Appropriateness of colonoscopy in Europe (EPAGE II). Chronic diarrhea and known inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for investigation of chronic diarrhea, management of patients with known inflammatory bowel disease (IBD), and for colorectal cancer (CRC) surveillance in such patients, and to report report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews, and primary studies regarding the evaluation of chronic diarrhea, the management of IBD, and colorectal cancer surveillance in IBD was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: According to the literature, colonoscopic evaluation may be justified for patients aged > 50 years with recent-onset chronic diarrhea or with alarm symptoms. Surveillance colonoscopy for CRC should be offered to all patients with extensive ulcerative colitis or colonic Crohn's disease of 8 years' duration, and to all patients with less extensive disease of 15 years' duration. Intervals for surveillance colonoscopy depend on duration of evolution, initial diagnosis, and histological findings. The EPAGE II criteria also confirmed the appropriateness of diagnostic colonoscopy for diarrhea of > 4 weeks' duration. They also suggest that, in addition to assessing extent of IBD by colonoscopy, further colonoscopic examination is appropriate in the face of persistent or worsening symptoms. Surveillance colonoscopy in IBD patients was generally appropriate after a lapse of 2 years. In the presence of dysplasia at previous colonoscopy, it was not only appropriate but necessary. CONCLUSIONS: Despite or perhaps because of the limitations of the available published studies, the panel-based EPAGE II (http://www.epage.ch) criteria can help guide appropriate colonoscopy use in the absence of strong evidence from the literature.

Childhood adversity and psychosis: examinig whether the association is due to genetic confounding using a monozygotic twin differences approach

Purpose: To test whether the association between childhood adversity and positive and negative psychotic experiences is due to genetic confounding. Method: Childhood adversity and psychotic experiences were assessed in a sample of 226 twins from the general population. A monozygotic (MZ) twin differences approach was used to assess possible genetic confounding. Results: In the whole sample, childhood adversity was significantly associated with positive (β =.45; SE=.16; p=.008) and negative psychotic experiences (β=.77; SE=.18; p<.01). Within-pair MZ twin differences in exposure to childhood adversity were significantly associated with differences in positive (β =.71; SE=.29; p=.016) and negative psychotic experiences (β =.98; SE=.38; p=.014) in a subsample of 86 MZ twin pairs. Conclusions: Individuals exposed to childhood adversity are more likely to report psychotic experiences. Furthermore, our findings indicate that unique environmental effects of childhood adversity contribute to the development of psychotic experiences.

Carie du biberon: un caillou dans la chaussure de la santé [The impact of childhood caries].

The early childhood caries affect primary dentition before the eruption of the permanent teeth. It is set to extended use of a bottle containing fermentable carbohydrates. The early childhood caries is not only a dental disease: it is a social, cultural and behavioral condition that reflects the practices and beliefs around the child. Swiss data indicate that in aged 2 children, one of for could be affected by this devastating oral disease, mainly in vulnerable populations. The primary care physician has an important role in the screening of preschool children, in determining the risk level of the child for early childhood caries. Physicians can advise families, especially pregnant women, about preventive measures and behavior, leading to a dramatic drop of early childhood caries prevalence.

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

Cytogenetic characterization of childhood acute lymphoblastic leukemia in Nicaragua.

