Familial partial lipodystrophy type 2 and obesity, two adipose tissue pathologies with different inflammatory profiles.

INTRODUCTION: The transition to metabolically unhealthy obesity (MUO) is driven by the limited expandability of adipose tissue (AT). Familial Partial Lipodystrophy type 2 (FPLD2) is an alternative model for AT dysfunction that is suitable for comparison with obesity. While MUO is associated with low-grade systemic inflammation, studies of inflammation in FPLD2 have yielded inconsistent results. Consequently, comparison of inflammation markers between FPLD2 and obesity is of great interest to better understand the pathophysiological defects of FPLD2. OBJECTIVE: To compare the levels of inflammatory biomarkers between a population of patients with FPLD2 due to the same 'Reunionese' LMNA variant and a population of patients with obesity (OB group). METHODS: Adiponectin, leptin, IL-6, TNF-α and MCP-1 plasma levels were measured by enzyme-linked immuno assays for 60 subjects with FPLD2 and for 60 subjects with obesity. The populations were closely matched for age, sex, and diabetic status. RESULTS: Metabolic outcomes were similar between the two populations. Adiponectinemia and leptinemia were lower in the FPLD2 group than in the OB group (p < 0.01 for both), while MCP-1 levels were higher in the FPLD2 than in the OB group (p < 0.01). Levels of other inflammatory markers were not significantly different. CONCLUSIONS: Insulin-resistant patients with FPLD2 and obesity share common complications related to AT dysfunction. Inflammatory biomarker analyses demonstrated that MCP-1 levels and adiponectin levels differ between patients with FPLD2 and patients with obesity. These two AT pathologies thus appear to have different inflammatory profiles.

Lipoatrophic diabetes in familial partial lipodystrophy type 2: From insulin resistance to diabetes.

AIM: Subjects with Familial Partial Lipodystrophy type 2 (FPLD2) are at high risk to develop diabetes. To better understand the natural history and variability of this disease, we studied glucose tolerance, insulin response to an oral glucose load, and metabolic markers in the largest cohort to date of subjects with FPLD2 due to the same LMNA variant. METHODS: A total of 102 patients aged > 18 years, with FPLD2 due to the LMNA 'Reunionese' variant p.(Thr655Asnfs*49) and 22 unaffected adult relatives with normal glucose tolerance (NGT) were enrolled. Oral Glucose Tolerance Tests (OGTT) with calculation of derived insulin sensitivity and secretion markers, and measurements of HbA1c, C-reactive protein, leptin, adiponectin and lipid profile were performed. RESULTS: In patients with FPLD2: 65% had either diabetes (41%) or prediabetes (24%) despite their young age (median: 39.5 years IQR 29.0-50.8) and close-to-normal BMI (median: 25.5 kg/m2 IQR 23.1-29.4). Post-load OGTT values revealed insulin resistance and increased insulin secretion in patients with FPLD2 and NGT, whereas patients with diabetes were characterized by decreased insulin secretion. Impaired glucose tolerance with normal fasting glucose was present in 86% of patients with prediabetes. Adiponectin levels were decreased in all subjects with FPLD2 and correlated with insulin sensitivity markers. CONCLUSIONS: OGTT reveals early alterations of glucose and insulin metabolism in patients with FPLD2, and should be systematically performed before excluding a diagnosis of prediabetes or diabetes to adapt medical care. Decreased adiponectin is an early marker of the disease. Adiponectin replacement therapy warrants further study in FPLD2.

A recurrent familial partial lipodystrophy due to a monoallelic or biallelic LMNA founder variant highlights the multifaceted cardiac manifestations of metabolic laminopathies.

