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BACKGROUND While randomized clinical trials have shown the benefit of thrombolysis and endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS), we aimed to describe in a real-life study the differences between older (>80 years old) and younger patients treated for AIS. METHODS Thousand patients treated with thrombolysis and/or EVT were consecutively included in a prospective monocentric database (admitted from December 2015 to May 2019 in our comprehensive stroke center). Demographic data with detailed history, baseline physical examinations and treatments, laboratory and imaging data, prestroke functional status, and outcome 3 months after stroke were analyzed. RESULTS Older patients (n = 357) had more baseline comorbidities and lower levels of prestroke independence (modified Rankin scale ≤2; 67.2% vs. 96.1%) and more severe strokes (median National Institute of Health Stroke Score [NIHSS] 15 vs. 12; p

COVID-19 limitation strategies have led to widespread school closures around the world. The present study reports children’s mental health and associated factors during the COVID-19 school closure in France in the spring of 2020. We conducted a cross-sectional analysis using data from the SAPRIS project set up during the COVID-19 pandemic in France. Using multinomial logistic regression models, we estimated associations between children’s mental health, children’s health behaviors, schooling, and socioeconomic characteristics of the children’s families. The sample consisted of 5702 children aged 8–9 years, including 50.2% girls. In multivariate logistic regression models, children’s sleeping difficulties were associated with children’s abnormal symptoms of both hyperactivity-inattention (adjusted Odds Ratio (aOR) 2.05; 95% Confidence Interval 1.70–2.47) and emotional symptoms (aOR 5.34; 95% CI 4.16–6.86). Factors specifically associated with abnormal hyperactivity/inattention were: male sex (aOR 2.29; 95% CI 1.90–2.76), access to specialized care prior to the pandemic and its suspension during school closure (aOR 1.51; 95% CI 1.21–1.88), abnormal emotional symptoms (aOR 4.06; 95% CI 3.11–5.29), being unschooled or schooled with assistance before lockdown (aOR 2.13; 95% CI 1.43–3.17), and tutoring with difficulties or absence of a tutor (aOR 3.25; 95% CI 2.64–3.99; aOR 2.47; 95% CI 1.48–4.11, respectively). Factors associated with children’s emotional symptoms were the following: being born pre-term (aOR 1.34; 95% CI 1.03–1.73), COVID-19 cases among household members (aOR 1.72; 95% CI 1.08–2.73), abnormal symptoms of hyperactivity/inattention (aOR 4.18; 95% CI 3.27–5.34) and modest income (aOR 1.45; 95% CI 1.07–1.96; aOR 1.36; 95% CI 1.01–1.84). Multiple characteristics were associated with elevated levels of symptoms of hyperactivity-inattention and emotional symptoms in children during the period of school closure due to COVID-19. Further studies are needed to help policymakers to balance the pros and cons of closing schools, taking into consideration the educational and psychological consequences for children.

ObjectiveTo examine the relationship between young adults' labor force participation and depression in the context of the COVID-19 pandemic.Design, setting, participantsData come from the nationally-representative EPICOV cohort study set up in France, and were collected in 2020 and 2021 (3 waves of online or telephone interviews: 02/05/2020–12/06/2020; 26/10/2020–14/12/2020; 24/06/2021–09/08/2021) among 2,217 participants aged 18–30 years. Participants with prior mental health disorder (n = 50) were excluded from the statistical analyses.ResultsUsing Generalized Estimating Equation (GEE) models controlled for participants' socio-demographic and health characteristics and weighted to be nationally-representative, we found that compared to young adults who were employed, those who were studying or unemployed were significantly more likely to experience depression assessed using the PHQ-9 (multivariable ORs, respectively: OR: 1.29, 95% CI 1.05–1.60 and OR: 1.50, 1.13–1.99). Stratifying the analyses by age, we observed that unemployment was more strongly associated with depression among participants 25–30 years than among those who were 18–24 years (multivariable ORs, respectively, 1.78, 95% CI 1.17–2.71 and 1.41, 95% CI 0.96–2.09). Being out of the labor force was, to the contrary, more significantly associated with depression among participants 18–24 years (multivariable OR: 1.71, 95% CI 1.04–2.82, vs. 1.00, 95% CI 0.53–1.87 among participants 25–30 years). Stratifying the analyses by sex, we found no significant differences in the relationships between labor market characteristics and depression (compared to participants who were employed, multivariable ORs associated with being a student: men: 1.33, 95% CI 1.01–1.76; women: 1.19, 95% CI 0.85–1.67, multivariable ORs associated with being unemployed: men: 1.60, 95% CI 1.04–2.45; women: 1.47, 95% CI 1.01–2.15).Conclusions and relevanceOur study shows that in addition to students, young adults who are unemployed also experience elevated levels of depression in the context of the COVID-19 pandemic. These two groups should be the focus of specific attention in terms of prevention and mental health treatment. Supporting employment could also be a propitious way of reducing the burden of the COVID-19 pandemic on the mental health of young adults.

