Background: Sarcopenia is defined by the loss of muscle mass and function with a considerable prevalence which increases morbidity and mortality. We aimed to develop and validate a simple tool for screening of sarcopenia in Iranian older population.Methods: In this study, we included 2,211 adults aged 60 years or older that participated in the stage II of Bushehr Elderly Health (BEH) program, a population-based prospective cohort study. We defined sarcopenia as reduced skeletal muscle strength plus low muscle mass. The study sample was divided into two parts; development set which were allocated to the development of the model  and validation set (n = 712) were allocated to validation of the model.Results: There were 22.9% of men and 23.2% women classified as having sarcopenia based on EWGSOP-2.After selection of variables, the final models named SarSA-Mod (Sarcopenia Scoring Assessment Models) were developed with area to under curves (AUC) of 0.82 (0.79–0.86) and 0.87 (0.84–0.90) in men and women, respectively. The final model included “age,” “weight,” and “calf circumference” in both sexes. The sensitivity and specificity and positive and negative predictive values for sarcopenia were 84.3, 76.0, 49.8, and 94.5% for women, 85.4, 64.8, 40.2, and 94.2% for men, respectively. The model performance was tested in the validation set with accuracy 91 and 84% among women and men, respectively.Conclusions: Sarcopenia could be detected using SarSA-Mod, as a simple screening test with high accuracy among both sexes. Also, this screening test is valid, feasible, reliable and cost-effective compared to other tools. Sarcopenia is a geriatric disease, characterized by loss of skeletal muscle mass and muscle function, leading to adverse effects such as physical disability, poor quality of life and increased mortality , 2. The Moreover, individuals with sarcopenia are not aware of the disease in the earlier stage but gradually, critical events in physical and functional disability occur . TherefoEuropean Working Group on Sarcopenia in Older People (EWGSOP) and Asian Working Group for Sarcopenia (AWGS) commonly recommended the use of diagnostic algorithms for sarcopenia and also, they recommended to use of dual-energy X-ray absorptiometry (DXA) and/or bioelectrical impedance analysis (BIA)  for diagOther screening tools were recently developed to identify older adults at higher risk for sarcopenia. The SARC-F questionnaire is a simple and easy for screening of sarcopenia in older adults . HoweverAlthough, there are various screening tools for sarcopenia, there is no consensus on the best tool for all older people in the world and most of these methods have not tested with other ethnic populations. Therefore, in the present study, the aim was to develop a simple, cost-effective, non-invasive model of parameters to identify sarcopenia in order to facilitate sarcopenia screening in clinical setting of Iranian older population. Finally, the accuracy and diagnostic value of this model compared with other screening tools in a community-dwelling older adult population.The methodology of Bushehr Elderly Health (BEH) program has been previously described elsewhere . In summ2 (kg/m2).Body composition was measured using dual x-ray absorptiometry . Appendicular skeletal muscle mass (ASM) for each participant was derived as the sum of upper and lower limb muscle mass and the skeletal muscle mass index (SMI) as ASM/height0 and the hand in a neutral position. The measurement was carried out three times for each hand and maximum grip strength was calculated by taking the highest measurement from both hands (2). Waist circumference (WC) was measured at a point midway between the iliac crest and the lowest rib in standing position and hip circumference was measured at the most part of the hip, using a flexible tape,. Upper arm circumference was measured at the midpoint between the olecranon process and the acromion of right arm, as well as, forearm circumference was measured from the widest level with the arm hanging freely at the side. Mid-thigh circumference was measured at a midpoint between trochanterion  and tibialelaterale (top of the tibia bone) of right thigh. Calf circumference was measured at the widest level while the participant was standing upright. All measurements were read to the nearest 0.1 cm.Muscle strength was measured by handgrip strength, using a digital dynamometer. The participant seated, elbow at side and 90th hands . Usual wth hands , 19. HeiBlood pressure (BP) was measured twice in a seated position after 15 min rest using a standard mercury sphygmomanometer. The average of the two measurements was considered as the participant's blood pressure.Sarcopenia was defined as low muscle strength plus reduced skeletal muscle mass based on the criteria set by EWGSOP-2 . In a reThe SARC-F questionnaire and SARC-F with calf circumference were used to compare the new tool obtained from the current study. Strength, ambulation, rising from a chair, stair climbing and history of falling are five domains that are assessed. A score of four or more indicates a risk of sarcopenia . AnotherIn the current study, we developed a statistical model for screening sarcopenia. Proposed model: “Sarcopenia Scoring Assessment Model (SarSA-Mod)” is based on a prediction equation for screening sarcopenia regarding factors effect on this disease in our study population. SarSA-Mod has been built of three variables including age, weight and calf circumference in both genders.Details on the methods of developing and validation of SarSA-Mod are explained in the statistical section.t-tests on the whole dataset.Differences in between-group characteristics were examined by student's n = 1,499), called “development set,” which were allocated to the development of the model as in true validation, and 33%; one third of the dataset (n = 712), named “validation set” were allocated to validation of the model. This method is a cross validation as named the holdout model. After dividing the dataset into two sets as earlier mentioned, analysis for developing the model in the development set begun and all analysis were stratified by sex.To develop a statistical screening model to identify patients with sarcopenia, “True validation” or “holdout validation” method was used . Using rCandidate variables including age, waist circumference, hip circumference, thigh, upper arm circumference, calf circumference and also weight and BMI were selected based on previous studies, cost-effectiveness, feasibility and availability of variables to be measured, and the results of bivariate analysis.Chi-square test was used to estimate the effect of each variable with the outcome (sarcopenia) as the dependent variable.Logistic regression analysis was applied in the development of the final model. To choose the best model, we considered the goodness of fit of the models in both genders.After selecting final model, ß coefficient of each variable was used to calculate its index weight. To discriminate the effect of each variable, the values were rounded to the nearest integer and multiplied by 10, and the final values were used to develop a suitable scoring model.The ability of the model to separate those with sarcopenia from those without sarcopenia was evaluated using receiver operating characteristic (ROC) curves and the area under the ROC curve. A suitable cut-off point was selected the maximum value of Youden's index with regards to sensitivity and specificity for the model SarSA-Mod , 24.Then, sensitivity, specificity, positive and negative predictive values (PPV & NPV) and the accuracy of the scores were evaluated using the “validation set,” which was left aside so far and not engaged in the model development process. In order to select and validate the final criteria for our scoring model, the model was applied to the validation set, using ROC analyses.P-value < 0.05 was defined as being statistically significant.All analysis was performed using SPSS  and STATA . P < 0.001). There were no differences in DBP in men and SBP in both sexes irrespective of the presence of sarcopenia.There were 22.9% of men and 23.2% women classified as having sarcopenia based on EWGSOP-2. The characteristics of the participants by sex and sarcopenia status are shown in The ROC (receiver operating characteristic) curves analyses were performed on the final scoring models for both genders. The full models had values of area under curve (AUC) as 0.82 (95%CI: 0.79–0.86) for men and 0.87 (95% CI: 0.84–0.90) for women. Based on the ROC curves analyses, cut-off points of −19.07 and −14.19 were selected for men and women, respectively; as appropriate for the models.The score of −19.07 correctly classified 69.4% of men with sarcopenia with a sensitivity of 85.4% and a specificity of 64.8% and also, among women the score of −14.19 correctly classified 77.8% of women with a sensitivity of 84.3% and specificity of 76.0%.Next, the models were internally validated using the validation set. The performance of the models did not differ significantly in the development and validation datasets. In the validation sample, the model for men had a sensitivity of 87.6% and specificity of 62.8%, and correctly classified 69.2% of cases; and the model for women had sensitivity of 89.1% and specificity of 77.7%, and correctly classified 80.7% of patients .P < 0.001).The AUC of SarSA-Mod, SARC-F, SARCF-Calf (31 cm) and SARCF-Calf (33/34 cm) in both sexes of total population are given in Also we compared our models with calf circumference alone. The AUCs of calf circumference were 0.20, 0.15, and 0.25 for total population, women and men, respectively .In the present study, the sarcopenia screening models for men and women were developed and validated in an Iranian population. Multivariate models were created based on selected variables and good discrimination ability of the models was found with the AUC of 0.82 and 0.87 for men and women, respectively. Based on the ROC curves analyses, the cut-off points of −19.07 and −14.19 were selected for men and women, respectively, and these scores could correctly classify sarcopenic patients with excellent discriminatory power.To develop SarSA-Mod, important variables associated with sarcopenia or low muscle mass clinically or statistically significant, were examined. Of these factors, the best variables were selected as potential independent parameters of the models in both genders. First, a baseline model was identified according to age and weight which were important factors to develop the model in the previous studies , 26. TheAmong the anthropometric factors, measurement of calf circumference was simple and feasible and remained in our multivariate models in both genders. Studies have reported that calf circumference was highly correlated with muscle mass in both genders , 28. AlsTherefore, SarSA-Mods were developed based on simple variables including age, weight, and calf circumference to the final model in both sexes. It seems that SarSA-Mods can be easily used in a primary care setting for a screening of sarcopenia in the general population.In the present study, a scoring system was developed for screening sarcopenia using an index weight of each variable from linear regression analyses. However, several studies attempted for estimation of muscle mass by a variety of variables especially anthropometric parameters –32, but The most common screening tool for sarcopenia is a five-domain questionnaire, called SARC-F . This toSome studies exist that have developed the models incorporating the use of the anthropometric equation for muscle mass , 31. AltP < 0.001). Additionally, SarSA-Mod showed higher sensitivity and NPV than the SARC-F and SARCF-Calf in both genders and total subjects. Therefore, SarSA-Mod as a simple, non-invasive, and feasible tool, with high sensitivity and accuracy is better than SARC-F and SARCF-Calf for the detection of sarcopenia.The discriminative performance of SarSA-Mod was significantly superior to that of SARC-F (AUC = 0.86 and 0.57, respectively, The present results have to be interpreted within the context of strengths and potential limitations. First, the studied population was sampled from an urban population; as a result, the study's findings might not be generalizable to the rural population. Second, our models were developed in a cross-sectional cohort and similarly validated in a study set on the same population. There is a need for establishing the external validity of the models in other study populations.To the best of our knowledge, the current study is the first to develop and validate a sarcopenia screening model for Middle-East older people. Since SarSA-Mod is easy to calculate with simple variables, it is a useful screening model for sarcopenia in a primary care setting. The scores of SarSA-Mod can be used as an effective screening tool and help in identifying people with sarcopenia for interventions to prevent further adverse events.