RESUMEN
BACKGROUND & AIMS: Celiac disease (CD) is a common yet underdiagnosed autoimmune disease with substantial long-term consequences. High-accuracy point-of-care tests for CD antibodies conducted at youth primary health care centers may enable earlier identification of CD, but evidence about the cost-effectiveness of such strategies is lacking. We estimated the long-term cost-effectiveness of active case finding and mass screening compared with clinical detection in the Netherlands. METHODS: A decision tree and Markov model were used to simulate a cohort of 3-year-old children with CD according to each strategy, taking into account their impact on long-term costs (from a societal perspective) and quality-adjusted life-years (QALYs). Model parameters incorporated data from the GLUTENSCREEN project, the Dutch Celiac Society, the Dutch Pediatric Surveillance Unit, and published sources. The primary outcome was the incremental cost-effectiveness ratio (ICER) between strategies. RESULTS: Mass-screening produced 7.46 more QALYs and was 28,635 more costly compared with current care (ICER: 3841 per QALY), and case finding produced 4.33 more QALYs and was 15,585 more costly compared with current care (ICER: 3603 per QALY). At a willingness to pay of 20,000 per QALY, both strategies were highly cost-effective compared with current care. Scenario analyses indicated that mass screening is likely the optimal strategy, unless no benefit in detecting asymptomatic cases is assumed. CONCLUSIONS: An earlier identification of CD through screening or case finding in children using a point-of-care tests leads to improved health outcomes and is cost-effective in the long-term compared with current care. If the feasibility and acceptability of the proposed strategies are successful, implementation in Dutch regular care is needed.
RESUMEN
This position paper by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Coeliac Disease (SIG-CD) presents an update to the 2016 recommendations concerning early diet and the risk of coeliac disease (CD). This update adheres to the policy that mandates reviewing guidelines every 5 years, particularly when new data emerge. The 2024 statements and recommendations are essentially similar to the 2016 recommendations. Breastfeeding, whether any amount, exclusive, or of any duration, does not reduce the risk of developing CD. Introducing gluten into an infant's diet at any time between completed 4 months (≥17 weeks) and 12 months of age does not affect the cumulative incidence of CD, although earlier introduction may lead to earlier seroconversion and CD. In observational studies involving cohorts with a known risk for CD, consuming a high amount of gluten compared to a low amount during weaning and in the subsequent childhood years-specifically the first 2-3 years, and even up to 5 years in some studies-was associated with an increased risk for CD. However, the specific optimal amounts of gluten consumption remain undetermined due to insufficient evidence on safe thresholds, and the impact of restricting gluten in the diet of healthy children of unknown risk for CD is unknown. Thus, any recommendation on the gluten amount is currently unjustifiable for the general population and infants with known HLA risk types. There is no specific guidance on the type of gluten-containing foods to be introduced at weaning.
Asunto(s)
Lactancia Materna , Enfermedad Celíaca , Glútenes , Niño , Preescolar , Humanos , Lactante , Enfermedad Celíaca/etiología , Enfermedad Celíaca/dietoterapia , Dieta/efectos adversos , Dieta/normas , Dieta Sin Gluten , Glútenes/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: The effects of early feeding practices on the risk of coeliac disease (CD) remain debated. AIMS: To update evidence on these practices on the risk of CD and/or CD-related autoimmunity (CDA), defined as anti-transglutaminase or anti-endomysial antibody positivity METHODS: We searched MEDLINE, EMBASE and the Cochrane Library to May 2022 for randomised controlled trials (RCTs) and observational studies. RESULTS: We included 36 publications (30 studies). In the population at genetic risk of developing CD (HLA DQ2/DQ8-positive), exclusive or any breastfeeding and longer breastfeeding duration did not reduce the risk of developing CD/CDA during childhood. While a meta-analysis of four case-control studies showed a decreased risk for CD when gluten was introduced during breastfeeding, this was not shown in RCTs and cohort studies. Age at gluten introduction was not associated with cumulative CD/CDA risk, although two RCTs suggested that earlier gluten introduction was associated with earlier CDA appearance. Evidence from six observational studies suggests that consumption of a higher amount of gluten at weaning and/or thereafter may increase CD risk. There is insufficient evidence to determine the amount of gluten associated with an increased CD/CDA risk. Regarding whether infant feeding practices modulate the risk conferred by different HLA genotypes results were inconsistent. CONCLUSIONS: For the population at genetic risk of CD, breastfeeding and age at gluten introduction have no effect on its cumulative incidence during childhood. There is some evidence for an effect of the amount of gluten consumed at weaning and/or thereafter on CD/CDA risk.
