Immunological indicators of coeliac disease activity are not altered by long-term oats challenge.

Coeliac disease is a gluten-sensitive enteropathy that develops in genetically susceptible individuals. The disease exhibits many features of an autoimmune disorder. These include the production of highly specific anti-endomysial autoantibodies directed against the enzyme tissue transglutaminase. It is well accepted that wheat-, barley- and rye-based foods should be excluded in the gluten-free diet. Although several studies report that oats ingestion is safe in this diet, the potential toxicity of oats remains controversial. In the current study, 46 coeliac patients ingested oats for 1 year and were investigated for a potential immunogenic or toxic effect. Stringent clinical monitoring of these patients was performed and none experienced adverse effects, despite ingestion of a mean of 286 g of oats each week. Routine histological analysis of intestinal biopsies showed improvement or no change in 95% of the samples examined. Furthermore, tissue transglutaminase expression in biopsy samples, determined quantitatively using the IN Cell Analyzer, was unchanged. Employing immunohistochemistry, oats ingestion was not associated with changes in intraepithelial lymphocyte numbers or with enterocyte proliferation as assessed by Ki-67 staining. Finally, despite the potential for tissue transglutaminase to interact with oats, neither endomysial nor tissue transglutaminase antibodies were generated in any of the patients throughout the study. To conclude, this study reaffirms the lack of oats immunogenicity and toxicity to coeliac patients. It also suggests that the antigenic stimulus caused by wheat exposure differs fundamentally from that caused by oats.

Sustained benefits of a community dietetics intervention designed to improve oral nutritional supplement prescribing practices.

BACKGROUND: Healthcare professionals working in the community do not always prescribe oral nutritional supplements (ONS) according to best practice guidelines for the management of malnutrition. The present study aimed to determine the impact of a community dietetics intervention on ONS prescribing practices and expenditure 1 year later. METHODS: The intervention involved general practitioners (GPs), practice nurses, nurses in local nursing homes and community nurses. It comprised an education programme together with the provision of a new community dietetics service. Changes in health care professionals' nutrition care practices were determined by examining community dietetics records. ONS prescribing volume and expenditure on ONS were assessed using data from the Primary Care Reimbursement Service of the Irish Health Service Executive. RESULTS: Seven out of 10 principal GPs participated in the nutrition education programme. One year later, screening for malnutrition risk was better, dietary advice was provided more often, referral to the community dietetics service improved and ONS were prescribed for a greater proportion of patients at 'high risk' of malnutrition than before (88% versus 37%; P < 0.001). There was a trend towards fewer patients being prescribed ONS (18% reduction; P = 0.074) and there was no significant change in expenditure on ONS by participating GPs (3% reduction; P = 0.499), despite a 28% increase nationally by GPs on ONS. CONCLUSIONS: The community dietetics intervention improved ONS prescribing practices by GPs and nurses, in accordance with best practice guidelines, without increasing expenditure on ONS during the year after intervention.

An evaluation of a community dietetics intervention on the management of malnutrition for healthcare professionals.

BACKGROUND: Healthcare professionals working in the community setting have limited knowledge of the evidence-based management of malnutrition. The present study aimed to evaluate a community dietetics intervention, which included an education programme for healthcare professionals in conjunction with the introduction of a community dietetics service for patients 'at risk' of malnutrition. Changes in nutritional knowledge and the reported management of malnourished patients were investigated and the acceptability of the intervention was explored. METHODS: An education programme, incorporating 'Malnutrition Universal Screening Tool (MUST)' training, was implemented in eight of 10 eligible primary care practices (14 general practitioners and nine practice nurses attended), in seven private nursing homes (20 staff nurses attended) and two health centres (53 community nurses attended) in conjunction with a community dietetics service for patients at risk of malnutrition. Nutritional knowledge was assessed before, immediately after, and 6 months after the intervention using self-administered, multiple-choice questionnaires. Reported changes in practice and the acceptability of the education programme were considered using self-administered questionnaires 6 months after the intervention. RESULTS: A significant increase in nutritional knowledge 6 months after the intervention was observed (P < 0.001). The management of malnutrition was reported to be improved, with 69% (38/55) of healthcare professionals reporting to weigh patients 'more frequently', whereas 80% (43/54) reported giving dietary advice to prevent or treat malnutrition. Eighty-percent (44/55) of healthcare professionals stated that 'MUST' was an acceptable nutrition screening tool. CONCLUSION: An education programme supported by a community dietetics service for patients 'at risk' of malnutrition increased the nutritional knowledge and improved the reported management of malnourished patients in the community by healthcare professionals.