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Research Ethics Committee of Bushehr University of Medical Sciences. The patients/participants provided their written informed consent to participate in this study.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


There was a significant increase in the proportion of subjects with a protein intake level below the estimated averaged requirement (EAR) and a reduction in the proportion of subjects consuming protein above the recommended nutrient intake (RNI) across all population subgroups. Cereals ranked as the major sources of dietary protein, although their contribution to dietary protein gradually decreased as time went on. The contribution from meat steadily rose from 18.2% in 1991 to 28.7% in 2018. The proportion of energy gained from fat increased notably, reaching 34.2% in 2018. The elderly Chinese population experienced a significant reduction in dietary protein intake. Although the transformation of dietary patterns had positive effects on improving protein quality due to increases in animal source food, some elderly Chinese individuals currently face the risk of inadequate dietary protein intake.Unique rapid urbanization-related changes in China may affect the dietary protein intake of the aging population. We aimed to evaluate trends in dietary protein intake and major food sources of protein and estimate conformity to the dietary reference intakes (DRIs) in the elderly Chinese population. A sample of 10,854 elderly adults aged 60 years or older, drawn from 10 waves of the China Health and Nutrition Survey (CHNS) between 1991 and 2018, was included. Protein intake data were obtained on the basis of 3-day, 24 h dietary recalls. The dietary protein intake among elderly Chinese individuals declined from 63.3 g/day to 57.8 g/day over the 28-year period, with a −0.032 ± 0.0001 g/day change per year ( With the coming aging of society, the rapid growth of the elderly adult population has become a global issue. By 2030, one in six persons in the world will be 60 years of age or older . China iAn adequate intake of dietary protein in the aging population has been proposed as a potentially important modifiable factor not only for the maintenance of one’s body mass, muscle strength, energy balance, and physical performance, but also for counteracting inflammation, oxidation, and their downstream catabolic effects, thereby lowering the prevalence of age-related diseases ,6,7,8,9.Besides quantity, the quality of the consumed protein is also essential for promoting muscle health. Researchers considered animal-based protein an excellent source of high-quality protein, as it contains a large quantity of essential amino acids (EAAs) . FollowiWe utilized the data from the CHNS, a longitudinal household-based study of the Chinese population. A multistage, stratified sampling design was used to ensure that the CHNS provided a fair representation of both urban and rural areas and minimized the selection bias. The CHNS aimed to capture the economic, sociological, and demographic transformations that occurred in China and to reveal the effects on the health and nutritional status of the Chinese population. Health workers were trained and certified to collect the data. Additional details regarding CHNS data have been reported in detail elsewhere .Ten waves of the CHNS were included in this study, which were conducted in 1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, and 2018. We excluded disabled persons and those with missing data for diet, age, and gender. Finally, a total of 10,854 participants aged 60 and above with complete data collection were included in the analysis. The survey protocols, instruments, and processes used to obtain informed consent for this study were approved by the institutional review committees of the University of North Carolina at Chapel Hill, as well as by the National Institute for Nutrition and Health, which is affiliated with the Chinese Center for Disease Control and Prevention (201524). All participants provided informed written consent.Detailed dietary intake information on three meals and snacks for each individual was obtained through face-to-face interviews on three consecutive 24 h dietary recalls, including two weekdays and one weekend day . The traAccording to the China Food Composition Table, we computed the dietary protein intake (g), fat intake (g), and carbohydrate intake (g) from each food the participants consumed during the survey period. The total energy intake was estimated as the sum of energy from proteins, fats, and carbohydrates. The percentage of energy obtained from each nutrient was calculated as the proportion of energy from the nutrient of the overall energy intake. For example, for total protein, the percentage of energy = /total energy intake  × 100 .Based on the Chinese DRIs, we used the EAR and the RNI cut-off points to estimate the dietary protein intake levels. The EAR for protein intake is 60 g/day for males and 50 g/day for females (0.9 g/kg/day). The RNI for protein intake is 65 g/day for male and 55 g/day for females (1.0 g/kg/day). Food items contributing to dietary protein intake were grouped according to the China Food Composition Table. We listed the top five food groups, including cereals , meat , legumes (dried legumes and legume products), vegetables and fruits, and milk and eggs. Other groups were not included since they only share a contribution of less than 3%, respectively.Questionnaires were used to collect individuals’ information, including age, gender, education level, income level, and residential area. We grouped participants into two gender groups , two age groups (60–69 years and 70 years and above), two education levels (primary/illiterate and middle school and above), three income levels , and four residential areas .p < 0.05.We expressed continuous variables as medians (interquartile range), and categorical variables as numbers (percentages). Chi-square tests were used to compare differences among categorical variables. Trends in dietary protein intake were assessed by multivariable linear regression, treating the survey year as a continuous variable. Trends in conformity with protein-specific DRIs were tested using multivariable logistic regression models, including the survey year as a continuous variable. Per-year change was also calculated. Interactions between these variables and the survey year were examined by adding the product term of the time and variable of stratification into the multivariable linear regression model or the multivariable logistic regression model. The data were adjusted for all covariates, such as age, gender, education level, income level, and residence area. All data analyses were performed by SAS 9.4 , and statistical significance was set at a two-tailed p < 0.05). There were significant declines in dietary protein intake across all population subgroups . Older people who were aged 60–69 years showed a stronger decrease than those who were aged above 70 years. Having a higher education level and having a higher income decreased dietary protein intake more quickly compared to their respective counterparts. Additionally, participants living in cities showed a stronger decrease than participants living in villages.As shown in p < 0.05 for the trend for all). Both the largest increase in the prevalence of protein intake below the EAR and the largest decrease in the prevalence of protein intake above the RNI were observed in participants living in villages. A higher prevalence of protein intake below the EAR and a lower prevalence of protein intake above the RNI were observed in participants aged above 70 years, in participants with only a primary/illiterate education level, and in those living in villages, compared to their counterparts.From 1991 to 2018, we observed a significant reduction in daily protein intakes in all categories of elderly adults in China. As a consequence, there was a significant increase in the proportion of subjects with a protein intake below the EAR and a decline for those with an intake above the RNI across all population subgroups. There are some elderly Chinese individuals currently facing the risk of inadequate dietary protein intake. The quality of dietary protein among elderly Chinese individuals improved as the percentage of the contribution from animal-based protein gradually increased.China, with its significant elderly population, is one of the countries facing the most serious population aging-related challenges. Adequate protein intake is suggested for improving the physical performance and well-being of older adults. However, there is a decreasing trend in dietary protein intake among elderly Chinese people. The median protein intake among males (62.8 g/day) was already lower than the RNI (65 g/day) in 2018. Similarly, females with a 53.9 g/day intake were below the RNI (55 g/day). Hence, almost half of the elderly Chinese population did not meet the individual protein intake requirement, which may result in serious adverse consequences for healthy aging. Furthermore, epidemiological studies have suggested that current dietary protein intake recommendations may be insufficient for maintaining muscle mass and strength for the elderly and for improving their health . The reqBesides quantity, the quality of the consumed protein plays a critical role in the well-being of elderly adults . The curAlthough the elevated intake of animal protein improves the quality of dietary protein, it is also associated with a risk of obesity, osteoporosis, high blood pressure, and other chronic diseases due to the high levels of saturated fatty acids and cholesterol in meats . In the This transition in the source of dietary protein can be explained by the dietary Westernization in China. The traditional Chinese diet includes large amounts of cereals and vegetables and only small amounts of animal source foods. The Chinese modernization that occurred over the past 30 years has developed dramatically. The China National Nutrition Survey indicated