Asunto(s)
Enfermedad Celíaca , Humanos , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/genética , Lagunas en las EvidenciasRESUMEN
Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high-dimensional mass cytometry. We analyzed 188 intestinal biopsies and paired blood samples of newly-diagnosed, treatment-naive patients (n=42) and controls (n=26) in two independent cohorts. We applied mass cytometry (36-antibody panel) to resolve single cells and analyzed the data with unbiased Hierarchical-SNE. In addition, imaging-mass cytometry (IMC) was performed to reveal the spatial distribution of the immune subsets in the tissue. We identified 44 distinct immune subsets. Correlation network analysis identified a network of inflammation-associated subsets, including HLA-DR+CD38+ EM CD4+ T cells, T regulatory-like cells, PD1+ EM CD8+ T cells, neutrophils, CD27+ TCRγδ cells and NK cells. All disease-associated subsets were validated in a second cohort. This network was abundant in a subset of patients, independent of IBD subtype, severity or intestinal location. Putative disease-associated CD4+ T cells were detectable in blood. Finally, imaging-mass cytometry revealed the spatial colocalization of neutrophils, memory CD4+ T cells and myeloid cells in the inflamed intestine. Our study indicates that a cellular network of both innate and adaptive immune cells colocalizes in inflamed biopsies from a subset of patients. These results contribute to dissecting disease heterogeneity and may guide the development of targeted therapeutics in IBD.
Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Linfocitos T CD8-positivos , Humanos , Inflamación , Intestinos/patologíaRESUMEN
BACKGROUND & AIMS: Screening for celiac disease (CD) is recommended in children with affected first-degree relatives (FDR). However, the frequency of screening and at what age remain unknown. The aims of this study were to detect variables influencing the risk of CD development and develop and validate clinical prediction models to provide individualized screening advice. METHODS: We analyzed prospective data from the 10 years of follow-up of the PreventCD-birth cohort involving 944 genetically predisposed children with CD-FDR. Variables significantly influencing the CD risk were combined to determine a risk score. Landmark analyses were performed at different ages. Prediction models were created using multivariable Cox proportional hazards regression analyses, backward elimination, and Harrell's c-index for discrimination. Validation was done using data from the independent NeoCel cohort. RESULTS: In March 2019, the median follow-up was 8.3 years (22 days-12.0 years); 135/944 children developed CD (mean age, 4.3 years [range, 1.1-11.4]). CD developed significantly more often in girls (P = .005) and in Human Leukocyte Antigen (HLA)-DQ2 homozygous individuals (8-year cumulative incidence rate of 35.4% vs maximum of the other HLA-risk groups 18.2% [P < .001]). The effect of homozygosity DR3-DQ2/DR7-DQ2 on CD development was only present in girls (interaction P = .04). The prediction models showed good fit in the validation cohort (Cox regression 0.81 [0.54]). To calculate a personalized risk of CD development and provide screening advice, we designed the Prediction application https://hputter.shinyapps.io/preventcd/. CONCLUSION: Children with CD-FDR develop CD early in life, and their risk depends on gender, age and HLA-DQ, which are all factors that are important for sound screening advice. These children should be screened early in life, including HLA-DQ2/8-typing, and if genetically predisposed to CD, they should get further personalized screening advice using our Prediction application. TRIAL REGISTRATION NUMBER: ISRCTN74582487 (https://www.isrctn.com/search?q=ISRCTN74582487).