Background Fibrinogen concentrate is widely used in traumatic hemorrhagic shock despite weak evidence in the literature. The aim of the study was to evaluate the effect of fibrinogen concentrate administration within the first 6 hours on 24-hour all-cause mortality in traumatic hemorrhagic shock using a causal inference approach. Methods Observational study from a French multicenter prospective trauma registry was performed. Hemorrhagic shock was defined as transfusion of four or more red blood cell units within the first 6 hours after admission. The confounding variables for the outcome (24-hour all-cause mortality) and treatment allocation (fibrinogen concentrate administration within the first 6 hours) were chosen by a Delphi method. The propensity score was specified with a data-adaptive algorithm and a doubly-robust approach with inverse proportionality of treatment weighting allowed to compute the average treatment effect. Sensitivity analyses were performed. Results Of 14,336 patients in the registry during the study period, 1,027 in hemorrhagic shock were analyzed (758 receiving fibrinogen concentrate within 6 hours and 269 not receiving fibrinogen concentrate). The average treatment effect, expressed as a risk difference, was -0.031 (95% confidence interval, -0.084 to 0.021). All sensitivity analysis confirmed the results. Conclusions Fibrinogen concentrate administration within the first 6 hours of a traumatic hemorrhagic shock did not decrease 24-hour all-cause mortality. Level of evidence Prognostic, level III.

ObjectiveAlthough social inequalities in COVID-19 mortality by race, gender and socioeconomic status are well documented, less is known about social disparities in infection rates and their shift over time. We aim to study the evolution of social disparities in infection at the early stage of the epidemic in France with regard to the policies implemented.DesignRandom population-based prospective cohort.SettingFrom May to June 2020 in France.ParticipantsAdults included in the Epidémiologie et Conditions de Vie cohort (n=77 588).Main outcome measuresSelf-reported anosmia and/or ageusia in three categories: no symptom, during the first epidemic peak (in March 2020) or thereafter (during lockdown).ResultsIn all, 2052 participants (1.53%) reported anosmia/ageusia. The social distribution of exposure factors (density of place of residence, overcrowded housing and working outside the home) was described. Multinomial regressions were used to identify changes in social variables (gender, class and race) associated with symptoms of anosmia/ageusia. Women were more likely to report symptoms during the peak and after. Racialised minorities accumulated more exposure risk factors than the mainstream population and were at higher risk of anosmia/ageusia during the peak and after. By contrast, senior executive professionals were the least exposed to the virus with the lower rate of working outside the home during lockdown. They were more affected than lower social classes at the peak of the epidemic, but this effect disappeared after the peak.ConclusionThe shift in the social profile of the epidemic was related to a shift in exposure factors under the implementation of a stringent stay-at-home order. Our study shows the importance to consider in a dynamic way the gender, socioeconomic and race direct and indirect effects of the COVID-19 pandemic, notably to implement policies that do not widen health inequalities.

Sepsis and non-septic systemic inflammatory response syndrome (SIRS) are the same syndromes, differing by their cause, sepsis being secondary to microbial infection. Microbiological tests are not enough to detect infection early. While more than 50 biomarkers have been proposed to detect infection, none have been repeatedly validated. To assess the accuracy of circulating biomarkers to discriminate between sepsis and non-septic SIRS. The CAPTAIN study was a prospective observational multicenter cohort of 279 ICU patients with hypo- or hyperthermia and criteria of SIRS, included at the time the attending physician considered antimicrobial therapy. Investigators collected blood at inclusion to measure 29 plasma compounds and ten whole blood RNAs, and—for those patients included within working hours—14 leukocyte surface markers. Patients were classified as having sepsis or non-septic SIRS blindly to the biomarkers results. We used the LASSO method as the technique of multivariate analysis, because of the large number of biomarkers. During the study period, 363 patients with SIRS were screened, 84 having exclusion criteria. Ninety-one patients were classified as having non-septic SIRS and 188 as having sepsis. Eight biomarkers had an area under the receiver operating curve (ROC-AUC) over 0.6 with a 95% confidence interval over 0.5. LASSO regression identified CRP and HLA-DRA mRNA as being repeatedly associated with sepsis, and no model performed better than CRP alone (ROC-AUC 0.76 [0.68–0.84]). The circulating biomarkers tested were found to discriminate poorly between sepsis and non-septic SIRS, and no combination performed better than CRP alone.

Background Haemorrhagic shock is the leading cause of early preventable death in severe trauma. Delayed treatment is a recognized prognostic factor that can be prevented by efficient organization of care. This study aimed to develop and validate Red Flag, a binary alert identifying blunt trauma patients with high risk of severe haemorrhage (SH), to be used by the pre-hospital trauma team in order to trigger an adequate intra-hospital standardized haemorrhage control response: massive transfusion protocol and/or immediate haemostatic procedures. Methods A multicentre retrospective study of prospectively collected data from a trauma registry (Traumabase®) was performed. SH was defined as: packed red blood cell (RBC) transfusion in the trauma room, or transfusion ≥ 4 RBC in the first 6 h, or lactate ≥ 5 mmol/L, or immediate haemostatic surgery, or interventional radiology and/or death of haemorrhagic shock. Pre-hospital characteristics were selected using a multiple logistic regression model in a derivation cohort to develop a Red Flag binary alert whose performances were confirmed in a validation cohort. Results Among the 3675 patients of the derivation cohort, 672 (18%) had SH. The final prediction model included five pre-hospital variables: Shock Index ≥ 1, mean arterial blood pressure ≤ 70 mmHg, point of care haemoglobin ≤ 13 g/dl, unstable pelvis and pre-hospital intubation. The Red Flag alert was triggered by the presence of any combination of at least two criteria. Its predictive performances were sensitivity 75% (72–79%), specificity 79% (77–80%) and area under the receiver operating characteristic curve 0.83 (0.81–0.84) in the derivation cohort, and were not significantly different in the independent validation cohort of 2999 patients. Conclusion The Red Flag alert developed and validated in this study has high performance to accurately predict or exclude SH. Electronic supplementary material The online version of this article (10.1186/s13054-018-2026-9) contains supplementary material, which is available to authorized users.