that the population’s food consumption patterns have changed dramatically and experienced a shift from traditional dietary patterns to Western dietary patterns. Between 1991 and 2011, the consumption of animal source foods increased; over the same time period, the consumption of coarse grains, legumes, vegetables, and fruits remained low from 1982 to 2012 . The curThe strengths of the study included using the most recent dietary data from the CHNS, investigating the trends of dietary protein intake levels and food sources over the past 28 years among the elderly Chinese population, and examining recent conformity with protein-specific DRIs. There were some limitations in our study. First, the method of using three consecutive days of 24 h dietary recalls posed the risk of underestimation of the dietary intakes for episodically consumed foods. Second, recall bias from self-reported measurements may exist. Third, we did not examine the use of protein supplements because supplement use was reported by only 1.75% of elderly Chinese individuals aged above 60 years. In addition, there is limited information available on the use of supplements in the CHNS.This study provided important insights into the protein intake status transition among elderly Chinese individuals over a 28-year period. Elderly Chinese individuals experienced a significant decrease in their dietary protein intake and had a high prevalence of protein intake below the EAR (0.9 g/kg/day) and the RNI (1.0 g/kg/day). The transformation of their dietary patterns had positive effects on improving dietary protein quality, but it may also result in the development and exacerbation of adverse health conditions due to increases in animal source food consumption. Targeted interventions and education may be necessary to encourage the elderly Chinese population to meet the minimum protein intake recommendations by increasing legume consumption or using protein supplementation.


The aim was to compare the cognitive ability of people with RA with healthy controls (HCs).People with RA were recruited from the Norfolk Arthritis Register (NOAR), a population-based cohort study of people with inflammatory arthritis. Data on aged-matched HCs (people with no cognitive impairment) came from the comparison arm of The Dementia Research and Care Clinic Study (TRACC). People with RA and HCs performed a range of cognitive ability tasks to assess attention, memory, verbal fluency, language, visuospatial skills, emotional recognition, executive function and theory of mind. A score of <88 on the Addenbrooke’s Cognitive Examination III was considered cognitive impairment. Scores were compared using linear regression adjusting for age, sex, smoking status, education, BMI, anxiety and depression.Thirty-eight people with RA  were matched with 28 HCs . Twenty-three (60.5%) people with RA were considered to have mild cognitive impairment . People with RA had impairments in memory, verbal fluency, visuospatial functioning, executive function and emotional recognition in faces compared with HCs, after adjustment for confounders.People with RA had cognitive impairments in a range of domains. People with RA might benefit from cognitive impairment screening to allow for early administration of appropriate interventions. In this study, 60.5% of the people with RA had cognitive impairment.People with RA had impairments in memory, verbal fluency, executive function and emotional recognition.People with RA may require cognitive impairment screening, given the negative consequence on daily life.RA is a chronic inflammatory condition that results in swollen joints, pain and functional disability. RA is associated with increased risk of other conditions, with some evidence suggesting an association between RA and increased risk of dementia , but eviA precursor to dementia is mild cognitive impairment (MCI), involving memory and cognitive difficulties that have not developed into a loss of independence. People with MCI suffer from reduced quality of life , reducedTherefore, the objectives of this study were to assess the value and feasibility of conducting a range of tests that assess different cognitive domains in people with RA, and to examine whether people with RA exhibit a specific pattern of cognitive impairment compared with healthy controls (HC), after taking into account important confounding factors.The Norfolk Arthritis Register (NOAR) is a prospective inception cohort of people with inflammatory arthritis , situated in Norfolk, UK . RecruitControl data came from The Dementia Research and Care Clinic Study (TRACC). TRACC is a transdiagnostic study aiming to recruit and follow longitudinally participants from Norfolk and the neighbouring county of Suffolk with a range of diagnoses  in addition to a cohort of HCs for comparison. Participants were eligible to take part in the HC sample of TRACC if they were: (i) aged between 50 and 75 years; (ii) scored >88 on the Addenbrooke’s Cognitive Examination III ; and (iii) were not diagnosed with dementia or a current mental health disorder. Furthermore, to be included as controls in the present study, participants had to have no diagnosis of RA and have completed the same cognitive assessments as the NOAR participants.Both NOAR and TRACC received ethical approval , and all participants provided written informed consent.People with RA and HCs underwent a series of cognitive assessments aiming to assess a range of different cognitive domains. For all scales, higher scores indicate better cognitive function.The Addenbrooke’s Cognitive Examination III (ACE-III): cognitive tests assessing five cognitive domains, namely attention, memory, verbal fluency, language and visuospatial skills . A totalInstitute of Cognitive Neurology Frontal Screening (IFS): measure of executive function .Mini Social Cognition and Emotion Assessment (mini-SEA): faux-pas understanding (theory of mind test) and facial emotional recognition .Rey Complex Figure Test (RCFT): assessment of visuospatial function, in which participants copy abstract images before later drawing from memory .The participants with RA also completed a feedback form regarding the acceptability of the cognitive tests.Age, sex, smoking status  and education level  were self-reported by all participants. Height and weight were measured by research staff at assessments, and BMI (in kilograms per square metre) was calculated. Anxiety and depression severity were assessed by the Generalized Anxiety Disorder-7 (GAD-7)  and the t-tests or χ2 tests, depending on the data. Differences in the cognitive assessment scores between the people with RA and controls were assessed using linear regression, controlling for age, sex, BMI, smoking status, education, anxiety and depression. Given that each cognitive assessment has a different scale, to aid comparability the cognitive assessments were also standardized, and the standardized scores were compared between groups using linear regression (controlling for the same covariates). These standardized mean differences (SMDs) represent the mean difference in standard deviations of the assessment between people with RA and controls. Mean and median substitution was used to impute missing data. Analyses were performed using Stata v.14 .HCs from TRACC were age matched with the NOAR participants. Demographics, cognitive assessments and feedback were summarized using descriptive statistics, stratified by RA/HC status. Differences in characteristics between people with RA and HCs were assessed using Student’s unpaired Three patient partners were involved in the design of the study and piloted the assessments to check the acceptability and feasibility for future participants.s.d.) 8.0] years, 25 (65.8%) women, mean symptom duration = 9.8 (S.D. 6.3) years]. These people with RA were matched with 28 HCs from TRACC. There were more women, people of higher BMI, people with lower education and smokers in the RA group compared with the controls. Furthermore, the people with RA had significantly higher anxiety and depression scores compared with the controls , executive function (IFS) and emotional recognition from faces (Mini-SEA) . In totaThis study demonstrates that performing cognitive test batteries is feasible for people with RA, and these particular assessments are acceptable to participants . Furthermore, there is a clear signature of reduced cognitive ability in this group compared with controls. In total, 60.5% of the people with RA scored below the ACE-III cut-off, indicating cognitive impairment. When investigating the individual dimensions, people with RA had impaired memory, verbal fluency, executive function and emotional recognition compared with HCs. This was independent of confounding factors such as age, anxiety, depression, education and body mass. People with RA had impaired visuospatial functioning compared with HCs as measured by the ACE-III, but not with the RCFT. This could be attributable to differences in difficulty of the tasks, whereby the ACE-III contains a free-recall element (clock drawing), whereas the RCFT involves copying  a pre-specified abstract design. Lastly, there were no differences between the groups in terms of attention and theory of mind.et al. [et al. [et al. [A systematic review of studies using the ACE reported a cut-point of <88 for cognitive impairment, indicating that a majority of people (60.5%) with RA in this cohort have some cognitive impairment . This is [et al. : 30%) bu [et al. : 72.4%), [et al. , 20. Thi [et al. . This fi [et al. , indicat [et al. , 23.Our findings suggest that targeted cognitive screening is potentially needed as part of routine practice to detect clinically relevant cognitive changes in RA and other inflammatory diseases. In a clinical setting, it is noteworthy that cognitive assessments could be delivered remotely, which might be an important component of the future management of people with rheumatic diseases. These findings also highlight the need for a more detailed understanding of the risk factors leading to cognitive impairment in this group, in order to guide strategies for prevention and treatment. This includes, for example, the contribution of exposure to anti-inflammatory drug treatments, lifestyle factors  and related conditions, including pain, anxiety and depression. Furthermore, future research should address the relative contributions of physical and cognitive factors to functional ability in RA , 24.Our study has a number of strengths. We have examined a large array of cognitive assessments. The study was nested in a population-based cohort, allowing the selection of representative cases of RA. However, our participants were volunteers, and it is possible that concern over their cognitive ability might have motivated them to take part. No additional clinical or laboratory testing was performed as part of this study to investigate changes in cognition further. Furthermore, the ACE cut-off for MCI defines cognitive impairment associated with increased risk of dementia, and people below this threshold might require further assessment and monitoring . Given tIn conclusion, this study shows that people with RA have lower cognitive ability across a range of domains compared with HCs. Given the large detrimental effect that cognitive impairment can have on function and quality of life and the feasibility and acceptability of performing cognitive assessments for people with RA, screening of cognitive ability might be warranted in this clinical group.