Asunto(s)
Enfermedad Celíaca , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/genética , Niño , Preescolar , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Estudios Prospectivos , Factores de RiesgoRESUMEN
Coeliac disease is an immune-mediated condition characterized by chronic inflammation of the small bowel with villous atrophy driven by gluten ingestion in genetically predisposed individuals. It occurs frequently in both children and adults, affecting 1-4% of the population. The disease is associated with both gastrointestinal and extra-intestinal symptoms related to malabsorption and/or immune activation, and autoantibodies to tissue transglutaminase. Removal of gluten from the diet results in resolution of symptoms and enteropathy in the majority of patients. A good diagnostic work-up is important to avoid unnecessary restrictive diets in children. In this review on pediatric coeliac disease, we address epidemiology including predisposing environmental factors and possible preventive strategies, as well as the clinical presentation, diagnosis and follow-up. What is Known: â¢Primary prevention of coeliac disease is not possible; however, secondary prevention by targeting high-risk groups is recommended. â¢The diagnosis is safe without duodenal biopsies if specific conditions are met, also in asymptomatic children. What is New: â¢HLA-DQ typing is not routinely required for the diagnosis, whereas it can rule out coeliac disease if HLA-DQ2 and HLA-DQ8 are absent. â¢Follow-up could be improved by a more rational use of (laboratory) tests, increased intention to dietary compliance and quality of life.
Asunto(s)
Enfermedad Celíaca , Adulto , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/etiología , Niño , Glútenes , Prueba de Histocompatibilidad , Humanos , Intestino Delgado/patología , Calidad de VidaRESUMEN
Adequate follow-up in celiac disease is important to improve dietary compliance and treat disease-related symptoms and possible complications. However, data on the follow-up of celiac children is scarce. We aimed to assess current pediatric celiac follow-up practices across Europe. Pediatricians and pediatric gastroenterologists from 35 countries in Europe, Israel, Turkey, and Russia completed an anonymous survey which comprised a 52-item questionnaire developed by the ESPGHAN Special Interest Group on Celiac Disease. A total of 911 physicians, the majority of whom exclusively worked in pediatric care (83%) and academic institutions (60%), completed the questionnaire. Mean age and mean experience with celiac care were 48.7 years (± 10.6) and 15.7 years (± 9.9), respectively. The vast majority (≥ 92%) always assessed anthropometry, dietary adherence, and tissue-transglutaminase IgA-antibodies at every visit, with the first visit being between 3 and 6 months after diagnosis. Other parameters (% always tested) were as follows: complete blood count (60%), iron status (48%), liver enzymes (42%), thyroid function (38%), and vitamin D (26%). Quality of life was never assessed by 35% of the responding physicians. Transition to adult care was mostly completed via a written transition report (37%) or no formal transition at all (27%).Conclusions: Follow-up of celiac children and adolescents in Europe may be improved, especially regarding a more rational use of (laboratory) tests, dietary and QoL assessment, and transition to adult care. Evidence-based advice from international scientific societies is needed. What is Known: ⢠Follow-up in celiac disease is important to treat disease-related symptoms, improve dietary compliance, and prevent possible complications. ⢠There is a lack of consensus about the appropriate follow-up. What is New: ⢠Almost all European physicians assess anthropometry, tissue-transglutaminase IgA-antibodies, and dietary adherence at every visit, but there are large variations in other follow-up aspects. ⢠Follow-up could be improved by a more rational use of (laboratory) tests, increased intention to dietary compliance, and quality of life together with transition programs to adult care.
Asunto(s)
Enfermedad Celíaca , Calidad de Vida , Adolescente , Adulto , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/terapia , Niño , Dieta , Estudios de Seguimiento , Humanos , Encuestas y CuestionariosRESUMEN
Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine. Conclusions: We identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.