The use of oral nutritional supplements in an Irish community setting.

BACKGROUND: The frequency of oral nutritional supplement (ONS) prescribing has been increasing steadily in the Republic of Ireland (ROI). Available evidence indicates that health professionals in the community setting in the ROI have a poor level of knowledge about ONS. The objectives of the present study were to investigate ONS prescribing practices and to identify the types of patient who were prescribed these products. METHODS: Ten of 17 eligible general practitioners were recruited and asked to refer all patients (aged > 16 years) who were prescribed ONS during a 3-month period. Patients were interviewed by a community dietitian, using a questionnaire incorporating the Malnutrition Universal Screening Tool (MUST). ONS prescriptions were judged either to fulfil or not to fulfil a set of criteria developed for ONS prescribing in the community. RESULTS: The majority of patients were female (62/78). Their mean (SD) age was 79 (10.5) years. According to MUST criteria, 31 of 78 patients were at 'low risk', 18 of 78 were at 'medium risk' and 29 of 78 were at 'high risk' of malnutrition. Less than half of the patients (36/78) had a body mass index of < 20 kg m(-2). Only 21 of 78 patients reported having received dietary advice in addition to their ONS prescription. Almost one-third (31%) of ONS prescriptions did not fulfil the criteria. Social factors, such as living alone, and difficulties with cooking and shopping, influenced the need for ONS in almost 70% of cases. CONCLUSIONS: ONS were prescribed in accordance with the prescribing criteria in the majority of cases; however, some patients who were prescribed ONS were not 'at risk' of malnutrition. Social circumstances played an important part in determining the need for ONS prescriptions.

Haplotypes in the CTLA4 region are associated with coeliac disease in the Irish population.

Chromosomal region 2q33 encodes the immune regulatory genes, CTLA4, ICOS and CD28, which are involved in regulation of T-cell activity and has been studied as a candidate gene locus in autoimmune diseases, including coeliac disease (CD). We have investigated whether an association exists between this region and CD in the Irish population using a comprehensive analysis for genetic variation. Using a haplotype-tagging approach, this gene cluster was investigated for disease association in a case-control study comprising 394 CD patients and 421 ethnically matched healthy controls. Several SNPs, including CTLA4_CT60, showed association with disease; however, after correction for multiple-testing, CTLA4-658C/T was the only polymorphism found to show significant association with disease when allele, genotype, or carrier status frequency were analysed (carrier status (Allele C), P = 0.0016). Haplotype analysis revealed a haplotype incorporating the CD28/CTLA4 and two 5' ICOS polymorphisms to be significantly associated with disease (patients 24.1%; controls 31.5%; P = 0.035), as was a shorter haplotype composed of the CTLA4 markers only (30.9 vs 34.9%; P = 0.042). The extended haplotype incorporating CD28/CTLA4 and 5' ICOS is more strongly associated with disease than haplotypes of individual genes. This suggests a causal variant associated with this haplotype may be associated with disease in this population.

Chromosome 5q candidate genes in coeliac disease: genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1.

Genetic predisposition to coeliac disease (CD) is determined primarily by alleles at the HLA-DQB locus, and evidence exists implicating other major histocompatibility complex-linked genes (6p21) and the CTLA4 locus on chromosome 2q33. In addition, extensive family studies have provided strong, reproducible evidence for a susceptibility locus on chromosome 5q (CELIAC2). However, the gene responsible has not been identified. We have assayed genetic variation at the IL4, IL5, IL9, IL13, IL17B and NR3C1 (GR) loci, all of which are present on chromosome 5q and have potential or demonstrated involvement in autoimmune and/or inflammatory disease, in a sample of 409 CD cases and 355 controls. Thirteen single nucleotide polymorphisms were chosen on the basis of functional relevance, prior disease association and, where possible, prior knowledge of the haplotype variation present in European populations. There were no statistically significant allele or haplotype frequency differences between cases and controls. Therefore, these results provide no evidence that these loci are associated with CD in this sample population.