BACKGROUND: Within the frame of a twinning programme with Nicaragua, The La Mascota project, we evaluated in our study the contribution of cytogenetic characterization of acute lymphoblastic leukemia (ALL) as prognostic factor compared to clinical, morphological, and immunohistochemical parameters. METHODS: All patients with ALL treated at the only cancer pediatric hospital in Nicaragua during 2006 were studied prospectively. Diagnostic immunophenotyping was performed locally and bone marrow or blood samples were sent to the cytogenetic laboratory of Zurich for fluorescence in situ hybridization (FISH) analysis and G-banding. RESULTS: Sixty-six patients with ALL were evaluated. Their mean age at diagnosis was 7.3 years, 31.8% were >or=10 years. Thirty-four patients (51.5%) presented with hyperleucocytosis >or=50 x 10(9)/L, 45 (68.2%) had hepatosplenomegaly. Immunophenotypically 63/66 patients (95%) had a B-precursor, 2 (3%) a T- and 1 (1.5%) a B-mature ALL. FISH analysis demonstrated a TEL/AML1 fusion in 9/66 (14%), BCR/ABL fusion in 1 (1.5%), MLL rearrangement in 2 (3.1%), iAMP21 in 2 (3.1%), MYC rearrangement in 1 (1.5%), and high-hyperdiploidy in 16 (24%). All patients but two with TEL/AML1 fusion and high-hyperdiploidy were clinically and hematologically in the standard risk group whereas those with poor cytogenetic factors had clinical high-risk features and were treated intensively. CONCLUSIONS: Compared to Europe, the ALL population in Nicaragua is older, has a higher proportion of poor prognostic clinical and hematological features and receives more intensive treatment, while patients with TEL/AML1 translocations and high-hyperdiploidy are clinically in the standard risk group. Cytogenetics did not contribute as an additional prognostic factor in this setting.

Follow-up care amongst long-term childhood cancer survivors: a report from the Swiss Childhood Cancer Survivor Study.

In the Swiss Childhood Cancer Survivor Study, we aimed to assess the proportion of long-term survivors attending follow-up care, to characterise attendees and to describe the health professionals involved. We sent a questionnaire to 1252 patients, of whom 985 (79%) responded, aged in average 27 years (range 20-49). Overall, 183 (19%) reported regular, 405 (41%) irregular and 394 (40%) no follow-up. For 344, severity of late effects had been classified in a previous medical examination. Only 17% and 32% of survivors with moderate and severe late effects respectively had made regular visits a decade later. Female gender, after a shorter time since diagnosis, had radiotherapy, and having suffered a relapse predicted follow-up. In the past year, 8% had seen a general practitioner only, 10% a paediatric or adult oncologist and 16% other health specialists for a cancer related problem. These findings underline the necessity to implement tailored national follow-up programmes.

Obesity in long-term survivors of childhood acute lymphoblastic leukemia

Rapport de synthèse : Le traitement des leucémies aiguës chez l'enfant représente un des succès de la médecine moderne avec des taux de guérison avoisinant les 80% ce qui implique la nécessité de suivre les effets secondaires à long terme des traitements chez cette population de patients. Récemment plusieurs études internationales ont relevé une prévalence plus importante de surpoids et d'obésité chez les enfants traités pour une leucémie aiguë. L'origine de ce processus reste incertaine :aux effets secondaires bien connus et décrits des traitements (stéroïdes et radiothérapie) semblent s'ajouter des facteurs génétiques, familiaux (age, BMI au diagnostic, BMI parents et fratrie), environnementaux. L'objectif de ce travail est d'estimer la prévalence et les facteurs de risque pour le surpoids et l'obésité chez les enfants traités et guéris d'une leucémie aiguë en Suisse romande et de comparer ces résultats à ceux d'études internationales. Pour répondre à ces questions nous avons inclus 54 patients (40 de Lausanne et 14 de Genève) traités pour une leucémie aiguë. Seuls les enfants à 5 ans de leur première rémission clinique, sans atteinte du système nerveux central, testiculaire ou médullaire et traités par chimiothérapie seule sont retenus. Leur poids, taille sont enregistrés durant les phases précises de traitement (au diagnostic, à la rémission, fin de consolidation, milieumaintenance et en fin de traitement) puis annuellement jusqu'à 12 ans post fin de traitement. Le BMI (kg/ml) et sa déviation standard BMI-SDS (spécifique pour Page et le sexe) pour les patients et leurs parents sont calculés selon les valeurs internationales (IOTF) respectivement BMI-SDS >1.645 (p<0.05) pour le surpoids et> 1.96 (p<0.025) pour l'obésité. Les résultats de ce travail confirment une prévalence double de surpoids (30% versus 17%) et quadruple d'obésité (18% versus 4%) au sein de la population d'enfants traités pour une leucémie aiguë comparées à la population suisse standard. Les facteurs de risque impliqués sont le BMI initial au diagnostic et le BMI maternel contrairement à Page, sexe, stéroïdes et au BMI paternel. Ces données confirment une prévalence significative d'enfants en surpoids/obèses au sein de cette population avec des résultats similaires à ceux retrouvés dans des études internationales récentes. Les facteurs de risque identifiés semblent plutôt liés à l'environnement familial qu'aux traitements. Ces constatations pourraient être le résultat d'interactions complexes entre "le background génétique", les facteurs environnementaux, les habitudes socioculturelles (activité physique, status nutritionnel) paramètres non évalués dans cette revue. Des études plus larges, prospectives sont nécessaires pour clarifier les rôles des différents facteurs de risque et de leurs interactions ;celles-ci devraient inclure des données génétiques (LEPR), taux de leptine, activité physique et le status nutritionnel. Enfin, l'identification des patients à risque est cruciale afin de prévenir les effets secondaires cardio-vasculaires, métaboliques bien connus liés au surpoids et à l'obésité.

