Determinants of adherence and consequences of the transition from adolescence to adulthood among young people with severe haemophilia (TRANSHEMO): A multicentric French national observational cross-sectional study based on the FranceCoag registry.

INTRODUCTION: It is necessary to gain insights into adherence to healthcare in people with severe haemophilia (PwSH), especially during the transition from paediatric to adult care, which is an important phase in lives of young people with childhood chronic disease. This adherence can be considered as a marker of successful transition. OBJECTIVES: The main objective of the quantitative phase of the TRANSHEMO project was to compare the adherence to healthcare between adolescents and young adults (YAs) with severe haemophilia. The secondary objective was to identify the determinants (facilitators and barriers) of this adherence and associations between these determinants. METHODS: A multicentre, observational, cross-sectional study was conducted in 2017-2019 on PwSH aged between 14 and 17 years (adolescents) or between 20 and 29 years (YAs), included in the FranceCoag registry and having completed the questionnaires. The adherence to healthcare (treatment regimens and clinical follow-up) was compared between adolescents and YAs using the chi-squared test. The determinants of this adherence were analysed by structural equation modelling. RESULTS: There were 277 participants, 107 adolescents, and 170 YAs. The rate of adolescents adhering to healthcare was 82.2%, while the rate of YAs was 61.2% (p < .001). The barriers to the adherence to healthcare were being YA, having repeated at least one school grade and presenting mental health concerns. CONCLUSION: Adolescents had better adherence to healthcare than YAs. According to the determinants enlightened in this project, targeted supportive strategies and adapted therapeutic education programs can be developed for young PwSH to facilitate their adherence to healthcare.

Molecular and clinicopathologic characterization of pediatric histiocytoses.

The spectrum of somatic mutations in pediatric histiocytoses and their clinical implications are not fully characterized, especially for non-Langerhans cell histiocytosis (-LCH) subtypes. A cohort of 415 children with histiocytosis from the French histiocytosis registry was reviewed and analyzed for BRAFV600E . Most BRAFWT samples were analyzed by next-generation sequencing (NGS) with a custom panel of genes for histiocytosis and myeloid neoplasia. Of 415 case samples, there were 366 LCH, 1 Erdheim-Chester disease, 21 Rosai-Dorfman disease (RDD), 21 juvenile xanthogranuloma (JXG, mostly with severe presentation), and 6 malignant histiocytosis (MH). BRAFV600E was the most common mutation found in LCH (50.3%, n = 184). Among 105 non-BRAFV600E -mutated LCH case samples, NGS revealed mutations as follows: MAP2K1 (n = 44), BRAF exon 12 deletions (n = 26), and duplications (n = 8), other BRAF V600 codon mutation (n = 4), and non-MAP-kinase pathway genes (n = 5). Wild-type sequences were identified in 17.1% of samples. BRAFV600E was the only variant significantly correlated with critical presentations: organ-risk involvement and neurodegeneration. MAP-kinase pathway mutations were identified in seven RDD (mostly MAP2K1) and three JXG samples, but most samples were wild-type on NGS. Finally, two MH samples had KRAS mutations, and one had a novel BRAFG469R mutation. Rarely, we identified mutations unrelated to MAP-kinase pathway genes. In conclusion, we characterized the mutational spectrum of childhood LCH and clinical correlations of variants and subtypes. Variants responsible for JXG and RDD were not elucidated in more than half of the cases, calling for other sequencing approaches.

Environmental exposures related to parental habits in the perinatal period and the risk of Wilms' tumor in children.

INTRODUCTION: Wilms' tumor is the most frequently diagnosed renal tumor in children. Little is known about its etiology. The aim of this study was to investigate the potential role of specific exposures related to parental habits such as parental smoking, maternal alcohol consumption and the use of household pesticides during pregnancy. METHODS: The ESTELLE study was a nationwide case-control study that included 117 Wilms' tumor cases and 1100 control children from the general French population, frequency-matched by age and gender. Unconditional logistic regression was used to estimate odds ratios and 95 % confidence intervals. RESULTS: After controlling for matching variables and potential confounders, the maternal use of any type of pesticide during pregnancy was associated with the risk of Wilms' tumor in children (OR 1.6 [95 % CI 1.1-2.3]). Insecticides were the most commonly reported type of pesticide and there was a positive association with their use (OR 1.7 [95 % CI 1.1-2.6]. The association was stronger when they were used more often than once a month (OR 1.9 [95 % CI 1.2-3.0]. Neither maternal smoking during pregnancy nor paternal smoking during preconception/pregnancy was associated with a risk of Wilms' tumor (ORs 1.1[95 % CI 0.7-1.8] and 1.1 [95 % CI 0.7-1.7], respectively). No association was observed with maternal alcohol intake during pregnancy (OR 1.2 [95 % CI 0.8-2.0]). CONCLUSION: Our findings suggest an association between the maternal use of household pesticides during pregnancy and the risk of Wilms' tumor.