Gender was a significant covariate for both MVPA in PE  and MVPA in leisure time , with higher MVPA in boys than girls. This study filled a gap in the scientific literature by demonstrating the full motivational sequence resulting in actual MVPA in PE classes. It also demonstrated that the main goal of PE of enhancing PA not only in school but also outside of school is working. The main motivator is needs satisfaction based on PE teachers' support.Given the low levels of physical activity (PA) in adolescence, there are challenges to increasing students' PA outside of the school setting. Thus, researchers emphasize the supportive role that physical education (PE) teachers can play in PA motivation both in and out of school. The aim of the present study was to examine an expanded trans-contextual model (TCM) model for the transit of teachers' perceived support of students' autonomy in terms of contextual and situational motivation in PE to objectively measured moderate-to-vigorous physical activity (MVPA) in PE across different PE contents as well as to the motivational sequence for, and participation in, subjective MVPA during leisure time. This cross-sectional study involved 283 high school students, of whom 43.9% were boys. The autonomous support students received and other motivational factors and objective measures of MVPA in PE and subjective MVPA in leisure time were measured. The results indicate that support for autonomy was significantly and directly related to needs satisfaction (β = 0.61,  Physical education (PE) is meant to not only keep children physically active in school but also encourage them to be physically active outside of school . StudentGiven the low levels of PA in adolescents, the challenges to increasing their PA outside of school include lack of access to facilities, unsafe neighborhoods, and attractive sedentary alternatives. Hence, maximum active movement time in PE should be a public health priority . There iThe current study aimed to explain how PE motivational factors impact MVPA in PE as well as during high school students' leisure time via the trans-contextual model (TCM) of behavioral change. The primary focus of the TCM is to explain the motivational transition from the PE domain to the leisure time domain triggered by support for autonomy . The undThe TCM integrates two classical behavioral theories—self-determination theory  and theSome authors have stated that qualitative motivation determines quantitative motivation . For ins(1) Both TPB and SDT are based on cognitive, i.e., decision-making, processes. Both theories stress that behavior is a conscious decision  and not (2) The theoretical premises of SDT include the preposition that autonomous motivations become intentions regarding behavior via beliefs . TPB inc(3) TPB is focused on the quantitative aspect of motivation, i.e., the strength of the intention. However, a strong intention does not always turn into actual behavior . Hence, The aim of the present study was to use the expanded TCM model to explore the transit of perceived teacher support for student autonomy through contextual and situational motivation in PE to objectively measured MVPA in PE across different PE contents as well as to the motivational sequence in the leisure time domain and subjective leisure time MVPA. Thus, the current study attempted to gather information on what has been missed in other studies, namely, the motivational sequence and its transition to PE and leisure-time MVPA. No other study has provided such a full picture to date.Using the TCM to explain the transition of motivation from PE to the leisure domain has received empirical support across multiple studies , 32, 33.Several hypotheses were developed : (1) in Initially, 318 students were selected for the study. Due to illness or other reasons, 35 students  did not attended one or more PE classes. They were subsequently withdrawn from the study. In the end, this cross-sectional study included 283 high school students. Among them, 43.9 % were boys, and 56.1% were girls. The ages of the participants varied from 15 to 17 years old, with a mean M = 15.62 years, and a standard deviation SD = 0.67 years. Body mass indexes ranged from 14.48 to 29.63, with a mean M = 20.5, and standard deviation SD = 2.54.Support for autonomy in PE was evaluated using a modified version of the short form of the Sport Climate Questionnaire . The si2 = 525.99; df = 101; RMSE = 0.122; [95% CI= 0.112–0.132]; Comparative fit index (CFI) = 0.971; Tucker–Lewis index (TLI) = 0.965; standardized root mean square residual (SRMR) = 0.057).Needs satisfaction in PE was assessed in terms of autonomy, competence, and relatedness using 16 items within three respective subscales. The development of the subscales is described in detail elsewhere . Satisfa2 = 514.47; df = 143; RMSE = 0.096 [95% CI = 0.087–0.105]; CFI = 0.978; TLI = 0.974; SRMR = 0.053), confirming the structure of the original scales. The Cronbach α's of the scales ranged from 0.811 to 0.932.Autonomous motivation in PE was identified using a revised version of the Perceived Locus of Causality (PLOC) scale developed by Vlachopoulos et al. . This sc2 = 262.64; df = 86; RMSE = 0.042 [95% CI = 0.036–0.048]; CFI = 0.993; TLI = 0.986; SRMR = 0.014), confirming the structure of the original scales. The Cronbach α's of the scales ranged from 0.817 to 0.899.To assess the autonomous motivation for participating in physical activities during leisure time, the BREQ-2 questionnaire was used . This 19The intention to participate in PE class and leisure-time PA over a two-week period was assessed with three items designed for leisure-time PA by Chatzisarantis et al.  and threPhysical activity in PE was measured using an accelerometer (Tri-axis ActiTrainer Activity Monitor) validated in other study . In accoPA in leisure time was measured using the short form of the International Physical Activity Questionnaire . The quGender was used as the control variable in this study.The protocol for this study was approved by the Ethics Committee of the Lithuanian Sports University (No. SMTEK-13), and the study was conducted in accordance with the Declaration of Helsinki. Study participants and their parents provided informed consent before participation. The subjective and objective measures were obtained from two schools in the city of Kaunas. Twenty classes in total across two grades (9th and 10th) were used. Students completed the paper questionnaire in the classroom two weeks before the objective measurements were taken. The Researchers explained the aim of, and procedures to be used in, the study prior to the completion of the questionnaire, which took 20–25 min to complete. The objective measurements of MVPA were taken two weeks later than the subjective measurements and across three PE lessons  within the two-week period. Actigraphs were attached to belts by the researchers and worn on students' left hips. All PE classes in Lithuania last 45 min. PA was monitored from the first minute of PE class until class ended (“from bell to bell”). Students changed into their PE clothes prior to the start of each class. However, PE class time included receiving instructions from the PE teachers, during which time the students did not really move; nonetheless, we were still specifically interested in determining the percentage of time students spent in moderate-vigorous activity during their entire “from bell to bell” PE lesson. We followed the same practice for all three PE classes in all schools and for all students.2/df statistic was used as a goodness of fit index for CFA and the SEMs, i.e., the fit was acceptable if 2 < χ2/df < 3. In addition, the root mean square error of approximation (RMSEA), along with its 90% confidence interval (CI), was used. The RMSEA is a population-based fit index that is insensitive to the sample size. Moreover, the SRMR, which is a direct assessment of how well and a priori model reproduces the sample data, was employed. Values of RMSE and SRMR < 0.05 were considered to indicate a very good fit, and values < 0.08 were interpreted as indicating a good fit. Also, the comparative fit index (CFI) and Tucker–Lewis index (TLI), both incremental indices used to compare the fit of a hypothesized model with that of a baseline model , were used. Values of CFI and TLI >0.90 indicate a good model fit, and values >0.95 reflects a very good model fit  and MPLUS 8.4 software. The means (Ms), standard deviations (SDs), and frequencies of the variables used in the study were measured. Pearson's r was used in correlational analyses. CFA was used to confirm the questionnaire's structure. Structural equation models (SEMs) were used to identify direct and indirect relationships. The χodel fit . StatistThe correlational analysis presented in 2 = 40.00, df = 23; CFI = 0.97; TLI = 0.93; RMSEA = 0.055 [90% CI= 0.024–0.083]; SRMR = 0.038). The results of the path analysis for the second model involving final outcomes of latent MVPA in PE and MVPA in leisure time also showed an acceptable fit . Latent MVPA in PE was aggregated from the observed MVPAs in classes emphasizing