Δευτέρα, 22 Ιανουαρίου 2018

Premorbid Activity Limitation Stages Are Associated with Post-Hospitalization Discharge Disposition

AbstractObjectiveActivity of daily living (ADL) stages and instrumental activity of daily living (IADL) stage have demonstrated associations with mortality and health service utilization among older adults. This cohort study aims to assess the associations of premorbid activity limitation stages with acute hospital discharge disposition among community-dwelling older adults.DesignStudy participants were Medicare beneficiaries aged 65 years and older who enrolled in the Medicare Current Beneficiary Survey (MCBS) between 2001 and 2009. Associations of premorbid stages with discharge dispositions were estimated with multinomial logistic regression models adjusted for covariates.ResultsThe proportions of elderly Medicare patients discharged to home with self-care, home with services, post-acute care facilities, and other dispositions were 59%, 15%, 19%, and 7%, respectively. The adjusted relative risk ratios (RRR) and 95% confidence intervals of post-acute care facilities versus home with self-care discharge increased with higher premorbid activity limitation stages (except non-fitting stage III): 1.7 (1.5-2.0), 2.4 (2.0-2.9), 2.4 (1.9-3.0), and 2.5 (1.6-4.1) for ADL stages I-IV; a similar pattern was found for IADL stages. The adjusted RRRs of discharge to home with services also increased with higher premorbid activity limitation stages compared to no limitation.ConclusionsRoutinely assessed activity limitation stages predict post-hospitalization discharge disposition among older adults, and may be used to anticipate post-acute care and services utilization by elderly Medicare beneficiaries. Objective Activity of daily living (ADL) stages and instrumental activity of daily living (IADL) stage have demonstrated associations with mortality and health service utilization among older adults. This cohort study aims to assess the associations of premorbid activity limitation stages with acute hospital discharge disposition among community-dwelling older adults. Design Study participants were Medicare beneficiaries aged 65 years and older who enrolled in the Medicare Current Beneficiary Survey (MCBS) between 2001 and 2009. Associations of premorbid stages with discharge dispositions were estimated with multinomial logistic regression models adjusted for covariates. Results The proportions of elderly Medicare patients discharged to home with self-care, home with services, post-acute care facilities, and other dispositions were 59%, 15%, 19%, and 7%, respectively. The adjusted relative risk ratios (RRR) and 95% confidence intervals of post-acute care facilities versus home with self-care discharge increased with higher premorbid activity limitation stages (except non-fitting stage III): 1.7 (1.5-2.0), 2.4 (2.0-2.9), 2.4 (1.9-3.0), and 2.5 (1.6-4.1) for ADL stages I-IV; a similar pattern was found for IADL stages. The adjusted RRRs of discharge to home with services also increased with higher premorbid activity limitation stages compared to no limitation. Conclusions Routinely assessed activity limitation stages predict post-hospitalization discharge disposition among older adults, and may be used to anticipate post-acute care and services utilization by elderly Medicare beneficiaries. Corresponding author: Ling Na lingna2000@gmail.com; Disclosures: The research for this manuscript was supported by the grant from the National Institutes of Health (R01AG040105). There are no personal conflicts of interest of any of the authors, and no authors reported disclosures beyond the funding source. The opinions and conclusions of the authors are not necessarily those of the sponsoring agency. We certify that no party having a direct interest in the results of the research supporting this article has or will confer a benefit on us or on any organization with which we are associated. This material has not been previously presented at a meeting. Acknowledgement: We thank Dr. Margaret G. Stineman, MD for her contribution in conceptualization of the study. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Effects of cane use and position on performance of the sit-to-stand task in stroke patients