Maternal and perinatal characteristics, congenital malformations and the risk of wilms tumor: the ESTELLE study.

PURPOSE: Wilms tumor (WT), or nephroblastoma, is an embryonic tumor that constitutes the most common renal tumor in children. Little is known about the etiology of WT. The aim of this study was to investigate whether maternal or perinatal characteristics were associated with the risk of WT. METHODS: The ESTELLE study is a national-based case-control study that included 117 cases of WT and 1,100 controls younger than 11 years old. The cases were children diagnosed in France in 2010-2011 and the controls were frequency matched with cases by age and gender. The mothers of case and control children responded to a telephone questionnaire addressing sociodemographic and perinatal characteristics, childhood environment, and lifestyle. Unconditional logistic regression models adjusted on potential cofounders were used to estimate the odds ratios (OR) and their confidence intervals (95% CI). RESULTS: High birth weight and the presence of congenital malformation were associated with WT (OR 1.9 [95% CI 1.0-3.7] and OR 2.5 [95% CI 1.1-5.8], respectively). No association with breastfeeding or folic acid supplementation was observed. CONCLUSIONS: Although potential recall bias cannot be excluded, our findings reinforce the hypothesis that high birth weight and the presence of congenital malformation may be associated with an increased risk of WT. Further investigations are needed to further elucidate the possible role of maternal characteristics in the etiology of WT.

Measuring eating motives in older adults with and without functional impairments with The Eating Motivation Survey (TEMS).

Gaining a better understanding which motives play a role in daily eating is crucial in order to develop personalized interventions promoting adequate diet. The Eating Motivation Survey (TEMS) is a comprehensive tool to assess manifold reasons for eating but has not been specifically applied in an older sample including very old persons and persons differing in functional status. Therefore, the first step of the study was to investigate whether the basic motives of TEMS are consistent in an older sample and comparable across older adults with and without functional impairments. Second, the study aimed at describing which motives underlie eating behavior in older age most often as well as to analyze the relationship between eating motives and functional status. 376 community-dwelling older persons aged 70 years and older filled in the brief survey version (15 motives à 3 items) of TEMS. The sample comprises 149 unimpaired and 227 impaired participants in terms of physical function. Confirmatory factor analysis yielded good model fit with RMSEA 0.036 and SRMR 0.048. Furthermore, multi-group analysis revealed a generally invariant factor structure across participants with and without functional impairments. Liking was rated to underlie eating behavior most often, followed by Health and Natural Concerns. Considering gender, age and BMI, significant associations between functional status and the motive Sociability emerged. Since the results suggest that the fifteen basic eating motives are generalizable in older age and across different functional states, TEMS might be a valuable tool in nutrition-related health promotion to developing individualized approaches considering health aspects as well as hedonistic factors.

Daily and per-meal animal and plant protein intake in relation to muscle mass in healthy older adults without functional limitations: an enable study.

OBJECTIVE: Animal protein sources are considered to be of higher quality than plant protein sources in terms of stimulating muscle metabolism. Our objective was to investigate whether protein intake from animal and plant sources on a daily and per-meal basis differs between healthy older adults with normal and with low muscle mass. METHODS: In this cross-sectional study including 100 healthy, community-dwelling adults (51 women) aged 75-85 years without functional limitations dietary intake was assessed using 7-day food records. Protein intake was classified by six animal and six plant protein sources. Skeletal muscle index (SMI) was determined based on bioelectrical impedance analysis and categorized into 'normal' or 'low' (men ≤ 8.50, women ≤ 5.75 kg/m2). The absolute animal and plant protein intake and their proportion of total protein intake were compared between these groups using Mann-Whitney U test. RESULTS: Daily protein intake was 0.96 ± 0.27 g/kg body weight (BW), 61 ± 10% hereof were from animal origin with no difference between men and women. SMI was low in 39% of men and 35% of women. No differences in absolute daily animal and plant protein intake between participants with normal vs. low SMI were observed. The proportion of animal protein was not different on neither a daily nor a per-meal basis between those with normal and those with low SMI. Women with low SMI consumed less animal protein (in g) for breakfast (4.8 ± 4.1 g vs. 8.5 ± 6.9 g, p = 0.031) and fewer meals per day with at least 50% animal protein (2.2 ± 0.9 vs. 2.7 ± 1.0, p = 0.046) compared to those with normal SMI. CONCLUSION: On a daily basis, the absolute and relative animal protein intake does not differ between healthy older adults without functional limitations with normal vs. low SMI. However, our results indicate that in women animal protein intake on a per-meal basis might be of relevance for the maintenance of muscle mass.

