosed primary NS. The demographic properties (age and sex), primary NS diagnosis, biochemical parameters at the time of diagnosis , C-reactive protein, complete blood count parameters, amount of 24-hour proteinuria, and MHR were recorded in all patients. MHR was calculated as the ratio of monocyte count to the HDL cholesterol level. The same parameters were also evaluated in the control group, and both groups were compared with regard to these parameters.Statistical analysisStudy data were statistically analyzed using Statistical Package for Social Sciences (SPSS) version 24.0 . The normality of the distribution of the study variables was tested with visual (histogram and likelihood graphics) and analytic methods (Kolmogorov-Smirnov/Shapiro-Wilk tests). The descriptive analyses were presented as mean and standard deviation for normally distributed variables and median and min-max values for non-normally distributed variables. Inter-group comparisons were carried out using Student's t-test for normally distributed variables and Mann-Whitney U test for non-normally distributed ones. The chi-square test was used to test the difference in frequencies between the groups. Correlation between continuous variables was tested with Pearson and Spearman correlation analysis tests, depending on the normality of distribution. A linear regression analysis was performed to determine factors affecting proteinuria. The diagnostic decision-making properties of the MHR value in predicting patients with primary NS were analyzed with the receiver operating characteristics (ROC) curve. When a significant cut-off value was observed, the sensitivity and specificity values were presented. A p-value of less than 0.05 was considered statistically significant.A total of 261 patients were enrolled in our study, 161 of whom were primary NS patients and 100 were healthy controls. Of these, 129 (49.4%) were women, and 132 (50.6%) were men. The mean age of the total study population was 35.92 ± 11.94 years.The primary NS group had a mean age of 36.04 ± 12.54 years, and it consisted of 75 (46.6%) women and 86 (53.4%) men. There was no significant difference between the study groups regarding age or sex . The etiology of primary NS was focal segmental glomerulosclerosis (FSGS) in 34% of patients, membranous glomerulonephritis in 29%, immunoglobulin A (IgA) nephropathy in 23%, and membranoproliferative glomerulonephritis (MPGN) in 14% , with a sensitivity of 68% and a specificity of 62% Figure .In our study, we investigated the effect of MHR on primary NS and its relationship with the severity of proteinuria. We found that MHR significantly increased in the primary NS group compared with the healthy control group. We detected a positive correlation between MHR and the severity of proteinuria and serum creatinine level. Our study is important in that it is the first study in the literature to examine the relationship of MHR with the severity of proteinuria in patients with primary NS.A review of the current literature indicates that many studies to date have shown that MHR, which is calculated by the ratio of these two parameters, which are known to be closely associated with endothelial dysfunction and inflammation, can be a new marker of inflammation and oxidative stress in systemic diseases, while it is also associated with the prognosis of some diseases. It is suggested that increased MHR level predicts disease progression .In a study conducted with 262 diabetes mellitus (DM) patients, it was found that MHR was significantly higher in the DM group compared with the healthy group. In that study, when the subjects were grouped as those with and without nephropathy, MHR was significantly higher in those who had nephropathy . A separAdditionally, we evaluated renal function based on serum creatinine level in patients with primary NS and analyzed its correlation with MHR. We detected a positive correlation between MHR and serum creatinine level . There are several studies in the literature which have examined the relationship between renal functions and MHR. In a study where 8,159 patients were analyzed, the effect of reduced renal function on MHR was evaluated. That study found a significantly higher MHR level in patients with reduced renal function . Kanbay Proteinuria is a diagnostic marker of NS while it also affects disease progression . When NSIn conclusion, our study is the first to compare the severity of proteinuria and renal functions with MHR. Our results revealed that increased MHR levels were significantly and independently correlated to the severity of proteinuria. We determined a positive correlation between serum creatinine and MHR. We believe that MHR can be used as a biomarker to detect inflammation, endothelial injury, and oxidative stress level and prove useful to predict prognosis in primary NS patients.


Latent Mycobacterium tuberculosis infection (LTBI) and active tuberculosis in prisoners are higher than the general population and are two public health concerns, especially in low- and middle-income countries. We conducted a cross-sectional study to determine the prevalence and the factors associated with LTBI among the inmate population detained in three Southern Italian penitentiaries. Tuberculin intradermal reaction skin test was performed on the inmates who agreed to participate in the study. In case of positivity, the QuantiFERON-TB test was performed. In those positive to QuantiFERON, chest X-ray films were performed, and treatment initiated. A total of 381 inmates accepted to participate. The prevalence of LTBI was 4.2%. In the analysis, LTBI was associated with no self-reported contact with active tuberculosis patients within the prisons, and 10% of subjects admitted the use of inhaled drugs. No HIV coinfections were found. No cases of active symptomatic tuberculosis were identified during the study period. Our results confirm that incarceration increases the risk of tuberculous infection. Non-EU nationality and a history of drug addiction appear to be major risk factors for tuberculosis infection in the penitentiary setting. Reinforcing tuberculosis control is essential to prevent its transmission in prisons. Tuberculosis (TB) is an infectious disease caused by various strains of mycobacteria, especially Mycobacterium tuberculosis, also called Koch’s bacillus . Until tTB happens to be a major public health problem also in the community population which cannot be controlled unless effective measures are taken to fight this disease in prisons ,18,19,20The Salerno prison institute houses about 390 inmates. The Salerno institute consists of a women’s section (in a separate building), a section with “common” inmates, a section with “high security” inmates, and finally a section that houses inmates with problems of “prisoner-on-prisoner physical violence” and the “worker” detainees. In the institute, there is also a managed psychiatric unit. The Eboli prison institute houses about 50 inmates, with reduced custody for drug addiction treatment. Finally, the prison of Vallo della Lucania is characterized for hosting about 40 “sex offenders” inmates.An observational cross-sectional study was conducted in prison facilities of the Salerno province to evaluate the prevalence of LBTI sustained by Mycobacterium tuberculosis. The Department of Territorial Activities, U.O.S.D. Protection for Adults and Minors of the ASL Salerno Criminal Area, operates in three different penitentiary facilities: Eboli, Vallo della Lucania, and Salerno. In June 2020, the Mantoux TST was performed on inmates of these three different penitentiary institutes who gave consent. Informed consent was executed privately one inmate at a time in written form upon scheduled medical visits in the prison