Haplotype variation at the IBD5/SLC22A4 locus (5q31) in coeliac disease in the Irish population.

In addition to the well-established association of coeliac disease (CD) with HLA-DQ (6p21) and possibly CTLA4 (2q33), there is considerable evidence for a susceptibility locus on chromosome 5q, which contains many potential candidates for inflammatory disease, including a cluster of cytokine genes in 5q31. CD cases and controls were genotyped for four single-nucleotide polymorphism (SNP) markers that together characterize >90% of the haplotype variation at the IBD5 locus encoding, among others, the SLC22A4 gene. IBD5 and SLC22A4 map to 5q31 and have recently been associated with Crohn's disease and rheumatoid arthritis. Haplotype frequencies do not differ significantly between CD cases and controls in the Irish population, and therefore the chromosome 5 CD susceptibility locus most likely lies elsewhere on 5q.

Comparison of nutritional risk screening tools in patients on admission to hospital.

BACKGROUND AND AIMS: Under nutrition has been frequently reported in patients on admission to hospital. Because this is not always detected promptly, screening for nutritional risk on admission has been widely advocated. Although there is no universally accepted 'gold standard' for defining undernutrition, the definition used by McWhirter, J.P. & Pennington, C.R. [(1994) Br. Med. J.308, 945] has been widely used by clinical nutrition specialists. This study aimed to compare the efficacy of two frequently used nutritional risk screening tools in detecting undernutrition according to this definition. METHODS: Both the Nutrition Risk Index [Veterans Affairs Total Parenteral Nutrition Co-operative Study Group (1991) N. Engl. J. Med.325, 525] and the Nutrition Risk Score [Reilly H.M. et al. (1995) Clin. Nutr.14, 269] were used to screen for undernutrition in 359 admissions to two acute teaching hospitals in Dublin. Undernutrition was defined as a Body Mass Index below 20 kg m(-2) and a triceps skinfold thickness or mid-arm muscle circumference below the 15th percentile. Comparison of stratification of nutritional risk by the two screening tools was carried out. RESULTS: Both screening tools identified over 40% (Nutrition Risk Index, 44%; Nutrition Risk Score, 46%) of all patients assessed as at nutritional risk on admission. However, one-third of the undernourished patients were classified as at no nutrition risk by the Nutrition Risk Index, while almost one-fifth of those undernourished were classified as at low risk by the Nutrition Risk Score. The degree of nutritional risk differed with the screening tool used, the Nutrition Risk Score classifying 29% of all patients as high risk while the Nutrition Risk Index classified only 5% as in the high risk category. CONCLUSIONS: Although a large proportion of patients on admission were classified as being at nutritional risk, the degree of risk was significantly different depending on the screening tool used. Both nutritional risk screening tools evaluated in this study failed to recognize many cases of undernutrition. Evaluation of the efficacy of nutritional screening tools should be promoted as seriously as the development of such tools.

Both under-nutrition and obesity increase morbidity following liver transplantation.

Malnutrition is common in patients awaiting liver transplantation and may contribute to operative and post-operative mortality, although this is controversial. We assessed the pre-operative nutritional status of 87 patients and the impact this had on mortality and morbidity following liver transplantation for chronic liver disease. Thirty six per cent of patients had more than 10% loss of body weight prior to transplantation. Nutritional depletion, considered present if triceps skin fold thickness or mid-arm muscle circumference were < 5th percentile, was present in 17% and 15% of the total group respectively. Patients whose pre-operative body weights were < 90% of their ideal body weight (IBW) had a longer hospital stay (p = 0.001) and required longer post-operative ventilatory support (p = 0.033). This group also required significantly more treatment with intravenous antibiotics (p = 0.001) suggesting an increased incidence of infective complications. Patients who were obese pre-operatively (body mass index > 30Kg/m2) also required a longer period in high dependency (p = 0.0003). No individual nutritional variable correlated with mortality. In the Irish population undergoing liver transplantation, we found a relatively low prevalence of malnutrition in comparison with other studies. Both under- nutrition and obesity significantly affected morbidity and length of hospital stay post-transplant, although no individual nutritional variable predicted survival post transplant.

Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease.

Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0.004 and 0.039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0.0001 and 0.0014 at D2S2214, respectively, and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.

