Evaluation des modalités de passage de la pédiatrie à la médecine pour adultes des enfants suivis pour diabéte de type I au CHU d'Amiens

AMIENS-BU Santé (800212102) / SudocSudocFranceF

Qualité de vie et satisfaction chez les enfants et adolescents sous pompe à insuline (évaluation d'une série de 41 patients diabétiques de type 1 pris en charge au CHU d'Amiens)

Les pompes à insuline sont très utilisées en pédiatrie. L objectif est d évaluer la qualité de vie et la satisfaction des sujets diabétiques ayant bénéficié de pompes à insuline à l âge pédiatrique et de les comparer aux paramètres clinico-biologiques. L étude, réalisée au CHU d Amiens, concerne 43 enfants et adolescents diabétiques de type 1 sous pompe depuis au moins 6 mois ou ayant arrêté la pompe. Un auto-questionnaire évalue de manière rétrospective l amélioration de la qualité vie sous pompe (2 versions +-12 ans). Il est inspiré du PedsQL TM (Qualité de vie et Module Diabète), complété par des items spécifiques à la pompe à insuline. Il se compose de 44 questions classées en 8 items (domaines physiques, psychiques et sociaux), du degré de satisfaction et d une zone de texte libre. 41 enfants (22 /19 ) sont inclus, âgés de 12,7 +-3,6 ans [5,5-19,5], sous pompe depuis l âge de 10 +-3 ans [3,5-14,6] et durant 2,7 +-1,7 ans [0,5-6,5], diabétiques depuis 4,6 +-2,5 ans [1,6-11,73] au moment de la mise sous pompe. Le score global de qualité de vie était positif, corrélé à l indication alternance hypoglycémies/hyperglycémies (p=0,03), au jeune âge à la mise sous pompe (p=0,025), particulièrement avant 8-9 ans (p<0,02), au bon équilibre glycémique avant pompe (p=0,04), au port de pompe depuis moins de 2 ans (p=0,016) et aux découvertes de diabète récentes (p=0,027). Il ne dépendait pas de la baisse de l hémoglobine glyquée (HbA1c), ni des hypoglycémies ou hyperglycémies. Les scores étaient positifs dans les 8 items : vie quotidienne et activités physiques, vie en société, scolarité, vie de famille dont anxiété des parents et des enfants, émotions et comportements, gestion du diabète et acceptation de la maladie, gestion de l insuline (doses et alimentation), injections (nombre, douleur). Les scores des items spécifiques à la pompe étaient supérieurs. Les points suivants font exception avec des moyennes négatives : oublis de l insuline, absences scolaires pour entretiens de diabétologie, problèmes techniques, remarques ou moqueries. Les scores moyens des 5 enfants ayant arrêté la pompe étaient négatifs. 92,6 % des parents et 90,2% des enfants sont satisfaits de la pompe dont 90,2 % des parents et 73,2% des enfants très satisfaits. La satisfaction est fortement corrélée à la qualité de vie (p<0,02) mais non liée à l amélioration glycémique. La pompe est un outil d autogestion du diabète et ne doit pas être considérée comme magique . La pompe peut engendrer des changements de l image corporelle, une sensation de normalité par la liberté et le respect du corps mais aussi de différence par sa visibilité. Notre questionnaire est rétrospectif et donc basé sur le souvenir. Un questionnaire validé et prospectif, adapté à la pompe à insuline dans le diabète de l enfant, pourrait être utile, aboutissant à un dialogue avec les sujets, et favorisant ainsi la relation parents-enfants et soignant-soigné.Insulin pumps are widely used in pediatrics. The objective is to assess the quality of life and satisfaction of diabetics who received insulin pumps during pediatric age and to compare the clinical and biological parameters.The study was conducted in Amiens University Hospital with 43 children and adolescents with type 1 diabetes who used the pump for at least 6 months or who stopped using pump. A retrospective self-administered questionnaire assessed improvements to the quality of life while using the pump (2 versions +- 12 years). It is based on the PedsQL TM (Quality of Life and Diabetes Module), supplemented by specific items about the insulin pump. It consists of 44 questions divided into eight sections (physical, psychological and social), the degree of satisfaction and a free text box. 41 children (22 /19 ) are included, aged 12.7 +- 3.6 years old [5.5 to 19.5], using the pump since the age of 10 +- 3 years [3.5 to 14.6] and for 2.7 years +- 1.7 [0.5 to 6.5], having diabetes for 4.6 +- 2.5 years [1.6 to 11.73] at the time of beginning pump treatment. The overall score for quality of life was positive, correlated with the indication "alternation hypoglycemia / hyperglycemia" (p = 0.03), with patients who were young when they began using the pump (p = 0.025), especially before 8-9 years old (p<0.02), with good glycemic control prior to pump use (p = 0.04), using the pump for less than 2 years (p = 0.016) and recently discovered they had diabetes (p = 0.027). It did not depend on the decrease in glycosylated haemoglobin (HbA1c), neither hypoglycemia nor hyperglycemia. The scores were positive in eight sections: physical activity and daily life, social life, education, family life including parental and children anxiety, emotions and behaviors, diabetes management and acceptance of the disease, management of insulin (doses and food), and injections (number, pain). The scores of sections specifically related to the pump were higher. The following items are exceptions with negative averages: forgetfulness of insulin, school absences for consultation of diabetology, technical problems, comments or jokes. The average scores of five children who stopped using the pump were negative. 92.6% of parents and 90.2% of children are satisfied with the pump with 90.2% of parents and 73.2% of children very happy. Satisfaction is strongly correlated with the quality of life (p <0.02) but not associated with improved glycemic levels.The pump is a "tool" for self-management of diabetes and should not be considered "magical." The pump can cause changes in body image, a feeling of "normalcy" by the freedom and respect for the body but also of "difference" in its visibility. Our questionnaire is retrospective and based on the memory.A validated and prospective questionnaire, suitable for insulin pump for children with diabetes, may be useful. It would lead to a dialogue with the subjects, with the aim to promote the parent-child and doctor-patient relationship.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Hypothyroïdies néonatales (existe-t-il des facteurs prédictifs de leur caractère transitoire?)

Devant l augmentation de l incidence globale des Hypothyroïdies Congénitales (HC) en France et dans le monde, avec une part grandissante des HC avec Glande en Place (GEP) et, parmi celles-ci, des Hypothyroïdies Transitoires (HT), nous avons étudié les données épidémiologiques lors du dépistage des enfants porteurs d HC avec GEP, née en Picardie entre 2004 et 2010. Notre objectif était d étudier l existence de facteurs prédictifs du caractère transitoire de ces hypothyroïdies avec GEP. L incidence des HC dans notre travail était de 1/2336 naissances Parmi les 72 enfants présentant une HC, 46 (63,9 %) présentaient une GEP au dépistage. Le traitement substitutif a pu être arrêté chez 13 patients (28,3 %), posant le diagnostic d une HT, à un âge moyen de 16,8 +/- 17,2 mois. La dose moyenne de L Thyroxine juste avant l arrêt était de 2,59 +/- 1,84 g/kg/jour.L étude des données cliniques, biologiques et d imagerie au dépistage n a pas permis d établir un score prédictif du caractère transitoire de l HC avec GEP. Au mieux pouvons-nous plutôt évoquer une HT chez un nouveau-né prématuré porteur d une HC avec GEP. A l inverse, un taux élevé de TSH au dépistage ou en macro-méthode semble en faveur d une Hypothyroïdie Persistante (HP). Aucune information ne peut être retenue des données de iodurie ou de l auto-immunité chez le bébé ou chez sa mère. Il n y avait pas non plus de différence significative pour l ensemble des autres paramètres étudiés. En conclusion, la même rigueur doit être employée pour le suivi régulier et rapproché de tous les enfants porteurs d une HC avec GEP afin d adapter au mieux la posologie du traitement, et d identifier les situations d HT. En cas d HT, un arrêt de la supplémentation par L Thyroxine devra être tenté selon un protocole bien établi.We notice a raise of incidence of congenital hypothyroidism (CT) in France and in the world, with a growing part of CH with Normally Located Gland (NLG), and, among these NLG, of Transient Hypothyroidism (TH). We studied epidemiologic datas at screening of children suffering from CT with NLG, born in Picardie between 2004 and 2010. We aimed to study the existence of predictive factors of TH. We noticed an incidence of CH of 1/2336. Among the 72 children with CH, 46 (63,9 %) had a NLG at screening. Substitutive treatment was stopped in 13 patients (28,3 %), considered as having TH. Mean age of children at discontinuation was 16,8 +/- 17,2 months. Mean dose of L Thyroxine before stopping was 2,59 +/- 1,84 g/kg/day. By studying clinical, biological and imaging datas at screening, we couldn t establish a predictive score of TH in patients with NLG. We could just feel reassured when the screened child was a premature. On the contrary, high rates of TSH at screening or at confirmation blood test seemed to indicate a Permanent Hypothyroidism (PH). We couldn t conclude about rates of urinary iodine or auto-antibodies in the baby or his mother. As a conclusion, regular and close follow-up of children with NLG is needed, in order to adjust doses of treatment, and to identify situations of TH, allowing us to discontinue treatment by L Thyroxine.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Presenting features and molecular genetics of primary hyperparathyroidism in the paediatric population