games (β = 0.59), practice in motor skills (β = 0.43), and non-formal physical activities (β = 0.53). The needs satisfaction in each of the models was a latent variable aggregated from the need for autonomy (β = 0.72), competence (β = 0.67), and relatedness (β = 0.75).In the PE domain, direct relationships in the model were observed between support for autonomy and needs satisfaction, needs satisfaction and RAI in PE, RAI and intention in PE, intention in PE and MVPA in games and practicing motor skills but not non-traditional physical activities. Intention in PE also predicted latent MVPA in PE. Meanwhile, RAI in leisure was directly predicted by RAI in PE, revealing a trans-contextual relationship. Further, RAI in leisure time as well as intention in PE predicted intention in leisure, which, in turn, was related to MVPA in leisure, again confirming the trans-contextual effect.Indirectly, support for autonomy was related to intention in PE, with the path mediated by latent needs satisfaction and RAI in PE, and had a trans-contextual effect on intention in leisure that was mediated by needs satisfaction, RAI in PE, and RAI in leisure. Accordingly, support for autonomy was related to RAI in PE through needs satisfaction and to RAI in leisure through needs satisfaction and RAI in PE. However, support for autonomy was not indirectly related to MVPA in any of the PE classes. It was indirectly associated with MVPA in leisure along a path mediated by needs satisfaction, RAI in PE, RAI in leisure, and intention in leisure. As a covariate, gender was significant for all physical activity indicators, revealing the association of the female gender with lower MVPA in PE, regardless of content, and MVPA in leisure time.The purpose of the current study was to examine the direct and indirect relationships of motivational factors in the PE and leisure domains and the associations of those motivational factors with objectively measured MVPA in PE class and subjectively measured MVPA in leisure with an expanded TCM. More specifically, a search was made for paths facilitating the transit of the effect of support for autonomy in PE to MVPA in PE across different PE contents and leisure-time PA through contextual and situational motivation in PE and leisure time. Given that PE is the only organized way to encourage PA and that PE teachers are obliged to deliver PE in such a manner as to encourage PA not only in PE classes but in leisure time , 52, it The results showed that students engaged in MVPA for around 35% of the time spent in PE class, varying from 34.48% in non-traditional PA to 36.19% in classes involving games. A recent meta-analysis of studies along this vein indicated very similar results, showing that, on average, students engaged in MVPA during 33.0% of their PE classes . SpecifiGender was a significant covariate in our study, indicating higher MVPA in PE class and leisure time for boys compared to girls. Many studies have also revealed that girls were less physically active in PE classes than boys –58. One The current study supports multiple propositions as the result of the use of the expanded TCM. Specifically, higher perceived support for autonomy in PE was directly and positively related to needs satisfaction, which, in turn, was directly and positively related to autonomous motivation in PE. The findings of another recent study revealed that needs for autonomy, competence and relatedness satisfaction were positively related to autonomous motivation . MeanwhiThe relationships within the leisure time context were as expected. Autonomous motivation was positively related to intention, and intention was positively related to leisure-time MVPA. Similar results were obtained when attempting to predict objectively measured MVPA in leisure time, although a study of Estonian adolescents found that leisure-time MVPA was not related to MVPA in PE class . This fiThe direct trans-contextual links within TCM were confirmed, thus validating the third premise of the current study. Namely, autonomous motivation for PA in PE predicted autonomous motivation in leisure time. This finding is in line with Vallerand's  theory tThe addition of needs satisfaction in the current study as a mediator confirmed the fourth hypothesis of this study, as needs satisfaction, along with autonomous motivation, mediated the indirect relationship between support for autonomy and intention to participate and be physically active in PE classes. In accordance with SDT, teachers' support for students' autonomy in the classroom substantially add to students' needs satisfaction, thus enhancing their autonomous motivations and shifting the locus of causality from the external to the internal , 67. HowMoreover, needs satisfaction was an important mediator for the transferring support for autonomy in PE to the leisure-time PA context, namely, autonomous motivation and intention in leisure as well as leisure-time MVPA. While the latent variable needs satisfaction was used in the current study, other studies have found unique mediation effects for the needs for autonomy and competence but not for relatedness satisfaction for autonomous motivation in PE and a mediation effect for the need for competence satisfaction for autonomous motivation in leisure . Other sSumming up, the results of this study provide clear indications that needs satisfaction should be included in the TCM, as it is an important predictor of autonomous motivation for PA in PE and leisure time as well as a significant mediator in transmitting the effect of perceived teachers' support for autonomy to other motivational factors in PE and even transferring it to the leisure-time domain. This study also confirmed that psychosocial factors are crucial for behavior. This fact should be considered not only by PE teachers engaged in PE practice but also by PE teacher educators. PE study programs should prepare future teachers to respond to students' needs and enhance their motivation by supporting needs satisfaction.First, among the strengths, objective measurements of MVPA in PE classes were taken. No other study, to the best of our knowledge, has measured PA in PE classes using objective methods when testing TCM. Second, each student's MVPA was measured for three different PE classes, namely, games, practicing motor skills, and non-traditional physical activities, covered the compulsory PE curriculum in Lithuania. Among the limitations, the main one is that leisure-time MVPA was identified via students' subjective evaluations. However, using these measurements should not have compromised the results of the model, given that subjectively measured MVPA correlates with objectively measured MVPA . The twoExtending the TCM with needs satisfaction produced two outcomes—objectively measured MVPA in PE and subjectively measured MVPA in leisure time—that met the main theoretical assumptions of the motivational sequence. Namely, perceived PE teacher support for autonomy was directly and positively associated with student needs satisfaction. Needs satisfaction was positively related to autonomous motivation in PE; in turn, the latter was positively associated with intention to be physically active in PE. Intention in PE predicted MVPA in games and motor skills PE classes and the averaged MVPA across three types of PE classes but in non-traditional PE classes. Needs satisfaction mediated the relationship between perceived support for autonomy and autonomous motivation and, alongside with autonomous motivation, the relationship between support for autonomy and intention. The indirect effect of support for autonomy on MVPA in PE was not confirmed. In the leisure-time domain, autonomous motivation time was related to intention to engage in leisure-time PA, and intention was associated with MVPA in leisure time. Trans-contextual relationships between autonomous motivation in PE and the corresponding motivation in leisure time as well as between intention in PE and intention in leisure time were observed. Finally, the indirect effect of support for autonomy on f motivation and MVPA in leisure was captured when mediated through need satisfactions, autonomous motivation, and intention in the PE sequence. The study filled a gap in the scientific literature by demonstrating the full motivational sequence resulting in actual MVPA in PE classes. It also demonstrated that the main goal of PE to enhance PA not only in school but also outside is being fulfilled. The main result is that needs satisfaction must be obtained with PE teachers' support.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Lithuanian Sports University (No. SMTEK-13). The study was conducted in accordance with the Declaration of Helsinki. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.BM and AE: conception and design. VP and AE: data acquisition. BM and DN: data analysis and interpretation. BM, AE, and VP: drafting the manuscript. DN and AE: critical revision for intellectual content. BM and AE: Administrative, technical or material support. All authors read and approved the final 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.