AIMS: LMNA-linked familial partial lipodystrophy type 2 (FPLD2) leads to insulin resistance-associated metabolic complications and cardiovascular diseases. We aimed to characterise the disease phenotype in a cohort of patients carrying an LMNA founder variant. METHODS: We collected clinical and biological data from patients carrying the monoallelic or biallelic LMNA p.(Thr655Asnfs*49) variant (n = 65 and 13, respectively) and 19 non-affected relative controls followed-up in Reunion Island Lipodystrophy Competence Centre, France. RESULTS: Two-thirds of patients with FPLD2 (n = 51) and one-third of controls (n = 6) displayed lipodystrophy and/or lean or android morphotype (P = 0.02). Although age and BMI were not statistically different between the two groups, the insulin resistance index (median HOMA-IR: 3.7 vs 1.5, P = 0.001), and the prevalence of diabetes, dyslipidaemia, and non-alcoholic fatty liver disease were much higher in patients with FPLD2 (51.3 vs 15.8%, 83.3 vs 42.1%, and 83.1 vs 33.3% (all P ≤ 0.01), respectively). Atherosclerosis tended to be more frequent in patients with FPLD2 (P = 0.07). Compared to heterozygous, homozygous patients displayed more severe lipoatrophy and metabolic alterations (lower BMI, fat mass, leptin and adiponectin, and higher triglycerides P ≤ 0.03) and tended to develop diabetes more frequently, and earlier (P = 0.09). Dilated cardiomyopathy and/or rhythm/conduction disturbances were the hallmark of the disease in homozygous patients, leading to death in four cases. CONCLUSIONS: The level of expression of the LMNA 'Reunionese' variant determines the severity of both lipoatrophy and metabolic complications. It also modulates the cardiac phenotype, from atherosclerosis to severe cardiomyopathy, highlighting the need for careful cardiac follow-up in affected patients.

Teriflunomide-exposed pregnancies in a French cohort of patients with multiple sclerosis.

OBJECTIVE: To describe pregnancies exposed to teriflunomide (TERIF) in women with multiple sclerosis (MS) in France over the period 2014-2016. METHODS: All 15- to 49-year-old women with MS in the national health insurance database were included. Pregnancies that had started between August 2014 and March 2016 were identified from their outcomes. Three groups according to treatment exposure were compared: TERIF, interferons (IFNs) or glatiramer acetate, and no medication. RESULTS: Among the 44,008 women with MS followed 24.5 months on average, 2,639 pregnancies were identified. There were 1,538 pregnancies (58.3%) that were not exposed to any MS treatment in accordance with the guidelines. A total of 673 pregnancies (25.5%) were exposed to IFN and/or glatiramer acetate, and possible or probable exposure to contra-indicated treatments was observed in 428 pregnancies (16.2%), of whom 47 pregnancies were exposed to TERIF. The annual incidence rate of pregnancies exposed to TERIF was 1.4 per 100 patient-years; i.e., 3 times less than the 2 control groups (5.6 and 4.7, respectively). The median exposure duration to TERIF was 45 days after conception. The outcomes comprised 23 live births, 22 abortions (3 times more than the 2 other groups), and 2 miscarriages. All newborns were healthy at birth. CONCLUSIONS: Despite specific TERIF guidelines for pregnancy-related issues and the availability of alternative therapies, some pregnancies exposed to TERIF were identified. Most of the cases were because of the absence of the recommended accelerated elimination procedure and appeared to be mostly unplanned pregnancies that probably reflect a lack of effective contraception.

Prevalence of mental disorders is higher in patients with multiple sclerosis than in the general population or in patients with rheumatoid arthritis in France.

BACKGROUND: Mental disorders (MDs) in multiple sclerosis (MS) patients decreases treatment adherence and quality of life, and increases the risk of disability progression and care consumption. OBJECTIVE: This study was to assess the prevalence of MDs in MS patients compared with healthy controls (HC) of the French general population and rheumatoid arthritis (RA) patients. METHODS: The 2015 prevalence of MDs for MS patients, RA patients and general population was estimated using a random population-based data sample from 'National Inter-Scheme Information System on Health Insurance' in the 2011-2015 period. Two control groups (1:5 ratio for the HC and 1:1 for the RA group) were matched to the MS group for year of birth, gender, area of residence and health insurance scheme. RESULTS: A total of 1145 MS patients were identified (sex ratio of 2.5 (F/M); median age 50 years). The prevalence of MDs was higher in the population of patients with MS (37.3%) than in the French general population (13.6%), and to a lesser extent in the RA group (21.1%) leading to the prevalence ratios of 2.8 (95% confidence intervals (CIs) 2.5-3.0) and 1.9 (95% CI 1.7-2.3), respectively. CONCLUSIONS: This study confirmed that MS patients are at a higher risk of MDs than the French general population or RA patients.

Both active and sham low-frequency rTMS single sessions over the right DLPFC decrease cue-induced cravings among pathological gamblers seeking treatment: A randomized, double-blind, sham-controlled crossover trial.

Background Craving is a core symptom of addictive disorders, such as pathological gambling for example. Over the last decade, several studies have assessed the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the addiction field, which triggers the dorsolateral prefrontal cortex (DLPFC) to decrease craving. The STIMJEU study investigated whether a single session of low-frequency (LF, i.e., 1 Hz) rTMS applied to the right DLPFC reduced cue-induced gambling craving in a sample of treatment-seeking pathological gamblers. Methods Thirty patients received both active and sham rTMS in random order and were blinded to the condition in a within-subject crossover design. Outcome measures included self-reported gambling craving (Visual Analog Scale and Gambling Craving Scale) and physiological measures (heart rate and blood pressure). Results The rTMS sessions were associated with a significant decrease in the gambling urge, regardless of whether the session was active or sham. When controlling cue-induced craving levels, no effects were observed on craving for active rTMS. Overall, rTMS was well-tolerated, and the credibility of the sham procedure was assessed and appeared to be appropriate. Conclusions We failed to demonstrate the specific efficacy of one session of LF rTMS to decrease cue-induced craving in pathological gamblers. A strong placebo-effect and rTMS parameters may partly explain these results. Yet, we are convinced that rTMS remains a promising therapeutic method. Further studies are required to examine its potential effect.

Gambling disorder-related illegal acts: Regression model of associated factors.

Background and aims Gambling disorder-related illegal acts (GDRIA) are often crucial events for gamblers and/or their entourage. This study was designed to determine the predictive factors of GDRIA. Methods Participants were 372 gamblers reporting at least three DSM-IV-TR (American Psychiatric Association, 2000) criteria. They were assessed on the basis of sociodemographic characteristics, gambling-related characteristics, their personality profile, and psychiatric comorbidities. A multiple logistic regression was performed to identify the relevant predictors of GDRIA and their relative contribution to the prediction of the presence of GDRIA. Results Multivariate analysis revealed a higher South Oaks Gambling Scale score, comorbid addictive disorders, and a lower level of income as GDRIA predictors. Discussion and conclusion An original finding of this study was that the comorbid addictive disorder effect might be mediated by a disinhibiting effect of stimulant substances on GDRIA. Further studies are necessary to replicate these results, especially in a longitudinal design, and to explore specific therapeutic interventions.

Cognitive distortions and ADHD in pathological gambling: A national longitudinal case-control cohort study.

Introduction The primary outcome of our study was to assess the links between the level of cognitive distortions and the severity of gambling disorder. We also aimed at assessing the links between patient gambling trajectories and attention deficit and hyperactivity disorder (ADHD). Materials and methods The study population (n = 628) was comprised of problem and non-problem gamblers of both sexes between 18 and 65 years of age, who reported gambling on at least one occasion during the previous year. Data encompassed socio-demographic characteristics, gambling habits, the South Oaks Gambling Screen, the Gambling Attitudes and Beliefs Survey - 23, the Wender Utah Rating Scale - Child, and the Adult ADHD Self-report Scale. Results The cognitive distortions with the greatest correlation to the severity of gambling disorder were the "Chasing" and "Emotions." These two dimensions were able to distinguish between problem gamblers seeking treatment or not. While age of onset of gambling and length of gambling practice were not associated with the level of distorted cognitions, a period of abstinence of at least 1 month was associated with a lower level of distorted cognitions. The presence of ADHD resulted in a higher level of distorted cognitions. Conclusion Cognitive work is essential to the prevention, and the treatment, of pathological gambling, especially with respect to emotional biases and chasing behavior. The instauration of an abstinence period of at least 1 month under medical supervision could be a promising therapeutic lead for reducing gambling-related erroneous thoughts and for improving care strategies of pathological gamblers.