Asunto(s)
Enfermedad Celíaca/sangre , Enfermedad Celíaca/genética , MicroARN Circulante/sangre , MicroARN Circulante/genética , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad Celíaca/dietoterapia , Niño , Preescolar , MicroARN Circulante/aislamiento & purificación , Dieta Sin Gluten/métodos , Regulación hacia Abajo/genética , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , RNA-Seq/métodos , Resultado del Tratamiento , Regulación hacia Arriba/genéticaRESUMEN
Introduction: Coeliac disease (CD) occurs in 1% of the population, develops early in life and is severely underdiagnosed. Undiagnosed and untreated disease is associated with short-term and long-term complications. The current healthcare approach is unable to solve the underdiagnosis of CD and timely diagnosis and treatment is only achieved by active case finding. Aim: to perform a case finding project to detect CD children who visit the Youth Health Care Centres (YHCCs) in a well-described region in the Netherlands to evaluate whether it is feasible, cost-effective and well accepted by the population. Methods/analysis: Prospective intervention cohort study. Parents of all children aged 12 months and 4 years attending the YHCCs for a regular visit are asked whether their child has one or more CD-related symptoms from a standardised list. If so, they will be invited to participate in the case finding study. After informed consent, a point of care test (POCT) to assess CD-specific antibodies against tissue transglutaminase (TG2A) is performed onsite the YHCCs. If the POCT is positive, CD is highly suspected and the child will be referred to hospital for definitive diagnosis according to the Guideline Coeliac Disease of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guideline. Main outcomes: Incidence rate of new CD diagnoses in the study region in comparison to the one in the same age diagnosed by standard of care in the rest of the Netherlands.Feasibility and cost-effectiveness of active CD case finding at the YHCCs. All costs of active case finding, diagnostics and treatment of CD and the potential short-term and long-term consequences of the disease will be calculated for the setting with and without case finding.Ethical acceptability: by questionnaires on parental and healthcare professionals' satisfaction.A statistical analysis plan was prepared and is published on the GLUTENSCREEN website (Statistical-Analysis-Plan-11-5-2021_def.pdf (glutenscreen.nl) and added as annex 1). Ethics and dissemination: The Medical Ethics Committee Leiden approved this study. If we prove that case finding at the YHCC is feasible, cost-effective and well accepted by the population, implementation is recommended. Trial registration number: NL63291.058.17.
Asunto(s)
Enfermedad Celíaca , Adolescente , Enfermedad Celíaca/diagnóstico , Niño , Estudios de Cohortes , Atención a la Salud , Diagnóstico Precoz , Humanos , Lactante , Países Bajos/epidemiología , Estudios ProspectivosRESUMEN
Among the human milk oligosaccharides (HMOS), the galactosyllactoses (GLs) are only limitedly studied. This study aims to describe the presence and relative levels of HMOS, including GLs, in human milk (HM) according to maternal Secretor and Lewis (SeLe) phenotype and lactation stage. Relative levels of 19 HMOS were measured in 715 HM samples collected in the first 4 months postpartum from 371 donors participating in the PreventCD study. From a subset of 24 Dutch women (171 HM samples), samples were collected monthly up to 12 months postpartum and were additionally analyzed for relative and absolute levels of ß6'-GL, ß3'-GL and α3'-GL. Maternal SeLe phenotype or HM group was assigned based on the presence of specific fucosylated HMOS. Most HMOS, including ß6'- and ß3'-GL, were present in the vast majority (≥75%) of HM samples, whereas others (e.g., LNDFH II, 2'-F-LNH and α3'-GL) only occurred in a low number (<25%) of samples. Clear differences were observed between the presence and relative levels of the HMOS according to the maternal phenotype and lactation stage. Absolute concentrations of ß6'-GL and ß3'-GL were higher in HM group IV samples compared to samples of the other three HM groups. ß3'-GL was also higher in HM group II samples compared to HM group I samples. ß3'-GL and ß6'-GL were stable over lactation stages. In conclusion, presence and levels of HMOS vary according to HM group and lactation stage. Not all HMOS behave similarly: some HMOS depend strongly on maternal phenotype and/or lactation stage, whereas others do not. ß3'-GL and ß6'-GL were present in low concentrations in over 75% of the analyzed HM samples and showed differences between HM groups, but not between the lactation stages.
