Smoking and mental disability : A mixed observational study using a diverse sample of medical-social establishments and services / Tabagisme et handicap psychique : étude observationnelle mixte dans un échantillon diversifié d'établissements et de services médico-sociaux.

INTRODUCTION: A multi-center observational study was carried out in ten ESMS, using a mixed methodology (site visits, questionnaire survey, semi-directive group interviews with professionals and individual interviews with users). PURPOSE OF THE RESEARCH: The aim of this article is to describe the management and prevention of smoking in ESMS for people with mental health disorders, and to characterize and identify the smoking behaviors and representations of ESMS users and the professionals working there. RESULTS: The study made it possible to distinguish between ESMS in terms of the organization of smoking areas and tobacco prevention initiatives. It also revealed that 37 percent of respondents among the professionals said they smoked tobacco, with some of them explaining that they smoked with users and sometimes gave them cigarettes. With regard to prevention, there was a consensus among professionals that they should help users who wanted to stop smoking. Professionals were divided, however, on the need for more active prevention, citing the users' freedom and the fact that ESMS are places where people live. Among the users, 47 percent said they were smokers. Of the users who smoked, 55 percent said they wanted to stop. Interviews with the users revealed that twelve of them wanted to quit, with some asking for help and more assistance from professionals. CONCLUSIONS: This report suggests that intervention research could be developed in ESMS for people with mental health disorders, who could benefit from the smoking prevention actions identified in the facilities and services investigated.

Introduction: Une étude observationnelle multicentrique a été réalisée dans dix ESMS et mobilisait une méthodologie mixte (visite des structures, enquête par questionnaires, entretiens semi-directifs collectifs avec des professionnels et individuels avec des usagers). But de l'étude: Cet article vise à décrire la gestion et la prévention du tabagisme dans des établissements et services médico-sociaux (ESMS) accueillant des personnes avec un trouble psychique, et à caractériser et identifier les comportements tabagiques et les représentations de leurs usagers et professionnels. Résultats: L'étude a permis de distinguer les ESMS au regard de l'organisation des espaces du tabagisme et des actions de prévention du tabac. Elle a permis également de constater que 37 % des professionnels qui ont répondu déclaraient fumer du tabac, une partie d'entre eux expliquant fumer avec les usagers et leur donner parfois des cigarettes. Concernant la prévention, un consensus se dégageait chez les professionnels sur le fait d'aider les usagers qui souhaitaient arrêter. Les professionnels étaient cependant divisés à l'égard d'une prévention plus active, invoquant la liberté de l'usager et le fait que les ESMS sont des lieux de vie. 47 % des usagers se disaient fumeurs. 55 % des usagers fumeurs déclaraient vouloir arrêter. Les entretiens avec les usagers ont permis de constater que douze d'entre eux souhaitaient arrêter, une partie réclamant de l'aide et d'être davantage aidés par les professionnels. Conclusions: Cet état des lieux invite à développer des recherches interventionnelles dans les ESMS accueillant des personnes avec un trouble psychique qui pourraient tirer profit des actions de prévention du tabac repérées dans des structures enquêtées.

Information overload in the context of COVID-19 pandemic: A repeated cross-sectional study.

OBJECTIVES: To assess the psychometric properties of the Coronavirus Information Overload scale (CovIO) and explore relationships between CovIO, its predictors and several health behaviours related to the COVID-19 pandemic, using Cancer Information Overload (CIO) scale results as a reference for comparison. METHODS: 2003 participants representative of the French adult population answered a self-administered questionnaire over two waves of polling (N1(June 2020)= 1003, N2(January 2021)= 1000). Respondents were randomized to fill CovIO or CIO scale. Psychometric properties of scales were evaluated with Confirmatory Factor Analysis (CFA). Predictors were assessed using multivariate linear regression. RESULTS: CovIO scale showed satisfactory psychometric properties (α=0.86, ω=0.86, RMSEA=0.050) without any measurement invariance issue. CovIO increased between waves of sampling and was significantly linked to education, health literacy and trust in institutions among other variables. A negative relationship between information overload and preventive behaviours was also observed. CONCLUSION: The CovIO scale is a valid tool for assessing COVID-19 information overload. The dynamical formation of information overload and links with theorised predictors, especially, health literacy are confirmed. PRACTICE IMPLICATIONS: Longitudinal designs could help better understand the potential detrimental effect of information overload and improving public health campaigns. Interventions to reduce the degree of overload are needed.

"FastSchool": A single session of an interprofessional pain management program for chronic pain patients inspired by cognitive behavioral therapy.