Tube feeding patients with advanced dementia: an ethical dilemma.

Many patients with dementia lose the ability to feed themselves in the advanced stages of the disease. Tube feeding is sometimes initiated to overcome feeding difficulties. Recent studies have questioned the appropriateness of tube feeding in these patients. There is limited research to support the benefits of enteral nutrition in patients with advanced dementia. Deciding whether to tube feed or to withhold tube feeding from a patient with dementia poses a difficult challenge, and many carers may make decisions without adequate information and with an overly hopeful view of the future clinical course. Numerous studies have examined opinions about life-sustaining treatments; many individuals do not want to be tube fed if they were to develop dementia. Results from studies examining the opinions of physicians and other health professionals regarding the use of tube feeding in these patients are conflicting. A number of factors, such as race and cultural background may affect decisions. Healthcare professionals, relatives and patients must be aware of the realistic expectations of tube feeding in patients with dementia, as it can be difficult to withdraw once it has been initiated.

Flow cytometric measurement of intracellular migration inhibition factor and tumour necrosis factor alpha in the mucosa of patients with coeliac disease.

There is increasing evidence that proinflammatory cytokines contribute to many of the small intestinal features in coeliac disease. The aim of the study was to investigate the expression of two proinflammatory cytokines, migration inhibition factor (MIF) and tumour necrosis factor alpha (TNF-alpha) in duodenal biopsy specimens from patients with coeliac disease on a gluten-free diet and normal control subjects. A flow cytometric system was used to analyse intracellular protein levels of MIF and TNF-alpha in freshly isolated cells from duodenal biopsies taken from 12 patients with treated coeliac disease and 10 healthy control subjects. From the biopsy specimens, single cell suspensions of the epithelium and lamina propria were prepared using EDTA/DTT and enzymes. Intracellular cytokine expression was studied in intraepithelial lymphocytes (IELs), lamina propria T cells (LP T) and intestinal epithelial cells using different surface labelling antibodies. MIF protein was constitutively expressed in IELs, LP T cells and epithelial cells from normal intestinal mucosa. In contrast, although TNF-alpha was found in LP T cells, this cytokine was virtually undetectable in either IELs or epithelial cells. In coeliac disease, intracellular levels of MIF were significantly higher in epithelial cells compared with control subjects (P = 0.005). Raised levels of TNF-alpha were found in epithelial cells (P = 0.03) as well as IELs (P = 0.045) from coeliac patients compared with controls. The findings from this study show up-regulated expression of MIF and TNF-alpha in IELs and epithelial cells of histologically normal mucosa in patients with coeliac disease. Increased expression of proinflammatory cytokines in cells occupying the epithelial layer could help explain the rapidity with which the coeliac mucosa may respond to gluten challenge.

Home tube feeding: an integrated multidisciplinary approach.

BACKGROUND: Long-term enteral tube feeding is increasingly required by patients in the community setting. A previous study of 50 adults on home enteral tube feeding in the Dublin area found that some experienced logistical problems and many individuals did not choose to seek advice from their GP regarding their tube feeding. AIMS: To assess the contribution of health professionals to the care of patients on enteral tube feeding in the community. METHODS: GPs and hospital dietitians were surveyed using postal questionnaires and nutritional company representatives using structured interviews, to assess their involvement with patients on home tube feeding. Completed questionnaires were received from 77 dietitians and 80 GPs. Ten company representatives were interviewed. RESULTS: Hospital dietitians carry out most of the initial education and training of patients, in addition to the nutritional aftercare. General practitioners tend not to be involved, although nutrition specialists working in the nutritional products area report encountering patients with tube-feeding complications in the community. CONCLUSIONS: Improved co-ordination between hospital and community services and more consistent monitoring of those on home enteral tube feeding would be an advantage to such patients.

Apparent low frequency of undernutrition in Dublin hospital in-patients: should we review the anthropometric thresholds for clinical practice?