sections, by the prison doctor in duty. No incentives were offered to the inmate participants.The data processing complied with the general authorization for scientific research purposes granted by the Italian Data Protection Authority  since the data do not entail any significant personalized impact on the data subjects. Approval by an institutional and/or licensing committee was not required since experimental protocols were not applied in the study.Protocols and screening were conducted as suggested by the World Health Organization and in conformity with the ethical guidelines of the 1975 Declaration of Helsinki.One prison section at the time was tested. The eligibility criteria were as follows: who freely accepted to participate; having had no previous treatment for tuberculosis; having no tuberculosis disease at the study outset. The following variables were also evaluated: sex, weight, height, comorbidities such as cancer, transplants, diabetes mellitus (DM), hypertension (HT) rheumatoid arthritis (RA), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), psychiatric disorders, and any other immunosuppressive disease, abuse of drugs  or alcohol, along with the quantity and time of consumption, fever, weight loss, night sweats, hemoptysis, and BCG vaccination scar.Variables were collected from prison records as at inmate entrance, clinical visits are carried out in the central infirmaries of the prisons. During the visits, anamnestic and clinical information are privately collected by the doctor on duty. The reliability of inmate declarations is a limitation that could lead to recall biases.®) v. 20 for MacIntosh® .The statistical data analysis was expressed as frequencies, percentages, and Fisher’s test. All statistical analyses were performed using the Statistical Program for Social Sciences  of M. tuberculosis PPD RT23  on the left forearm. TSTs were read 72 h after being administered, by measuring the maximum transverse diameter of induration with a millimetre ruler. The LTBI status was determined by the size of TST induration in the absence of a reported previous positive test. An induration of ≥10 mm was considered a positive result for HIV-negative individuals, and an induration of ≥5 mm was considered a positive result for HIV-infected individuals.The “TUBERTESTAll subjects with positive Mantoux performed blood sampling for QuantiFERON-TB. Subsequently, the protocol provided that positive subjects took chest X-rays films. In case of positivity to X-rays or onset of symptoms, they would be hospitalized, while if negative they would start therapy for LTBI. We followed the Italian guidelines, which indicate to administer isoniazid and rifampin for three months or isoniazid for six months . Therapy®”. The general inmate population at the time of the screening was composed of 420 prisoners eligible to participate in the study, 383 (91.19%) men, 37 (8.81%) women, and 83 (19.76%) foreigners. Among these 420, the prevalence of comorbidities was: 6 inmates with COPD, 1 inmate with CKD, 37 inmates with HT, 18 inmates with type 2 DM, 80 with anxious-depressive syndrome, and one HIV (human immunodeficiency virus)-positive. Age ranges were as follows: 23 inmates between 60–80 years ; 61 inmates between 50–69 years (of these nine refused); 265 inmates between 30–49 years (29 refused); 71 inmates between 18–29 years (none refused). Overall, 39 (9.29%) inmates refused to be screened, two (5.13%) of them were female. Education level was homogeneous as 418 inmates attended compulsory school and two graduates (neither were positive). The mean incarceration time was 52 months. Prisoners who accepted to participate in the study were 381 (90.71%) and of these 330 (78.1%) were Italian, 51 (21.9%) were foreigners, 110 (28.87%) were people who inject drugs (PWIDs). There was only one HIV-positive inmate; he accepted to be tested and resulted negative to the “TUBERTEST®”. Further information about the characteristics of these subjects is provided in Among the 381 participants, 31 (8.13%) resulted positive to the “TUBERTESTThese patients were put in sanitary isolation and brought to the nearest hospital for chest X-rays. Since none were symptomatic, hospitalization was not required.According to guidelines, latent TB therapy was initiated, and fortunately, only one inmate refused. Overall, only seven inmates completed the treatment in our penitentiary facilities due to six transfers to other prisons and four releases from prison. Compliance of these ten subjects was unfortunately not evaluable since we could not perform a follow-up. On the other hand, of the seven treated inmates, none reported side effects to the TB treatment and/or onset of TB symptoms during the following 6 months.According to the World Health Organization (WHO), about two billion people, or one-third of the world population, have been exposed to the tuberculosis pathogen . AnnuallThe difficulties encountered in prison for the control of TB include the lack of possibility, in some Penitentiary Health Centers, to organize the execution of Mantoux intradermal reaction to newly arrived inmates, the need to send the positive prisoners to external facilities with the penitentiary police escort to perform a chest X-ray, and the difficulty in guaranteeing sanitary isolation with all the necessary precautions while still guaranteeing air for daily walking .p value < 0.01). Overall, 8 out of 51 foreign prisoners (15.69%) were positive. Surprisingly, we did not find a significative correlation between LTBI and the use of injected drugs. Treatment management was difficult due to the long period of therapy required that clashes with the prison reality. In fact, only seven (38.88%) inmates completed the 6 months therapy in our penitentiary facilities. The lack of therapeutic compliance derived from one refusal, six inmates transfer to other penitentiary facilities, and four releases from prison. We advocated for the conclusion of the treatment to both the inmates and the new hosting penitentiary facility. Unfortunately, we were not able to have feedback on the therapy follow-through, and this is a limit of our study. Another limit is that we considered only three facilities. There is no clear way to predict the development of tuberculosis among prisoners, especially if asymptomatic. In a resource-poor setting such as the prison environment, only screening can be a viable way [The magnitude of LTBI within the Italian prison system, as previously mentioned, remains mostly unknown. The prevalence observed in our study is 4.72%. We found that being foreign is related with a higher frequency of LTBI (able way ,37. MoreRecent literature reviews show a risk of false-positive results in tuberculin tests in subjects who received the BCG vaccination. If BCG vaccination is given after the first year of life, as presumably in our cases, more frequent, persistent, and larger skin test reactions are produced . TubercuIn conclusion, our results confirm that incarceration increases the risk of tuberculous infection. According to our data, the high number of non-EU prisoners seems to be one of the main factors related to TB infection recurrence in prisons. Reinforcing TB control is essential to prevent its transmission in penitentiary facilities. To develop proper screening and preventive programs, it is fundamental to highlight the factors that increase the risk of LTBI in this kind of population. Therefore, more studies are needed in this field. According to the current knowledge, we propose to perform a TST on all prisoners, especially to the new inmates, to select those needing further investigations and then TB therapy. Only an adequate screening strategy could help contain the again-increasing incidence of LTBI in prisons.