Background: Electrodermal hyporeactivity has been proposed as a marker of suicidal risk. The EUDOR-A study investigated the prevalence of electrodermal hyporeactivity among patients with depression and its association with attempted and completed suicide.Methods: Between August 2014 and March 2016, 1,573 in- and outpatients with a primary diagnosis of depression (active or remission phase) were recruited at 15 European psychiatric centers. Each patient was followed-up for 1 year. Electrodermal activity was assessed at baseline with the ElectroDermal Orienting Reactivity Test. Data on the sociodemographic characteristics, clinical diagnoses, and treatment of the subjects were also collected. The severity of the depressive symptoms was assessed through the Montgomery–Asberg Depression Rating Scale. Information regarding number, time, and method of suicide attempts was gathered at baseline and at the end of the 1-year follow-up. The same data were collected in case of completed suicide.Results: Hyporeactive patients were shown to be significantly more at risk of suicide attempt compared to reactive patients, both at baseline and follow-up. A sensitivity of 29.86% and a positive predictive value (PPV) of 46.77% were found for attempted suicide at baseline, while a sensitivity of 35.36% and a PPV of 8.92% were found for attempted suicide at follow-up. The sensitivity and PPV for completed suicide were 25.00 and 0.61%, respectively. However, when controlled for suicide attempt at baseline, the association between hyporeactivity and follow-up suicide attempt was no longer significant. The low number of completed suicides did not allow any analysis. Suicidal behavior is one of the most common and serious psychiatric emergencies , and suiElectrodermal activity (EDA) refers to electrical events in the skin caused by the activity of eccrine sweat glands in palmar skin . VariatiEDA is characterized by a tonic and phasic component. The tonic component represents the basic level of conductance, while the phasic component is related to the faster changing elements of the signal that can be associated with a stimulus or be “spontaneous” or “non-specific” , 8.The amplitude of the electrodermal response increases linearly with perceived arousal when subjects are exposed to emotional stimuli –12. ElecMany studies have focused on electrodermal hyporeactivity as a possible biomarker for depression –22, and Further studies indicated a correlation between electrodermal reactivity and the type and level of suicide risk. A meta-analysis based on 297 depressed patients and 59 healthy subjects concluded that electrodermal hyporeactivity is strongly associated with a high suicide risk. The authors reported a sensitivity of 96.6% and a negative predictive value (NPV) of 92.9% for suicide and a sensitivity of 83.3% and a NPV of 92.7% for suicide and/or violent attempt, thus indicating that a test of electrodermal hyporeactivity may have a high discriminative validity for vulnerability to suicide . AnotherOverall, the most recent review available about the EDA literature reported that, despite the features and quality of the studies included (quite outdated and employing a wide variety of designs), electrodermal hyporeactivity seemed to be a reliable feature of depression and a potentially useful marker of suicidal risk .The EUDOR-A study was aimed at assessing the effectiveness and the usefulness of the ElectroDermal Orienting Reactivity (EDOR) Test as a support in the suicide risk assessment of depressed patients and to assess the predictive value of electrodermal hyporeactivity, measured through the EDOR Test, for suicide and suicide attempt in adult patients with a primary diagnosis of depression . With thThe design of the EUDOR-A naturalistic, observational study has been thoroughly described elsewhere, including sample size calculation . The EUDPatients were recruited at 15 psychiatric clinics in nine different European countries. Recruitment took place from August 2014 to March 2016 (t0) . All in-A comprehensive clinical assessment was performed to collect information concerning the sociodemographic characteristics of the patients, diagnosis and treatment, and previous suicide attempts. Immediately after the assessment, the EDOR Test was performed. Each enrolled patient was then followed-up for 1 year (from August 2015 to March 2017) (t1).The final recruited sample included 1,573 in- and outpatients with a primary diagnosis of depression (active or remission phase).The CONSORT flow diagram, modified for a non-randomized trial, is shown in Electrodermal reactivity was assessed at baseline, t0, with the EDOR Test. The EDOR Test , 26 was Since previous research has reported that hyporeactivity is independent of time of day , the EDOOnce the test was finished, pseudoanonymized and encrypted data were sent over the Internet for remote analyses at Emotra AB. The experts who analyzed the test data were blinded to the clinical assessment of the patients. After the analyses, a test report was sent back to the predefined e-mail addresses of the authorized staff at the remitting center.The test report contained information on the quality of the assessment and four categories of reactivity: hyporeactivity, on the verge of hyporeactivity, reactivity, and hyperreactivity. Based on previous literature  and sincSuicide attempt was defined as an act of intentional self-harm with the intent to die , 35.Information regarding previous suicide attempts, including number, time, and method (assigning appropriate ICD-10 codes) of suicide attempts, was collected using a semi-structured interview administered at baseline (t0), before the EDOR Test. Suicide attempt before the EDOR Test was recorded as a yes or no variable.The same variables were collected at the 1-year follow-up (t1) at each center using a similar semi-structured interview, administered in person or by phone. Completed suicide during follow-up was also recorded as a yes or no variable, the method used was recorded, and appropriate ICD-10 codes were assigned.With regards to suicide attempts and completed suicides, the use of a violent method was recorded as a yes or no variable.Data on socio-demographics, clinical diagnoses (primary and secondary psychiatric and somatic diagnoses), and treatment  of the participants were gathered at baseline.Assessment of depression was performed with the clinician-rated Montgomery–Asberg Depression Rating Scale (MADRS) at t0 , 37. Thet-tests, or Mann–Whitney U-tests as appropriate. The association between hyporeactivity and the method used for the suicide attempt was tested using a chi-square test.The utilized quantitative measures (age and MADRS) were graphed to look for outliers or inconsistent values, and none was found. The association between hyporeactive status and baseline sociodemographic and clinical measures was tested using chi-square tests of independence, Fisher's exact tests, The sensitivity, specificity, and positive and negative predictive values of the EDOR Test were calculated for suicide attempts before the test, suicide attempts during follow-up, and completed suicide during follow-up. These analyses were also performed separately for patients with a diagnosis of unipolar depression (F32 and F33) and bipolar depression (F31). Receiver operating characteristic (ROC) curves were conducted to look at the area under the ROC curve (AUC) for each outcome.Furthermore, a logistic regression was conducted to estimate the increased risk of suicide attempt for hyporeactive patients. Odds ratios (OR) of suicide attempt were estimated using the log-binomial model in reactive and hyporeactive patients, adjusting for sex, age, type of care, use of antidepressant, and primary psychiatric diagnosis. To further investigate and compare the information that the EDOR Test provides, the OR of suicide attempt at follow-up was estimated, adjusting for history of suicide attempt. All analyses were conducted using SPSS v25 and at an alpha level of 0.05.The study protocol received ethical approval from the local ethics committee in each participating center where the research project was performed. The participants received information from their clinicians about the study and that the EDOR Test was being studied as a new tool for helping clinicians in assessing the risk of suicide in depressed patients. They were also informed that the results of the test would be interpreted by an independent expert and then communicated to their physicians. A signed informed consent form was obtained from each patient. To ensure confidentiality, data was pseudoanonymized. There was unanimous agreement among all researchers and the ethical committees that it would be unethical, based on the results from previous research , 38, to N = 1,370) of the total sample were analyzed. One hundred fifty one (9.60%) patients were excluded due to missing data or because of not meeting the inclusion criteria. Additionally, 52 (3.30%) patients were excluded from the analyses because they were lost to follow-up  than male , and one participant had missing gender data. Furthermore, 37.15% of the study population had attempted suicide at baseline (before the EDOR Test), where 32.02% (n = 163) used a violent method (not shown). Five patients had missing data regarding suicide attempt method at baseline. A total of 82 patients (5.98%) attempted suicide during follow-up, and 20 patients (24.10%) used a violent method (not shown). Four patients had missing data regarding suicide attempt method during follow-up. Eight patients (0.58%) died by suicide during the follow-up period. Of the total population, 75.69% had reactive electrodermal activity, with only 0.58% testing hyperreactive. Majority of the patients (38.54%) had a diagnosis of F33  followed by F32  where 32.63% were diagnosed. A total of 21.46% had a diagnosis of F31 (bipolar disorder), while 23.06 and 35.98% also had a secondary psychiatric and