Based on evolutionary theory, a recent model in affective neuroscience delineated six emotional brain systems at the core of human personality: SEEKING, CARING, PLAYFULNESS, FEAR, ANGER, SADNESS. The Affective Neuroscience Personality Scales (ANPS) assess their functioning. Using a person-centred approach of the ANPS, this study: (i) examined the existence of latent personality profiles, (ii) studied their gender invariance, (iii) assessed their longitudinal (4 years) stability, and (iv) explored how they relate to several intrapersonal, interpersonal, and emotion regulation skills. Latent Profile Analysis in 2 samples (Canadian, longitudinal, N = 520; French, cross-sectional, N = 830) found that, qualitatively, 3 profiles characterized both populations and genders, with one distinction for the second profile where the French women endorsed slightly higher and lower scores for, respectively, the negative and positive emotions. Whilst not being quantitatively similar across genders, the personality profiles remained consistent across time in the longitudinal sample. Associations between profiles and intrapersonal (e.g. depression), interpersonal (e.g. empathy), and emotion regulation skills measures (e.g. emotional intelligence) offered concurrent validity evidence. This person centred approach to ANPS offers a holistic and parsimonious way to study affective personality dimensions. It opens promising avenues for future studies on the predictive value of ANPS profiles, and for personality-targeted interventions.

Background Transporting a severely injured patient directly to a trauma center (TC) is consensually considered optimal. Nevertheless, disagreement persists regarding the association between secondary transfer status and outcome. The aim of the study was to compare adjusted mortality between road traffic trauma patients directly or secondarily transported to a level 1 trauma center (TC) in an exclusive French trauma system with a physician staffed prehospital emergency medical system (EMS). Methods A retrospective cohort study was performed using 2015–2017 data from a regional trauma registry (Traumabase®), an administrative database on road-traffic accidents and prehospital-EMS records. Multivariate logistic regression models were computed to determine the role of the modality of admission on mortality and to identify factors associated with secondary transfer. The primary outcome was day-30 mortality. Results: During the study period, 121.955 victims of road-traffic accident were recorded among which 4412 trauma patients were admitted in the level 1 regional TCs, 4031 directly and 381 secondarily transferred from lower levels facilities. No significant association between all-cause 30-day mortality and the type of transport was observed (Odds ratio 0.80, 95% confidence interval (CI) [0.3–1.9]) when adjusted for potential confounders. Patients secondarily transferred were older, with low-energy mechanism and presented higher head and abdominal injury scores. Among all 947 death, 43 (4.5%) occurred in lower-level facilities. The population-based undertriage leading to death was 0.15%, 95%CI [0.12–0.19]. Conclusion In an exclusive trauma system with physician staffed prehospital care, road-traffic victims secondarily transferred to a TC do not have an increased mortality when compared to directly transported patients.

Background: The pain trajectory after ankle surgeries for osteoarthritis is relevant to describe. The purpose of this prospective study was to describe pain after ankle surgery and explore the link between perioperative factors and the development of postoperative pain. Methods: Duration, severity, type of preoperative pain, psychological distress, opioid consumption, and type of surgery were evaluated in 49 patients who were followed for 18 months. Acute postoperative pain in the first 10 days after surgery was modeled by a pain trajectory. Univariate analysis was conducted to identify predictors of acute pain trajectory and chronic pain. Results: Eighty-seven percent of patients had preoperative chronic pain, 34% had a high postoperative pain trajectory, 44% of whom reported chronic pain at 18 months. The patients who developed a high acute pain trajectory had higher preoperative opioid consumption (50% vs 19.4%, P = .04), a higher incidence of preoperative neuropathic pain (68.8% vs 32.3%, P = .02), a higher brief pain inventory score (51.5 vs 34, P = .01), and a higher psychological distress score (8 vs 3, P = .002). The patients who developed chronic pain had a higher brief pain inventory score (42 vs 33, P = .04), a higher psychological distress score (6 vs 4, P = .04), and a higher preoperative pain intensity (8 vs 6, P = .008). No association was found between the type of ankle surgery and pain. Conclusion: Patients with psychological distress and more severe preoperative pain were more at risk to develop acute pain and chronic pain after ankle surgery regardless of the surgery performed. Level of Evidence: Level II, prospective comparative study.

BACKGROUND: Short versions of the European Health Literacy Survey (HLS-EU) questionnaire are increasingly used to measure and compare health literacy (HL) in populations worldwide. As no validated versions of these questionnaires have thus far appeared in French, this study aimed to study the psychometric properties of the French translation of the 16- and 6-item short versions (HLS-EU-Q16 and HLS-EU-Q6), including their measurement invariance across sex, age, and education level. METHODS: A consensual French version of the HLS-EU-Q16 and HLS-EU-Q6 was developed by following the current recommendations for transcultural questionnaire adaptation. It was then completed by 317 patients recruited in waiting rooms of general practitioners in the Paris area (France). Structural validity was studied with the Rasch model for the HLS-EU-Q16 and confirmatory factorial analysis (CFA) for the HLS-EU-Q6. Concurrent and convergent validity, respectively, were assessed by scores on the Functional Communicative Critical Health Literacy (FCCHL) questionnaire and the physicians' evaluations of their patient's HL. RESULTS: The 16 items of the HLS-EU-Q16 were Rasch homogenous but meaningful differential item functioning (DIF) was found across sex, age, and/or education level for eight items. The CFA model fit for the HLS-EU-Q6 was poor. The overall scores for both HLS-EU short versions correlated poorly with the FCCHL scores. Similarly, HL levels defined using either short-version score did not agree with physicians' HL assessments. CONCLUSION: The French version of the HLS-EU-Q16 has acceptable psychometric properties, despite meaningful DIF for age, sex and education level and a poor discriminative power among subjects with average to high HL level. We recommend its use to measure HL in populations with sufficient reading skills to discriminate between subjects with low to average HL. Also, sensitivity analyses should be performed to evaluate the potential measurement bias due to DIF. Our results did not demonstrate the validity of the HLS-EU-Q6. ispartof: PLOS ONE vol:13 issue:12 ispartof: location:United States status: published

