Participation in prospective studies of children with high risk for type 1 diabetes. Psychological effects, experience, and study compliance

AbstractAim: The overall aim of the thesis was to examine the psychosocial effects and family reactions to participation in longitudinal studies with their children at high risk for type 1 diabetes. Additionally, we aimed to develop a shorter form for the children to measure their anxiety when thinking of their risk of developing type 1 diabetes, which could be used in The Environmental Determinants of Diabetes in the Young (TEDDY) study.Methods: We used parental questionnaires from the five-year visit in the Diabetes Prediction in Skåne study (DiPiS) to investigate parental anxiety when participating with their high-risk child. Anxiety was measured using the 6-item short State Anxiety Inventory (SAI) form, and logistic regression was used to examine factors associated with parental anxiety. The TEDDY cohort was used to develop a reliable and valid short form of the State Anxiety Subscale (SAI-CH) by using item-total correlation. The TEDDY cohort was also used to investigate parental study satisfaction and study visit compliance. Paper III identified factors associated with study satisfaction at two timepoints using multiple linear regression. In the last paper, we used variables collected in the first year of the study to identify, through multiple linear regression, those factors associated with study visit compliance in the subsequent three years.Results: In the DiPiS study, we found that most of the parents were not anxious when thinking about their child’s risk of type 1 diabetes. Anxiety levels were higher in mothers of children with islet autoantibodies and parents with a family history of type 1 diabetes, those with accurate risk perception, and those who experienced higher frequencies of worry. In the second paper, we described the development of a reliable and valid short 6-item form, which was subsequently chosen for continued use in the TEDDY study. Paper III revealed high overall parental study satisfaction in the TEDDY study, with mothers reporting higher mean satisfaction scores than fathers. Country of residence, staff consistency, the accuracy of parents’ perception of their child’s type 1 diabetes risk, and beliefs that something can be done to prevent diabetes in the child were all associated with higher study satisfaction for both mothers and fathers. In Paper IV, we identified modifiable and non-modifiable variables collected in the first year of TEDDY that were associated with study visit compliance in the three subsequent years. Mothers who completed fewer visits were likelier to be smokers and experience anxiety about their child’s type 1 diabetes risk. On the other hand, mothers who completed more visits were older, participating with their first-born child, had actively participating fathers, and were more satisfied with their study participation.Conclusion: Understanding the family’s reactions and experiences during participation in longitudinal screening studies can enhance our understanding of the study’s impact on the family. Attending to the collected information throughout the study can help provide families with the appropriate support, and information, and ultimately improve study satisfaction and visit compliance

The COVID-19 breaker : PCR to the rescue ! : Chronicle of a crisis management at the Clinical Microbiology Laboratory of CHU Liège

peer reviewedThe SARS-CoV-2 outbreak in December 2019 in China and its expansion across the world and Europe have requested the participation of clinical laboratories as major players in the diagnosis of COVID-19, to perform PCR tests mainly on nasopharyngeal swabs. In Belgium, the first confirmed COVID-19 patient was diagnosed in early February, the first of many, especially travelers returning from winter sports. In order to meet the ever-increasing demands for testing, the Clinical Microbiology Laboratory of the CHU of Liege had to adapt to this situation: firstly, by developing manual PCR tests and then automated solutions, permitting to increase the number of analyzes by ensuring a short turnaround time of results. Then, a system for the communication of results on a large scale has been set up, and finally solutions to deal with the lack of sampling devices have been found. This first wave of the pandemic has also highlighted an unprecedented solidarity within the institution. In this article, we recount the chronology of the management of this unprecedented health crisis within the Clinical Microbiology Laboratory of the CHU of Liege.L’émergence du virus SARS-CoV-2 en décembre 2019 en Chine et son expansion à travers le monde et l’Europe ont sollicité la participation des laboratoires de Biologie clinique en tant qu’acteurs majeurs dans le diagnostic de la COVID-19, via la réalisation de tests PCR principalement sur des prélèvements nasopharyngés. En Belgique, le premier patient confirmé COVID-19 a été diagnostiqué début février, avant d’être suivi par de nombreux cas d’infections, initialement chez des vacanciers revenant des sports d’hiver. Afin de répondre à l’augmentation du nombre de tests, le laboratoire de Microbiologie clinique du CHU de Liège a dû s’adapter en développant des tests PCR, d’abord manuels puis automatisés. Ceux-ci ont permis d’augmenter le nombre d’analyses, tout en garantissant un temps de rendu des résultats court, en mettant en place un système de communication des résultats à grande échelle et en trouvant des solutions pour faire face à la pénurie des dispositifs de prélèvement. Cette première vague de la pandémie a aussi révélé une solidarité sans précédent au sein de l’institution. Dans cet article, nous retraçons la chronologie de la gestion de cette crise sanitaire inédite au sein du laboratoire de Microbiologie clinique du CHU de Liège

