[Proposal for the delineation of postoperative primary clinical target volumes in maxillary sinus and nasal cavity cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers du sinus maxillaire et des cavités nasales.

In this article, we propose a consensus delineation of postoperative clinical target volumes for the primary tumour in maxillary sinus and nasal cavity cancers. These guidelines are developed based on radioanatomy and the natural history of those cancers. They require the fusion of the planning CT with preoperative imaging for accurate positioning of the initial GTV and the combined use of the geometric and anatomical concepts for the delineation of clinical target volume for the primary tumour. This article does not discuss the indications of external radiotherapy (nor concurrent systemic treatment) but focuses on target volumes when there is an indication for radiotherapy.

Assessing domain match and feasibility of candidate instruments matching with OMERACT endorsed domains to measure flare in knee and hip osteoarthritis.

PURPOSE: To evaluate the domain match (truth) and feasibility of candidate instruments assessing flare in knee and hip osteoarthritis (OA) according to the identified domains. MATERIAL AND METHODS: From a literature review (575 papers), instruments were selected and evaluated using the truth and feasibility elements of the OMERACT Filter 2.2. These were evaluated by 26 experts, including patients, in two Delphi survey rounds. The final selection was obtained by a vote. RESULTS: 44 instruments were identified. In Delphi Round 1, five instruments were selected. In Round 2, all instruments obtained at least 75 % in terms of content match with the endorsed domains and feasibility. In the final selection, the Flare-OA questionnaire obtained 100 % favorable votes. CONCLUSION: Through consensus of the working group, the Flare-OA questionnaire was selected as the best candidate instrument to move into a full assessment of its measurement properties using the OMERACT Filter 2.2.

Validation and optimization of the French Generic Adherence for Chronic Diseases Profile (GACID-P) using classical test and item response theory.

BACKGROUND: The Generic Adherence for Chronic Diseases Profile is a French generic scale (GACID-P) developed to measure adherence in several disease areas such as cardiology, rheumatology, diabetes, cancer and infectiology. METHOD: We aimed to study the measurement invariance of the Generic Adherence for Chronic Diseases Profile by an item response model, optimize the new instrument version from item response model and qualitative content analyses results, and validate the instrument. The metric properties of the optimized version were studied according to classical test theory and item response model analysis. RESULTS: A sample of 397 patients consulting at two French hospitals (in diabetes, cardiology, rheumatology, cancerology and infectiology) and in four private practices was recruited; 314 (79%) patients also completed the questionnaire 15 days later. Factor analyses revealed four dimensions: "Forgetting to take medication", "Intention to comply with treatment", "Limitation of risk-related consumer habits" and "Healthy lifestyle". The item response model and content analyses optimized these four dimensions, regrouping 32 items in four dimensions of 25 items, including one item conditioned on tobacco use. The psychometric properties and scale calibration were satisfactory. One score per dimension was calculated as the sum of the items for the dimensions "Forgetting to take medication" and "Intention to comply with treatment" and as a weighted score according to the item response model analysis for the two other dimensions because of differential item functioning found for two items. CONCLUSION: Four adherence profile scores were obtained. The instrument validity was documented by a theoretical approach and content analysis. The Generic Adherence for Chronic Diseases Profile is now available for research targeting adherence in a broad perspective.

Development and validation of the Flare-OA questionnaire for measuring flare in knee and hip osteoarthritis.