Background: The frequency of chronic postsurgical pain (CPSP) after knee replacement remains high, but might be decreased by improvements to prevention. Objectives: To identify pre- and postsurgical factors predictive of CPSP 6 months after knee replacement. Study Design: Single-center prospective observational study. Setting: An orthopedic unit in a French hospital. Methods: Consecutive patients referred for total or unicompartmental knee arthroplasty from March to July 2013 were prospectively invited to participate in this study. For each patient, we recorded preoperative pain intensity, anxiety and depression levels, and sensitivity and pain thresholds in response to an electrical stimulus. We analyzed OPRM1 and COMT single-nucleotide polymorphisms. Acute postoperative pain (APOP) in the first 5 days after surgery was modeled by a pain trajectory. Changes in the characteristics and consequences of the pain were monitored 3 and 6 months after surgery. Bivariate analysis and multivariate logistic regression were conducted to identify predictors of CPSP. Results: We prospectively evaluated 104 patients in this study, 74 (28.8%) of whom reported CPSP at 6 months. Three preoperative factors were found to be associated with the presence of CPSP in multivariate logistic regression analysis: high school diploma level (OR = 3.83 [1.20 – 12.20]), consequences of pain in terms of walking ability, as assessed with the Brief Pain Inventory short form “walk” item (OR = 4.06 [1.18 – 13.94]), and a lack of physical activity in adulthood (OR = 4.01 [1.33 – 12.10]). One postoperative factor was associated with the presence of CPSP: a high-intensity APOP trajectory. An association of borderline statistical significance was found with the A allele of the COMT gene (OR = 3.4 [0.93 – 12.51]). Two groups of patients were identified on the basis of their APOP trajectory: high (n = 28, 26%) or low (n = 80, 74%) intensity. Patients with high-intensity APOP trajectory had higher anxiety levels and were less able to walk before surgery (P < 0.05). Limitations: This was a single-center study and the sample may have been too small for the detection of some factors predictive of CPSP or to highlight the role of genetic factors. Conclusion: Our findings suggest that several preoperative and postoperative characteristics could be used to facilitate the identification of patients at high risk of CPSP after knee surgery. All therapeutic strategies decreasing APOP, such as anxiety management or performing knee replacement before the pain has a serious effect on ability to walk, may help to decrease the risk of CPSP. Further prospective studies testing specific management practices, including a training program before surgery, are required. Key words: Chronic postsurgical pain, opioids, arthroplasty, pain trajectory, genetics, COMT, predictive factors

Context Besides GNAS gene mutations, the molecular pathogenesis of somatotroph adenomas responsible for gigantism and acromegaly remains elusive. Objective To investigate alternative driver events in somatotroph tumorigenesis, focusing on a subgroup of acromegalic patients with a paradoxical increase in growth hormone (GH) secretion after oral glucose, resulting from ectopic glucose-dependent insulinotropic polypeptide receptor (GIPR) expression in their somatotropinomas. Design, Setting, and Patients We performed combined molecular analyses, including array-comparative genomic hybridization, RNA/DNA fluorescence in situ hybridization, and RRBS DNA methylation analysis on 41 somatotropinoma samples from 38 patients with acromegaly and three sporadic giants. Ten patients displayed paradoxical GH responses to oral glucose. Results GIPR expression was detected in 13 samples (32%), including all 10 samples from patients with paradoxical GH responses. All GIPR-expressing somatotropinomas were negative for GNAS mutations. GIPR expression occurred through transcriptional activation of a single allele of the GIPR gene in all GIPR-expressing samples, except in two tetraploid samples, where expression occurred from two alleles per nucleus. In addition to extensive 19q duplications, we detected in four samples GIPR locus microamplifications in a certain proportion of nuclei. We identified an overall hypermethylator phenotype in GIPR-expressing samples compared with GNAS-mutated adenomas. In particular, we observed hypermethylation in the GIPR gene body, likely driving its ectopic expression. Conclusions We describe a distinct molecular subclass of somatotropinomas, clinically revealed by a paradoxical increase of GH to oral glucose related to pituitary GIPR expression. This ectopic GIPR expression occurred through hypomorphic transcriptional activation and is likely driven by GIPR gene microamplifications and DNA methylation abnormalities.

The Cannabis abuse screening test (CAST) is a short test used for screening those with problematic cannabis use. Recently, its invariance toward age was tested in an Israeli sample of cannabis users, but this study had some sample and methodological limitations: it was conducted in a volunteer sample aged 18–40 and considered the CAST items as continuous variables, although they are based on 5-point Likert scales. We thus tested the CAST invariance toward age (15–24, 25–34, and 35–64 years old) using a French probabilistic sample of 1,351 past-year cannabis users aged 15–64 and using appropriate methods for categorical items and survey weights. Factors retained (non-recreational use and problems) were the same as those mentioned in previous studies. Scalar invariance held for the “problems” factor but only partial scalar invariance was supported for the “non-recreational use” factor. Caution is thus needed when the CAST score is compared across age groups.