OBJECTIVES: Multidisciplinary approaches to treating chronic pain have been proven effective. Currently, chronic pain patients face lengthy waitlists in pain medicine departments. To overcome this problem, we developed the "FastSchool" program to educate patients about pain management and treatment. In this study, we evaluated the benefit of a "FastSchool" session on pain and catastrophizing in chronic pain patients. METHODS: Included patients had chronic non-cancer pain, no more than 2 visits to a pain medicine department. Patients attended a single 3-hour session, conducted by an interprofessional team. Four topics were addressed: chronic pain mechanisms, pharmacological therapies, physical activity, and the management of analgesics. Patients completed questionnaires at baseline and at 3 months post-session to assess pain interference, pain intensity, and catastrophizing. RESULTS: The study population included 88 patients; 71 completed the follow-up questionnaires. Pain interference (p = 0.002), average pain intensity (p = 0.013), and catastrophizing (p < 0.001) decreased 3 months after FastSchool. At M3, 35 % of patients felt their pain had improved based on the Patient Global Impression of Change. CONCLUSION: FastSchool, an innovative short-term educational program inspired by cognitive behavioral therapy, showed positive results in reducing pain impact. PRACTICE IMPLICATIONS: Implementation of FastSchool in pain medicine departments would reduce waitlist times for non-pharmacological treatment.

Validity of the French version of Catquest-9SF and use of an electronic notepad for entering patient-reported outcome measures.

BACKGROUND: The Catquest-9SF questionnaire is a patient reported outcome measure that quantifies the visual benefits from cataract surgery. The purpose of this study was to translate and adapt the Catquest-9SF questionnaire for France, to assess its psychometric properties via Rasch analysis, and to assess its validity when completed using an electronic notepad. METHODS: The Catquest-9SF questionnaire was translated following the guidelines of the International Society for Pharmacoeconomics and Outcomes Research. Catquest-9SF and clinical data were collected from patients before and after routine cataract surgery. All questionnaire data were collected via an electronic notepad. Rasch analysis was performed to assess psychometric properties, and sensitivity to change was analysed for patients with complete paired pre- and post-operative questionnaires. RESULTS: A complete filled-in preoperative questionnaire was obtained for 848 patients. Rasch analysis showed good precision (person separation: 2.32, person reliability: 0.84), ordered category probability curves, no item misfit, and unidimensionality. The respondents were slightly more able than the level of item difficulty (targeting: -1.12 logits). Sensitivity was analysed on 211 paired questionnaires, and the postoperative questionnaires showed a clear ceiling effect. The effect size was 2.6. The use of an electronic notepad for completing the questionnaire worked out very well after some adjustments. CONCLUSIONS: The French version of Catquest-9SF has good psychometric properties and is suitable for use in French-speaking patients. The use of the Catquest-9SF questionnaire in an electronic format showed good validity.

Incidence and risk factors of COVID-19-like symptoms in the French general population during the lockdown period: a multi-cohort study.

BACKGROUND: Our main objectives were to estimate the incidence of illnesses presumably caused by SARS-CoV-2 infection during the lockdown period and to identify the associated risk factors. METHODS: Participants from 3 adult cohorts in the general population in France were invited to participate in a survey on COVID-19. The main outcome was COVID-19-Like Symptoms (CLS), defined as a sudden onset of cough, fever, dyspnea, ageusia and/or anosmia, that lasted more than 3 days and occurred during the 17 days before the survey. We used delayed-entry Cox models to identify associated factors. RESULTS: Between April 2, 2020 and May 12, 2020, 279,478 participants were invited, 116,903 validated the questionnaire and 106,848 were included in the analysis. Three thousand thirty-five cases of CLS were reported during 62,099 person-months of follow-up. The cumulative incidences of CLS were 6.2% (95% Confidence Interval (95%CI): 5.7%; 6.6%) on day 15 and 8.8% (95%CI 8.3%; 9.2%) on day 45 of lockdown. The risk of CLS was lower in older age groups and higher in French regions with a high prevalence of SARS-CoV-2 infection, in participants living in cities > 100,000 inhabitants (vs rural areas), when at least one child or adolescent was living in the same household, in overweight or obese people, and in people with chronic respiratory diseases, anxiety or depression or chronic diseases other than diabetes, cancer, hypertension or cardiovascular diseases. CONCLUSION: The incidence of CLS in the general population remained high during the first 2 weeks of lockdown, and decreased significantly thereafter. Modifiable and non-modifiable risk factors were identified.

Cancer information overload: Association between a brief version of the CIO scale and multiple cancer risk management behaviours.

OBJECTIVES: To demonstrate the best psychometric properties of the revised 5-item Cancer Information Overload (CIO) scale over the 10- and 8-item versions, for both English and French native speakers, and to explore the relationships between CIO and several cancer risk management behaviours in a large sample of caregivers, cancer survivors and healthy subjects. METHODS: 2809 participants (2568 from France, 241 from Australia) from two cancer survivor networks answered a self-administered questionnaire. After assessing the psychometric properties we studied the impact of CIO on health behaviours using multivariate logistic regression. RESULTS: Internal consistency assessment and Confirmatory Factor Analysis (CFA) showed satisfactory results (α = 0.87 and 0.83, ω = 0.87 and 0.83, RMSEA = 0.078 and 0.081 for the 8-item and 5-item versions respectively), as well as multi-group CFA where measurement invariance was partial for one item only in each version. CIO was independently associated with smoking, sunburns, and rare skin checks, but not with alcohol misuse. CONCLUSION: The 5-item version of the CIO scale showed adequate psychometric properties and discriminant association with multiple prevention behaviours. PRACTICE IMPLICATIONS: The 5-item CIO scale is valid and can help push research forward in the domain of disease prevention and message acceptance. Its role in clinical practice remains to be determined.

