Toward a rigorous assessment of the statistical performances of methods to estimate the Minimal Important Difference of Patient-Reported Outcomes: A protocol for a large-scale simulation study.

Interpreting observed changes over time in Patient-Reported Outcomes (PRO) measures is still considered a challenge. Indeed, concluding an observed change at group level is statistically significant does not necessarily equate this change is meaningful from the perspective of the patient. To help interpret within and/or between group changes in the measure over time, the estimation of the Minimal Important Difference (MID) of the instrument - the smallest value that patients consider as a perceived change - is useful. In the last 30 years, a plethora of methods and estimators have been proposed to derive this MID value using clinical data from sample of patients. MIDs for hundreds of PROs have been estimated, with frequently a substantial variability in the results depending on the method used. Nonetheless, a rigorous assessment of the statistical performances of numerous proposed methods for estimating MIDs by experimental design such as Monte-Carlo study has never been performed. The purpose of this paper is to thoroughly depict a protocol for a large-scale simulation study designed to investigate the statistical performances, especially bias against a true populational value, of the common proposed estimators for MID. This paper depicts how investigated methods and estimators were retained after the conduct of a systematic review, the design of a conceptual model that formally defines what is the true populational MID value and the translation of the conceptual model into a model allowing the simulation of responses of items to a hypothetical PRO at two times of measurement along with the response to a Patient Global Rating of Change at the second time under the constraint of a known true MID value. A statistical analysis plan is depicted in order to conclude if working hypotheses on what could be appropriate MID estimators will be verified. Strengths, assumptions, and limits of the simulation model are exposed. Finally, we show how this protocol could be the basis for fostering future methodological research on the issue of interpreting changes in PRO measures.

Taste and smell alterations affect nutritional status in children under chemotherapy.

AIM: This study aimed to evaluate the incidence of self-reported taste and smell alterations (TSA) in cancer paediatric patients and evaluate the impact of TSA on nutritional status in this population. We also developed and validated a composite score to detect TSA in children undergoing chemotherapy. METHODS: Paediatric patients who were undergoing chemotherapy in a paediatric oncology unit were included. TSA were assessed from the Gustonco questionnaire from which a composite score was developed and internally validated, eating behaviour was assessed using Child Eating Behaviour Questionnaire, and major weight loss was defined from nutritional status. All data were calculated at 1, 3 and 6 months after chemotherapy start. Associations between nutritional status and scores were studied by using logistic models. RESULTS: Among 49 patients included, TSA occurred in 71.7% of patients at 1 month after chemotherapy start and persisted at 3 and 6 months. TSA led to altered appetite since 1 month after chemotherapy start. The occurrence of a major weight loss at 6 months seemed to be associated with a high Gustonco score. CONCLUSION: Taste and smell alterations often occurred in paediatric cancer patients after chemotherapy start and seemed to be associated with impaired nutrition at 6 months after chemotherapy.

Evaluating the impact of calibration of patient-reported outcomes measures on results from randomized clinical trials: a simulation study based on Rasch measurement theory.

BACKGROUND: Meaningfully interpreting patient-reported outcomes (PRO) results from randomized clinical trials requires that the PRO scores obtained in the trial have the same meaning across patients and previous applications of the PRO instrument. Calibration of PRO instruments warrants this property. In the Rasch measurement theory (RMT) framework, calibration is performed by fixing the item parameter estimates when measuring the targeted concept for each individual of the trial. The item parameter estimates used for this purpose are typically obtained from a previous "calibration" study. But imposing this constraint on item parameters, instead of freely estimating them directly in the specific sample of the trial, may hamper the ability to detect a treatment effect. The objective of this simulation study was to explore the potential negative impact of calibration of PRO instruments that were developed using RMT on the comparison of results between treatment groups, using different analysis methods. METHODS: PRO results were simulated following a polytomous Rasch model, for a calibration and a trial sample. Scenarios included varying sample sizes, with instrument of varying number of items and modalities, and varying item parameters distributions. Different treatment effect sizes and distributions of the two patient samples were also explored. Cross-sectional comparison of treatment groups was performed using different methods based on a random effect Rasch model. Calibrated and non-calibrated approaches were compared based on type-I error, power, bias, and variance of the estimates for the difference between groups. RESULTS: There was no impact of the calibration approach on type-I error, power, bias, and dispersion of the estimates. Among other findings, mistargeting between the PRO instrument and patients from the trial sample (regarding the level of measured concept) resulted in a lower power and higher position bias than appropriate targeting. CONCLUSIONS: Calibration does not compromise the ability to accurately assess a treatment effect using a PRO instrument developed within the RMT paradigm in randomized clinical trials. Thus, given its essential role in producing interpretable results, calibration should always be performed when using a PRO instrument developed using RMT as an endpoint in a randomized clinical trial.