OBJECTIVE: Ability to assess flares in osteoarthritis (OA) of the knee and hip (KHOA) is important in clinical care and research. Using mixed methods, we developed a self-reported instrument measuring flare and assessed its psychometric properties. METHODS: We constructed questionnaire items from semi-structured interviews and a focus group (patients, clinicians) by using a dual-language (English-French) approach. A Delphi consensus method was used to select the most relevant items. Patients with OA from Australia, France and the United States completed the preliminary Flare-OA, HOOS, KOOS and Mini-OAKHQOL questionnaires online. We used a factor analysis and content approach to reduce items and determine structural validity. We tested the resulting questionnaire (score 0-100) for internal consistency, convergent and known-groups validity. RESULTS: Initially, 180 statements were generated and reduced to 33 items in five domains (response 0 = not at all, to 10 = absolutely) by Delphi consensus (50 patients, 116 professionals) and an expert meeting. After 398 patients (mean [SD] age 64 [8.5] years, 70.4% female, 86.7% knee OA) completed the questionnaire, it was reduced to 19 items by factor analysis and a content approach (RMSEA = 0.06; CFI = 0.96; TLI = 0.94). The Cronbach's alpha was >0.9 for the five domains and the whole questionnaire. Correlation coefficients between Flare-OA and other instrument scores were as predicted, supporting construct validity. The difference in Flare-OA score between patients with and without flare (31.8) largely exceeded 2 SEM (10.2). CONCLUSION: Flare-OA is a valid and reliable patient-reported instrument for assessing the occurrence and severity of flare in patients with KHOA in clinical research.

[Dosimetric and toxicity comparison of IMRT and 3D-CRT of non-small cell lung cancer]. / Comparaison dosimétrique et de la toxicité de la radiothérapie conformationnelle avec modulation d'intensité et de la radiothérapie conformationnelle tridimensionnelle des carcinomes bronchiques non à petites cellules.

PURPOSE: Although three-dimensional conformal radiotherapy (3D-CRT) remains the gold standard as a curative treatment for NSCLC when surgery is not possible, intensity modulated radiotherapy (IMRT) is increasingly used routinely. The purpose of this study was to assess the clinical (immediate toxicities) and dosimetric impact of IMRT compared to 3D-CRT in the treatment of locally advanced (stages IIIA to IIIC) non-small cell lung cancer (NSCLC) treated with concomitant radiochemotherapy, while IMRT in lung cancer was implemented in the radiotherapy department of the Jean-Perrin Center. PATIENTS AND METHODS: Between March 2015 and October 2019, 64 patients treated with concomitant radiochemotherapy were retrospectively included. Thirty-two received 3D-CRT and 32 IMRT. The radiotherapy prescription was 66Gy in 33 fractions of 2Gy. RESULTS: IMRT has improved coverage of target volumes (V95 increased by 14.81% in IMRT; P<0.001) without increasing doses to OARs and reducing dysphagia (RR=0.67; P=0.027). Low doses to the lung were not significantly increased in IMRT (pulmonary V5 increased by 7.46% in IMRT). CONCLUSION: Intensity modulated radiotherapy, compared with the standard RC3D technique, improve the coverage of target volumes without increasing the dose to the OARs. It also improves the immediate tolerance of the treatment by reducing the number of dysphagia.

[Predictive factors for mandibular osteoradionecrosis after irradiation of head and neck cancers]. / Facteurs prédictifs de l'ostéoradionécrose mandibulaire après irradiation des cancers des voies aérodigestives supérieures.

The identification of the different risk factors for mandibular osteoradionecrosis (ORN) must be done before and after the management of patients with head and neck cancer. Various clinical criteria for this severe radiation-induced complication are related to the patient (intrinsic radiosensitivity, malnutrition associated with thin weight loss, active smoking intoxication, microcapillary involvement, precarious oral status, hyposalivation) and/or related to the disease (oral cavity, large tumor size, tumor mandibular invasion). Therapeutic risk factors are also associated with a higher risk of ORN (primary tumor surgery, concomitant radio-chemotherapy, post-irradiation dental avulsion, preventive non-observance with the absence of stomatological follow-up and daily installation of gutters fluoride and, non-observance curative healing treatments). Finally, various dosimetric studies have specified the parameters in order to target the dose values distributed in the mandible, which increases the risk of ORN. An mean mandibular dose greater than 48-54Gy and high percentages of mandibular volume receiving 40 to 60Gy appear to be discriminating in the risk of developing an ORN.

[Proposal for the delineation of postoperative primary clinical target volumes in ethmoid cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers de l'ethmoïde.