Asunto(s)
Lactancia/fisiología , Fenómenos Fisiologicos Nutricionales Maternos/genética , Leche Humana/química , Oligosacáridos/análisis , Trisacáridos/análisis , Adulto , Femenino , Humanos , Fenotipo , Periodo PospartoRESUMEN
Single genetic mutations predispose to very early onset inflammatory bowel disease (VEO-IBD). Here, we identify a de novo duplication of the 10p15.1 chromosomal region, including the IL2RA locus, in a 2-year-old girl with treatment-resistant pancolitis that was brought into remission by colectomy. Strikingly, after colectomy while the patient was in clinical remission and without medication, the peripheral blood CD4:CD8 ratio was constitutively high and CD25 expression was increased on circulating effector memory, Foxp3+, and Foxp3neg CD4+ T cells compared to healthy controls. This high CD25 expression increased IL-2 signaling, potentiating CD4+ T-cell-derived IFNγ secretion after T-cell receptor (TCR) stimulation. Restoring CD25 expression using the JAK1/3-inhibitor tofacitinib controlled TCR-induced IFNγ secretion in vitro. As diseased colonic tissue, but not the unaffected duodenum, contained mainly CD4+ T cells with a prominent IFNγ-signature, we hypothesize that local microbial stimulation may have initiated colonic disease. Overall, we identify that duplication of the IL2RA locus can associate with VEO-IBD and suggest that increased IL-2 signaling predisposes to colonic intestinal inflammation.
Asunto(s)
Colitis/etiología , Colitis/metabolismo , Duplicación de Gen , Predisposición Genética a la Enfermedad , Subunidad alfa del Receptor de Interleucina-2/genética , Interleucina-2/metabolismo , Transducción de Señal , Edad de Inicio , Alelos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Estudios de Casos y Controles , Cromosomas Humanos Par 10 , Colitis/diagnóstico , Citocinas/metabolismo , Resistencia a Medicamentos , Expresión Génica , Estudios de Asociación Genética , Sitios Genéticos , Humanos , Inmunohistoquímica , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/etiología , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Activación de Linfocitos , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismoRESUMEN
The aim of this study was (1) to prospectively evaluate the nationwide implementation of the ESPGHAN-guidelines for the diagnosis of celiac disease (CD), (2) to investigate the incidence and clinical presentation of diagnosed childhood CD (0-14 years) in the Netherlands, and (3) to compare the findings with national survey data from 1975 to 1990 and 1993 to 2000 using the same approach. From 2010 to 2013, all practicing paediatricians were invited to report new celiac diagnoses to the Dutch Pediatric Surveillance Unit. Data were collected via questionnaires. A total of 1107 children with newly diagnosed CD were reported (mean age, 5.8 years; range, 10 months-14.9 years; 60.5% female). After the introduction of the non-biopsy approach in 2012, 75% of the diagnoses were made according to the guideline with a significant decrease of 46.3% in biopsies. The use of EMA and HLA-typing significantly increased with 25.8% and 62.1%, respectively. The overall incidence rate of childhood CD was 8.8-fold higher than in 1975-1990 and 2.0-fold higher than in 1993-2000. During the study period, the prevalence of diagnosed CD was 0.14%, far below 0.7% of CD identified via screening in the general Dutch paediatric population. Clinical presentation has shifted towards less severe and extra-intestinal symptoms.Conclusion: ESPGHAN guidelines for CD diagnosis in children were effectively and rapidly implemented in the Netherlands. Incidence of diagnosed CD among children is still significantly rising with a continuous changing clinical presentation. Despite the increasing incidence of diagnoses, significant underdiagnosis still remains. What is Known: ⢠Since 2000 the incidence of diagnosed childhood CD in the Netherlands has shown a steady rise. ⢠The rise in incidence has been accompanied by a changing clinical presentation at diagnosis. What is New: ⢠The ESPGHAN guidelines 2012 for CD diagnosis were effectively and rapidly implemented in the Netherlands. ⢠The incidence of diagnosed childhood CD in the Netherlands has continued to rise significantly during the reported period.