Background Despite the development of multimodal analgesia for postoperative pain management, opioids are still required for effective pain relief after knee arthroplasty. We aimed to identify the determinants of post-operative pain intensity and post-operative opioid requirement in this context. Methods In this observational prospective study, we recorded patient characteristics, pre-operative pain intensity, anxiety and depression levels, sensitivity and pain thresholds in response to an electrical stimulus, and mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) single-nucleotide polymorphisms. Multivariate linear regression models were used to identify predictors of post-operative pain at rest and opioid requirement. Results We included 109 patients. Pre-operative pain at rest (p = 0.047), anxiety level (p = 0.001) and neuropathic pain symptoms (p = 0.030) were independently and positively associated with mean post-operative pain intensity adjusted for mean post-operative morphine equivalent dose (MED). Mean post-operative pain intensity at rest was lower (p = 0.006) in patients receiving celecoxib and pregabalin in the post-operative period, with all other variables constant. Mean post-operative MED over 5 days was low, but highly variable (78.2 ± 32.1 mg, from 9.9 to 170 mg). Following adjustment for mean post-operative pain intensity, it was independently negatively correlated with age (p = 0.004), and positively correlated with associated paracetamol treatment (p = 0.031). No genetic effect was detected in our sample. Conclusions Our findings suggest that clinicians could use the pre-operative pain profile, in terms of anxiety levels, neuropathic pain symptoms, and chronic pre-operative pain intensity, to improve the efficacy of pain management after knee surgery.

Background PROMIS-29 is a new generic standardized questionnaire measuring self-reported health status. It was developed as part of the Patient Reported Outcome Measurement Information System (PROMIS) in the United States. The objective of this study was to carry out the psychometric validation of a French-language version of PROMIS-29 and to establish general population reference values for France. Methods Quota sampling was conducted by an independent polling company (Ipsos) to obtain a general population sample (n = 1,501) representative with regards to: gender, age, occupation, region, and population density of the place of residence. Data collected included the results of the questionnaires PROMIS-29 and Short Form Health Survey (SF-36), the presence of selected chronic diseases, and socio-demographic information. Results The French PROMIS-29 demonstrated excellent factorial validity, confirming the 7-factor model of the original PROMIS-29. The use of modern measurement methods indicated that the PROMIS-29 scales satisfy the important characteristics of unidimensionality and, for five of the seven composite scales, invariance across age, educational level and gender. Gender and age specific (10-year intervals) reference values were generated for PROMIS-29 use in France. Conclusion The French version of PROMIS-29 is a valid and reliable measure of self-reported health status in the French population. The instrument's sensitivity to change needs to be evaluated before its use in longitudinal studies can be recommended.

We report on the psychometric properties of the Mental Health and Social Inadaptation Assessment for Adolescents (MIA), a self‐report instrument for quantifying the frequency of mental health and psychosocial adaptation problems using a dimensional approach and based on the DSM‐5. The instrument includes 113 questions, takes 20–25 minutes to answer, and covers the past 12 months. A population‐based cohort of adolescents (n = 1443, age = 15 years; 48% males) rated the frequency at which they experienced symptoms of Attention Deficit Hyperactivity Disorder (ADHD), Conduct Disorder, Oppositional Defiant Disorder, Depression, Generalized Anxiety, Social Phobia, Eating Disorders (i.e. DSM disorders), Self‐harm, Delinquency, Psychopathy as well as social adaptation problems (e.g. aggression). They also rated interference with functioning in four contexts (family, friends, school, daily life). Reliability analyses indicated good to excellent internal consistency for most scales (alpha = 0.70–0.97) except Psychopathy (alpha = 0.46). The hypothesized structure of the instrument showed acceptable fit according to confirmatory factor analysis (CFA) [Chi‐square (4155) = 9776.2, p = 0.000; Chi‐square/DF = 2.35; root mean square error of approximation (RMSEA) = 0.031; Comparative Fit Index (CFI) = 0.864], and good convergent and discriminant validity according to multitrait‐multimethods analysis. This initial study showed adequate internal validity and reliability of the MIA. Our findings open the way for further studies investigating other validity aspects, which are necessary before recommending the wide use of the MIA in research and clinical settings.

International audience; The purpose of the present work was to study the change in morphine metabolic ratio in obese subjects before and after Roux-en-Y Gastric Bypass (RYGB) and to identify clinical and/or biological factors associated with this change. The pharmacokinetics (PK) of oral morphine (30mg), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was performed in patients before (n=25; mean BMI=43.2 (35.4-61.9)kg/m2), 7-15days (n=16) and 6 months after RYGB (n=19; mean BMI=32.3 (25.4-46.0)kg/m2). Morphine Cmax and AUC0-inf were significantly increased and morphine Tmax significantly shortened at 6 months after RYGB compared with preoperative data, indicating an important increase in the rate and extent of morphine absorption. The morphine metabolic ratio 0-inf M3G+M6G/Morphine, decreased significantly from the preoperative to 6 months postoperative period with an average of -26% (range -74%; +21%; p=0.004), but not in the immediate post-operative period. The change in morphine metabolic ratio was associated with a change in BMI, fat mass in kg, and triglyceride levels (rho=0.5, p≤0.04). The degree of change in several markers of low-grade inflammation, or the level of liver steatosis and fibrosis before surgery, was not associated with the change in morphine metabolic ratios. Our findings indicate that RYGB-induced weight loss significantly decreases morphine metabolic ratio, arguing for an effect of morbid obesity on glucuronidation. With glucuronide exposure at 6 months similar to preoperative values, a higher morphine AUC0-inf should encourage reducing morphine dosage in patients undergoing RYGB and chronically receiving immediate-release oral morphine.