Background: Intracranial hemorrhage is a severe and possibly fatal consequence of anticoagulation therapy. Idarucizumab is used in dabigatran-treated patients suffering from intracranial hemorrhage (ICH) to reverse the anticoagulant effect of dabigatran. Systematic review of real-life mortality in these patients is missing.Objectives: A review of all published dabigatran-related ICH cases treated with idarucizumab was performed. We aimed to estimate in-hospital mortality rate in these patients.Method: We searched PubMed and Scopus for all published cases of ICH in idarucizumab/dabigatran-treated patients until May 15, 2021. The assessed outcome was in-hospital mortality.Results: We identified six eligible studies (case series) with 386 patients and 54 single case reports. In-hospital mortality rate was 11.4% in the case series and 9.7% in the case reports.Conclusions: Our analysis provides clinically relevant quantitative data regarding in-hospital mortality in idarucizumab/dabigatran-treated patients with ICH, which is estimated to be 9.7–11.4%. Idarucizumab is a specific reversal agent of dabigatran, which achieves instantaneous reversal of anticoagulation after application seemingly without prothrombotic or other serious side effects , 2. The Intracranial hemorrhage in dabigatran-treated patients is a rare event, with estimated yearly incidences of 0.1% for the standard dose and 0.12% for the reduced dose . Due to The aim of this systematic review was to summarize all published cases of dabigatran-treated patients with ICH who were treated with idarucizumab in order to quantitatively evaluate the in-hospital mortality rate.We searched PubMed and Scopus until May 15, 2021 for studies reporting dabigatran reversal with idarucizumab in patients with ICH using the terms: “idarucizumab” or “reversal” or “dabigatran” and “hemorrhagic stroke” or “ICH” or “intracranial bleeding.” The search was limited from January 1, 2013 to May 15, 2021, since the term “idarucizumab” was first reported in 2014. In addition, we searched the references of related letters, reviews, and editorials to identify other potentially eligible studies. We also contacted experts in the field to identify studies that have been potentially missed. To be eligible for this analysis, all studies had to provide data about the in-hospital mortality in dabigatran-treated patients with ICH after reversal with idarucizumab. This study was reported according to the PRISMA statement .The outcome assessed was in-hospital mortality. Eligible studies were assessed independently by the first two authors. Individual patient data were extracted from single case reports and case series whenever possible using prespecified forms. Quality evaluation of the included studies was conducted using a tool for the assessment of case series .Patient characteristics and in-hospital mortality were described based on two different prespecified approaches: individual patient data from single case reports and case series that provided individual patient data were pooled together to form a unified group of patients. Case series that provided aggregate data rather than individual patient data were reported separately.Among 676 articles identified from the initial literature search, 22 studies were eligible and included in the analysis , 2, 5–24Quality assessment can be found in Forty-four (11.4%) out of 386 patients in the case series and 4 (9.7%) out of 41 patients in the single case reports died. The characteristics of patients are summarized in Out of 435 patients, individual data  were only available for 54, which did not allow us to perform an individual patient characteristic analysis.Our systematic review of data from published case reports and case series shows an estimated real-life in-hospital mortality of 9.7–11.4% in this patient population. Previous studies have reported the in-hospital mortality rate among warfarin- and direct oral anticoagulant (DOAC)-treated patients with ICH, which ranged from 25 to 33% and from 18 to 27%, respectively . In the Our review has several limitations. Heterogeneity of the cases  and missing data  are the main limitations of this study. Individual data were available for only 54 out of 435 patients, which could limit the assessment of how representative the cohort is. Comparison with patients with ICH who were not treated with idarucizumab would be valuable; however, there are no applicable published real-life data. Finally, we cannot exclude the presence of publication bias, particularly regarding the analysis of case reports. On the other hand, the strength of the study is consideration of all published cases.In conclusion, our systematic review of all published cases of dabigatran-related patients with ICH treated with idarucizumab provides a real-life quantitative estimate for real-life in-hospital mortality. This estimate seems to suggest the clinically relevant efficacy and safety of dabigatran reversal in real-life treatment of patients with ICH. However, this needs to be assessed in a propensity-score matched analysis or, ideally, in a prospective study of appropriate size.The original contributions presented in the study are included in the article/SF and DS: study design, data acquisition, statistical analysis and interpretation, and manuscript preparation. MŠ and GN: data acquisition, statistical analysis and interpretation, and critical revision of the manuscript. JO: study concept and design, statistical analysis and interpretation, manuscript preparation, and study supervision. All authors contributed to the article and approved the submitted version.SF, MŠ, and JO reported speaker fees from Bayer, Boehringer Ingelheim, and Pfizer. GN reported speaker fees/advisory boards/research support from Abbott, Amgen, Bayer, Boehringer Ingelheim, Elpen, and Pfizer outside the submitted study. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background:Chlamydia pneumoniae (CPn) is a common community-acquired pneumonia. In the literature, CPn infection is demonstrated to exhibit an association with Alzheimer dementia (AD). We executed the present nationwide, population-based research with the goal of probing the association of CPn infection and antibiotic therapy with AD risk.Methods: We conducted a cohort study using a database extracted from Taiwan's National Health Insurance Research Database (NHIRD). All medical conditions for each enrolled individuals were categorized using the International Classification of Diseases, ninth Revision classifications. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between CPn pneumonia-associated hospitalizations and AD were estimated using Fine and Gray's survival analysis and adjusted for comorbidities. The effects of the antibiotics on the HRs for AD in the patients with CPn pneumonia-associated hospitalization were also analyzed.Results: Our analyses included 6,628 individuals, including 1,657 CPn-infected patients, as well as 4,971 controls matched by age, index date, and sex (1:3). In this study, patients hospitalized for CPn pneumonia exhibited a significantly higher AD risk . We also noted an association of macrolide use (≥15 days) and fluoroquinolone use (≥15 days) with decreased AD risk.Conclusions: We determined CPn pneumonia to be associated with a relatively high AD risk. The result in this study confirmed the findings from previous literatures, by using a large, nationwide, population-based database. Appropriate macrolide and fluoroquinolone treatment may attenuate this risk. Dementia is one of the major global health problems. In Taiwan, the prevalence is 4–8% for a population aged≥65 in community studies  may be implicated in AD pathology and certain antibiotics were determined to exhibit some degree of effectiveness in treating moderate AD  program was implemented in 1995 and provides healthcare coverage to 99% of the population (being more than 23 million people). The NHI Administration randomly reviews the records of ambulatory care visits and in-patient claims periodically so as to verify the accuracy of the diagnoses . The detThis study involved a cohort design. Using the NHIRD, we selected adult patients aged >50 years who had been diagnosed with AD (331.0) based on the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes between 2000 and 2015, and confirmed these patients' diagnoses by linking the records of at least three visits for AD in consecutive years, or at least one hospitalization for AD, during the study period. All diagnoses of AD were made by board-certified psychiatrists or neurologist in Taiwan. The date of the AD diagnosis was at least 1 year after the CPn pneumonia diagnosis. We identified patients with CPn pneumonia using the ICD-9-CM code 483.1. We confirmed these patients' diagnoses by linking the records of at least one hospitalization for CPn pneumonia, in the study period, and the reason why we decided on the enrolled exposures of CPn as pneumonia due to CPn, was because one previous population-based study had confirmed the accuracy of the diagnosis of pneumonia from the NHIRD as 98.3% , marital status, education , seasons, geographical area of residence , urbanization level of residence (levels 1–4), and monthly income . The urbanization level of residence was defined according to the population and various indicators of the level of development. Level 1 was defined as a population of >1,250,000, and a specific designation as political, economic, cultural, and metropolitan development. Level 2 was defined as a population between 500,000 and 1,249,999, and as playing a key role in the politics, economy, and culture. Urbanization levels 3 and 4 were defined as a population between 149,999 and 499,999, and <149,999, respectively , and the duration of the usage of antibiotics was calculated by dividing the cumulative dosages by the DDD of the antibiotics.Data on the usage of macrolides and fluoroquinolones antibiotics were acquired from the Longitudinal Health Insurance Database (LHID), a sub-database of the NHIRD. The data of the defined daily dosage (DDD) were obtained from the WHO Collaborating Centre for Drug Statistics Methodology , hypertension , hyperlipidemia (ICD-9-CM 272), coronary artery disease , obesity (ICD-9-CM 278), all cancers (ICD-9-CM 140–208), and other chlamydia infections  and other pneumonia . These comorbidities were included with the references from previous studies using health databases  was employed to execute the assessment of the aforementioned comorbidities. In the CCI, Only patients diagnosed with CPn pneumonia of more than 1 year prior to the index date were considered. CPn pneumonia was identified from the NHIRD by using the corresponding ICD-9 code (ICD-9-CM code 483.1). All the covariates as aforementioned were included.2 tests and the Fisher's exact test. Continuous variables, which were presented as the mean and SD, were compared using the Student's t-tests. The primary goal of this study was to determine as to whether a patient's clinical characteristics, such as CPn pneumonia, were associated with AD. Associations between those outcomes and clinical characteristics were investigated using the Fine and Gray's survival analysis in a generalized estimating equation (GEE) model. The regression results are presented as adjusted HRs with corresponding 95% CIs. The threshold for statistical significance was p < 0.05. All data analyses were conducted using the SPSS V.22 (SPSS).Categorical variables, which were presented as percentages, were compared using the χIn total, 1,657 patients were diagnosed with Cpn pneumonia during the study period. A total of 182 enrollee were identified with AD during the follow-up period.Patients with CPn pneumonia also tended to be living in northern and middle Taiwan and residing more in the regions of urbanization levels 1 and 2. There were no differences in the distribution of sex, age, marital status, and education between these two groups.p < 0.001; In our applied Fine & Gray's competing risk model, compared with the control group, we determined patients with CPn pneumonia to have a higher risk of AD . Additionally, hyperlipidemia, CAD, anxiety, sleep disorder, and alcohol use disorder exhibited associations with a relatively high risk of AD. Patients who visited medical centers or regional hospitals to seek medical care were also noted to be at relatively high risk. Although the percentage of hypertension in CPn exposed cohort was higher than that in the unexposed cohort (p < 0.001), in Fine & Gray's survival analysis, there were no significant differences for hypertension between the two cohorts (p = 0.087). However, patients who sought medical care in Autumn and with cancer revealed a reduced risk of AD. Further studies are needed to clarify why patients with these comorbidities were associated with a decreased risk. Moreover, our study also indicated that patients who were treated with macrolides (≥15 days) and fluoroquinolones (≥15 days) could attenuate the risk of AD.By employing a nationwide population database, our executed study is the first to demonstrate an association between CPn pneumonia and AD development in Taiwan. Patients with CPn pneumonia exhibited a nearly 1.6-fold increased risk of AD   genotype may be involved in the CPn–AD association  could decrease the risk of developing AD. In one clinical practice guideline, continue antibiotic therapy is strongly recommended in patients with CPn infection until they achieve clinical stability including resolution of vital sign abnormalities, appetite, and normal mentation  with the mouth or nose. CPn reinfection among older adults is common, and outbreaks have been reported in settings of close contact and crowding, such as nursing homes, schools, prisons, and military barracks , or rehabilitation availability could not be assessed in our executed study due to the lack of such data in the NHIRD.Besides, we could not include