Effect of fibrinogen concentrate administration on early mortality in traumatic hemorrhagic shock: A propensity score analysis.

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.

Validity of the French version of the Autonomy Preference Index and its adaptation for patients with advanced cancer.

BACKGROUND: While patient-centered care is recommended as a key dimension for quality improvement, in case of serious illness, patients may have different expectations regarding information and participation in medical decision-making. In oncology, anticipation of disease worsening remains difficult, especially when patient's preferences towards prognosis medical information are unclear. Valid tools to explore patients' preferences could help targeting end-of-life discussions, which have been shown to decrease aggressiveness of end-of-life care. Our aim was to establish the validity and reliability of the French version of the Autonomy Preference Index (API) among patients with incurable cancer and in primary care setting. Three supplementary items were specifically developed to evaluate preparedness to anticipate disease deterioration among patients with incurable cancer. METHODS: The psychometric properties of the API translated into French were assessed among patients consecutively recruited from January to March 2017 in the waiting rooms of 19 general practitioners (N = 391) and in an oncology (N = 187) clinic in Paris. Relationships between the newly-developed items and the API subscale scores were studied. RESULTS: A three correlated factors confirmatory model (two factors related to decision-making and a factor related to information-seeking preferences) showed an acceptable fit on the whole sample and no measurement invariance issue was found across settings, age, sex and educational level. Internal consistency and test-retest reliability were acceptable for the information-seeking and decision-making subscales. One of the newly-developed items on patients' ability to anticipate a decision on the use of artificial respiration if a sudden deterioration of their illness occurred was not related to the API subscale scores. CONCLUSION: The French version of the API was found valid and reliable for use in general practice and oncology settings. The additional items on patient preparedness to anticipate disease deterioration can be of interest to ensure that patient values guide all end-of-life clinical decisions.

Pain Trajectory After Ankle Surgeries for Osteoarthritis.

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.

Hypermethylator Phenotype and Ectopic GIP Receptor in GNAS Mutation-Negative Somatotropinomas.

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.

Development and validation of a pre-hospital "Red Flag" alert for activation of intra-hospital haemorrhage control response in blunt trauma.

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.

Automatic Measurement of the Total Visceral Adipose Tissue From Computed Tomography Images by Using a Multi-Atlas Segmentation Method.

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.

Validation of the French version of the Functional, Communicative and Critical Health Literacy scale (FCCHL).

BACKGROUND: Health literacy is a key asset, defined as the capacity to acquire, understand and use information in ways which promote and maintain good health. OBJECTIVES: To assess the reliability and validity of the French translation of the Functional, Communicative and Critical Health Literacy (FCCHL) scale. METHODS/PARTICIPANTS: A cross-sectional survey using an online questionnaire was proposed to all members of Seintinelles association. Exploratory and confirmatory factorial analyses were conducted. RESULTS: Data from 2342 respondents (45.8% had cancer history) were analysed. The FCCHL scale was well-accepted (missing value by item ≤0.7%). Factor analysis revealed an acceptable fit of three-factor model (comparative fit index = 0.922, root mean square error of approximation = 0.065 and standardized root mean square residual = 0.052). The FCCHL showed satisfactory reliability (α = 0.77) and scalar invariance was reached for education and deprivation, but not for age. Known group validity was verified as mean scale scores differed according to education, deprivation and age, as expected. CONCLUSION: The French version of the FCCHL provides a brief reliable and valid measure to explore the dimensions of health literacy. It could be used by health professionals to screen for health literacy level in order to develop this skill and to tailor health communication.

The effect of morbid obesity on morphine glucuronidation.

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.

Predictive Factors of Chronic Post-Surgical Pain at 6 Months Following Knee Replacement: Influence of Postoperative Pain Trajectory and Genetics.

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.

APG101 efficiently rescues erythropoiesis in lower risk myelodysplastic syndromes with severe impairment of hematopoiesis.

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.

A Method to Improve the Semiquantification of 18F-FDG Uptake: Reliability of the Estimated Lean Body Mass Using the Conventional, Low-Dose CT from PET/CT.

UNLABELLED: 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). METHODS: 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. RESULTS: 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; P < 0.0001), 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; P < 0.0001). 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]). CONCLUSION: 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.

Rasch analysis for assessing unidimensionality and identifying measurement biases of malignancy scores in oncology. The example of the Weiss histopathological system for the diagnosis of adrenocortical cancer.

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.