Audit report on the AIM - Jefferson, Keokuk Early Childhood Iowa Area Board, d/b/a Jefferson/Keokuk Early Childhood Iowa Area for the year ended June 30, 2011

Audit report on the AIM - Jefferson, Keokuk Early Childhood Iowa Area Board, d/b/a Jefferson/Keokuk Early Childhood Iowa Area for the year ended June 30, 2011

Low predictive value of elevated blood pressure during childhood and adolescence

Background: Screening of elevated blood pressure (BP) in children has been advocated to early identify hypertension. However, identification of children with sustained elevated BP is challenging due to the high BP variability. The value of an elevated BP measure during childhood and adolescence for the prediction of future elevated BP is not well described. Objectives: We assessed the positive (PPV) and negative (NPV) predictive value of high BP for sustained elevated BP in cohorts of children of the Seychelles, a rapidly developing island state in the African region. Methods: Serial school-based surveys of weight, height, and BP were conducted yearly between 1998-2006 among all students of the country in four school grades (kindergarten [G0, mean age (SD): 5.5 (0.4) yr], G4 [9.2 (0.4) yr], G7 [12.5 (0.4) yr] and G10 (15.6 (0.5) yr]. We constituted three cohorts of children examined twice at 3-4 years interval: 4,557 children examined at G0 and G4, 6,198 at G4 and G7, and 6,094 at G7 and G10. The same automated BP measurement devices were used throughout the study. BP was measured twice at each exam and averaged. Obesity and elevated BP were defined using the CDC (BMI_95th sex-, and age-specific percentile) and the NHBPEP criteria (BP_95th sex-, age-, and height specific percentile), respectively. Results: Prevalence of obesity was 6.1% at G0, 7.1% at G4, 7.5% at G7, and 6.5% at G10. Prevalence of elevated BP was 10.2% at G0, 9.9% at G4, 7.1% at G7, and 8.7% at G10. Among children with elevated BP at initial exam, the PPV of keeping elevated BP was low but increased with age: 13% between G0 and G4, 19% between G4 and G7, and 27% between G7 and G10. Among obese children with elevated BP, the PPV was higher: 33%, 35% and 39% respectively. Overall, the probability for children with normal BP to remain in that category 3-4 years later (NPV) was 92%, 95%, and 93%, respectively. By comparison, the PPV for children initially obese to remain obese was much higher at 71%, 71%, and 62% (G7-G10), respectively. The NPV (i.e. the probability of remaining at normal weight) was 94%, 96%, and 98%, respectively. Conclusion: During childhood and adolescence, having an elevated BP at one occasion is a weak predictor of sustained elevated BP 3-4 years later. In obese children, it is a better predictor.