data on psychosocial, environmental, and genetic factors in our analyses due to the same reason. However, despite these limitations, our derived data are highly likely to be valid and representative due to the NHIRD containing data covering all hospitals within Taiwan and over 99% of the population for the relevant 15-year period.This study determined CPn pneumonia to be associated with an estimated 1.6-fold increased risk of AD, which should alert physicians to be attentive to the risk of AD following CPn pneumonia, especially after 8 years of tracking. We noted the AD risk to be reduced among CPn pneumonia patients when administered appropriate antibiotics. We recommend the execution of additional studies based on extensive or national data sets to corroborate the present findings and elucidate the corresponding underlying mechanisms.http://nhird.nhri.org.tw/en/index.html) are maintained in the NHIRD (http://nhird.nhri.org.tw/). The NHRI is a nonprofit foundation established by the government. Only citizens of Taiwan who fulfill the requirements of conducting research projects are eligible to apply for access to the NHIRD. The use of the NHIRD is limited to research purposes only. Applicants must follow the Computer-Processed Personal Data Protection Law (http://www.winklerpartners.com/?p=987) and the related regulations of the National Health Insurance Administration and NHRI, and an agreement must be signed by the applicant and their supervisor upon application submission. All applications are reviewed for approval of data release.The data on the study population that were obtained from the NHIRD . Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.The contributions of the authors are listed as the following: HO and N-ST: study concept and design. W-CC, C-HC, and N-ST: acquisition of data. W-CC, C-HC, H-AC, Y-CK, P-CW, and N-ST: analysis and interpretation of data. HO: drafting of the manuscript. N-ST: critical revision of the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: The inflammatory bowel disease disability index (IBD-DI) was used to access body functional consequences and disease burden. However, Chinese population data are considerably limited.Objective: We aimed to screen for disability in patients with Crohn's disease (CD) and to assess potential associations with clinical parameters as well as indices related to sarcopenia.Methods: This cross-sectional study includes 146 CD patients from Ruijin Hospital in Shanghai, China. All patients were screened for disability and sarcopenia on the basis of the IBD-DI scale, and the criteria for Asian Working Group for Sarcopenia, respectively. Clinical and demographic variables were collected.Results: Approximately 52.05% of the subjects suffered from moderate or severe disabilities. The prevalence of sarcopenia , Patient-Generated Subjective Global Assessment score or PG-SGA≥4 , and high-level C- reactive protein  were higher in patients with moderate to severe disability than in those without to minimal disability. By multivariate regression modeling, the following were identified as independent factors related to moderate to severe disability: disease activity  and body mass index (BMI) .Conclusions: Disability is common in CD patients. Our study showed that moderate to severe disability is not directly associated with muscle mass or muscle quantity but is mostly correlated with disease activity as well as BMI. Thus, close monitoring and follow-up should be conducted on patients who are at high risk of disability, and effective measures should be taken, which may be the best way to prevent disability. The prevalence of inflammatory bowel disease (IBD) has markedly increased in mainland China . Crohn'sThe International Classification of Functioning, Disability, and Health (ICF) of the World Health Organization defines disability as an objective measure of loss of functioning and impairment in patient activity . The InfInflammatory bowel diseases are often associated with malnutrition and significant alteration in body composition . Bryant Liu et al.  reportedn = 197) under anti-TNF-α therapy were included at Ruijin Hospital in Shanghai from February 2019 to June 2019. All CD patients were included in the study, independent of occupational activity, gender, race, or social class. Specifically, these participants were diagnosed with CD by their treating physicians and met the criteria established by the Inflammatory Bowel Disease Group of the Chinese Society of Gastroenterology. The following exclusion criteria were applied: patients with metabolic diseases  whose related indices were not well-controlled after hospitalization; patients with gastrointestinal tumors or tumors at other sites; patients with impaired water and mineral metabolism caused by cortical hormone therapy; and patients with metal implants (such as cardiac pacemakers) that could influence bioelectrical impedance results. Fifty-one patients were not included for missing values in the variables of body composition, BMI or others  sociodemographic data, including age, gender, height, weight, and smoking and drinking habits; (b) disease characteristics, including disease duration and disease activity assessed by Crohn's disease activity index (CDAI). Patients with CDAI ≤150 were considered in clinical remission, whereas those with CDAI >150 were considered in the active phase.We assessed body composition by multifrequency bioelectrical impedance analysis using the InBody S10 body water analyzer (InBody Korea). We also evaluated the total fat mass, body fat percentage, total muscle mass, skeletal muscle mass, and the muscle/fat ratio of the patients. This analyzer processes 30 impedance measurements by using six different frequencies  in each of five segments of the body  and 15 reactance measurements by using tetrapolar 8-point tactile electrodes at three different frequencies  in each of the aforementioned segments.2) was calculated. Loss of skeletal muscle mass was determined based on the criteria set by the Asian Working Group for Sarcopenia (2019)  was measured as the sum of the muscle mass from the four limbs, and the ASM index (kg/ma (2019) : ASMI <7Measurement was performed with the participant in the following position: seated on an armless chair, with feet supported on the floor, hips and knees flexed at 90°, arms parallel to the body, elbows flexed at 90°, and forearms and wrists in a neutral position. The dominant side was measured three times at 1-min intervals, with verbal stimulation applied. The results were expressed in kilogram-force (kg), and the mean of the three measures was used. Muscle weakness was determined based on the criteria set by the Asian Working Group for Sarcopenia : handgriPatient-Generated Subjective Global Assessment (PG-SGA) was recommended as a nutritional assessment scale for IBD patients by the Inflammatory Bowel Disease Group of the Chinese Society of Gastroenterology. The PG-SGA assessment