Asunto(s)
Enfermedad Celíaca , Biopsia , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Masculino , Países Bajos/epidemiología , Estudios ProspectivosRESUMEN
Celiac disease (CeD) is an immune-mediated disorder triggered by exposure to dietary gluten proteins in genetically predisposed individuals. In addition to the host genome, the microbiome has recently been linked to CeD risk and pathogenesis. To progress in our understanding of the role of breast milk microbiota profiles in CeD, we have analyzed samples from a sub-set of mothers (n = 49) included in the PreventCD project, whose children did or did not develop CeD. The results of the microbiota data analysis indicated that neither the BMI, HLA-DQ genotype, the CeD condition nor the gluten-free diet of the mothers could explain the human milk microbiota profiles. Nevertheless, we found that origin country, the offspring's birth date and, consequently, the milk sampling date influenced the abundance and prevalence of microbes in human milk, undergoing a transition from an anaerobic to a more aerobic microbiota, including potential pathogenic species. Furthermore, certain microbial species were more abundant in milk samples from mothers whose children went on to develop CeD compared to those that remained healthy. These included increases in facultative methylotrophs such as Methylobacterium komagatae and Methylocapsa palsarum as well as in species such as Bacteroides vulgatus, that consumes fucosylated-oligosaccharides present in human milk, and other breast-abscess associated species. Theoretically, these microbiota components could be vertically transmitted from mothers-to-infants during breastfeeding, thereby influencing CeD risk.
RESUMEN
OBJECTIVE: To study the optimal cut-off value for anti-tissue transglutaminase type 2 IgA antibodies (TG2A) in serum to select for diagnostic small bowel biopsies for celiac disease in children with type 1 diabetes mellitus. STUDY DESIGN: Children with type 1 diabetes mellitus with elevated TG2A titers and duodenal biopsies performed during the course of their diabetes treatment were included. Anti-endomysial antibodies were recorded if present. The optimal TG2A cut-off value, expressed as the ratio between obtained value and upper limit of normal (ULN), was determined using receiver operating characteristic curve analysis and compared with the cut-off value used in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines in terms of sensitivity, specificity, positive and negative predictive value. RESULTS: We included 63 children. The optimal cut-off value for performing biopsies is demonstrated to be 11 times the ULN. Raising the cut-off value from 3 times the ULN to 11 times the ULN changed sensitivity from 96% to 87% and increased specificity from 36% to 73%, increased the positive predictive value from 88% to 94% and lowered negative predictive value from 67% to 53%. The percentage of normal histology was decreased from 12% to 6%. CONCLUSIONS: Increasing the TG2A cut-off value for performing duodenal biopsies in children with type 1 diabetes mellitus and suspected celiac disease leads to a substantial reduction of unnecessary biopsies. We advocate to adapt the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2012 guidelines for this group of children, including monitoring patients with TG2A levels of less than 11 times the ULN over time.
Asunto(s)
Enfermedad Celíaca/diagnóstico , Diabetes Mellitus Tipo 1/complicaciones , Proteínas de Unión al GTP/sangre , Transglutaminasas/sangre , Adolescente , Anticuerpos , Biopsia/efectos adversos , Enfermedad Celíaca/sangre , Enfermedad Celíaca/etiología , Niño , Preescolar , Femenino , Humanos , Intestino Delgado/inmunología , Masculino , Proteína Glutamina Gamma Glutamiltransferasa 2 , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Procedimientos InnecesariosRESUMEN
BACKGROUND: In youth with inflammatory bowel disease (IBD), health-related quality of life (HRQOL) has been shown to be affected by individual disease factors and specific psychological factors. The innovative aim of this study is to examine the combined impact of psychological factors (illness perceptions, cognitive coping, anxiety, and depression) on HRQOL, over and above the associations of demographic and disease factors with HRQOL in youth with IBD. METHOD: Data on clinical disease activity, illness perceptions, cognitive coping, anxiety, depression, and HRQOL were prospectively collected in 262 consecutive youth (age 10-20, 46.6% male) with confirmed IBD. Multiple linear regression analyses tested the associations of demographic, disease, and psychological variables with HRQOL in separate groups for Crohn's disease (CD; N = 147) and ulcerative colitis and IBD unclassified (UC/IBD-U; N = 115), using age-specific validated instruments. RESULTS: In both disease groups, more negative illness perceptions (ß = - .412; ß = - .438, p < .001) and more depression (ß = - .454; ß = - .279, p < .001) were related to lower HRQOL. In the UC/IBD-U group, more anxiety was related to lower HRQOL (ß = - .201, p = .001). The model with the psychological variables explained a large and significant amount of variance in both groups: 74% and 83%, respectively (p < .001). CONCLUSION: In 10-20-year-old IBD patients, negative illness perceptions and depression were significantly and more strongly associated with lower HRQOL than demographic and disease factors. Thus, it is important to integrate psychological factors in the treatment for IBD patients. To improve HRQOL in young IBD patients, psychological interventions should be targeted at negative illness perceptions and depression.