ABSTRACTObjectiveTo examine the effect of cane use and cane positions on the sit-to-stand (STS) performance of stroke patients.DesignIn a crossover study, 30 stroke patients performed STS test in seven situations in a random sequence: without a cane, three positions with a regular cane (parallel to the ankle, parallel to the 5th toe, and 10 cm in front of the 5th toe), and the same three positions with a quad cane. The peak vertical ground reaction force (GRF) and maximum vertical cane support force during STS were recorded.ResultsUsing a cane significantly reduced the peak GRF by 3%~9% of body weight compared to that without a cane (p=0.000~0.023). Different cane positions strongly influenced the maximum cane support force and peak GRF. When the cane was closer to the ankle, the maximal cane support force increased by 6.7%~8.6% of body weight, which resulted in a decrease in the peak GRF.ConclusionsBoth types of cane reduced lower extremities' load during STS. When the cane was closer to the trunk, the load on legs was lessened, while the load on the upper extremity increased. Upper extremity's load during STS was greater when using quad cane than using regular cane. Objective To examine the effect of cane use and cane positions on the sit-to-stand (STS) performance of stroke patients. Design In a crossover study, 30 stroke patients performed STS test in seven situations in a random sequence: without a cane, three positions with a regular cane (parallel to the ankle, parallel to the 5th toe, and 10 cm in front of the 5th toe), and the same three positions with a quad cane. The peak vertical ground reaction force (GRF) and maximum vertical cane support force during STS were recorded. Results Using a cane significantly reduced the peak GRF by 3%~9% of body weight compared to that without a cane (p=0.000~0.023). Different cane positions strongly influenced the maximum cane support force and peak GRF. When the cane was closer to the ankle, the maximal cane support force increased by 6.7%~8.6% of body weight, which resulted in a decrease in the peak GRF. Conclusions Both types of cane reduced lower extremities' load during STS. When the cane was closer to the trunk, the load on legs was lessened, while the load on the upper extremity increased. Upper extremity's load during STS was greater when using quad cane than using regular cane. Correspondence to: Dr. Mau-Roung Lin, Institute of Injury Prevention and Control, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan, R.O.C., Phone: 886-2-27398755; Fax: 886-2-27398755; E-mail: mrlin@tmu.edu.tw Financial support: This work was funded by the National Health Research Institute (NHRI-EX100-9805PI) and the Ministry of Technology and Science (MOST106-2314-B-038-046), Taiwan. No commercial party having a direct or indirect interest in the subject matter of this research has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Conflicts of interest: The authors have no conflicts of interest to declare. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Ontogeny-related pharmacogene changes in the pediatric liver transcriptome

Objectives The majority of drug dosing studies are based on adult populations, with modification of the dosing for children based on size and weight. This rudimentary approach for drug dosing children is limited, as biologically a child can differ from an adult in far more aspects than just size and weight. Specifically, understanding the ontogeny of childhood liver development is critical in dosing drugs that are metabolized through the liver, as the rate of metabolism determines the duration and intensity of a drug's pharmacologic action. Therefore, we set out to determine pharmacogenes that change over childhood development, followed by a secondary agnostic analysis, assessing changes transcriptome wide. Materials and methods A total of 47 human liver tissue samples, with between 10 and 13 samples in four age groups spanning childhood development, underwent pair-end sequencing. Kruskal–Wallis and Spearman's rank correlation tests were used to determine the association of gene expression levels with age. Gene set analysis based on the pathways in KEGG utilized the gamma method. Correction for multiple testing was completed using q-values. Results We found evidence for increased expression of 'very important pharmacogenes', for example, coagulation factor V (F5) (P=6.7×10−7), angiotensin I converting enzyme (ACE) (P=6.4×10−3), and solute carrier family 22 member 1 (SLC22A1) (P=7.0×10−5) over childhood development. In contrast, we observed a significant decrease in expression of two alternative CYP3A7 transcripts (P=1.5×10−5 and 3.0×10−5) over development. The analysis of genome-wide changes detected transcripts in the following genes with significant changes in mRNA expression (P

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Proteomic Analysis of Alterations in Aeromonas hydrophila Outer Membrane Proteins in Response to Oxytetracycline Stress

Microbial Drug Resistance , Vol. 0, No. 0.