included (i) body weight, (ii) dietary intake, (iii) symptoms, (iv) movement and body function, (v) relationship between disease and nutritional requirement, (vi) metabolism requirement, and (vii) physical examination. According to the criteria, the scores indicated the following: 0–1, good nutritional status; 2–3, light malnutrition requiring nutritional education and/or nutritional intervention; 4–8, moderate malnutrition requiring nutritional intervention; and ≥9, severe malnutrition requiring symptom improvement and nutritional therapy. Patients with scores ≥4 were defined as having moderate or severe malnutrition. Those with scores <4 were enrolled in the low PG-SGA group.CD-related disability was assessed based on the IBD-DI . The oriP < 0.05 indicated statistical significance. For normally distributed continuous data, the mean (standard deviation [SD]) was used as the measure of central location, whereas for continuous data with non-normal distribution, the median (interquartile range) was used. These characteristics were compared between the moderate to severe disability group and the no disability and minimal disability group by using Pearson's chi-square or Fisher's exact test to compare proportions. The odds ratio (OR) and its 95% confidence interval (CI) were calculated to determine the association of risk factors with moderate or severe disabilities. Statistically significant variables in the univariate analyses were then included in a multivariate regression model to identify the independent risk factors of moderate to severe disability by backward elimination analysis.The data were analyzed using SPSS version 22.0. P = 0.012), moderate to severe disability , PG-SGA≥4  compared to the remission phase. The active phase subjects were also more frequently disability and sarcopenia compared with patients with the remission phase.P < 0.05). The moderate to severe disability group had higher CDAI and PG-SGA scores, compared with the without to minimal disability group (P < 0.05). No significant differences in age, duration of disease, and hemoglobin levels were found between the moderate to severe disability group and the without to minimal disability group (P > 0.05). The prevalence of sarcopenia , PG-SGA≥4 , and high-level CRP  were higher in the moderate to severe disability group than in the without to minimal disability group.In CD patients, the variables that were significantly correlated with the IBD-DI were BMI, CDAI, PG-SGA, ASMI, handgrip strength, and CRP .In univariate regression models, disability was significantly associated with BMI , sex , CDAI , BMI , sarcopenia , and CRP  .By multivariate analysis, the BMI  and disease activity  were identified as the most significant factors predicting disability.In the past 20 years, CD has markedly increased and become a common disease of the digestive system in China . About 7We used the scale developed by Gower-Rousseau et al., which consisted of 14 items. The later Korean, Portuguese, and Prevost versions containing 14 items showed good reliability and validity. We determined the average IBD-DI score, which was 33.62 ± 9.63, similar results were observed in the Gower-Rousseau study. In the current study, 52.05% of the CD patients had a moderate to severe disability, whose results were similar to those reported by Marinelli et al.  and YoonP = 0.001). However, this was the first study to concurrently demonstrate that BMI was significantly associated with disability. A Portugal study reported that BMI was related to the quality of life in IBD patients; moreover, the effect of BMI on the psychological and physical quality of life was mediated via the mechanisms of body image . The patients with moderate to severe disability had lower BMI than those without or with minimal disability . Research has shown that sarcopenia is a progressive and generalized syndrome characterized by the loss of skeletal muscle mass and muscle strength with adverse outcomes, such as frailty, poor quality of life, and mortality . However, this finding was not supported by the multivariate analysis. Nonetheless, close attention to the clinical CRP score should be given attention.In the univariate analysis, moderate to severe disability was found in 2.25 times more female than male CD patients. This finding is consistent with the studies conducted among French  and SpanIn China, CD patients have poor access to IBD treatment centers and specialist doctors. Moreover, doctors focus more on disease treatment and remission than the quality of life and disability in CD patients . AlthougWe also identified several limitations. First, this study is a single-center cross-sectional study. This research sample size was small and the size of the cohort was only defined by the number of consecutive outpatients during the sample collection. Selection bias could not be excluded and not all Chinese CD patients could be represented, considering the sample; moreover, the correlation between patient disability and demographic and disease characteristics at a certain time node does not imply causality. Second, selection bias could not be avoided because not all patients who were surveyed were willing to participate. Third, a cross-sectional protocol provides limited evidence concerning changes over time, which would be better assessed by a future longitudinal study. Furthermore, multicenter, larger sample clinical observational research, longitudinal follow-up and intervention studies would be required to determine the reversal of disability for the successful management of disease activity and BMI.We demonstrated that disability is strongly related to disease activity and body mass in CD patients. In the management of the disease, not only the regular progression of the disease but also disability and BMI should be investigated during the regular treatment of clinical outpatients. In conclusion, close monitoring and follow-up should be conducted for patients with a high risk of disability, and effective measures should be adopted, which may be the best approach to preventing disability and helping patients return to normal life. This would also allow for a novel multidisciplinary approach based on collaborative efforts between gastroenterologists, nurses, nutritionists, and psychologists to improve the quality of life in general.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Ethics and Research Committee of Ruijin Hospital. The patients/participants provided their written informed consent to participate in this study.DB, JZ, and YS: conceptualization. DB, YG, YJ, ZH, and YT: investigation. DB, JZ, and YS: methodology. YS: funding acquisition. DB and YJ: data curation. DB: writing—original draft preparation. YG, ZH, JZ, and YS: writing—review and editing. YT, JZ, and YS: project administration. JZ and YS: supervision. QC and ZH: validation. All authors have read and agreed to the published 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.