Posttraumatic growth inventory: challenges with its validation among French cancer patients.

BACKGROUND: The Posttraumatic growth inventory (PTGI) aims to assess the positive psychological changes that individuals can perceive after a traumatic life event such as a cancer diagnosis. Several French translations of the PTGI have been proposed, but comprehensive data on their psychometric properties are lacking. This study aimed to provide a more complete assessment of the psychometric properties of one of the most used PTGI translations in early-stage breast cancer and melanoma patients. METHODS: A sample of 379 patients completed the PTGI two years after their cancer diagnosis. A confirmatory analysis was first performed to determine whether the initial five-factor structure of the PTGI was adequate for this French version. As issues were identified in the translation and in the questionnaire structure, we performed an exploratory analysis to determine the most suitable structure for this questionnaire. Validity and reliability of the evidenced structured were then assessed. RESULTS: The exploratory analysis evidenced a four-factor structure close to the initial structure: four of the five initial domains were recovered, and items from the unrecovered domain were split into the other domains. This new structure showed good internal consistency and acceptable validity. CONCLUSIONS: This study highlights that the process of translation and cross-cultural validation of questionnaires is crucial to obtain valid and reliable psychometric instruments. We advise French psycho-oncology researchers and psychotherapists to (i) use the revised translation of Lelorain et al. (2010) proposed in this manuscript and (ii) use the four scores newly evidenced with a grouping of two response categories.

Evaluation of the link between the Guttman errors and response shift at the individual level.

PURPOSE: Methods for response shift (RS) detection at the individual level could be of great interest when analyzing changes in patient-reported outcome data. Guttman errors (GEs), which measure discrepancies in respondents' answers compared to the average sample responses, might be useful for detecting RS at the individual level between two time points, as RS may induce an increase in the number of discrepancies over time. This study aims to establish the link between recalibration RS and the change in the number of GEs over time (denoted index [Formula: see text]) via simulations and explores the discriminating ability of this index. METHODS: We simulated the responses of individuals affected or not affected by recalibration RS (defined as changes in the patients' standard of measurement) to determine whether simulated individuals with recalibration had a greater change in the number of GEs over time than individuals without recalibration. The effects of factors related to the sample, the questionnaire structure and recalibration were investigated. As an illustrative example, the change in the number of GEs was computed in patients suffering from eating disorders. RESULTS: Within simulations, simulated individuals affected by recalibration had, on average, a greater change in the number of GEs over time than did individuals without RS. Some of the parameters related to the questionnaire structure and recalibration magnitude appeared to have substantial effects on the values of [Formula: see text]. Discriminating abilities appeared, however, globally low. CONCLUSION: Some evidence of the link between recalibration and the change in GEs was found in this study. GEs could be a valuable nonparametric tool for RS detection at a more individual level, but further investigation is needed.

Investigation of measurement invariance in longitudinal health-related quality of life in preemptive or previously dialyzed kidney transplant recipients.

PURPOSE: Kidney transplantation (KT) can impact patients' evaluation of health-related quality of life (HRQoL) as they adapt to their new life with a graft and its changes. Patients may adapt to KT in a different way, depending on whether they were on dialysis prior to transplantation or not (i.e. preemptive group). This may result in lack of measurement invariance between these patients' groups and/or over time (i.e. response shift, RS) which may invalidate the between-group comparison of HRQoL change scores. The aim of this study was to investigate and compare RS before and after KT between these two patients' groups. Measurement invariance was investigated between groups and over time with three measurement occasions. METHODS: Adult patients completed the SF-36 at the last visit before KT, and 3, 6 months after. A structural equation model-based procedure was used to (i) detect and take into account measurement non-invariance between groups and RS, if appropriate, (ii) identify the period of occurrence of RS, (iii) study the heterogeneity of RS between the two groups. RESULTS: Before KT (i.e. baseline), measurement invariance was not rejected between dialyzed (n = 196) and preemptive (n = 178) patients' groups. Between baseline and 3 months after KT, similar uniform recalibration was detected on the general health domain in both groups. Uniform recalibration was found between 3- and 6 months after KT on the vitality domain for preemptive patients only. CONCLUSION: HRQoL, adjusted for RS, increased overall for preemptive and dialyzed kidney transplant patients after transplantation. RS may reflect differing adaptation processes following KT.