The congenital soidum diarrhea and Spint2: from the molecules to the disease

La diarrhée congénitale de sodium est une maladie génétique très rare. Les enfants touchés par cette maladie présentent une diarrhée aqueuse sévère accompagnée d'une perte fécale de sodium et bicarbonates causant une déshydratation hyponatrémique et une acidose métabolique. Des analyses génétiques ont identifié des mutations du gène Spint2 comme cause de cette maladie. Le gène Spint2 code pour un inhibiteur de sérine protéase transmembranaire exprimé dans divers épithéliums tels que ceux du tube digestif ou des tubules rénaux. Le rôle physiologique de Spint2 n'est pas connu. De plus, aucun partenaire physiologique de Spint2 n'a été identifié et le mécanisme d'inhibition par Spint2 nous est peu connu. Le but de ce projet est donc d'obtenir de plus amples informations concernant la fonction et le rôle de Spint2 dans le contexte de la diarrhée congénitale de sodium, cela afin de mieux comprendre la physiopathologie des diarrhées et peut-être d'identifier de nouvelles cibles thérapeutiques. Un test fonctionnel dans les ovocytes de Xenopus a identifié les sérine protéases transmembranaires CAPI et Tmprssl3 comme potentielles cibles de Spint2 dans la mesure où ces deux protéases n'étaient plus bloquées par le mutant de Spint2 Y163C qui est associé avec la diarrhée congénitale de sodium. Des expériences fonctionnelles et biochimiques plus poussées suggèrent que l'inhibition de Tmprssl3 par Spint2 est le résultat d'une interaction complexe entre ces deux protéines. Les effets des sérine protéases transmembranaires sur l'échangeur Na+-H+ NHE3, qui pourrait être impliqué dans la pathogenèse de la diarrhée congénitale de sodium ont aussi été testés. Un clivage spécifique de NHE3 par la sérine protéase transmembranaire Tmprss3 a été observé lors d'expériences biochimiques. Malheureusement, la pertinence physiologique de ces résultats n'a pas pu être évaluée in vivo, étant donné que le modèle de souris knockout conditionnel de Spint2 que nous avons créé ne montrait une réduction de l'expression de Spint2 que de 50% et aucun phénotype. En résumé, ce travail met en évidence deux nouveaux partenaires possibles de Spint2, ainsi qu'une potentielle régulation de NHE3 par des sérine protéases transmembranaires. Des expériences supplémentaires faites dans des modèles animaux et lignées cellulaires sont requises pour évaluer la pertinence physiologique de ces données et pour obtenir de plus amples informations au sujet de Spint2 et de la diarrhée congénitale de sodium. - The congenital sodium diarrhea is a very rare genetic disease. Children affected by this condition suffer from a severe diarrhea characterized by watery stools with a high fecal loss of sodium and bicarbonates, resulting in hyponatremic dehydration and metabolic acidosis. Genetic analyses have identified mutations in the Spint2 gene as a cause of this disease. The spint2 gene encodes a transmembrane serine protease inhibitor expressed in various epithelial tissues including the gastro-intestinal tract and renal tubules. The physiological role of Spint2 is completely unknown. In addition, physiological partners of Spint2 are still to be identified and the mechanism of inhibition by Spint2 remains elusive. Therefore, the aim of this project was to get insights about the function and the role of Spint2 in the context of the congenital sodium diarrhea in order to better understand the pathophysiology of diarrheas and maybe identify new therapeutic targets. A functional assay in Xenopus oocytes identified the membrane-bound serine proteases CAPI and Tmprssl3 as potential targets of Spint2 because both proteases were no longer inhibited by the mutant Spint2 Y163C that has been associated with the congenital diarrhea. Further functional and biochemical experiments suggested that the inhibition of Tmprssl3 by Spint2 occurs though a complex interaction between both proteins. The effects of membrane-bound serine proteases on the Na+-H+ exchanger NHE3, which has been proposed to be involved in the pathogenesis of the congenital sodium diarrhea, were also tested. A specific cleavage of NHE3 by the membrane-bound serine protease Tmprss3 was observed in biochemical experiments. Unfortunately, the physiological relevance of these results could not be assessed in vivo since the conditional Spint2 knockout mouse model that we generated showed a reduction in Spint2 expression of only 50% and displayed no phenotype. Briefly, this work provides two new potential partners of Spint2 and emphasizes a putative regulation of NHE3 by membrane-bound serine proteases. Further work done in animal models and cell lines is required to assess the physiological relevance of these results and to obtain additional data about Spint2 and the congenital diarrhea.