It is proposed to delineate the anatomo-clinical target volumes of primary tumor (CTV-P) in ethmoid cancers treated with post-operative radiotherapy. This concept is based on the use of radioanatomy and the natural history of cancer. It is supported by the repositioning of the planning scanner with preoperative imaging for the replacement of the initial GTV and the creation of margins around it extended to the microscopic risk zones according to the anatomical concept. This article does not discuss the indications of external radiotherapy but specifies the volumes to be delineated if radiotherapy is considered.

Predictive factors of functional independence after optimal reperfusion in anterior circulation ischaemic stroke with indication for intravenous thrombolysis plus mechanical thrombectomy.

BACKGROUND AND PURPOSE: Intravenous thrombolysis plus mechanical thrombectomy (IVT + MT) is the best current management of acute stroke due to large-vessel occlusion and results in optimal reperfusion for most patients. Nevertheless, some of these patients do not subsequently achieve functional independence. The aim was to identify baseline factors associated with 3-month independence after optimal reperfusion and to validate a prediction model. METHODS: All consecutive patients with intracranial anterior large-vessel occlusion, with indication for IVT + MT and achieving optimal reperfusion (defined as modified Treatment in Cerebral Ischaemia score 2b-3), from the THRACE trial and the ETIS registry, were included in order to identify a prediction model. The primary outcome was 3-month independence [modified Rankin Scale (mRS) score ≤ 2]. Multivariate inferences invoked forward logistic regression, multiple imputation and bootstrap resampling. Predictive performance was assessed by c-statistic. Model validation was conducted on patients from the ASTER trial. RESULTS: Amongst 139 patients (mean age 65.5 years; 54.3% female), predictors of 3-month mRS ≤ 2 (n = 82) were younger age [odds ratio 0.62 per 10-year increase; 95% confidence interval (CI) 0.53-0.72] and higher Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (odds ratio 1.65 per 1-point increase; 95% CI 1.47-1.86) with c-statistic 0.77. Model validation (n = 104/181 patients with 3-month mRS ≤ 2) demonstrated a moderate discrimination (c-statistic 0.74; 95% CI 0.66-0.81) combining age and ASPECTS. The validation model was improved by the adjunction of three candidate variables that were found to be predictors. Addition of baseline National Institutes of Health Stroke Scale (NIHSS) score, history of vascular risk factor and onset-to-reperfusion time significantly improved discrimination (c-statistic 0.85; 95% CI 0.83-0.87). CONCLUSIONS: After optimal reperfusion, younger age, higher ASPECTS, lower NIHSS score, shorter onset-to-reperfusion time and absence of vascular risk factor were predictive of independence and could help to guide patient management.

Ten years psychosocial outcomes among adolescents following suicide attempts - early recurrence and psychosocial outcomes.

OBJECTIVES: A suicide attempt (SA) is a major risk factor of recurrent SA in adolescence and may be associated with psychological or social problems in the future. REPEATERS is a longitudinal study which examines the long-term psychosocial outcome of adolescents following attempted suicide. It focuses on the impact of early recurrence (i.e., within the first year of the index SA) - data which is, in fact, poorly documented. METHODS: Ten years after the index SA, a self-reporting questionnaire was sent to all adolescents who had attempted suicide and were followed up by the CHRU (Regional University Hospital Centre) de Nancy, France, between 1994 and 2003 and their parents. The purpose of this questionnaire was to assess psychosocial outcomes. Data concerning SA were collected retrospectively. RESULTS: After ten years, 146 of the 309 adolescents who had attempted suicide and were participating in the study had responded: 90% lived with a partner and 41% had children. The mean (SD) current emotional life of suicide attempt survivors scored 7.3 (2.3) on a scale of 0 to 10. Compared to the general population of the same age, responders felt more depressed than their peers (29% vs. less than 8% of males and 20% of females), had more suicidal thoughts (14% vs. 5%), and had more SAs (27% vs. 0.3%). Moreover, the risk of recurrence over the ten year period was associated with suicide recurrence in the first year after the index SA (odds ratio [OR]=2.3; 95% confidence interval [CI]=1.1-4.9) and with a lower level of education at ten years (OR=0.37; 95% CI=0.19-0.45). CONCLUSIONS: Although a favorable outcome was reported ten years after the event for the majority of adolescents who had attempted suicide, some with a lower level of education were nevertheless at increased risk of recurrence and depression. Post-intervention strategies are therefore essential in order to evaluate risk factors which may persist if not taken into consideration.

Impact of terminating reimbursement of symptomatic slow-acting drugs in osteoarthritis in France on volume and cost of drug deliveries, assessed with administrative databases.

WITH OSTEOARTHRITIS (OA): As one of the leading causes of disability in adults worldwide, its toll on patients and its economic burden for payers are substantial. The issue of change in OA management with the evolution of reimbursement schemes needs to be addressed. OBJECTIVE: To assess the impact of terminating the reimbursement of symptomatic slow-acting drugs in OA (SYSADOAs) in France in terms of volume and cost, from a healthcare payer perspective. PRINCIPAL RESULTS: We obtained costs and volumes from French public national databases. We considered three exposure periods around cutoff dates according to decisions of decreased then terminated SYSADOA reimbursement. The periods included 19 345 (control), 20 066 (secondary), and 16 200 (primary) patients, respectively. Mean ages were 66.2 (±11.8), 65.3 (±11.6) and 64.6 (±11.5) years and about 70% were women. The volume of nonsteroidal anti-inflammatory drug (NSAID) deliveries estimated by defined daily doses (DDDs) decreased during the periods from 40.5 (±76.3) DDDs per patient in 2008 to 29.6 (±66.4) in 2015. The volume of analgesic deliveries increased slowly over the three periods, from 70.2 (±108.9) DDDs in 2008 to 76.9 (±123.1) in 2015 for all patients. MAJOR CONCLUSIONS: Our results did not show a measurable impact of terminating SYSADOA reimbursement on the delivery of NSAIDs and analgesics or on hospitalizations. However, neither do they allow for concluding that terminating SYSADOA reimbursement did not generate an increase in deliveries of non-reimbursed drugs, with their associated potential risks for public health.

Predictors of fatigue and persistent fatigue in early rheumatoid arthritis: a longitudinal observational study, data from the ESPOIR cohort.

OBJECTIVE: To determine, in a cohort of patients with early rheumatoid arthritis (RA), factors associated with fatigue at baseline, describe its evolution over 5 years of follow-up, and determine baseline predictors of persistent fatigue. METHOD: We selected patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA included in the ESPOIR cohort. Using bivariable and multivariable logistic regression models, we examined baseline variables associated with baseline fatigue (defined by visual analogue scale fatigue > 20) and baseline predictors of persistent fatigue (if the patient experienced fatigue at all visits during the 5 year follow-up period). RESULTS: We analysed 673 patients; 80.7% reported fatigue at baseline. At baseline, fatigue was associated with female gender, younger age, greater severity of morning stiffness, sleep problems, higher Health Assessment Questionnaire levels, presence of sicca symptoms, history of thyroid problems, and presence of psychological distress (depressive or anxiety symptoms). At 5 years of follow-up, the percentage of fatigued patients who reported fatigue at all time-points since baseline was 24.6% (referred to as 'persistent fatigue'). Independent baseline predictors were presence of sicca symptoms, greater severity of morning stiffness, and psychological distress. CONCLUSIONS: Fatigue is a frequent symptom in RA. The presence of sicca symptoms, greater severity of morning stiffness, and presence of psychological distress at baseline were associated with baseline fatigue and persistent fatigue at 5 years. We did not observe any association between baseline fatigue or persistent fatigue and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate.

Translation and cross-cultural adaptation into Italian of the self-administered FLARE-RA questionnaire for rheumatoid arthritis.

The aim was to provide a translation into Italian with cross-cultural adaptation of the French FLARE-Rheumatoid Arthritis (RA) questionnaire, and to test its acceptability, feasibility, reliability and construct validity in a single-centre cohort study. The French version of the FLARE-RA questionnaire was cross-culturally adapted and translated into Italian following an established forward-backward translation procedure, with independent translations and backtranslations. To validate the Italian version we tested the internal validity with Cronbach's alpha, test-retest reliability with the intraclass correlation coefficient, agreement between assessments with Bland-Altman plots and construct validity with Spearman's correlation coefficients. The questionnaire was tested on 283 consecutive RA outpatients (mean age 56.1±13.9 years, 226/283 females, median disease duration 12.6 years ranging from 0.2 to 70.6). For the global score (11 items) the Cronbach's alpha coefficient was 0.94. The intraclass correlation coefficient was 0.87 (95% CI, 0.76-0.96). The correlation of FLARE-RA global score was 0.59 (95% CI, 0.50-0.66) with the Disease Activity Score on 28 joints, 0.63 (95% CI, 0.55-0.71) with the Simplified Disease Activity Index, 0.77 (95% CI, 0.71-0.83) with the RA Impact of Disease and 0.67 (95% CI, 0.59-0.73) with the Health Assessment Questionnaire. The Italian version of the FLARE-RA is feasible, brief and easy to administer. The translated and cross-cultural adapted showed accordingly to be valid and reliable. This questionnaire has some practical advantages, such as clarity, comprehensiveness, simplicity, and a minimum filling time. The development of cross-cultural adapted questionnaires in different languages is of pivotal importance to obtain standardized and comparable data across countries.

Nuclear power plant: state of knowledge of the population living in the area of the Cattenom special intervention plan. A cross-sectional study.

In France information campaigns are periodically conducted within a 10 km radius of nuclear power plants on the protective actions to be adopted in the event of a nuclear accident. The aim of this study was to assess the knowledge of the inhabitants of the Cattenom PPI area on the recommended actions to be adopted in the event of a nuclear accident after the information campaign that took place from 2016 to 2017 and compare its results with a similar study carried out before the information campaign. We performed a cross-sectional study in the Cattenom PPI area after the 2016-2017 information campaign. We administered questionnaires in ten municipalities selected by lot. These questionnaires contained queries on the general protective actions and required approach to taking potassium iodide (KI). The results obtained were compared with the results of a study conducted before the information campaign in the same area. Out of 200 questionnaires administered, 122 people responded. Only 40% of respondents remembered the information campaign. Only 16% knew all of the recommended protective actions. 78% of households had KI and only 60% knew the objective of KI intake. Compared to the results of the study before the information campaign, KI coverage was better (69% versus 78%, p = 0.02) and the dosage was better known (16% versus 28%, p = 0.0003). This study provides an overview of the effectiveness of information campaigns on the procedure in the event of a nuclear accident. This study highlights the insufficient knowledge of people living in the Cattenom PPI area.

The American English version of the validated French Flare Assessment in RA Questionnaire (FLARE-RA).

OBJECTIVE: To evaluate use of a British English version of the validated French FLARE-RA questionnaire among American English speaking patients. In addition, to create a culturally adapted American English (AmE) FLARE-RA questionnaire and to examine its attributes of patient-reported RA flare status. METHODS: Using standardized cultural adaptation guidelines, we cognitively debriefed 25 American English speaking rheumatoid arthritis (RA) outpatients and created AmE-FLARE-RA with their input. One hundred three additional RA patients were recruited. Patients completed the Routine Assessment of Patient Index Data 3 (RAPID3), patient global visual analogue scale (VAS), AmE-FLARE-RA, and self-reports of flare. Physician global VAS, physician-assessed flare, swollen and tender joint count (TJC), and clinical disease activity index (CDAI) were documented. AmE-FLARE-RA and disease activity measures were compared between patient-reported and physician-reported flare categories. RESULTS: Patients were female (89%), with mean (SD) age 51.1 (± 15.3) years and mean disease duration (SD) 11.9 (± 10.1) years, with 26% in remission/low disease activity. Total AmE-FLARE-RA scores, RAPID3, CDAI, and patient global VAS were significantly higher for both patient-reported flares and physician-reported flares compared with non-flaring patients by self- or physician report (p < 0.05). Total AmE-FLARE-RA scores correlated significantly with RAPID3 (corr = 0.50, p < 0.0001) and with CDAI (corr = 0.45, p < 0.0001). Across "no flares," "one flare," and "several flare" groups, there was a non-significant increase in AmE-FLARE-RA scores (p = 0.07). CONCLUSION: The British English FLARE-RA was successfully adapted for AmE-speaking RA patients. AmE-FLARE-RA significantly correlated with RAPID3 and CDAI and distinguished between patient-reported and physician-reported flares, making it useful to detect flares in American RA patients.Key Points• The American English FLARE-RA (AmE-FLARE-RA) questionnaire is the result of cognitive debriefing with American RA patients using the British English version of the validated French FLARE-RA and incorporates patient-recommended language modifications..• Patients self-reporting flares had significantly higher AmE-FLARE-RA scores, compared with those without flares at the time of visit. AmE-FLARE-RA scores correlate with RAPID3 and CDAI.• There was a non-statistically significant trend using the AmE-FLARE-RA scores when examining patients with no flare, one flare, or several flares.• AmE-FLARE-RA total scores are uniformly elevated (~ 6.0 on a 0-10 scale), regardless of discordance between patient and MD assessment of flare at time of visit (~ 30%).

Optimizing DyNaChron instrument for assessing chronic nasal dysfunction symptoms by Rasch analysis.

BACKGROUND: The DyNaChron (Dysfonctionnement Nasal Chronique) questionnaire is a self-reporting 78-item instrument assessing six symptoms and their consequences of chronic nasal dysfunction. Patients complete items of a symptom domain only when it is present but in case the patient presents several or all symptoms, its length can limit its use. Here, we aimed to optimize, or shorten, the DyNaChron for clinical use. METHODS: A total of 640 patients in 14 rhinology outpatient clinics all over France completed the original DyNaChron questionnaire before the first rhinologic clinic and 15 days later. The optimization process involved Rasch analysis and then qualitative content analyses. Rasch analysis flagged items with a floor/ceiling effect or with important differential item functioning and an expert committee decided whether to retain the flagged items on the basis of clinical importance and statistical characteristics. The psychometric properties of the optimized version were studied according to classical test theory and Rasch analysis. RESULTS: Rasch analysis revealed 4 items with underfit, 6 with an extreme score, 2 that were highly locally dependent and 16 with differential item functioning which 5 of these 16 items were retained after content analysis. In total, 19 flagged items were removed. Factorial analysis confirmed the preservation of the initial instrument structure in the optimized scale; psychometrics properties and scale calibration were the same as or better than the original version. CONCLUSION: The shortened DyNaChron optimizes the quality of assessment by deleting redundant items and reduces the burden on respondents; the structure is preserved and the psychometrics properties are improved.

Comparison of a video versus paper questionnaire on functional limitation in lower limb osteoarthritis.

INTRODUCTION: The video Animated Activity Questionnaire (AAQ) was developed to assess the impact of lower limb osteoarthritis (OA) on daily functional activities. The objective of the study was to compare the video and the HOOS/KOOS paper questionnaires and to assess the effect of order of administration. MATERIAL AND METHODS: Patients recruited in the KHOALA cohort were randomized in two groups: AAQ questionnaire first (AAQ-first group) and HOOS (hip)/KOOS (knee) questionnaire first (H/KOOS-first group). Within group differences between AAQ and HOOS/KOOS scores were compared using a Student t-test. The Spearman correlation coefficient between AAQ score and HOOS/KOOS score was calculated in each group then compared, using Fisher z-transformation. RESULTS: Among 200 randomized patients, 188 (65.8 years, 66.0% women) completed the questionnaires: 99 in the AAQ-first group and 89 in the H/KOOS-first group. The AAQ score was 85.9 (SD: 13.7) in the AAQ-first versus 87.8 (SD: 13.1) in the H/KOOS-first group (p = 0.34). The H/KOOS score was 72.5 (SD: 21.2) in the AAQ-first versus 73.5 (SD: 18.4) in the H/KOOS-first group (p = 0.71). The Spearman correlation coefficient between AAQ and H/KOOS in the AAQ-first was 0.84[0.77-0.89] and 0.73[0.61-0.81] in H/KOOS-first group. These correlations differed between groups significantly (p = 0.02). CONCLUSION: This study found video AAQ and paper HOOS/KOOS questionnaire highly correlated, with a moderate but significant effect of order administration of video and paper questionnaires evidencing a stronger correlation when the videos were viewed first.

Surgery in reference centers improves survival of sarcoma patients: a nationwide study.

BACKGROUND: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. PATIENTS AND METHODS: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). RESULTS: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]. CONCLUSION: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.

Health resource use and costs of symptomatic knee and/or hip osteoarthritis.

BACKGROUND: Data on the economic consequences of hip and knee osteoarthritis (OA) are scarce. We aimed to estimate the annual direct and indirect costs for patients followed for hip and/or knee OA in the Knee and Hip Osteoarthritis Long term Assessment (KHOALA) cohort. METHODS: The KHOALA cohort, set up from 2007 to 2009, is a French multicenter study of 878 individuals with symptomatic knee/hip OA who were 40-75 years old. Resources used were collected annually for 5 years. Costs were assigned by using official sources and expressed in 2018 euros per patient. RESULTS: The mean annual total costs per patient over the 5-year study period were 2,180 ± 5,305€. The mean annual direct medical costs per patient were 2,120 ± 5,275€ and mean annual indirect costs per patient 180 ± 1,735€ for people of working age. Costs increased slightly over the study period. Drugs were the largest cost share, representing over 50% of all direct costs. However, the proportion attributable to OA drugs accounted for only 10.5% of drug costs. The second cost share was hospitalizations; hip and knee prosthetic surgery accounted for 27% of surgery hospitalization costs. Health professional visits were the third cost share, accounting for 3% of direct medical costs. The median costs induced could be as high as 2 billion €/year (IQR 0.7-4.3) in France. CONCLUSION: Hip and knee OA costs were substantial and increased over the study period in France. However, the costs attributable to OA represented only a small fraction of overall costs.

Clinical follow-up of 411 patients with relapsing and progressive multiple sclerosis 10 years after discontinuing mitoxantrone treatment: a real-life cohort study.

BACKGROUND AND PURPOSE: Mitoxantrone (MITOX) has been used to treat patients with aggressive multiple sclerosis (MS) for decades. We aimed to describe the effectiveness and adverse events over 10 years post-MITOX in patients with relapsing and progressive MS from an exhaustive real-life database. METHODS: Data from patients who received MITOX before 1 January 2006 were collected from the MS Lorraine registry. Expanded Disability Status Scale (EDSS) scores and annual relapse rates (ARRs) year by year during follow-up and the year prior to MITOX were compared. Time to the first relapse and a 1-point increase in EDSS score were used in Cox multivariate models to find associations with potential predictive factors. RESULTS: A total of 411 patients were included. The ARR for the 155 relapsing patients had decreased from 2.0 (SD 1.20) the year before treatment to 0.3 (SD 0.31) by year 10 (P < 0.0001). The EDSS score increased from 2.8 (SD 1.44) to 4.8 (SD 1.90) by year 10 (P < 0.0001). A high ARR at MITOX initiation was associated with a longer time to a 1-point increase in EDSS score (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99; P = 0.04). The EDSS score in 256 progressive patients increased from 5.0 (SD 1.33) to 6.5 (SD 1.26) by year 10 (P < 0.0001). We identified four cases of acute myeloid leukemias. CONCLUSIONS: Patients with the most active forms of MS are the most likely to benefit from MITOX in the long term.