somatic diagnosis, respectively. Moreover, at baseline, 83.06% were currently treated with antidepressants, whereas 16.06% were treated with psychotherapy. Out of these participants, 15.18% (n = 179) received both antidepressants and psychotherapy.The cohort had a higher proportion of female patients (p < 0.001), type of care (p < 0.001), primary psychiatric diagnosis (p < 0.01), and MADRS total scores (p < 0.001) in patients who attempted suicide at baseline compared to the study population.There were significant differences with regards to age  tested reactive .There was no statistical difference in the demographic (age and gender) or clinical  variables between patients who were reactive and hyporeactive in the group of patients that had already attempted suicide at baseline and the group that attempted suicide during follow-up (p < 0.001), tested with chi-square, between the number of patients classified as hyporeactive and reactive with regards to suicide attempt before the EDOR Test. The EDOR Test had high specificity (79.91%) but lower sensitivity (29.86%) coupled with a lower positive predictive value (PPV) value (46.77) as well  between the number of patients classified as hyporeactive and reactive with regards to suicide attempts at follow-up, and sensitivity was higher for risk of suicide attempt at follow-up than at baseline. However, the PPV value was much lower for suicide attempts during follow-up than for suicide attempts at baseline, and the discriminatory ability of the test did not improve  of suicide attempts at baseline . AdjustiSimilarly, there was also a statistically significant increased risk  of suicide attempt during follow-up in hyporeactive patients compared to reactive patients . The risAn OR was estimated for suicide attempts at follow-up using both hyporeactivity and history of suicide attempts as independent variables . The OR This study found a statistically significant increased risk of suicide attempt at baseline and suicide attempt at follow-up in hyporeactive patients compared to reactive patients. The risk of suicide attempts after 1 year among hyporeactive patients was almost twofold the risk of suicide attempts at follow-up among reactive patients. This risk also did not significantly change when we adjusted for demographic and clinical covariates. Hyporeactivity was no longer significantly associated with a higher risk of suicide attempt at follow-up when suicide attempt at baseline was added to the regression model. Suicide attempt at baseline instead turned out to be a significant risk factor for future suicide attempts in comparison to hyporeactivity, where patients with a history of attempted suicide had almost eight times higher risk for a future suicide attempt compared to patients with no history of suicide attempt. The odds ratio for completed suicide was not computed due to the low number of suicides during the 1-year follow-up. Even if the increased suicide attempt risk associated with hyporeactivity is significant from a statistical point of view, its small effect size does not allow one to make a meaningful clinical decision about a specific patient. Moreover, a previous suicide attempt appears to be a much stronger factor than hyporeactivity. Overall, the results of this study show that hyporeactivity, as a standalone measure, has a limited clinical significance for the determination of suicide risk.The sensitivity, NPV, and PPV of the EDOR Test were lower than in previous studies , 31. In However, the results should be discussed in the light of some relevant strengths, limitations, and considerations about the study. The study has several strengths. While previous investigations were conducted using smaller samples recruited in a single psychiatric center , 31, then = 509) of the sample reported a lifetime history of suicide attempt at baseline. Since the study sample mostly includes patients with a diagnosis of major depression, this result can be considered very similar to the one reported in epidemiological studies on depressed patients. Comparing the results of two large research projects on bipolar and depressed patients in Finland, Holma et al. (I2 = 97.2%) and 33.9% , respectively. During the 1-year follow-up, around 6% (n = 82) of the EUDOR-A sample attempted suicide. In the study by Holma et al. , and a longer follow-up might have yielded more completed suicides, thus improving the power of the analysis. Indeed in the study by Thorell et al.  reportinThe major limitation of the EUDOR-A study is the non-blinded design of the study, which was chosen due to ethical reasons. Clinicians were aware of the results of the EDOR Test, which might have led them to increase the intensity of care for patients who were hyporeactive. Therefore, the reduction of attempted suicide at follow-up in hyporeactive patients and thus the increased number of false positives might be due to the above-mentioned increase in the intensity of care—for instance, additional precaution plans and preventive measures might have been put in place due to the expectation from the carers that hyporeactive patients were more prone to suicidal behavior, diminishing the suicidal behavior that would have developed otherwise. Unfortunately, a measure of intensity of care was not included in the protocol of the study, and it is not possible to evaluate if additional suicide preventive measures for hyporeactive patients increased the number of false positives and subsequently decreased the measured sensitivity and specificity of the EDOR Test.Another limitation lies in the different patterns of association between hyporeactivity and suicidal behaviors shown by unipolar and bipolar depressed patients see –4. This The EUDOR-A study partly confirms previous literature that also reports electrodermal hyporeactivity in depressed patients who attempt suicide compared to non-suicidal depressed patients , 29, 44.In line with previous research , 29, 31,The main finding of the EUDOR-A study is that an electrodermal hyporeactive response pattern to neutral stimuli is associated with a history of suicide attempts as well as with an increased risk of such behavior during a 12-month follow-up period after being tested. However, the sensitivity and specificity of the EDOR Test were not sufficient to support its use as a suicide risk assessment tool in clinical practice. The statistically significant association of hyporeactivity with suicide attempts is promising and should be further investigated. Future research should address and overcome the limitations that emerged from the current study, including the inclusion of a control group, with clinicians blinded to the results of the EDOR Test or, if impossible due to ethical reasons, a detailed collection of the data about the preventive interventions applied to hyporeactive and reactive patients, allowing one to measure the intensity of treatment delivered to each patient.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Committee to Protect People southern Mediterranean I (Comité de Protection des Personnes Sud Méditerranée I), Marseilles (France), approved on December 5, 2014; Ethics Committee of the Medical Faculty of the University of Rostock (Ethikkommission an der Medizinischen Fakultät der Universität Rostock), Rostock (Germany), approved on August 8, 2014; Ethics Committee of the Medical Faculty of the University of Tuebingen (Ethikkommission an der Medizinischen Fakultät der Eberhard Karls Universität Tübingen), Tuebingen (Germany), approved on September 9, 2014; Regional and Institutional Ethics Committee (Regionális és Intézményi Kutatásetikai Bizottság), Budapest (Hungary), approved on October 31, 2014; Independent Ethics Committee of the University Hospital , Bari , approved on May 5, 2014; Regional Ethics Committee , Genoa , approved on December 9, 2014; Intercompany Ethics Committee AOU “Maggiore della Carità” , Novara , approved on July 25, 2014; Bioethical Committee of the Medical University of Warsaw (Komisja Bioetyczna przy Warszawskim Uniwersytecie Medycznym), Warsaw (Poland), approved on March 18, 2014; Bioethical Committee of the Institute of Psychiatry and Neurology (Instytut Psychiatrii i Neurologii Komisja Bioetyczna), Warsaw (Poland), approved on September 19, 2013; Ethics Committee of the Western Lisbon Hospital , Lisbon , approved on April 30, 2014; Ethics Committee of the “Iuliu Hatieganu” University of Medicine and Pharmacy (Univeritatea se Medicină şi Farmacie “Iuliu Hatieganu” Comisia de Etică), Cluj-Napoca (Romania), approved on April 111, 2014; Research Ethics Committee of Principado de Asturias (Comité de Ética de la Investigación del Principado de Asturias), Oviedo (Spain), approved on June 3, 2014; Clinical Research Ethics Committee (Comité Ético de Investigación Clínica), Madrid (Spain), approved on March 3, 2015; Regional Ethics Committee of Lund , Lund (Sweden), approved on August 25, 2014. The patients/participants provided their written informed consent to participate in this study.VC and GH conceived and designed the analysis, contributed to writing, and reviewed the first draft. NP contributed to the statistical analysis and wrote the first draft. MI organized the database, performed the data analysis, and contributed to drafting and reviewing the manuscript. MS was the project coordinator, conceptualized the manuscript and the methodology, reviewed, and edited the first draft. HG contributed to formal analysis. PZ and CG collected the data and contributed to organizing the database and drafting the manuscript. MA, EB-G, AB, DC, PC, GD, JE, RG, CJ, MH, MC, PMR, PS, and MW collected the data. All authors contributed to manuscript revision and read and approved the submitted version.The EUDOR-A study was promoted and funded by EMOTRA AB, Sweden.For the EUDOR-A study, the participating centres  received funding by EMOTRA AB, Sweden to perform the study. The remaining 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.