BACKGROUND The visceral adipose tissue (VAT) volume is a predictive and/or prognostic factor for many cancers. The objective of our study was to develop an automatic measurement of the whole VAT volume using a multi-atlas segmentation (MAS) method from a computed tomography. METHODS A total of 31 sets of whole-body computed tomography volume data were used. The reference VAT volume was defined on the basis of manual segmentation (VATMANUAL). We developed an algorithm, which measured automatically the VAT volumes using a MAS based on a nonrigid volume registration algorithm coupled with a selective and iterative method for performance level estimation (SIMPLE), called VATMAS_SIMPLE. The results were evaluated using intraclass correlation coefficient and dice similarity coefficients. RESULTS The intraclass correlation coefficient of VATMAS_SIMPLE was excellent, at 0.976 (confidence interval, 0.943-0.989) (P < 0.001). The dice similarity coefficient of VATMAS_SIMPLE was also good, at 0.905 (SD, 0.076). CONCLUSIONS This newly developed algorithm based on a MAS can measure accurately the whole abdominopelvic VAT.

The Quebec Longitudinal Study of Kindergarten Children (QLSKC) is an ongoing population-based prospective longitudinal study presently spanning ages 6-29 years, designed to study the prevalence, risk factors, development and consequences of behavioural and emotional problems during elementary school. Kindergarten boys and girls attending French-speaking public schools in the Canadian province of Quebec during the 1986-87 and 1987-88 school years were included in the cohort: 2000 children representative of the population and 1017 children exhibiting disruptive behaviour problems. To date, 12 waves of data have been collected, and three generations of participants have been involved in the study (i.e. the study child, his parents and the first child of the study child). Information on demographics, psycho-social and lifestyle factors, child and family member characteristics (physical and mental health), and outcomes such as psychiatric diagnoses, delinquency or school diploma were assessed during three important developmental stages (childhood, adolescence and early adulthood). Blood samples were also collected in early adulthood for genetic analyses. Information on publications, available data and access to data can be found on the following website (http://www.gripinfo.ca/Grip/Public/www/).

The Affective Neuroscience Personality Scales (ANPS) is a personality instrument based on six evolutionary-related brain systems that are at the foundation of human emotions and behaviors: SEEKING, CARING, PLAYFULNESS, FEAR, ANGER, and SADNESS. We sought to assess for the short and long versions of the ANPS: (a) the longitudinal measurement invariance and long-term (4-year) stability and (b) the sex measurement invariance. Using data from a Canadian cohort ( N = 518), we used single-group confirmatory factor analysis to assess longitudinal invariance and multiple-group confirmatory factor analysis to assess sex invariance, according to a five-step approach evaluating five invariance levels (configural, metric, scalar, residual, and complete). Results supported full longitudinal invariance for both versions for all invariance levels. Partial residual invariance was supported for sex invariance. The long-term stability of both versions was good to excellent. Implications for personality assessment and ANPS development are discussed.

The aim of this study was to evaluate, in a predominantly white population, correlations between radiological and pathological diagnoses based on the latest classifications of pulmonary adenocarcinomas. We analysed data from patients undergoing lung resection for ground glass nodules (GGNs) less than 3 cm and whose solid component was

International audience; PURPOSE: Liver metastases develop in 50 percent of patients with colorectal carcinoma. Recurrent liver disease is usual. Repeat liver resection remains the only curative treatment. The aim of this study was to review our data on repeat hepatectomy and to analyze potential prognostic factors of survival.METHOD: Patients who underwent repeat liver resection for metastases of colorectal carcinoma between January 1992 and August 2007 were identified from a prospective database and their medical records were analyzed. RESULTS: Of 62 patients who underwent a second hepatectomy, 15 underwent a third hepatectomy, and two underwent a fourth hepatectomy. There was no perioperative mortality. Morbidity was less than 20 percent for the first and second hepatectomies. Overall 5-year survival rate after first hepatectomy was 40 percent. Univariate analysis identified three risk factors confirmed by log-rank test and multivariate Cox regression analysis: serum carcinoembryonic antigen concentrations >5 ng/ml at first hepatectomy (HR = 2.265; CI = 1.140-4.497; P = 0.020), anatomic resection (HR = 2.124; CI = 1.069-4.218; P = 0.031), and tumors ≥3 cm at the second resection (HR = 2.039; CI = 1.013-4.103; P = 0.046). CONCLUSION: Our study shows that repeat hepatectomy for liver metastases of colorectal carcinoma may be performed with low mortality and morbidity. Preoperative concentration of carcinoembryonic antigen at first hepatectomy, tumor size, and type of anatomic resection are independent prognostic factors.