Determinants of adherence and consequences of the transition from adolescence to adulthood among young people with severe haemophilia (TRANSHEMO): study protocol for a multicentric French national observational cross-sectional study.

INTRODUCTION: Severe haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life. METHODS AND ANALYSIS: We present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14-17 years) with those from a group of young adults (aged 20-29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants' views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag. ETHICS AND DISSEMINATION: The study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public. TRIAL REGISTRATION NUMBER: NCT02866526; Pre-results.

Amount, Distribution, and Quality of Protein Intake Are Not Associated with Muscle Mass, Strength, and Power in Healthy Older Adults without Functional Limitations-An enable Study.

To maintain muscle mass in older age, several aspects regarding the amount and distribution of protein intake have been suggested. Our objective was to investigate single and combined associations of daily protein intake, evenness of protein distribution across the three main meals, number of meals providing ≥0.4 g protein/kg body weight (BW), and number of meals providing ≥2.5 g leucine, with muscle mass, strength, and power in successful agers. In this cross-sectional study in 97 healthy community-dwelling adults without functional limitations aged 75-85 years, protein intake was assessed using 7-day food records. Muscle mass, leg muscle strength, leg muscle power, and handgrip strength were measured according to standardized protocols. Mean daily protein intake was 0.97 ± 0.28 g/kg BW and the coefficient of variance between main meals was 0.53 ± 0.19. Per day, 0.72 ± 0.50 meals providing ≥0.4 g protein/kg BW and 1.11 ± 0.76 meals providing ≥2.5 g leucine were consumed. No correlations between single or combined aspects of protein intake and skeletal muscle index, leg muscle power, leg muscle strength, or handgrip strength were observed (Spearman's r of -0.280 to 0.291). In this sample of healthy older adults without functional limitations, aspects of protein intake were not associated with muscle mass, strength, or power.

NUT carcinoma in children and adults: A multicenter retrospective study.

BACKGROUND: Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor defined by the presence of NUT rearrangement with a poor prognosis. This rare cancer is underdiagnosed and poorly treated. OBJECTIVE: The primary objective of this study was to describe the clinical, radiologic, and biological features of NUT carcinoma. The secondary objective was to describe the various treatments and assess their efficacy. METHODS: This retrospective multicenter study was based on review of the medical records of children and adults with NUT carcinoma with specific rearrangement or positive anti-NUT nuclear staining (>50%). RESULTS: This series of 12 patients had a median age of 18.1 years (ranges: 12.3-49.7 years). The primary tumor was located in the chest in eight patients, the head and neck in three patients, and one patient had a multifocal tumor. Nine patients presented regional lymph node involvement and eight distant metastases. One-half of patients were initially misdiagnosed. Specific NUT antibody was positive in all cases tested. A transient response to chemotherapy was observed in four of 11 patients. Only two patients were treated by surgery and five received radiotherapy with curative intent. At the end of follow-up, only one patient was still in remission more than 12 years after the diagnosis. Median overall survival was 4.7 months (95% confidence interval [CI]: 2.1-17.7). CONCLUSION: NUT carcinoma is an aggressive disease refractory to conventional therapy. Early diagnosis by NUT-specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma to identify the specific rearrangement of NUT gene is useful to propose the optimal therapeutic strategy.

Paediatric anaplastic large cell lymphoma with leukaemic presentation in children: a report of nine French cases.

This study aimed to describe the clinical features and outcome of anaplastic large cell lymphoma (ALCL) with leukaemic presentation in children. Among 267 patients included in the French paediatric ALCL database between 1989 and 2012, nine (3%) were described as having cytologically detectable circulating tumour cells. Clinical features combined fever (8/9), nodal and extra-nodal disease (9/9), including hepato-splenic (9/9) and lung involvement (7/9). The level of hyperleucocytosis ranged from 30 to 120 × 10(9) /l, with 12-90% of tumour cells. Diagnosis relied on a lymph node biopsy, with a positive ALK+ antibody immunostain in all nine cases, a T-cell immunophenotype in 7/9 cases and CD3 positivity in 5/9 cases. A small cell component was present in 6/9 cases. Only four patients achieved a complete remission with first-line therapy and 3/4 relapsed. Four patients are alive with a median follow-up of 31 months, two of them after allogeneic haematopoietic stem cell transplantation (HSCT), and five patients died, two of them of disease. In conclusion, ALCL with leukaemic presentation is very unusual and should be considered as high-risk lymphoma requiring new therapeutic strategies. The respective role of new agents and allogeneic HSCT in first complete remission still has to be assessed.