The primary objective of the present study was to evaluate the frequency of positive tests for alcohol and drugs during roadside testing or after road accidents among drivers in the Brittany region of France. The study’s secondary objective was to describe the blood concentrations of the substances found during these tests, in order to provide a scientific basis for the establishment or modification of legislative threshold values for road injuries prevention. We performed a cross-sectional study of a database compiled by Rennes University Hospital’s toxicology laboratory in the Brittany region of France between 2010 and 2018. Driver’s age, sex, and test status (positive or negative), and blood levels of ethanol, 9-tetrahydrocannabinol (THC), methylene dioxymethamphetamine (MDMA), amphetamine, benzoylecgonine and 6-monoacetylmorphine (6-MAM) were collected. Twelve thousand four hundred and ninety-seven drivers  age: 29 (15–94)) have provided roadside blood samples, giving a total of 25,998 test results. Among the 10,996 drivers with at least one positive test, the median blood concentrations of ethanol, THC, MDMA, amphetamine, benzoylecgonine, and 6-MAM were respectively 1.82 g/L, 2.41 ng/mL, 138.4 ng/mL, 67.7 ng/mL, 173.3 ng/mL, and 0.97 ng/mL. 1159 (10.54%) of the 10,996 drivers tested positive for two or more substances, and 151 (1.4%) tested positive for three or more substances. With the exception of heroin, the currently recommended threshold values appear to be appropriate for road injuries prevention with regard to the concentrations observed in offenders. The risper se legislation)  . In the slation) . At presslation) . Accordislation) .Assays for these psychoactive substances are requested by the traffic police during random roadside testing or after a crash has occurred. The primary objective of the present study was evaluate the frequency of positive tests for alcohol and drugs during roadside testing or after road accidents among drivers in the Brittany region of France between 2010 and 2018. The secondary objective was to describe the blood concentrations of substances found during these tests, in order to provide a scientific basis for the establishment or modification of legislative thresholds for road injuries prevention.22.1Following a request by the police, Rennes University Hospital’s toxicology laboratory carries out assays on blood samples taken (i) after a crash, (ii) in the context of checkpoints  or (iii) during random roadside testing, at any time of day and any location. In the last two cases, blood samples were taken after positive oral fluid test or alcohol tester. Since the proportion of each of these three origins is unknown, we pooled the results together. The requested drug screens include ethanol, the cannabinoid THC, MDMA, other amphetamines, the cocaine metabolite benzoylecgonine, and the heroin metabolite 6-MAM. For each sample, several data are recorded in the toxicology laboratory’s database: the tested person’s sex and date of birth, the date and place of the roadside testing or the crash, the substances sought , the date of the analytical result, the result (positive or negative), and the blood concentration of analyte in positive tests. Although morphine has been assayed in the laboratory, there is still uncertainty as to the source of this substance; morphine can come either from medical care (morphine or codeine) or from narcotics. In order to be sure of the narcotic intake, we chose to keep only 6-MAM in this study.We conducted a cross-sectional study of data extracted from the laboratory’s database for the period between January 1st, 2010, and November 22nd, 2018.2.2The psychoactive substances were obligatorily assayed using the analytical methods set in the French Highway Code . Alcohol2.3We analyzed (i) the dataset as a whole, (ii) each substance class, and (iii) samples that were positive for two or more substances. All analyses were performed using SAS software  and SAS Enterprise Guide®. Quantitative variables (age and plasma concentration) were described as the mean, median, standard deviation (SD), range and interquartile range (IQR), and qualitative variables  were described as the number (percentage). 3Between 2010 and 2018, a total of 25,998 toxicological analysis results  were logged in the laboratory’s database. The general characteristics of the tested drivers and the requests for alcohol and drug tests are summarized in We described the general characteristics of the drivers with positive tests , performAs in the study population as a whole, the great majority of the positive assays (83.6%) came from male drivers; this was true for all substances . HoweverThe highest positive test rates were observed for alcohol and cannabis  . With reThe abuse of multiple psychoactive substances  appeared4The results of this large, cross-sectional analysis of data collected between 2010 and 2018 by Rennes University Hospital’s toxicology laboratory provides an interesting overview of DUIA and DUID in the Brittany region of France. >40% of the blood assays were positive for at least one psychoactive substance - mainly ethanol and cannabis. To the best of our knowledge, the present study is the first of this magnitude to have explored the patterns of psychoactive substance consumption (including multiple substance abuse) among drivers in France, the consumption profiles, and the blood concentrations.The great majority of the blood tests assessed in the present study (86.5%) concerned men. In the literature, male sex is associated with more time spent driving, a greater frequency of speeding violations, and greater alcohol consumption  . Along wAccording to a report from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), alcohol is the most commonly used psychoactive substance among drivers in Europe, and cannabis is the most commonly used narcotic . Our resThe most frequently detected narcotic in our study was THC, with a positivity rate of 62.5%. The consumers were predominant young males, as previously reported in France . The higAccording to the literature data, the prevalence of heroin experimentation among 18–64 year olds in France is low, with an estimated value of 1.5% in 2017 . It is tWith regard to cocaine, the literature data show a fourfold increase in consumption in France over two decades  , which cPer se legislation therefore appears to be relevant. In view of our results for the median blood concentrations of MDMA and amphetamine , the minimum regulatory threshold of 10 ng/mL appears to be appropriate.Regarding amphetamines, none of the drivers in our study tested positive for methamphetamine, MDEA or MDA. Although epidemiological studies tend to show an increase in methamphetamine seizures in Europe over recent years, these substances are infrequently used in France; this might explain our results . In lineper se legislation on one hand and impairment-type legislation based on a threshold set (apart from 6-MAM) on the other. “Zero tolerance” is a clear message to drivers and is coherent from a legal standpoint: the law cannot establish an offence and then leave it unpunished.In the context of impairment-type legislation, one can question the relevance of regulatory thresholds for narcotic drugs. The literature data on impaired driving skills under the influence of narcotics vary considerably from one country to another . Our res4.1Our findings must be interpreted in the context of three potential limitations.Firstly, the number of BAC requests was probably underestimated, since a blood alcohol test is only requested if it is impossible to obtain a valid test result in expired air or if the driver cannot or will not blow into the test device. Given that these tests are targeted, ethanol was not the most frequently requested analyte. However, it was associated with a high positivity rate (82.2%).Secondly, we decided to analyse tests for 6-MAM (a specific heroine metabolite) and not tests for morphine (a non-specific heroine metabolite) because of the difficulty of discriminating between opioid misuse on one hand and the medical use of morphine on the other . Hence, Thirdly, our research was dependent on test requests by law enforcement officers; multiple substance abuse may therefore have been underestimated. Furthermore, a study of French and Belgian drivers showed that many new psychoactive substances are found in combination with other commonly abused drugs. In 2018, Wille et al showed that the positivity rate for new psychoactive substances was 7% in blood samples obtained during roadside testing in Belgium, and was 11% in oral fluid samples obtained from negatively screened test pads . Lastly,5Overall, 10,996 of the 12,487 drivers (87.98%) were positive for at least one of the prohibited substances. Levels of multiple substance abuse in Brittany are high. Our results also show that the thresholds set out in the current legislation are appropriate (with the exception of that for heroin). As the threshold concentrations set under impairment-type legislation (i) vary widely from one country to another, and (ii) rarely take the issue of multiple substance abuse into account, an impairment-based approach does not necessarily appear to be relevant to road injury prevention. Repression based on proof of the consumption of one or more illegal substances while the driver is using his/her vehicle has the advantage of being clear and readily understandable. However, France’s strict legislation limits academic research on the substances discussed here – thus slowing identification of the large number of other psychoactive drugs likely to functionally impair a person’s driving ability.This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.Brendan Le Daré: Methodology, Collection and/or assembly of data, Data analysis and interpretation, Manuscript writing, Final approval of manuscript. Adeline Degremont: Methodology, Collection and/or assembly of data, Data analysis and interpretation, Manuscript writing, Final approval of manuscript. Clémence Couty: Conceptualization, Data analysis and interpretation, Final approval of manuscript. Alain Baert: Final approval of manuscript. Renaud Bouvet: Final approval of manuscript. Isabelle Morel: Conceptualization, Final approval of manuscript. Thomas Gicquel: Conceptualization, Methodology, Collection and/or assembly of data, Data analysis and interpretation, Manuscript writing, Final approval of manuscript.All authors contributed significantly, and all authors agree with the content of the manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.