International audienceAim: To describe the presenting features and molecular genetics of primary hyperparathyroidism (PHPT) in the paediatric population.Methods: Retrospective study of 63 children diagnosed with primary PHPT from 1998 to 2018.Results: Compared to older children, infants were often asymptomatic (54% vs 15%, P = 0.002) with a milder form of PHPT. When symptomatic, children and adolescents mostly presented with non-specific complaints such as asthenia, depression, weight loss, vomiting or abdominal pain. A genetic cause of PHPT was identified in about half of this cohort (52%). The infancy period was almost exclusively associated with mutation in genes involved in the calcium-sensing receptor (CaSR) signalling pathway (i.e. CaSR and AP2S1 genes, 'CaSR group'; 94% of infants with mutations) whereas childhood and adolescence were associated with mutation in genes involved in parathyroid cell proliferation (i.e. MEN1, CDC73, CDKN1B and RET genes, 'cell proliferation group'; 69% of children and adolescents with mutations). Although serum calcium levels did not differ between the two groups (P = 0.785), serum PTH levels and the urinary calcium/creatinine ratio were significantly higher in 'cell proliferation group' patients compared to those in the 'CaSR group' (P = 0.001 and 0.028, respectively).Conclusion: Although far less common than in adults, PHPT can develop in children and is associated with significant morbidity. Consequently, this diagnosis should be considered in children with non-specific complaints and lead to monitoring of mineral homeostasis parameters. A genetic cause of PHPT can be identified in about half of these patients

Presenting features and molecular genetics of primary hyperparathyroidism in the paediatric population

International audienceAim To describe the presenting features and molecular genetics of primary hyperparathyroidism (PHPT) in the paediatric population. Methods Retrospective study of 63 children diagnosed with primary PHPT from 1998 to 2018. Results Compared to older children, infants were often asymptomatic (54% vs 15%, P = 0.002) with a milder form of PHPT. When symptomatic, children and adolescents mostly presented with non-specific complaints such as asthenia, depression, weight loss, vomiting or abdominal pain. A genetic cause of PHPT was identified in about half of this cohort (52%). The infancy period was almost exclusively associated with mutation in genes involved in the calcium-sensing receptor (CaSR) signalling pathway (i.e. CaSR and AP2S1 genes, ‘CaSR group’; 94% of infants with mutations) whereas childhood and adolescence were associated with mutation in genes involved in parathyroid cell proliferation (i.e. MEN1 , CDC73 , CDKN1B and RET genes, ‘cell proliferation group’; 69% of children and adolescents with mutations). Although serum calcium levels did not differ between the two groups ( P = 0.785), serum PTH levels and the urinary calcium/creatinine ratio were significantly higher in ‘cell proliferation group’ patients compared to those in the ‘CaSR group’ ( P = 0.001 and 0.028, respectively). Conclusion Although far less common than in adults, PHPT can develop in children and is associated with significant morbidity. Consequently, this diagnosis should be considered in children with non-specific complaints and lead to monitoring of mineral homeostasis parameters. A genetic cause of PHPT can be identified in about half of these patients

Increasing knowledge in IGF1R defects: lessons from 35 new patients

International audienceBACKGROUND: The type 1 insulin-like growth factor receptor (IGF1R) is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. Recently, a cohort of patients carrying an IGF1R defect was described, from which a clinical score was established for diagnosis. We assessed this score in a large cohort of patients with identified IGF1R defects, as no external validation was available. Furthermore, we aimed to develop a functional test to allow the classification of variants of unknown significance (VUS) in vitro.METHODS: DNA was tested for either deletions or single nucleotide variant (SNV) and the phosphorylation of downstream pathways studied after stimulation with IGF-I by western blot analysis of fibroblast of nine patients.RESULTS: We detected 21 IGF1R defects in 35 patients, including 8 deletions and 10 heterozygous, 1 homozygous and 1 compound-heterozygous SNVs. The main clinical characteristics of these patients were being born small for gestational age (90.9%), short stature (88.2%) and microcephaly (74.1%). Feeding difficulties and varying degrees of developmental delay were highly prevalent (54.5%). There were no differences in phenotypes between patients with deletions and SNVs of IGF1R. Functional studies showed that the SNVs tested were associated with decreased AKT phosphorylation.CONCLUSION: We report eight new pathogenic variants of IGF1R and an original case with a homozygous SNV. We found the recently proposed clinical score to be accurate for the diagnosis of IGF1R defects with a sensitivity of 95.2%. We developed an efficient functional test to assess the pathogenicity of SNVs, which is useful, especially for VUS

Dissertatio historica de initiis monarchiae Babyloniorum, quam, cum cons. ampliss. Colleg. Philos. in Reg. Acad. Upsal. sub praesidio ... Jacobi Arrhenii ... publico examini modeste subjicit Petrus Hagberg Gestr. In audit. Gustav. maj. ad d. 25. Maji. Anni MDCCV.

International audienceBackground : The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedlybecause of changing environmental factors, which are yet largely unknown. The purpose of the study was tounravel environmental markers associated with T1D. Methods : Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends ofthe patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis.The analysis took into account the matching between cases and controls. A second analysis used propensity scoremethods. Results : We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnutcocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a petby old age. Conclusions : The found statistical association of new environmental markers with T1D calls for replication in othercohorts and investigation of new environmental areas

Additional file 1: of Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

The questionnaire used in the current study. (PDF 620 kb