The Environmental Determinants of Diabetes in the Young (TEDDY) Study

The etiology of type 1 diabetes (T1D) remains unknown, but a growing body of evidence points to infectious agents and/or components of early childhood diet. The National Institutes of Health has established the TEDDY Study consortium of six clinical centers in the United States and Europe and a data coordinating center to identify environmental factors predisposing to, or protective against, islet autoimmunity and T1D. From 2004-2009, TEDDY will screen more than 360,000 newborns from both the general population and families already affected by T1D to identify an estimated 17,804 children with high-risk HLA-DR,DQ genotypes. Of those, 7,801 (788 first-degree relatives and 7,013 newborns with no family history of T1D) will be enrolled in prospective follow-up beginning before the age of 4.5 months. As of May 2008, TEDDY has screened more than 250,000 newborns and enrolled nearly 5,000 infants--approximately 70% of the final cohort. Participants are seen every 3 months up to 4 years of age, with subsequent visits every 6 months until the subject is 15 years of age. Blood samples are collected at each visit for detection of candidate infectious agents and nutritional biomarkers; monthly stool samples are collected for infectious agents. These samples are saved in a central repository. Primary endpoints include (1) appearance of one or more islet autoantibodies (to insulin, GAD65 or IA-2) confirmed at two consecutive visits; (2) development of T1D. By age 15, an estimated 800 children will develop islet autoimmunity and 400 will progress to T1D; 67 and 27 children have already reached these endpoints

Approche globale des éthiques dans les relations sociétés/nature

3 priorités scientifiques à aborder d'ici 2030 : Accroître la réflexivité sur les pratiques de recherche dans les laboratoires dans une démarche collective, ce qui exige du temps et des espaces de délibération dédiés. Utiliser les éthiques environnementales non pas au service de la résolution de conflits entre les humains et la nature, mais comme des aiguillons critiques pour réexaminer les pratiques sous un angle moins anthropocentré et plus sensible aux enjeux de justices sociale et écologique. Repenser l’arbitrage entre protection de la nature et protection des humains dans une démarche plus inclusiv

Approche globale des éthiques dans les relations sociétés/nature

3 priorités scientifiques à aborder d'ici 2030 : Accroître la réflexivité sur les pratiques de recherche dans les laboratoires dans une démarche collective, ce qui exige du temps et des espaces de délibération dédiés. Utiliser les éthiques environnementales non pas au service de la résolution de conflits entre les humains et la nature, mais comme des aiguillons critiques pour réexaminer les pratiques sous un angle moins anthropocentré et plus sensible aux enjeux de justices sociale et écologique. Repenser l’arbitrage entre protection de la nature et protection des humains dans une démarche plus inclusiv

Approche globale des éthiques dans les relations sociétés/nature

3 PRIORITÉS SCIENTIFIQUES À ABORDER D’ICI 2030 Accroître la réflexivité sur les pratiques de recherche dans les laboratoires dans une démarche collective, ce qui exige du temps et des espaces de délibération dédiés Utiliser les éthiques environnementales non pas au service de la résolution de conflits entre les humains et la nature, mais comme des aiguillons critiques pour réexaminer les pratiques sous un angle moins anthropocentré et plus sensible aux enjeux de justices sociale et écologique Repenser l’arbitrage entre protection de la nature et protection des humains dans une démarche plus inclusiv

Approche globale des éthiques dans les relations sociétés/nature

3 priorités scientifiques à aborder d'ici 2030 : Accroître la réflexivité sur les pratiques de recherche dans les laboratoires dans une démarche collective, ce qui exige du temps et des espaces de délibération dédiés. Utiliser les éthiques environnementales non pas au service de la résolution de conflits entre les humains et la nature, mais comme des aiguillons critiques pour réexaminer les pratiques sous un angle moins anthropocentré et plus sensible aux enjeux de justices sociale et écologique. Repenser l’arbitrage entre protection de la nature et protection des humains dans une démarche plus inclusiv

Metabolite-related dietary patterns and the development of islet autoimmunity

The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s)

Psychological manifestations of celiac disease autoimmunity in young children

BACKGROUND AND OBJECTIVES: Psychological symptoms can be associated with celiac disease; abstract however, this association has not been studied prospectively in a pediatric cohort. We examined mother report of psychological functioning in children persistently positive for tissue transglutaminase autoantibodies (tTGA), defined as celiac disease autoimmunity (CDA), compared with children without CDA in a screening population of genetically at-risk children. We also investigated differences in psychological symptoms based on mothers' awareness of their child's CDA status. METHODS: The Environmental Determinants of Diabetes in the Young study followed 8676 children to identify triggers of type 1 diabetes and celiac disease. Children were tested for tTGA beginning at 2 years of age. The Achenbach Child Behavior Checklist assessed child psychological functioning at 3.5 and 4.5 years of age. RESULTS: At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA (all Ps ≤ .03). Unaware-CDA mothers also reported more child anxiety and depression, withdrawn behavior, aggressive behavior, and sleep problems than 440 mothers aware of their child's CDA status (all Ps ≤.04). At 4.5 years, there were no differences. CONCLUSIONS: In 3.5-year-old children, CDA is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child's CDA status. Mothers' knowledge of their child's CDA status is associated with fewer reports of psychological symptoms, suggesting that awareness of the child's tTGA test results affects reporting of symptoms

Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study

A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes