Adrian G. Thomas

Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn's disease

BACKGROUND Glutamine is traditionally considered a nonessential amino acid but may be conditionally essential in patients with catabolic conditions. Glutamine-supplemented foods in these patients have been shown to prevent deterioration of gut permeability, protect against the development of intestinal mucosal atrophy, and improve nitrogen balance. Animal models of inflammatory bowel disease suggest that glutamine-enriched enteral diets may lead to less severe intestinal damage, less weight loss, improved nitrogen balance, and reduced disease activity. The purpose of the current study was to compare the efficacy of a glutamine-enriched polymeric diet with a standard low-glutamine polymeric diet in the treatment of active Crohns disease. METHODS Eighteen children with active Crohns disease were randomly assigned to receive a 4-week course of either a standard polymeric diet with a low glutamine content (4% of amino acid composition; group S) or a glutamine-enriched polymeric diet (42% of amino acid composition; Group G). The two diets were isocaloric and isonitrogenous with an identical essential amino acid profile. Remission rates were analysed on an intent-to-treat basis. Changes in clinical and laboratory parameters of disease activity were also compared after 4 weeks of nutritional treatment. RESULTS Two of the children, both in group G, were withdrawn from the trial because of nontolerance of the diet. There was no difference between the two groups in proportion of patients achieving remission (intent-to-treat basis): 5 (55.5%) of 9 in group S versus 4 (44.4%) of 9 in group G (p = 0.5). Improvement in mean paediatric Crohns disease activity index (PCDAI) was significantly more in group S (p = 0.002) but changes in orosomucoid level, platelet count, and weight were not different between the groups. CONCLUSIONS The findings suggest that a glutamine-enriched polymeric diet offers no advantage over a standard low-glutamine polymeric diet in the treatment of active Crohns disease. Rather, it appears to be less effective in improving PCDAI. The reported beneficial effects of glutamine seen in many catabolic states must be viewed with caution when extrapolating to the management of Crohns disease.

Gastrostomy tube feeding in children with cerebral palsy: a prospective, longitudinal study

We report a longitudinal, prospective, multicentre cohort study designed to measure the outcomes of gastrostomy tube feeding in children with cerebral palsy (CP). Fifty‐seven children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) were assessed before gastrostomy placement, and at 6 and 12 months afterwards. Three‐quarters of the children enrolled (43 of 57) had spastic quadriplegia; other diagnoses included mixed CP (6 of 57), hemiplegia (3 of 57), undiagnosed severe neurological impairment (3 of 57), ataxia (1 of 57), and extrapyramidal disorder (1 of 57). Only 7 of 57 (12%) could sit independently, and only 3 of 57 (5%) could walk unaided. Outcome measures included growth/anthropometry, nutritional intake, general health, and complications of gastrostomy feeding. At baseline, half of the children were more than 3SD below the average weight for their age and sex when compared with the standards for typically‐developing children. Weight increased substantially over the study period; the median weight z score increased from ‐3 before gastrostomy placement to ‐2.2 at 6 months and ‐1.6 at 12 months. Almost all parents reported a significant improvement in their childs health after this intervention and a significant reduction in time spent feeding. Statistically significant and clinically important increases in weight gain and subcutaneous fat deposition were noted. Serious complications were rare, with no evidence of an increase in respiratory complications.

Impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy

The aim of this prospective cohort study was to evaluate the impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy (CP). Short‐Form 36 version II was used to measure quality of life in carers of 57 Caucasian children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) six and 12 months after insertion of a gastrostomy tube. Responses were calibrated against a normative dataset (Oxford Healthy Life Survey III). Six months after gastrostomy feeding was started, a substantial rise in mean domain scores for mental health, role limitations due to emotional problems, physical functioning, social functioning, and energy/vitality were observed. At 12 months after gastrostomy placement, carers reported significant improvements in social functioning, mental health, energy/vitality (mean increase >9.8 points; p<0.03), and in general health perception (mean increase 6.35 points; p=0.045) compared with results at baseline. Moreover, the values obtained for these domains at 12 months were not significantly different from the normal reference standard. Carers reported a significant reduction in feeding times, increased ease of drug administration, and reduced concern about their childs nutritional status. This study has demonstrated a significant, measurable improvement in the quality of life of carers after insertion of a gastrostomy feeding tube.

Systematic review : tolerable amount of gluten for people with coeliac disease

Background  The threshold amount of gluten in ‘gluten‐free’ products that can be tolerated by people with coeliac disease is unclear.

A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease

Aliment Pharmacol Ther 2011; 33: 946–953

Natalizumab therapy for moderate to severe Crohn disease in adolescents.