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Improving Genomic Prediction in Cassava Field Experiments by Accounting for Inter-plot Competition

Plants' competing for available resources is an unavoidable phenomenon in a field. We conducted studies in cassava (Manihot esculenta Crantz) in order to understand the pattern of this competition. Taking into account the competitive ability of genotypes while selecting parents for breeding advancement or commercialization can be very useful. We assumed that competition could occur in two levels i) at the genotypic level, which we called as inter-clonal, and ii) at the plot level irrespective of the type of genotype, which we call as inter-plot competition or competition error. Modification in incidence matrices was applied in order to relate neighboring genotype/plot to the performance of a target genotype/plot with respect to its competitive ability. This was added into a genomic selection model to simultaneously predict the direct and competitive ability of a genotype. Predictability of the models was tested through a 10-fold cross-validation method repeated five times. The best model was chosen as the one with the lowest prediction root mean squared error (pRMSE) compared to that of the base model having no competitive component. Results from our real data studies indicated that less than 10% increase in accuracy was achieved with GS-inter-clonal competition model but this value reached up to 25% with a GS-competition error model. We also found that the competitive influence of a cassava clone is not just limited to the adjacent neighbors but spreads beyond them. Through simulations we found that a 26% increase of accuracy in estimating trait genotypic effect can be achieved even in the presence of high competitive variance.



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An Overexpressed Q Allele Leads to Increased Spike Density and Improved Processing Quality in Common Wheat (Triticum aestivum)

Spike density and processing quality are important traits in the modern wheat production that is controlled by multiple gene loci. The associated genes have been intensively studied and new discoveries have been constantly reported during the past few decades. However, no gene playing significant roles in the development of these two traits was identified. In the current study, a common wheat mutant with extremely compact spikes and good processing quality was isolated and characterized. A new allele (Qc1) of Q gene (an important domestication gene) responsible for the mutant phenotype was cloned and the molecular mechanism for the mutant phenotype was studied. Results revealed that Qc1 was originated from a point mutation that interferes with the miRNA172-directed cleavage of the Q transcripts, leading to its overexpression. It also reduces the longitudinal cell size of rachises, resulting in an increased spike density. Furthermore, Qc1 increases the number of vascular bundles, which suggests a higher efficiency in the transportation of assimilates in the spikes of the mutant than that of WT. This accounts for the improved processing quality. The effects of Qc1 on spike density and wheat processing quality were confirmed by analyzing nine common wheat mutants possessing four different Qc alleles. These results deepen our understanding of the key roles of Q gene and provide new insights for the potential application of Qc alleles in wheat quality breeding.



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A scoring model for predicting advanced colorectal neoplasia in a screened population of asymptomatic Japanese individuals

Abstract

Background

Risk stratification of screened populations could help improve colorectal cancer (CRC) screening. Use of the modified Asia-Pacific Colorectal Screening (APCS) score has been proposed in the Asia-Pacific region. This study was performed to build a new useful scoring model for CRC screening.

Methods

Data were reviewed from 5218 asymptomatic Japanese individuals who underwent their first screening colonoscopy. Multivariate logistic regression was used to investigate risk factors for advanced colorectal neoplasia (ACN), and a new scoring model for the prediction of ACN was developed based on the results. The discriminatory capability of the new model and the modified APCS score were assessed and compared. Internal validation was also performed.

Results

ACN was detected in 225 participants. An 8-point scoring model for the prediction of ACN was developed using five independent risk factors for ACN (male sex, higher age, presence of two or more first-degree relatives with CRC, body mass index of > 22.5 kg/m2, and smoking history of > 18.5 pack-years). The prevalence of ACN was 1.6% (34/2172), 5.3% (127/2419), and 10.2% (64/627) in participants with scores of < 3, ≥ 3 to < 5, and ≥ 5, respectively. The c-statistic of the scoring model was 0.70 (95% confidence interval, 0.67–0.73) in both the development and internal validation sets, and this value was higher than that of the modified APCS score [0.68 (95% confidence interval, 0.65–0.71), P = 0.03].

Conclusions

We built a new simple scoring model for prediction of ACN in a Japanese population that could stratify the screened population into low-, moderate-, and high-risk groups.