// Anna Raimbault 1, 2, 3, 4, 5, * , Cecile Pierre-Eugene 1, * , Alexandra Rouquette 6 , Celine Deudon 1 , Lise Willems 7 , Nicolas Chapuis 1, 2, 3, 4, 5 , Stephanie Mathis 1, 2, 3, 4, 5 , Claudia Kunz 8 , Harald Fricke 8 , Olivier Kosmider 1, 2, 3, 4, 5 , Valerie Bardet 1, 2, 3, 4, 5 , Michaela Fontenay 1, 2, 3, 4, 5 , on behalf of the Groupe Francophone des Myelodysplasies 1 Assistance Publique-Hopitaux de Paris, Service d’Hematologie Biologique, Hopitaux Universitaires Paris Centre, Hopital Cochin, Paris, France 2 Universite Paris Descartes, Faculte de Medecine, Paris, France 3 Institut National de la Sante et de la Recherche Medicale (INSERM) U1016, Paris, France 4 Centre National de la Recherche Scientifique, Unite Mixte de Recherche 8104, Paris, France 5 Institut Cochin, Department of Development, Reproduction and Cancer, Paris, France 6 Departement d’Epidemiologie et de Biostatistiques, Hopitaux Universitaires Paris Centre, Paris, France 7 Assistance Publique-Hopitaux de Paris, Service d’Hematologie Clinique, Hopitaux Universitaires Paris Centre, Hopital Cochin, Paris, France 8 APOGENIX, GmbH, Heidelberg, Germany * These authors have contributed equally to this work Correspondence to: Michaela Fontenay, e-mail: michaela.fontenay@inserm.fr Keywords: myelodysplastic syndromes, erythropoiesis, CD95, CD95 ligand, anemia Received: September 07, 2015 Accepted: January 02, 2016 Published: February 18, 2016 ABSTRACT CD95, a member of the death receptor family initiates a caspase-dependent apoptosis, when activated by its ligand CD95L, thought to negatively regulate erythrocyte production in the bone marrow. We have previously shown that CD95 is overexpressed in two thirds of patients with a lower risk myelodysplastic syndrome (MDS) and that resistance to erythropoiesis-stimulating agents (ESA) is linked to poor residual erythropoiesis. In the present study, we show that CD95 overexpression and previous transfusion are independent predictive factors of ESA resistance. To investigate an alternative therapeutic strategy of anemia in ESA-resistant patients, we have conducted a preclinical study of the effects of APG101, a fusion protein consisting of the extracellular domain of human CD95 and the Fc region of human IgG1 on MDS erythropoiesis in vitro . APG101 increases the number of burst-forming unit-erythroid (BFU-E) progenitors derived from CD34 + progenitors in liquid culture and improves overall proliferation rate of erythroid precursors by inhibiting apoptosis. APG101 rescues BFU-E growth in MDS patients presenting with attrition of erythroid progenitors at baseline, independently of CD95 or CD95L expression level. Our data show that overexpression of CD95 at diagnosis is a hallmark of ESA resistance and that severe impairment of erythropoiesis is predictive of erythroid response to APG101 in vitro . These data provide a rationale for further clinical investigation of APG101 in an attempt to treat anemia in lower risk MDS patients.

The standardized uptake lean body mass (SUL), calculated using lean body mass (LBM), is essential for the semiquantification of (18)F-FDG uptake using PET coupled with CT to avoid a bias linked to the adipose mass. It allows the evaluation of a response to therapy according PERCIST 1.0. The aim of this study was to evaluate the reliability of a method for the estimation of the LBM using the data of the low-dose CT from PET/CT acquired over standard acquisition fields (from skull base to ischia, from vertex to ischia, from skull base to mid thigh, from vertex to mid thigh).We wrote an automated program that determined the LBM from a CT with limited fields of acquisition and applied this method in a large (184 patients) and heterogeneous population. Its results were compared with the measurement of LBM from whole-body CT (reference standard) and the results of 5 predictive equations described in the literature.The results of LBM measurement evaluated with this technique were much closer to the reference standard than those obtained by the mathematic formulas. The intraclass correlations (ICC) of this technique compared with the reference standard were excellent (the best ICC being obtained for the largest acquisition field, from vertex to mid thigh: ICC, 0.994; 95% confidence interval [95% CI], 0.992-0.995; P0.0001), much better than the ICC obtained with the mathematic formulas (the best ICC for a mathematic formula was 0.841; 95% CI, 0.714-0.903; P0.0001). Moreover, the analysis with the Bland-Altman plot showed that the differences in mean lean masses between the studied technique and the reference standard was the smallest for the proposed technique (for the largest acquisition field, mean difference 0.2 kg with the narrowest 95% CI [-1.8 to 2.2 kg]).This technique could be easily implemented on computers used in practice to allow a more reliable assessment of the SUL in clinical practice notably for the therapeutic evaluations after PERCIST 1.0.

International audience; The International Classification of Functioning, Disability and Health (ICF) published in 2001 describes the consequences of health conditions with three components of impairments in body structures or functions, activity limitations and participation restrictions. Two of the new features of the conceptual model were the possibility of feedback effects between each ICF component and the introduction of contextual factors conceptualized as moderators of the relationship between the components. The aim of this longitudinal study is to provide empirical evidence of these two kinds of effect. Structural equation modeling was used to analyze data from a French population-based cohort of 548 patients with knee osteoarthritis recruited between April 2007 and March 2009 and followed for three years. Indicators of the body structure and function, activity and participation components of the ICF were derived from self-administered standardized instruments. The measurement model revealed four separate factors for body structures impairments, body functions impairments, activity limitations and participation restrictions. The classic sequence from body impairments to participation restrictions through activity limitations was found at each assessment time. Longitudinal study of the ICF component relationships showed a feedback pathway indicating that the level of participation restrictions at baseline was predictive of activity limitations three years later. Finally, the moderating role of personal (age, sex, mental health, etc.) and environmental factors (family relationships, mobility device use, etc.) was investigated. Three contextual factors (sex, family relationships and walking stick use) were found to be moderators for the relationship between the body impairments and the activity limitations components. Mental health was found to be a mediating factor of the effect of activity limitations on participation restrictions.