Many clinical studies reported deficits in basic and complex cognitive functions in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the extent in which deficits in basic functions  contribute to complex cognitive impairments  in adults with ADHD is not well-studied. So far, literature show only one study, revealing that basic functions explain 27–74% of executive dysfunctions. Yet, the authors reported that findings could be affected by the selection of neuropsychological tests. The goal of the present research is to replicate such a finding using a different sample and a different set of neuropsychological tests.Forty-eight adult patients with ADHD were compared with 48 healthy controls in basic cognitive functions, namely processing speed and distractibility and more complex cognitive functions, namely selective attention, cognitive flexibility, planning, working memory, verbal fluency, and verbal memory. Basic and complex cognitive functions were assessed using the Vigilance and Sustained Attention, Selective Attention, N-Back, Tower of London, Trail Making Test, Word Fluency, and Verbal Learning and Memory.Logistic regression analyses showed that impairments in complex cognitive functions explained 25% of the variance in ADHD diagnosis. The explained variance dropped from 25% to 9% after considering basic functions of processing speed and distractibility. This 64% reduction highlights the importance of basic functions for impairments in complex functions in patients with ADHD. Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder that negatively affects several life domains. Individuals with ADHD have a higher risk to experience academic and occupational difficulties, and problems in their interpersonal relationships relative to their peers –3. The mBesides the behavioral symptoms of ADHD, studies have reported impairments in basic cognitive processes such as slow processing speed, distractibility, and increased reaction time variability –9. ProceImpairments in complex cognitive functions such as executive functioning and memory have also been reported in ADHD –20, for Basic cognitive processes can be seen as a foundation of complex cognitive processes . For exaThe above-mentioned questions have been partly addressed in children with ADHD. Metin et al.  and SaluIn adolescents and adults with ADHD the topic received less attention, despite the overwhelming evidence documenting basic impairments in processing speed and distractibility ,15,31–33In a recent study, Butzbach et al.  have dirIn response, using a different adult sample and a different test selection, the present study aims to replicate Butzbach and colleagues work in adults with ADHD , followiThe contribution of the present study to the literature can be explained as it follows: Butzbach et al.  reportedthe extent to which basic functions  and complex cognitive functions  are impaired in adults with ADHD, compared to healthy controls.the extent to which impairments in complex cognitive functions contribute to variance in adult ADHD diagnosis when impairments in basic cognitive functions are considered.Briefly, the present study aims to examine the following:Based on the abovementioned literature, see for example ,14,21, aFifty-four adults diagnosed with ADHD were recruited from the SRH hospital, Karlsbad-Langensteinbach, Germany. Each individual in this patient group underwent extensive diagnostic assessment that included a clinical interview based on the DSM-IV ADHD diagnostic criteria. ADHD symptoms, perceived cognitive impairments, and related functional impairments of the patient group were also assessed using the Conners’ Adult ADHD Rating Scales (CAARS) , the WeiThe control group was recruited through public advertisements. We initially considered 104 participants for the inclusion to the control group before we excluded individuals who report a diagnosis of psychiatric disorders. Next, 48 controls were selected case by case to match the patient group in age, IQ and educational years. A nonparametric comparison  revealed no significant differences between patients with ADHD and controls in age and educational years. However, patients with ADHD had a significantly lower level of educational attainment than controls. The CAARS, WFIRS, and FLei scales were used to measure ADHD symptoms and related functional impairments. The CII scale and the GET test were applied to determine noncredible symptom report and performance. In addition, five subtests from the Vienna Test System (VTS)  were useThe CAARS  was admiThe CII  was deveThe GET  was desiThe WFIRS ,38 was uThe Flei  was a seThe WAFV is a subtest of the VTS  and was Using factor analysis, the construct validity of the WAFV was checked with other tests, namely the Cognitrone , DiscrimThe WAFS  was anotThe construct validity of the WAFS was investigated , resultsThe 2-back VTS subtest was used to measure working memory . During Although the construct validity of the n-back test has been questioned as it showed no or weak correlations with other working memory tests  and dividing it by the working time of the Trial A in order to control for the processing speed. Accordingly, higher scores indicated lower performance.A number of studies showed that the TMT test, in particular Trial B, had good convergent and discrimination validity to measure cognitive flexibility ,56. UsinThe RWT  is a star = .81). Scores on a different version of the test (words starting with the letter ‘P’) were adequately correlated with scores on the test (r = .671) [The RWT was proven to distinguish between healthy individuals and patients with psychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, and patients with brain injury ,57. Test = .671) .In the VLMT , the exaThe test offers four scores: (1) the immediate recall after hearing the list once, (2) sum of correctly recalled words from the first five trials , (3) number of correctly recalled words from list A after a 20–30 minutes delay , and (4) the number of correctly recognized words from list A at the end of the test . Only delayed recall scores are analyzed as they reflect memory capacity and minimize the effect of learning . Scores An early version of the VLMT  was ableThe study was approved by the ethical committee of the medical faculty of the university of Heidelberg, Germany, as it meets the Helsinki Declaration standards. Participants performed the neuropsychological tests individually. In the beginning of each session, the examiner explained the goal and the structure of the testing  to the participants. Next, participants were asked to sign the informed consent forms if they agreed with the procedures. Thereafter, participants reported their demographic information and completed the MWT-B (IQ) test, followed by performing the neuropsychological tests. To avoid introducing fatigue or order effects, the order of neuropsychological tests was altered and counterbalanced across participants. Participants were allowed to take short breaks as needed. After completing the neuropsychological tests, participants filled out self-reported scales, namely the CAARS, WFIRS, and FLei. The GET test was administered either before or after the other neuropsychological tests.Participants were debriefed at the end of the assessment. The testing duration for each participant was approximately 2–3 hours.Basic cognitive functions can be defined as simple fundamental cognitive processes such as distractibility and processing speed, which may be prerequisites for task performance. Complex cognitive functions refer to a higher level of cognitive processes such as planning and working memory, which rely on the combination and interaction of more basic functions . Based oThe basic functions assessed in the present study were processing speed and distractibility: processing speed was measured by mean reaction times on the WAFV. Distractibility was measured by both the mean dispersion of reaction time  and number of omission errors in the WAFV. The complex cognitive functions assessed were selective attention, cognitive flexibility, planning, working memory, verbal fluency, and verbal memory, which were measured respectively