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Using video games to improve pediatric disaster education

Gamification of EMS training takes center stage the 2018 NAEMSP Annual Meeting

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Hepatic portal venous gas due to polystyrene sulfonate-induced enteritis

Abstract

A 78-year-old man with acute right lower abdominal pain and nausea was referred to our hospital. Computed tomography (CT) demonstrated hepatic portal venous gas and a thickened wall of the terminal ileum, and colonoscopy demonstrated ulcers and erosions of the ileocecal region. Histological examination of biopsy samples revealed basophilic crystals consistent with the component of calcium polystyrene sulfonate (CPS). This patient started taking CPS 2 months prior for chronic hyperkalemia. The symptoms resolved soon after ceasing CPS, and subsequent imaging studies confirmed the disappearance of the portal venous gas and ileocolitis.



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Risk Factors for Hidradenitis Suppurativa in Patients with Inflammatory Bowel Disease

Abstract

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by recurrent nodules, abscesses, and sinus tracts that can be debilitating and significantly impair quality of life. Small studies and case reports have suggested a possible association between HS and inflammatory bowel disease (IBD).

Aims

We performed a case–control study to further characterize IBD patients with HS in terms of smoking status, BMI, sites affected by HS, IBD type and features, and IBD medication history.

Methods

A total of 38 patients with HS and IBD were identified and matched on age, gender, and IBD type to 136 controls with IBD but not HS. Clinical characteristics of interest were obtained through extensive review of the electronic health record.

Results

Among patients with HS and IBD, the most common sites affected by HS were the inguinal, perianal, and axillary regions. Relative to patients with IBD alone, patients with HS and IBD were nearly six times more likely to be current smokers (p < 0.01) and nearly 11 times more likely to be obese (p < 0.01). Patients with HS and Crohn's were significantly more likely to have ileocolonic and perianal disease than patients with CD only (OR 8.31, 95% CI 2.90–23.80 and OR 2.85, 95% CI 1.19–6.81, respectively; p < 0.01 for both).

Conclusions

Relative to patients with IBD who do not develop HS, patients with IBD and HS are more likely to be overweight or obese, to be former or current smokers, and to have ileocolonic and/or perianal disease.



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Reliability of a two-colour chewing gum test to assess masticatory performance in complete denture wearers

Abstract

The aim of this study was to test the reliability of a method to measure the masticatory performance of complete denture wearers employing a colour-mixing ability test and assessment by visual and electronic colourimetric analysis. A sample of 75 subjects was selected from patients who received new conventional complete dentures. Masticatory tests were performed using a two-colour chewing gum that was masticated for 5, 10, 20, 30 and 50 chewing cycles, performed in a random order. The mixing level of the two colours of the chewed gum was assessed visually by two independent raters based on a 5-point ordinal scale. The specimens were flattened into a 1 mm width wafer, scanned and saved as a two-sided digital image. Each pair of images was submitted to an electronic colourimetric analysis to assess the level of colour mixture, measured by the circular variance of hue (VOH). Overall inter and intra-rater agreement in visual analysis was 64% and 68%, respectively (almost 99% of scores ranged within ±1 point), whilst overall weighted kappa was >0.80. A proportional increase in the level of mixture occurred with increased number of chewing cycles (p<0.001). Similarly, VOH and the visual analysis were highly correlated (r= -0.89; p<0.001). Bland-Altman plots revealed excellent agreement and extremely low systematic error between duplicated VOH measures. It was concluded that the two-colour chewing gum test is a reliable method to assess the masticatory performance in complete denture wearers using both visual and electronic colourimetric analyses.

This article is protected by copyright. All rights reserved.



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Analyses of karyotype by G-banding and high-resolution microarrays in a gender dysphoria population

Abstract

Gender Dysphoria is characterized by a marked incongruence between the cerebral sex and biological sex. To investigate the possible influence of karyotype on the etiology of Gender Dysphoria we carried out the cytogenetic analysis of karyotypes in 444 male-to-females (MtFs) and 273 female-to-males (FtMs) that attended the Gender Identity Units of Barcelona and Málaga (Spain) between 2000 and 2016. The karyotypes from 23 subjects (18 MtFs and 5 FtMs) were also analysed by Affymetrix CytoScan™ high-density (HD) arrays. Our data showed a higher incidence of cytogenetic alterations in Gender Dysphoria (2.65%) than in the general population (0.53%) (p < 0.0001). When G-banding was performed, 11 MtFs (2.48%) and 8 FtMs (2.93%) showed a cytogenetic alteration. Specifically, Klinefelter syndrome frequency was significantly higher (1.13%) (p < 0.0001), however Turner syndrome was not represented in our sample (p < 0.61). At molecular level, HD microarray analysis revealed a 17q21.31 microduplication which encompasses the gene KANSL1 (MIM612452) in 5 out of 18 MtFs and 2 out of 5 FtMs that corresponds to a copy-number variation region in chromosome 17q21.31. In conclusion, we confirm a significantly high frequency of aneuploidy, specifically Klinefelter syndrome and we identified in 7 out of 23 GD individuals the same microduplication of 572 Kb which encompasses the KANSL1 gene.



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Identification of rare RTN3 variants in Alzheimer’s disease in Han Chinese

Abstract

Reticulon 3 (RTN3) is a neuronally-expressed reticulon family protein that was previously shown to negatively regulate BACE1, a protease that is required for the generation of β-amyloid peptides (Aβ) from amyloid precursor protein. Despite biochemical and morphological evidence that supports a role of RTN3 in the formation of neuritic amyloid plaques, no systematic analyses of RTN3 mutations in patients with Alzheimer's disease (AD) have yet been reported. RTN3 were targeted sequenced in 154 sporadic early-onset and 285 late-onset AD patients. Luciferase reporter assay and kymographs were performed to analysis the expression of RNT3 and BACE1-RFP particle mobility on cells transfected with wild-type or variants RTN3 constructs. We identified heterozygous variants such as c.-8G > T, c.17C > A, c.42C > T, and c.116C > T from patients in the early-onset AD group and c.-8G > T, c.17C > A, from patients in the late-onset AD group. Such variants of RTN3 were not observed in control individuals. Further biochemical studies show that the RTN3 c.-8G > T variant in the 5′-untranslated region appears to cause reduced expression of RTN3. The RTN3 c.116 C > T variant causes a change of codon T39 to M39 (T39 M). Overexpression of RTN3 T39 M in cultured neurons led to impaired axonal transport of BACE1. The variants found in this study are likely genetic modifiers for RTN3-mediated formation of neuritic plaques in AD.



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Reconstructing the demographic history of the Himalayan and adjoining populations

Abstract

The rugged topography of the Himalayan region has hindered large-scale human migrations, population admixture and assimilation. Such complexity in geographical structure might have facilitated the existence of several small isolated communities in this region. We have genotyped about 850,000 autosomal markers among 35 individuals belonging to the four major populations inhabiting the Himalaya and adjoining regions. In addition, we have genotyped 794 individuals belonging to 16 ethnic groups from the same region, for uniparental (mitochondrial and Y chromosomal DNA) markers. Our results in the light of various statistical analyses suggest a closer link of the Himalayan and adjoining populations to East Asia than their immediate geographical neighbours in South Asia. Allele frequency-based analyses likely support the existence of a specific ancestry component in the Himalayan and adjoining populations. The admixture time estimate suggests a recent westward migration of populations living to the East of the Himalaya. Furthermore, the uniparental marker analysis among the Himalayan and adjoining populations reveal the presence of East, Southeast and South Asian genetic signatures. Interestingly, we observed an antagonistic association of Y chromosomal haplogroups O3 and D clines with the longitudinal distance. Thus, we summarise that studying the Himalayan and adjoining populations is essential for a comprehensive reconstruction of the human evolutionary and ethnolinguistic history of eastern Eurasia.