How do people who use drugs receiving Opioid Medication Therapy perceive their treatment ? A multicentre study.

BACKGROUND: The resurgence of heroin use and the misuse of pharmaceutical opioids are some of the reasons for a worldwide increase in opioid dependence. Opioid Medication Therapies (OMT) have amply demonstrated their efficacy. From a medical point of view, the main objectives of OMT concern medical and social outcomes, centred on risk reduction and the cessation of opioid use. But patient points of view can differ and few studies have explored opioid-dependent patient viewpoints on their OMT. This variable seems important to consider in a patient-centred approach. The aim of our study was to explore points of view of people who use drugs (PWUD) treated with OMT, in a large multicentre sample. METHOD: A cross-sectional multicentre study explored the points of view of PWUD with Opioid Use Disorder following OMT. Data regarding the patients' points of view were collected using a self-administered questionnaire developed by the scientific committee of the study. A descriptive analysis and an exploratory factor analysis were performed to explore the structure of items exploring patient viewpoints. RESULTS: 263 opioid dependent PWUD were included, a majority were men consuming heroin prior to being prescribed OMT. 68% were on methadone, 32% were on buprenorphine. Most PWUD identified a positive impact on their lives, with 92.8% agreeing or strongly agreeing that OMT had changed a lot of things in their lives. The exploratory factor analysis identified three factors: (F1) items related to points of views concerning the objectives and efficacy of OMT; (F2) items related to the legitimacy of OMT as a treatment compared to a drug, (F3) items related to experiences and relationships with OMT. CONCLUSION: Patient viewpoints on efficacy were correlated with the pharmacological benefits of OMT and with the associated psychosocial measures. The implications of OMT in relationships, such as the feeling of being judged, concerned a majority. Points of view were ambivalent concerning the role of OMT as a treatment or as a drug. Involving patient points of view in therapeutic strategies decisions could help enhance positive views among PWUD on OMT and help PWUD towards their recovery. TRIAL REGISTRATION: OPAL study was registered: (NCT01847729).

Comparative assessment of complete-coverage, fixed tooth-supported prostheses fabricated from digital scans or conventional impressions: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Intraoral scanners have significantly improved over the last decade. Nevertheless, data comparing intraoral digital scans with conventional impressions are sparse. PURPOSE: The purpose of this systematic review and meta-analysis was to determine the impact of impression technique (digital scans versus conventional impressions) on the clinical time, patient comfort, and marginal fit of tooth-supported prostheses. MATERIAL AND METHODS: The authors conducted a literature search based on the Population, Intervention, Comparison, and Outcome (PICO) framework in 3 databases to identify clinical trials with no language or date restrictions. The mean clinical time, patient comfort, and marginal fit values of each study were independently extracted by 2 review authors and categorized according to the scanning or impression method. The authors assessed the study-level risk of bias. RESULTS: A total of 16 clinical studies met the inclusion criteria. The mean clinical time was statistically similar for digital scan procedures (784 ±252 seconds) and for conventional impression methods (1125 ±159 seconds) (P>.05). The digital scan techniques were more comfortable for patients than conventional impressions; the mean visual analog scale score was 67.8 ±21.7 for digital scans and 39.6 ±9.3 for conventional impressions (P<.05). The mean marginal fit was 80.9 ±31.9 µm and 92.1 ±35.4 µm for digital scan and conventional impressions, respectively, with no statistically significant difference (P>.05). CONCLUSIONS: Digital scan techniques are comparable with conventional impressions in terms of clinical time and marginal fit but are more comfortable for patients than conventional impression techniques.

The minimal perceived change: a formal model of the responder definition according to the patient's meaning of change for patient-reported outcome data analysis and interpretation.