by number of commission errors on the WAFS, time of Trial B/time of Trial A on the TMT, number of correct responses on the TOL, number of correct responses on the 2-back, number of correctly generated words within two minutes in the RWT, and number of correctly recalled words in the delayed recall phase of the VLMT.Scores on the TOL, RWT, N-back, and VLMT tests were inverted by multiplying them by (-1). This inversion aims to unify the interpretation of scores from different tests used in the present study: the higher score is, the greater impairment in the measured cognitive ability.p ≤.006); while no indication of a deviation from the normal distribution was found for mean reaction times on the WAFV and scores on the RWT (p ≥.084). Thus, other assumptions for parametric testing such as homogeneity of variance were not checked further. Because the data violated the normality assumption of t-tests, Mann-Whitney tests were performed to test differences between patients and healthy controls in basic and more complex cognitive processes. Due to multiple comparisons and possible inflation of alpha error, the acceptable p-value was set to.005 instead of.05, following the Bonferroni correction. In addition, effect sizes for non-parametric Mann-Whitney tests were calculated using the following formula: (r = z/square root of N) where N represents the total number of cases  and Rosenthal (1991)). Interpretations of effect sizes were based on Cohen’s criteria [SPSS software (version 26) was used to run all statistical tests in the study. The data was checked for normality. The Shapiro-Wilk tests showed that data deviated from the normal distribution for the TMT, N-back, TOL, VLMT, WAFS, omission errors and standard deviations on the WAFV tests .X2 (df) = 5.71 (8), p = .679) and the Omnibus test (X2 (df) = 19.23 (6), p = .004). The Hosmer and Lemeshow test is a goodness of fit test, which describes how well data fits the statistical regression model. Specifically, it calculates whether the observed values do not match the expected values from the model, suggesting poor predictions and lack of fit. Here, low p-values indicate that the model should be rejected. The omnibus test indicates whether the new model describes group membership better than pure chance. Put differently, the test indicates whether the inclusion of a block of variables is significantly better than a model with only the intercept.To investigate the contribution of complex cognitive functions to variance in ADHD diagnosis, a logistic regression was performed. The dependent variable was a binary group variable (the control group versus the patient group). The independent variables were all test variables of complex cognitive functions. These independent variables were implemented in one model (step) to test whether the probability of group membership  can be predicted from scores on the abovementioned set of neuropsychological tests. The data fulfilled the assumptions of logistic regression as evident by the Hosmer & Lemeshow test (X2 (df) = 14.05 (8), p = .080 for the first model and X2 (df) = 4.99 (8), p = .758 for the second model) and the Omnibus test (X2 (df) = 20.22 (3), p = .000 for the first model and X2 (df) = 28.10 (9), p = .001 for the second model).To test the contribution of impairments in complex cognitive functions to variance in adult ADHD diagnosis after considering impairments in basic cognitive functions, a hierarchical logistic regression was performed. In the first model, measures of basic cognitive processes were entered as predictors. In the second model, measures of complex cognitive processes were entered as predictors. The dependent variable was a binary group variable (the control group versus the patient group). The data fulfilled the assumptions of logistic regression as confirmed by the Hosmer & Lemeshow test . Adding complex cognitive functions to this model increased the explained group differences by 9% (Nagelkerke R2 of model 2 (.358) minus Nagelkerke R2 of model 1 (.27) = .09). Without controlling for basic cognitive functions, complex cognitive functions explained about 25% of the group differences /.25): Subtracting the increase in R2(.09) when adding complex functions from R2(.25) of the model that includes only complex functions and divide the outcome value by R2of the model that includes only complex functions) of complex cognitive functions when explaining differences between patients with ADHD and healthy controls.Taken altogether, the contribution of complex functions dropped from.25 to.09 after controlling for basic functions. Consequently, basic functions may account for approximately 64% (r = -.35) and increased level of distractibility , effect sizes were medium. However, the groups did not differ in reaction time variability. Patients with ADHD also showed impairments in selective attention , and memory functions , but not in planning, working memory, cognitive flexibility and verbal fluency. Previous studies revealed inconsistent results regarding group differences between adults with ADHD and controls in various executive functions. For example, some studies reported deficits in patients with ADHD in planning [In line with ADHD literature –9,25, replanning ,62, cognplanning ,64, and planning –67, whilplanning –71. Cognplanning ,54. A stplanning  showed tRemarkably, our study found similar reaction time variability between the groups, which seems odd, as most of the previous studies suggest reaction time variability as a promising endophenotype for ADHD ,72. KoflThe present study also showed that the contribution of complex functions to variance in ADHD diagnosis when basic functions are not considered was 25%. This contribution dropped to 9% when basic functions are considered. This 64% reduction in variance in ADHD explained by complex processes when basic processes are already considered demonstrates the importance of basic processes for complex functions. This main finding replicates the study of Butzbach and colleagues ,27,30. TThe present study emphasizes the role of basic processes on more complex cognitive functions in adult ADHD. The study is also in line with findings from other studies using different approaches such as applying a diffusion model in a reaction time task in children with ADHD. The diffusion model was used to differentiate between decisional (complex functions) and non-decisional time (basic functions) by analyzing the distribution of reaction time for both correct and incorrect responses as well as response accuracy ,27. ThisOur study may contribute to an ongoing discussion on the conceptualization of ADHD and whether the disorder is more related to bottom-up, top-down cognitive deficiencies, or their interplay. Several studies discussed that bottom-up processing speed  and distThe significant group differences in the educational attainment could have influenced the outcomes. In the German educational system, educational levels are not truly hierarchical in nature. One might speculate that larger group differences in simple and complex cognitive functions become evident in a sample of adults with ADHD that have lower educational attainments compared to healthy controls. Having said that, our tested groups showed similar IQs, suggesting that educational attainment may have had only a limited influence. The educational level was not included in hierarchical regression model because adding the educational level as a nominal variable in the model leads to difficulties to interpret the outcomes.Given the relevance of processing speed and distractibility, it may worthwhile for future studies to explore whether deficiencies in these functions occur during early perceptual processing or during the execution of motor response. It must be noted that a substantial number of patients with ADHD were diagnosed with one or more comorbid disorders, which may confound the conclusions drawn from this study. However, it can be argued that having comorbid disorders is typical for the nature of ADHD and can be attributed to the heterogeneity of this population –78.The present study replicated the findings of Butzbach and colleagues , confirm