Asunto(s)
Colitis Ulcerosa/psicología , Enfermedad de Crohn/psicología , Depresión/psicología , Enfermedades Inflamatorias del Intestino/psicología , Calidad de Vida/psicología , Adaptación Psicológica , Adolescente , Ansiedad/psicología , Niño , Femenino , Humanos , Masculino , Percepción , Estudios Prospectivos , Análisis de Regresión , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Coeliac disease is an immune-mediated enteropathy against dietary gluten present in wheat, rye and barley and is one of the most common lifelong food-related disorders worldwide. Coeliac disease is also considered to be a systemic disorder characterized by a variable combination of gluten-related signs and symptoms and disease-specific antibodies in addition to enteropathy. The ingestion of gluten leads to the generation of harmful gluten peptides, which, in predisposed individuals, can induce adaptive and innate immune responses. The clinical presentation is extremely variable; patients may have severe gastrointestinal symptoms and malabsorption, extraintestinal symptoms or have no symptoms at all. Owing to the multifaceted clinical presentation, diagnosis remains a challenge and coeliac disease is heavily underdiagnosed. The diagnosis of coeliac disease is achieved by combining coeliac disease serology and small intestinal mucosal histology during a gluten-containing diet. Currently, the only effective treatment for coeliac disease is a lifelong strict gluten-free diet; however, the diet is restrictive and gluten is difficult to avoid. Optimizing diagnosis and care in coeliac disease requires continuous research and education of both patients and health-care professionals.
Asunto(s)
Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/fisiopatología , Dieta Sin Gluten/métodos , Humanos , Mucosa Intestinal/anomalías , Mucosa Intestinal/patología , Poaceae/efectos adversos , Calidad de Vida/psicología , Factores de Riesgo , Triticum/efectos adversosRESUMEN
It is discussed that specific amino acids (AAs) have functional roles in early life. Understanding the AA composition in human milk (HM) during lactation assists in specifying these roles. To this end we assessed the levels of free AAs (FAAs), total AAs (free and bound, TAAs) and protein levels in HM in the first 6 months of lactation, and evaluated possible associations with infant gender. HM samples of 25 healthy Dutch mothers participating in the PreventCD study were collected monthly during the first 6 months of lactation. Of the participating mothers, 12 gave birth to a boy and 13 gave birth to a girl. Analyses of the HM samples revealed that levels of free glutamate, glutamine, aspartate, glycine, and serine significantly increased during months 1â»3 of lactation, both in absolute sense and relative to TAA levels. Evaluation of gender differences by mixed model analyses revealed an association between female infant gender and higher protein content (p = 0.0465) and TAA content (p = 0.0362) in HM during the first 3 months of lactation. Furthermore, there was a tendency for an association of male infant gender with higher levels of free glutamine (p = 0.0948) in HM during the first 3 months of lactation. These results show that FAA, TAA and protein levels in HM display a time-specific occurrence during lactation. Moreover, although confirmation is necessary in view of the small sample size, this study indicates that the AA composition in HM shows differential effects of the infant's sex.