Protein-energy undernutrition, or the possibility of its development, has been documented to occur frequently in patients on admission to hospital. Deterioration in nutritional status is known to occur in hospital. In a prospective study of 594 sequential hospital admissions, we aimed to assess the prevalence of undernutrition among patients on admission to two acute teaching hospitals in Dublin, Republic of Ireland using the widely-accepted anthropometric criteria applied in a large study from Dundee, Scotland, UK (McWhirter & Pennington, 1994) and to determine changes in nutritional status in hospital. The mean prevalence of undernutrition (11 %) was considerably lower than was reported from Dundee (40 %). Unintentional weight loss before admission and functional impairment on admission occurred to a similar extent in both centres. Weight loss in hospital occurred in the same proportion of patients, but less frequently among those undernourished on admission to hospital, in Dublin compared with Dundee. The patients found to be undernourished on admission in this study had a mortality rate in hospital (6.5 %) over three times that of the adequately nourished group (2 %). The magnitude of the difference in prevalence of undernutrition between the two centres cannot be explained by ethnicity, case-mix or age distribution. With the secular increase in BMI in the population, the thresholds for classifying patients as undernourished or at risk of nutritional deterioration may need to be reviewed. For clinical use, recent weight loss and functional status may be more appropriate variables to use in the evaluation of nutritional status on admission to hospital.

Clinical features of coeliac disease today.

Coeliac disease is an inflammatory disorder of the small intestine induced by dietary gluten. This frequently results in malabsorption of a range of important nutrients including iron, folic acid, calcium and fat-soluble vitamins. Coeliac disease in now considered to be a common disorder, possibly affecting 1:300 of the general population. Many patients present in adulthood, have minimal symptoms, and gastrointestinal manifestations are frequently absent. The diagnosis and screening for coeliac disease has been dramatically facilitated by testing for endomysial autoantibodies, although biopsy and demonstration of a characteristic histological lesion remains the definitive diagnostic investigation. Treatment with a gluten-free diet is effective but requires good patient compliance and monitoring to succeed.

Protein-energy undernutrition in hospital in-patients.

Impaired nutritional status has been frequently reported in surveys estimating its prevalence amongst patients in hospital. While there is no doubt that protein-energy undernutrition has serious implications for health, recovery from illness or surgery and hospital costs, lack of nationally or internationally accepted cut-off points and guidelines for most nutrition-related variables make nutritional assessment difficult and proper comparisons between studies impossible. In reviewing published work in which the prevalence of undernutrition has been assessed, it can be seen that each study defined undernutrition, or nutritional risk, using different methodology. This present review aims to highlight the problems which arise when deciphering these studies, and the resulting difficulty in determining the true prevalence of undernutrition and nutritional risk, amongst both general and specific groups of hospital in-patients. It is widely agreed that routine hospital practices can further adversely affect the nutritional status of sick patients in hospital. How this occurs, and the potential effects of impaired nutritional status on clinical outcome are examined. The methods currently available to assess nutritional status are evaluated in the knowledge that such assessments are difficult in clinical practice. The review concludes by proposing that if we want the medical and nursing professions to consider the nutritional status of hospital patients seriously, definitions of undernutrition and nutritional risk, and cut-off values for the nutritional variables measured must be agreed to allow evidence-based practice. Outcome measures which allow clear comparisons between groups and treatments must be used in studies assessing the effects of nutritional interventions.

Enteral tube feeding in the community: survey of adult patients discharged from a Dublin hospital.

BACKGROUND AND AIMS: No previous study has examined the state of patients on enteral tube feeding in the community in the Republic of Ireland. METHODS: Fifty adult patients discharged from a Dublin hospital on enteral tube feeding were assessed retrospectively. RESULTS: Sixty-six per cent of the sample were over 65 years of age. Patients required enteral tube feeding as a consequence of swallowing difficulties caused by stroke (46%) or cancer of the head and neck (24%). Most patients were on full nutritional support and, in total, had spent over 49 years tube feeding in the community. Geriatric stroke patients were found to have poor functional ability and nutritional assessment proved difficult to carry out on many of these patients. Problems encountered with feeding included blocked tubes (30%), infected stoma sites (16%), and logistical problems regarding feed and equipment. Nutritional follow-up was not routine in patients with poor mobility, and 55% of patients on long-term tube feeding had not been reviewed by a dietitian in over 1 year. Patients had little faith in their general practitioner's knowledge of enteral feeding. CONCLUSIONS: While patients and families appear to cope remarkably well with tube feeding in the community, more support is necessary to ensure appropriate feeding and to monitor the nutritional status of these patients.

Contribution of the MHC region to the familial risk of coeliac disease.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.