Marked Body Shape Concerns in Female Patients Suffering from Eating Disorders: Relevance of a Clinical Sub-Group.

Concerns about body shape and weight are core diagnostic criteria for eating disorders although intensity varies between patients. Few studies have focused on the clinical differences relative to the intensity of these concerns. Nonetheless, they might have a prognostic value. This study was aimed at identifying the characteristics associated with marked body shape concerns in patients with an eating disorder. Data was collected from a systematic and standardized clinical assessment of outpatients seeking treatment in our department for eating disorders. Only female patients, suffering from anorexia nervosa or bulimia nervosa, and with "no / mild" or "marked" body shape concerns according to the Body Shape Questionnaire, were included for the present study. We focused on sociodemographic characteristics, eating disorder characteristics, axis 1 disorders, types of attachment, self-esteem and dissociation. A multiple logistic regression was performed to identify factors related to "marked" body shape concerns. In our sample (123 participants, with a mean age of 24.3 years [range 16-61]), 56.9% had marked concerns with body shape. Marked body shape concerns were associated with a major depressive episode (OR = 100.3), the use of laxatives (OR = 49.8), a high score on the item "body dissatisfaction" of the Eating Disorders Inventory scale (OR = 1.7), a higher minimum body mass index (OR = 1.73), and a high score on the item "loss of control over behavior, thoughts and emotions" from the dissociation questionnaire (OR = 10.74). These results are consistent with previous studies, and highlight the importance of denial.

Gambling behaviors and psychopathology related to Attention-Deficit/Hyperactivity Disorder (ADHD) in problem and non-problem adult gamblers.

Previous studies showed that Pathological Gambling and Attention Deficit/Hyperactivity Disorder (ADHD) often co-occur. The aim of this study was to examine whether ADHD is associated with specific severity patterns in terms of gambling behavior, psychopathology and personality traits. 599 problem and non-problem-gamblers were recruited in addiction clinics and gambling places in France. Subjects were assessed with the Wender-Utah Rating Scale-Child, the Adult ADHD Self-Report Scale, the Mini International Neuropsychiatric Interview, the Temperament and Character Inventory, the South Oaks Gambling Screen and questionnaires assessing gambling related cognitive distortions and gambling habits. 20.7% (n=124) of gamblers were screened positive for lifetime or current ADHD. Results from the multivariate analysis showed that ADHD was associated with a higher severity of gambling-related problems and with more psychiatric comorbidity. Among problem gamblers, subjects with history of ADHD were also at higher risk for unemployment, psychiatric comorbidity and specific dysfunctional personality traits. This study supports the link between gambling related problems and ADHD in a large sample of problem and non-problem gamblers, including problem-gamblers not seeking treatment. This points out the necessity to consider this disorder in the prevention and in the treatment of pathological gambling.

Factors associated with suicidal risk among a French cohort of problem gamblers seeking treatment.

Compared to general population, pathological gamblers are 3.4 times more likely to attempt suicide. Our objective was to identify specific profiles of problem gamblers (PGs) with suicidal risk according to sociodemographic, clinical and gambling characteristics. The PGs cohort, called "EVALJEU" , consists in the inclusion of any new PG seeking treatment in our Department. Patients underwent a semi-structured clinical interview and completed self-report questionnaires. The "suicidal risk module" of the Mini International Psychiatric interview (MINI) allowed to constitute two groups of patients that were compared, according to the presence of a suicidal risk. A logistic regression was performed to identify factors related to suicidal risk in PGs. In our sample (N=194), 40.21% presented a suicidal risk. A history of major depression and anxiety disorders were predictors of suicidal risk as well as the perceived inability to stop gambling. Suicidality is a significant clinical concern in PGs. Therefore, three specific predictors, identified by our study, must be assessed.