BACKGROUND: Patient-Reported Outcomes (PROs) are standardized questionnaires used to measure subjective outcomes such as quality of life in healthcare. They are considered paramount to assess the results of therapeutic interventions. However, because their calibration is relative to internal standards in people's mind, changes in PRO scores are difficult to interpret. Knowing the smallest value in the score that the patient perceives as change can help. An estimator linking the answers to a Patient Global Rating of Change (PGRC: a question measuring the overall feeling of change) with change in PRO scores is frequently used to obtain this value. In the last 30 years, a plethora of methods have been used to obtain these estimates, but there is no consensus on the appropriate method and no formal definition of this value. METHODS: We propose a model to explain changes in PRO scores and PGRC answers. RESULTS: A PGRC measures a construct called the Perceived Change (PC), whose determinants are elicited. Answering a PGRC requires discretizing a continuous PC into a category using threshold values that are random variables. Therefore, the populational value of the Minimal Perceived Change (MPC) is the location parameter value of the threshold on the PC continuum defining the switch from the absence of change to change. CONCLUSIONS: We show how this model can help to hypothesize what are the appropriate methods to estimate the MPC and its potential to be a rigorous theoretical basis for future work on the interpretation of change in PRO scores.

Practical issues encountered while determining Minimal Clinically Important Difference in Patient-Reported Outcomes.

BACKGROUND: Using a real dataset, we highlighted several major methodological issues raised by the estimation of the Minimal Clinically Important Difference (MCID) of a Patient-Reported Outcomes instrument. We especially considered the management of missing data and the use of more than two times of measurement. While inappropriate missing data management and inappropriate use of multiple time points can lead to loss of precision and/or bias in MCID estimation, these issues are almost never dealt with and require cautious considerations in the context of MCID estimation. METHODS: We used the LIGALONGO study (French Randomized Controlled Trial). We estimated MCID on the SF-36 General Health score by comparing many methods (distribution or anchor-based). Different techniques for imputation of missing data were performed (simple and multiple imputations). We also consider all measurement occasions by longitudinal modeling, and the dependence of the score difference on baseline. RESULTS: Three hundred ninety-three patients were studied. With distribution-based methods, a great variability in MCID was observed (from 3 to 26 points for improvement). Only 0.2 SD and 1/3 SD distribution methods gave MCID values consistent with anchor-based methods (from 4 to 7 points for improvement). The choice of missing data imputation technique clearly had an impact on MCID estimates. Simple imputation by mean score seemed to lead to out-of-range estimate, but as missing not at random mechanism can be hypothesized, even multiple imputations techniques can have led to an slight underestimation of MCID. Using 3 measurement occasions for improvement led to an increase in precision but lowered estimates. CONCLUSION: This practical example illustrates the substantial impact of some methodological issues that are usually never dealt with for MCID estimation. Simulation studies are needed to investigate those issues. TRIAL REGISTRATION: NCT01240772 (ClinicalTrials.gov) registered on November 15, 2010.

How do doctors perceive and use patient quality of life? Findings from focus group interviews with hospital doctors and general practitioners.

PURPOSE: While studies on patients' quality of life (QoL) are numerous, to date few have addressed the issue of what QoL means for doctors and how they use patient-reported QoL. This study aimed to explore how doctors define the concept of "patient QoL" and how they use QoL assessments in clinical practice. METHODS: Focus group (FG) interviews were conducted with French hospital doctors and general practitioners. Transcripts of the FGs were explored using inductive thematic and lexical analyses. RESULTS: Twenty-one clinicians participated in four FGs. They all agreed that QoL was a subjective and unstable concept, different from that of health status. In practice, the assessment of patient QoL was conducted using an intuitive and non-structured approach. Most participants thought that it would give them more confidence in making decisions and provide better patient care. But it was also seen in some cases as putting them in an uncomfortable position. The assessment of QoL requires a favourable work and organizational setting. CONCLUSIONS: Patient QoL provides useful data for clinicians. Yet assessments are made without standardized tools. The use of such tools could be very valuable for some practitioners or in some situations, and a real source of problems for others. These problems could, however, be easily overcome with experience-sharing and training clinicians.

Comparison of longitudinal quality of life outcomes in preemptive and dialyzed patients on waiting list for kidney transplantation.

PURPOSE: The waiting list period for kidney transplantation can be lengthy and associated with a deteriorated health-related quality of life (HRQoL). It might also be experienced differently depending on the experience of renal replacement therapy (preemptive or dialyzed patients), and the type of dialysis. The main objective of this study is to measure and compare HRQoL changes in preemptive, hemodialysis (HD), and peritoneal dialysis (PD) patients during the waiting list period for kidney transplantation. METHODS: A sample of adult patients on kidney transplant waiting list from three French University Hospital centers was recruited. HRQoL was measured using the SF-36 and a specific questionnaire (ReTransQol), which were collected every 6 months before transplantation in preemptive, HD, and PD patients. Mixed-effects models taking into account time and possible confounding factors were used to compare HRQoL changes between the three groups. RESULTS: Preemptive (n = 230), HD (n = 177), and PD patients (n = 39) were enrolled. The renal replacement therapy modalities, time (time on waiting list and age at registration), and gender were associated with HRQoL changes. The HD and PD patients had a significantly lower perceived HRQoL on Role Physical, Social Functioning, and Role Emotional dimensions than the preemptive patients, with lower scores for PD compared to HD patients. The HRQoL scores of all patients were lower compared to the French general population for all dimensions. CONCLUSIONS: A better understanding of pre-transplantation patients' experience can help improving patient care with adapted educational programs and psychological support depending on the type of renal replacement therapy.

Modeling Early Gambling Behavior Using Indicators from Online Lottery Gambling Tracking Data: Longitudinal Analysis.

BACKGROUND: Individuals who gamble online may be at risk of gambling excessively, but internet gambling also provides a unique opportunity to monitor gambling behavior in real environments which may allow intervention for those who encounter difficulties. OBJECTIVE: The objective of this study was to model the early gambling trajectories of individuals who play online lottery. METHODS: Anonymized gambling-related records of the initial 6 months of 1152 clients of the French national lottery who created their internet gambling accounts between September 2015 and February 2016 were analyzed using a two-step approach that combined growth mixture modeling and latent class analysis. The analysis was based upon behavior indicators of gambling activity (money wagered and number of gambling days) and indicators of gambling problems (breadth of involvement and chasing). Profiles were described based upon the probabilities of following the trajectories that were identified for the four indicators, and upon several covariates (age, gender, deposits, type of play, net losses, voluntary self-exclusion, and Playscan classification-a responsible gambling tool that provides each player with a risk assessment: green for low risk, orange for medium risk and red for high risk). Net losses, voluntary self-exclusion, and Playscan classification were used as external verification of problem gambling. RESULTS: We identified 5 distinct profiles of online lottery gambling. Classes 1 (56.8%), 2 (14.8%) and 3 (13.9%) were characterized by low to medium gambling activity and low values for markers of problem gambling. They displayed low net losses, did not use the voluntary self-exclusion measure, and were classified predominantly with green Playscan tags (range 90%-98%). Class 4 (9.7%) was characterized by medium to high gambling activity, played a higher breadth of game types (range 1-6), and had zero to few chasing episodes. They had high net losses but were classified with green (66%) or orange (25%) Playscan tags and did not use the voluntary self-exclusion measure. Class 5 (4.8%) was characterized by medium to very high gambling activity, played a higher breadth of game types (range 1-17), and had a high number of chasing episodes (range 0-5). They experienced the highest net losses, the highest proportion of orange (32%) and red (39%) tags within the Playscan classification system and represented the only class in which voluntary self-exclusion was present. CONCLUSIONS: Classes 1, 2, 3 may be considered to represent recreational gambling. Class 4 had higher gambling activity and higher breadth of involvement and may be representative of players at risk for future gambling problems. Class 5 stood out in terms of much higher gambling activity and breadth of involvement, and the presence of chasing behavior. Individuals in classes 4 and 5 may benefit from early preventive measures.

Quantitative assessment of mucosal architecture using computer-based analysis of confocal laser endomicroscopy in inflammatory bowel diseases.

BACKGROUND AND AIMS: Confocal laser endomicroscopy (CLE) might discriminate mucosal lesions between Crohn's disease (CD) and ulcerative colitis (UC). However, the analysis of CLE images requires time-consuming methods, a long training time, and potential impediments, such as significant interobserver variability. Therefore, we developed a computer-based method to analyze mucosal architecture from CLE images and discriminate between healthy subjects and patients with inflammatory bowel disease (IBD) as well as between UC and CD patients. METHODS: We retrospectively screened patients who had undergone CLE either for an evaluation of IBD in remission or for colorectal cancer screening (control subjects) between 2009 and 2016. We assessed 14 morphologic and functional parameters in each CLE recording from 23 CD patients, 27 UC patients, and 9 control patients. Next, we constructed 2 scores, 1 for the IBD diagnosis and 1 for the differential diagnosis between UC and CD. RESULTS: In IBD patients, the mean intercrypt distance, wall thickness, and fluorescein leakage through the colonic mucosa were significantly increased compared with control patients by 155%, 188%, and 297%, respectively (P < .05). In UC patients, the same parameters were significantly increased by 109%, 117%, and 174%, respectively (P < .05), compared with CD patients. IBD diagnosis had 100% (95%CI, 93%; 100%) sensitivity and 100% (95%CI, 66%; 100%) specificity. IBD differential diagnosis provided discrimination of UC from CD patients with 92% (95%CI, 75%; 99%) sensitivity and 91% (95%CI, 72%; 99%) specificity. CONCLUSIONS: Confirming these results using prospective validation cohorts can substantiate that computer-based analysis of CLE images may provide new biomarkers for the diagnosis and characterization of IBD.

Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study.

AIMS: Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment. METHODS: Opioid PhArmacoLogy (OPAL) was a clinical survey of the sociodemographic characteristics, history and consequences of pathology associated with methadone maintenance treatment response and current addictive comorbidities. A subgroup of 72 methadone patients was genotyped. RESULTS: When comparing the three CYP2B6 genotype groups, the methadone (R)- and (S)-methadone enantiomer concentrations/doses (concentrations relative to doses) were different (P = .029, P = .0019). The CYP2D6 phenotypes did not seem to be relevant with regard to methadone levels. On multivariate analysis, neither the CYP2B6 genotype nor the CYP2D6 phenotype explained the (R)-methadone concentration/dose values (P = .92; P = .86); the (S)-methadone concentration/dose values (P = .052; P = .95 [although there was a difference between the TT group and GT and GG groups {P = .019}]); or opiate cessation (P = .12; P = .90). CONCLUSION: The genotyping of CYP2B6 G516T could be an interesting tool to explore methadone intervariability.

Guideline-Based Clinical Assessment Versus Procalcitonin-Guided Antibiotic Use in Pneumonia: A Pragmatic Randomized Trial.

STUDY OBJECTIVE: Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia. METHODS: We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals. We included emergency department (ED) patients older than 18 years with community-acquired pneumonia. Patients were randomly assigned to either the procalcitonin-guided or clinical assessment group. In accordance with past studies, we hypothesized that serial clinical assessment would be superior to procalcitonin-guided care. The primary outcome was antibiotic duration, and secondary outcomes included rates of antibiotic duration less than or equal to 5 days, and clinical success and combined serious adverse outcomes at 30 days in the intention-to-treat population. RESULTS: Of 370 eligible patients, 285 (77%) were randomly assigned to either clinical assessment- (n=143) or procalcitonin-guided care (n=142). Median age was 67 years (range 18 to 93 years) and 40% of patients were deemed to have Pneumonia Severity Index class IV or V. Procalcitonin algorithm adherence was 76%. Antibiotic duration was not significantly different between clinical assessment- and procalcitonin-guided groups (median 9 versus 10 days, respectively). Clinical success rate was 92% in each group and serious adverse outcome rates were similar (15% versus 20%, respectively). CONCLUSION: Guideline-based serial clinical assessment did not reduce antibiotic exposure compared with procalcitonin-guided care among ED patients with community-acquired pneumonia. The strategies were similar in terms of duration of antibiotic use and clinical outcomes.

Prevalence of hypobetalipoproteinemia and related psychiatric characteristics in a psychiatric population: results from the retrospective HYPOPSY Study.

BACKGROUND: Hypobetalipoproteinemia (HBL) is defined by plasma concentrations of LDL-cholesterol (LDL-C) lower than the fifth percentile for age and sex. Several psychiatric symptoms have been reported in association with HBL. The objective was to assess the prevalence of primary HBL in patients hospitalized in a psychiatric population and to better characterize the related psychiatric disorders. METHODS: HYPOPSY is a retrospective study including 839 adults hospitalized in the Psychiatry department of Nantes University Hospital during the year 2014, except patients with eating disorders. The prevalence of primary HBL was defined by a plasma LDL-C concentration ≤ 50 mg/dL. Secondary causes of HBL were excluded after a review of medical records (n=2). Related-psychiatric disorders in patients with and without HBL were recorded using the ICD-10 classification. RESULTS: Twenty cases of primary HBL (mean [SD] LDL-C: 42 [7] mg/dL) were diagnosed, leading to a prevalence of 2.39%. In comparison, the prevalence of HBL in a healthy control population was 0.57%. Psychiatric patients with HBL were characterized by a higher frequency of schizophrenia (p=0.044), hetero-aggression (p=0.015) and pervasive and specific developmental disorders (including autism) (p=0.011). CONCLUSIONS: The prevalence of HBL is 4-fold higher in psychiatric than in general population. More specifically, some statistically significant associations were found between low LDL-C concentrations and schizophrenia, autism and hetero-aggression. These data reinforce the hypothesis for a link between genetically low LDL-C levels and psychiatric disorders.

The quality of life in genetic neuromuscular disease questionnaire: Rasch validation of the French version.

INTRODUCTION: Slowly progressive, genetic neuromuscular diseases (gNMDs) often lead to important motor deficiencies and functional limitations. The Quality of Life in Genetic Neuromuscular Disease Questionnaire (QoL-gNMD) is a new health-related quality-of-life questionnaire developed for these patients. The purpose of the present study was to validate the French version of the QoL-gNMD and to calibrate its measurement system. METHODS: Both the QoL-gNMD and a validated generic questionnaire (WHOQOL-BREF) were administered to patients. Validation was performed using item response theory. The partial credit model (Rasch) was used to calibrate each domain. RESULTS: Three hundred fifteen adult patients were included. All 3 domains showed adequate psychometric properties (internal consistency: person separation index >0.77; repeatability: test-retest intraclass correlation coefficient >0.75, scalability coefficient >0.38) and fitted the partial credit model. The QoL-gNMD also demonstrated adequate concurrent validity with the WHOQOL-BREF. DISCUSSION: The QoL-gNMD showed adequate psychometric properties and can be used in clinical settings. Although not anchor-based, the minimum detectable change tables help in interpreting score change. Muscle Nerve 56: 1085-1091, 2017.

Validation of the French versions of the Hirschsprung's disease and Anorectal malformations Quality of Life (HAQL) questionnaires for adolescents and adults.

BACKGROUND: The Hirschsprung's disease Anorectal malformation QoL questionnaire (HAQL) is a disease-specific quality of life (QoL) questionnaire for patients with Hirschsprung's disease (HD) or anorectal malformations (ARM). It was originally proposed in Dutch and is currently being translated into other languages to obtain an internationally standardized instrument. In this work we validate a French adaptation of the HAQL for adolescents and adults. METHODS: The questionnaires were translated into French and sent to patients aged 12 years and older, followed for HD or ARM at three French university hospitals. Questionnaires were sent to 147 adolescents and 188 adults. The psychometric properties of the questionnaires were analyzed in terms of reliability and validity. RESULTS: The original HAQL structure was not satisfactory. A new structure was proposed, while aiming to remain close to the original structure. The proposed structure has acceptable reliability and validity properties and reflects both physical, as well as psychosocial aspects. CONCLUSIONS: A French version of the HAQL questionnaire for adults and adolescents is ready for use in France. In particular the score could discriminate between degrees of clinical status based on the Krickenbeck consensus, which can aid clinicians to inform patients about physical and psychosocial challenges they may expect.

Sustained quality of life improvement after intracoronary injection of autologous bone marrow cells in the setting of acute myocardial infarction: results from the BONAMI trial.

PURPOSE: Cardiac cell therapy is a promising treatment for acute myocardial infarction (AMI), leading to cardiac function improvement. However, whether it translates into quality of life (QoL) improvement is unclear. We hypothesized that administration of bone marrow cells (BMC) to patients with AMI improves QoL. METHODS: In the multicenter BONAMI trial (NCT00200707), patients with reperfused AMI and decreased myocardial viability were randomized to intracoronary autologous BMC infusion (n = 52) or state-of-the-art therapy (n = 49). QoL data, derived from the Minnesota Living with Heart Failure questionnaire (MLHFQ), were obtained 1, 3, and 12 months after AMI and analyzed using a Rasch-family model. RESULTS: Using this model, QoL improved over time in the BMC group (p = 0.025) but not in the control group. Furthermore, the BMC-group patients displayed a better QoL than the control-group patients at 3 and 12 months post-AMI (p = 0.034 and p = 0.003, respectively). These findings were not detected when analyzing MLHFQ data using a standard method. Cardiac function, myocardial viability, mortality, and number of major adverse cardiac events did not differ between treatment groups. CONCLUSION: Our results suggest that BMC therapy can improve QoL, stressing the need for confirmation trials and for systematic QoL assessment in cardiac cell therapy trials .