BackgroundAlthough several face-to-face programs are dedicated to informal caregivers of persons with dementia, they are not always accessible to overburdened or isolated caregivers. Based on a face-to-face intervention program, we adapted and designed a Web-based fully automated psychoeducational program (called Diapason) inspired by a cognitive approach. ObjectiveThis study aimed to evaluate through a pilot unblinded randomized controlled trial the efficacy and acceptability of a Web-based psychoeducational program for informal caregivers of persons with Alzheimer’s disease (PWAD) based on a mixed methods research design. MethodsWe recruited and randomized offline 49 informal caregivers of a PWAD in a day care center in Paris, France. They either received the Web-based intervention and usual care for 3 months (experimental group, n=25) or only usual care (control group, n=24). Caregivers’ perceived stress (PSS-14, primary outcome), self-efficacy, burden, perceived health status, and depression (secondary outcomes) were measured during 3 face-to-face on-site visits: at baseline, at the end of the program (month 3), and after follow-up (month 6). Additionally, semistructured interviews were conducted with experimental group caregivers at month 6 and examined with thematic analysis. ResultsIntention-to-treat analysis did not show significant differences in self-perceived stress between the experimental and control groups (P=.98). The experimental group significantly improved their knowledge of the illness (d=.79, P=.008) from baseline to month 3. Of the 25 participants allocated to the experimental group, 17 (71%) finished the protocol and entirely viewed at least 10 of 12 online sessions. On average, participants used the website 19.72 times (SD 12.88) and were connected for 262.20 minutes (SD 270.74). The results of the satisfaction questionnaire showed that most participants considered the program to be useful (95%, 19/20), clear (100%, 20/20), and comprehensive (85%, 17/20). Significant correlations were found between relationship and caregivers’ program opinion (P=.01). Thus, positive opinions were provided by husbands and sons (3/3), whereas qualified opinions were primarily reported by daughters (8/11). Female spouses expressed negative (2/3) or neutral opinions (1/3). Caregivers expected more dynamic content and further interaction with staff and peers. ConclusionsIn this study, quantitative results were inconclusive owing to small sample size. Qualitative results indicated/showed little acceptance of the program and high expectations from caregivers. Caregivers did not rule out their interest in this kind of intervention provided that it met their needs. More dynamic, personalized, and social interventions are desirable. Our recruitment issues pointed out the necessity of in-depth studies about caregivers’ help-seeking behaviors and readiness factors. Trial RegistrationClinicaltrials.gov NCT01430286; http://clinicaltrials.gov/ct2/show/NCT01430286 (Archived by WebCite at http://www.webcitation/6KxHaRspL).

Purpose Many malignancy scores have been developed without comprehensive statistical or measurement validation, and in particular without verification of the necessary property of unidimensionality. Here, we used Rasch analysis to assess unidimensionality and identify measurement biases of malignancy scores. Methods The Weiss histopathological system (WHS), summing nine items of histopathological alteration, was used to evaluate 247 adrenocortical tumors. Rasch model analysis was implemented and compared to classical factor analytic methods to investigate the validity of item-score summation for both the original and modified WHS, to assess differential functioning of the WHS items across various factors related to patient and tumors, and to identify items or subtypes of tumors that could be considered for removal or exclusion from the WHS with the aims of improving measurement and relieving the burden on pathologists. Results The WHS does not meet the necessary property of unidimensionality and is severely affected by differential item functioning in relation to size and weight of the tumor. Moreover, items are not well distributed along the spectrum of malignancy, most being located in the upper part and several at the same place. Conclusion The WHS in its present form should be applied only to small or moderate size tumors, and better scoring systems could be developed by using more appropriately distributed items. Rasch analysis is a powerful method for developing, evaluating, refining and simplifying malignancy scores.

Several groups have published flow cytometry scores useful for the diagnosis or prognosis of myelodysplastic syndromes (MDS), mainly based on the detection of immunophenotypic abnormalities in the maturation of granulocytic/monocytic and lymphoid lineages. As anemia is the most frequent symptom of early MDS, the aim of this study was to identify markers of dyserythropoiesis relevant for the diagnosis of MDS analyzed by selecting erythroblasts in a whole no-lysis bone marrow strategy by using a nuclear dye. This prospective study included 163 patients, including 126 with cytopenias leading to MDS suspicion and 46 controls without MDS. In a learning cohort of 53 unequivocal MDS with specific markers, there was a significant difference between the coefficients of variation of mean fluorescence intensities of CD71 and CD36 in MDS patients compared with controls. These two parameters and the hemoglobin level were used to build a RED-score strongly suggestive of MDS if ≥ 3. Using the RED-score in the whole cohort, 80% of MDS or non-MDS patients were correctly classified. When combined with the flow score described by Ogata et al., this strategy allowed to reach a very high sensitivity of 88% of patients correctly classified.

Assess 50 years old and over patients' attitudes towards and experiences of generic substitution of prescription medicines. A special focus on information on patient attitude to generic drugs provided by their general practitioners (GPs).Prospective study of patients in 15 general practices and in 2 retirements home was surveyed using a self-questionnaire.Four hundred and forty patients were included. Four twenty eleven per cent of the patients stated that they knew of the difference between brand-name drugs and generics but only 57% knew it exactly in fact. Seventy seven per cent had received generics by their GPs; 45% reported to have received information from their physician. The study found that patients who report to have received information from their physician about generic substitution were more likely to have switch. Patient in retirement home more frequently refused substitution. Elderly patients (75 and more) were wrong with generics definition compared with others patients, and observed more adverse effects after switching (20% versus 9%--p=0.027); patients made more mistake using generics than brand-name drugs (15.5% versus 7%--p0.005); two thirds of the patients (72%) were satisfied with switching, and 57% reported to want more information and 85% of them that it comes from their GPs.Most of the patients are satisfied with generics. GPs are in an ideal position to inform their patients adequately about the equivalence of brand-name and generic drugs. Patient education is the best way to use generics in the future. More efforts must be devoted to provide adequate information to patients and GPs.