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Gastrointestinal Tract Pathology in a BALB/c Niemann–Pick Disease Type C1 Null Mouse Model

Abstract

Background

Niemann–Pick disease, type C (NPC) is a rare lysosomal storage disorder characterized by progressive neurodegeneration, splenomegaly, hepatomegaly, and early death. NPC is caused by mutations in either the NPC1 or NPC2 gene. Impaired NPC function leads to defective intracellular transport of unesterified cholesterol and its accumulation in late endosomes and lysosomes. A high frequency of Crohn disease has been reported in NPC1 patients, suggesting that gastrointestinal tract pathology may become a more prominent clinical issue if effective therapies are developed to slow the neurodegeneration. The Npc1nih mouse model on a BALB/c background replicates the hepatic and neurological disease observed in NPC1 patients. Thus, we sought to characterize the gastrointestinal tract pathology in this model to determine whether it can serve as a model of Crohn disease in NPC1.

Methods

We analyzed the gastrointestinal tract and isolated macrophages of BALB/cJ cNctr-Npc1m1N/J (Npc1/) mouse model to determine whether there was any Crohn-like pathology or inflammatory cell activation. We also evaluated temporal changes in the microbiota by 16S rRNA sequencing of fecal samples to determine whether there were changes consistent with Crohn disease.

Results

Relative to controls, Npc1 mutant mice demonstrate increased inflammation and crypt abscesses in the gastrointestinal tract; however, the observed pathological changes are significantly less than those observed in other Crohn disease mouse models. Analysis of Npc1 mutant macrophages demonstrated an increased response to lipopolysaccharides and delayed bactericidal activity; both of which are pathological features of Crohn disease. Analysis of the bacterial microbiota does not mimic what is reported in Crohn disease in either human or mouse models. We did observe significant increases in cyanobacteria and epsilon-proteobacteria. The increase in epsilon-proteobacteria may be related to altered cholesterol homeostasis since cholesterol is known to promote growth of this bacterial subgroup.

Conclusions

Macrophage dysfunction in the BALB/c Npc1/ mouse is similar to that observed in other Crohn disease models. However, neither the degree of pathology nor the microbiota changes are typical of Crohn disease. Thus, this mouse model is not a good model system for Crohn disease pathology reported in NPC1 patients.



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Cost-effectiveness analyses of genetic and genomic diagnostic tests

Cost-effectiveness analyses of genetic and genomic diagnostic tests

Cost-effectiveness analyses of genetic and genomic diagnostic tests, Published online: 22 January 2018; doi:10.1038/nrg.2017.108

Next-generation sequencing is fuelling a rise in the number of genomic diagnostic tests, which compete with existing interventions for limited health-care budgets. This Perspective presents key approaches and challenges that must be considered by decision-makers assessing the relative cost-effectiveness of new genomic tests.

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Functional genomics: A drop in an ocean of gene variants

Functional genomics: A drop in an ocean of gene variants

Functional genomics: A drop in an ocean of gene variants, Published online: 22 January 2018; doi:10.1038/nrg.2018.1

Functional genomics: A drop in an ocean of gene variants

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Technique: SNP-CLINGing onto your post in the genome

Technique: SNP-CLINGing onto your post in the genome

Technique: SNP-CLINGing onto your post in the genome, Published online: 22 January 2018; doi:10.1038/nrg.2018.2

Technique: SNP-CLINGing onto your post in the genome

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Paediatric Patients with Coeliac Disease on a Gluten-Free Diet: Nutritional Adequacy and Macro- and Micronutrient Imbalances

Abstract

Purpose of Review

A strict, lifelong gluten-free diet is the cornerstone for management of coeliac disease. Elimination of gluten from the diet may be associated with nutritional imbalance; however, the completeness of this diet in energy and macro- and micronutrients in children is not well described. Understanding the nutritional adequacy of the gluten-free diet in children during this critical period of growth and development when dietary intake is strongly influential is important.

Recent Findings

Children, regardless of whether they have eliminated gluten from their diet, have a tendency to consume excess fat and insufficient fibre, iron, vitamin D and calcium, compared to recommendations. In the context of a gluten-free diet, these imbalances may be worsened or have more significant consequences. Paediatric studies have demonstrated that intakes of folate, magnesium, zinc and selenium may decrease on a gluten-free diet.

Summary

Nutritional inadequacies may be risks of a gluten-free diet in a paediatric population. The potential implications of these inadequacies, both short and long term, remain unclear and warrant further investigation and clarification.



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