Gambling among European professional athletes. Prevalence and associated factors.

In Europe, the prevalence of gambling disorders in the general population ranges from 0.15 to 6.6%. Professional athletes are known for having risk factors for addictive behaviors, such as young age or sensation seeking, though no study has yet tried to evaluate the prevalence of gambling and gambling disorders among this specific population. The goals of this study were to estimate the prevalence of gambling, problematic or not, among European professional athletes and to explore the factors that are associated with gambling practice and gambling problems in professional athletes. A self-completion questionnaire was specifically designed for this study. The questionnaires were distributed by European Union athletes to professional ice hockey, rugby, handball, basketball, football, indoor football, volleyball, and cricket teams in Spain, France, Greece, Ireland, Italy, Sweden, and the United Kingdom. Socio-demographic variables (age, sex, education, marital and parental status, sport, country of birth, and country of practice), variables linked to gambling (gambling habits, screening of gambling problems with the Lie/Bet questionnaire, and gambling related cognitions), and impulsive behavior data (urgency, premeditation, perseverance, and sensation seeking [UPPS]-Short Form questionnaire) were gathered. There were 1,236 questionnaires filled out. The percentage of professional athletes that had gambled at least once during the previous year was 56.6%. The prevalence of problem gambling, current or past, was 8.2%. A certain number of variables were associated with the gambling status. In particular, betting on one's own team (OR = 4.1, CI95% [1.5-11.5]), betting online (OR = 2.9, CI95% [1.6-5.4]), gambling regularly (OR = 4.0, CI95% [2.1-7.6]), and having a high positive urgency score (OR = 1.5, CI95% [1.3-1.7]) were associated with gambling problems, current or past, among professional athletes. Professional athletes are particularly exposed to both gambling and problem gambling.

The Guttman errors as a tool for response shift detection at subgroup and item levels.

PURPOSE: Statistical methods for identifying response shift (RS) at the individual level could be of great practical value in interpreting change in PRO data. Guttman errors (GE) may help to identify discrepancies in respondent's answers to items compared to an expected response pattern and to identify subgroups of patients that are more likely to present response shift. This study explores the benefits of using a GE-based method for RS detection at the subgroup and item levels. METHODS: The analysis was performed on the SatisQoL study. The number of GE was determined for each individual at each time of measurement (at baseline T0 and 6 months after discharge M6). Individuals showing discrepancies (with many GE) were suspected to interpret the items differently from the majority of the sample. Patients having a large number of GE at M6 only and not at T0 were assumed to present RS. Patients having a small number of GE at T0 and M6 were assumed to present no RS. The RespOnse Shift ALgorithm in Item response theory (ROSALI) was then applied on the whole sample and on both groups. RESULTS: Different types of RS (non-uniform recalibration, reprioritization) were more prevalent in the group composed of patients assumed to present RS based on GE. On the opposite, no RS was detected on patients having few GE. CONCLUSIONS: Guttman errors and item response theory models seem to be relevant tools to discriminate individuals affected by RS from the others at the item level.

Towards a Validation of the Three Pathways Model of Pathological Gambling.

With the aim of validating the three pathways hypothesis of pathological gambling (Blaszczynski and Nower in Addiction 97:487-499, 2002) 372 pathological gamblers meeting DSM IV (2000) criteria were assessed via a structured clinical interview as well as being subjected to personality tests and evaluation of their gambling practices. Our results show that it is possible to identify three subgroups corresponding to the three pathways: behaviourally conditioned problem gamblers, emotionally vulnerable problem gamblers and antisocial impulsivist problem gamblers. Our results particularly demonstrate that impulsivist gamblers preferentially choose semi-skilful gambling (horse racing and sports gambling) whereas emotionally vulnerable gamblers are significantly more attracted to games of chance (one-armed bandits, scratch cards, etc.) This led us to propose a functional presentation of the three pathways model which differs somewhat from the Blaszczynski and Nower presentation.

Power and sample size determination for the group comparison of patient-reported outcomes using the Rasch model: impact of a misspecification of the parameters.

BACKGROUND: Patient-reported outcomes (PRO) are important as endpoints in clinical trials and epidemiological studies. Guidelines for the development of PRO instruments and analysis of PRO data have emphasized the need to report methods used for sample size planning. The Raschpower procedure has been proposed for sample size and power determination for the comparison of PROs in cross-sectional studies comparing two groups of patients when an item reponse model, the Rasch model, is intended to be used for analysis. The power determination of the test of the group effect using Raschpower requires several parameters to be fixed at the planning stage including the item parameters and the variance of the latent variable. Wrong choices regarding these parameters can impact the expected power and the planned sample size to a greater or lesser extent depending on the magnitude of the erroneous assumptions. METHODS: The impact of a misspecification of the variance of the latent variable or of the item parameters on the determination of the power using the Raschpower procedure was investigated through the comparison of the estimations of the power in different situations. RESULTS: The power of the test of the group effect estimated with Raschpower remains stable or shows a very little decrease whatever the values of the item parameters. For most of the cases, the estimated power decreases when the variance of the latent trait increases. As a consequence, an underestimation of this variance will lead to an overestimation of the power of the group effect. CONCLUSION: A misspecification of the item difficulties regarding their overall pattern or their dispersion seems to have no or very little impact on the power of the test of the group effect. In contrast, a misspecification of the variance of the latent variable can have a strong impact as an underestimation of the variance will lead in some cases to an overestimation of the power at the design stage and may result in an underpowered study.

Overall performance of Oort's procedure for response shift detection at item level: a pilot simulation study.

OBJECTIVE: This simulation study was designed to provide data on the performance of Oort's procedure (OP) for response shift (RS) detection (regarding type I error, power, and overall performance), according to sample characteristics, at item level. A specific objective was to assess the impact of using different information criteria (IC), as alternatives to the LRT (likelihood-ratio test), for global assessment of RS occurrence. METHODS: Responses to five binary items at two times of measurement were simulated. Thirty-six combinations of sample characteristics [sample size (n), "true change," correlations between the two latent variables and presence/absence of uniform recalibration RS (ur)] were considered. A thousand datasets were generated for each combination. RS detection was performed on each dataset following OP. Type I error and power of the global assessment of RS occurrence, as well as overall performance of the OP, were assessed. RESULTS: The estimated type I error was close to 5 % for the LRT and lower than 5 % for the IC. The estimated power was higher for the LRT as compared to the AIC, which was the highest among the other IC. For the LRT, the estimated power for n = 100 and for the combination of n = 200 and ur = 1 item was below 80 %. Otherwise, for other combinations of sample characteristics, the estimated power was above 90 %. CONCLUSION: For the LRT, higher values of power were estimated compared to IC with appropriate values of type I error. These results were consistent with Oort's proposal to use the LRT as the criterion to assess global RS occurrence.

RespOnse Shift ALgorithm in Item response theory (ROSALI) for response shift detection with missing data in longitudinal patient-reported outcome studies.

PURPOSE: Some IRT models have the advantage of being robust to missing data and thus can be used with complete data as well as different patterns of missing data (informative or not). The purpose of this paper was to develop an algorithm for response shift (RS) detection using IRT models allowing for non-uniform and uniform recalibration, reprioritization RS recognition and true change estimation with these forms of RS taken into consideration if appropriate. METHODS: The algorithm is described, and its implementation is shown and compared to Oort's structural equation modeling (SEM) procedure using data from a clinical study assessing health-related quality of life in 669 hospitalized patients with chronic conditions. RESULTS: The results were quite different for the two methods. Both showed that some items of the SF-36 General Health subscale were affected by response shift, but those items usually differed between IRT and SEM. The IRT algorithm found evidence of small recalibration and reprioritization effects, whereas SEM mostly found evidence of small recalibration effects. CONCLUSION: An algorithm has been developed for response shift analyses using IRT models and allows the investigation of non-uniform and uniform recalibration as well as reprioritization. Differences in RS detection between IRT and SEM may be due to differences between the two methods in handling missing data. However, one cannot conclude on the differences between IRT and SEM based on a single application on a dataset since the underlying truth is unknown. A next step would be to implement a simulation study to investigate those differences.

Method variation in the impact of missing data on response shift detection.

PURPOSE: Missing data due to attrition or item non-response can result in biased estimates and loss of power in longitudinal quality-of-life (QOL) research. The impact of missing data on response shift (RS) detection is relatively unknown. This overview article synthesizes the findings of three methods tested in this special section regarding the impact of missing data patterns on RS detection in incomplete longitudinal data. METHODS: The RS detection methods investigated include: (1) Relative importance analysis to detect reprioritization RS in stroke caregivers; (2) Oort's structural equation modeling (SEM) to detect recalibration, reprioritization, and reconceptualization RS in cancer patients; and (3) Rasch-based item-response theory-based (IRT) models as compared to SEM models to detect recalibration and reprioritization RS in hospitalized chronic disease patients. Each method dealt with missing data differently, either with imputation (1), attrition-based multi-group analysis (2), or probabilistic analysis that is robust to missingness due to the specific objectivity property (3). RESULTS: Relative importance analyses were sensitive to the type and amount of missing data and imputation method, with multiple imputation showing the largest RS effects. The attrition-based multi-group SEM revealed differential effects of both the changes in health-related QOL and the occurrence of response shift by attrition stratum, and enabled a more complete interpretation of findings. The IRT RS algorithm found evidence of small recalibration and reprioritization effects in General Health, whereas SEM mostly evidenced small recalibration effects. These differences may be due to differences between the two methods in handling of missing data. CONCLUSIONS: Missing data imputation techniques result in different conclusions about the presence of reprioritization RS using the relative importance method, while the attrition-based SEM approach highlighted different recalibration and reprioritization RS effects by attrition group. The IRT analyses detected more recalibration and reprioritization RS effects than SEM, presumably due to IRT's robustness to missing data. Future research should apply simulation techniques in order to make conclusive statements about the impacts of missing data according to the type and amount of RS.

Power and sample size determination in the Rasch model: evaluation of the robustness of a numerical method to non-normality of the latent trait.

Patient-reported outcomes (PRO) have gained importance in clinical and epidemiological research and aim at assessing quality of life, anxiety or fatigue for instance. Item Response Theory (IRT) models are increasingly used to validate and analyse PRO. Such models relate observed variables to a latent variable (unobservable variable) which is commonly assumed to be normally distributed. A priori sample size determination is important to obtain adequately powered studies to determine clinically important changes in PRO. In previous developments, the Raschpower method has been proposed for the determination of the power of the test of group effect for the comparison of PRO in cross-sectional studies with an IRT model, the Rasch model. The objective of this work was to evaluate the robustness of this method (which assumes a normal distribution for the latent variable) to violations of distributional assumption. The statistical power of the test of group effect was estimated by the empirical rejection rate in data sets simulated using a non-normally distributed latent variable. It was compared to the power obtained with the Raschpower method. In both cases, the data were analyzed using a latent regression Rasch model including a binary covariate for group effect. For all situations, both methods gave comparable results whatever the deviations from the model assumptions. Given the results, the Raschpower method seems to be robust to the non-normality of the latent trait for determining the power of the test of group effect.