Objectives:This study evaluated the safety, tolerability, and efficacy of natalizumab, a humanized monoclonal immunoglobulin-G4 antibody to α4 integrin, in adolescent patients with moderately to severely active Crohn disease (CD). Patients and Methods:In a single-arm study, 38 adolescent patients (ages 12–17 y) with active CD (Pediatric Crohn Disease Activity Index [PCDAI] >30) received 3 intravenous infusions of natalizumab (3 mg/kg) at 0, 4 and 8 weeks. The primary analysis was safety, assessed by adverse events, laboratory results, and vital signs. Pharmacokinetic and pharmacodynamic measurements and formation of anti-natalizumab antibodies also were analyzed. Efficacy outcomes were assessed by changes in PCDAI, quality of life (IMPACT III), and levels of C-reactive protein and serum albumin. Results:Thirty-one patients (82%) received 3 natalizumab infusions. The most common adverse events were headache (26%), pyrexia (21%) and CD exacerbation (24%). Clinical response (≥15-point decrease from baseline PCDAI) and remission (PCDAI ≤10) rates were greatest at week 10 (55% and 29%, respectively). Three patients (8%) tested positive for anti-natalizumab antibodies. The peak level (61.0 and 66.3 μg/mL) and half-life (92.3 and 96.3 h) of natalizumab were comparable after the first and third infusions. Mean α4 integrin receptor saturation was 93% at 2 hours and <40% at 4 weeks after the first and third infusions. Increase from baseline in circulating lymphocytes ranged from 106% to 122% at 2 weeks and 45% to 65% at 4 weeks after each infusion. Conclusion:Natalizumab (3 mg/kg) was well tolerated in these adolescent patients with active CD, with a safety and efficacy profile similar to that of adult natalizumab-treated CD patients. Future studies should evaluate long-term safety and efficacy.

Systematic Review of the Evidence Base for the Medical Treatment of Paediatric Inflammatory Bowel Disease

Objective: To systematically review the evidence base for the medical (pharmaceutical and nutritional) treatment of paediatric inflammatory bowel disease. Methods: Key clinical questions were formulated regarding different treatment modalities used in the treatment of paediatric (not adult-onset) IBD, in particular the induction and maintenance of remission in Crohn disease and ulcerative colitis. Electronic searches were performed from January 1966 to December 2006, using the electronic search strategy of the Cochrane IBD group. Details of papers were entered on a dedicated database, reviewed in abstract form, and disseminated in full for appraisal. Clinical guidelines were appraised using the AGREE instrument and all other relevant papers were appraised using Scottish Intercollegiate Guidelines Network methodology, with evidence levels given to all papers. Results: A total of 6285 papers were identified, of which 1255 involved children; these were entered on the database. After critical appraisal, only 103 publications met our criteria as evidence on medical treatment of paediatric IBD. We identified 3 clinical guidelines, 1 systematic review, and 16 randomised controlled trials; all were of variable quality, with none getting the highest methodological scores. Conclusions: This is the first comprehensive review of the evidence base for the treatment of paediatric IBD, highlighting the paucity of trials of high methodological quality. As a result, the development of clinical guidelines for managing children and young people with IBD must be consensus based, informed by the best-available evidence from the paediatric literature and high-quality data from the adult IBD literature, together with the clinical expertise and multidisciplinary experience of paediatric IBD experts.

Growth in children with Helicobacter pylori infection and dyspepsia

Aims: To compare the height, weight, and body mass index (BMI) of children presenting with dyspeptic symptoms and Helicobacter pylori infection, to those with dyspepsia but without the infection. Methods: A retrospective chart review of 257 children was performed. 13C urea breath test was performed to detect H pylori infection; weight and height were recorded and BMI was calculated. Weight, height, and BMI SD scores were determined using the 1990 UK normative data. The Index of Multiple Deprivation 2004 (IMD 2004) scores, which measure deprivation at small area level, were calculated from the patients’ postcodes. Results: Ninety seven of the 257 children were H pylori positive. The mean age at diagnosis and presenting symptoms of H pylori positive and negative patients were similar. The mean IMD 2004 scores for children with H pylori infection were significantly higher compared to H pylori negative patients, suggesting that children with the infection came from relatively more deprived areas. The mean weight and height SD score were significantly lower for children with H pylori infection compared to those without. However, this difference was no longer significant after adjusting for socioeconomic deprivation and ethnic differences between the groups. Conclusion: Children with dyspepsia and H pylori infection were shorter and lighter than patients with similar symptoms but no infection. The differences in anthropometry may be due to socioeconomic and ethnic factors rather than H pylori infection.

Does gastrostomy tube feeding in children with cerebral palsy increase the risk of respiratory morbidity

Background: Children with severe neurological impairment may have significant oral motor dysfunction and are at increased risk of nutritional deficiencies, poor growth, and aspiration pneumonia. Gastrostomy tube feeding is increasingly being used for nutritional support in these children. Aim: To examine the occurrence of respiratory morbidity before and after gastrostomy feeding tube insertion in children with severe neurological disabilities. Methods: This study was nested in a longitudinal, prospective, uncontrolled, multicentre cohort study designed to investigate the outcomes of gastrostomy tube feeding in 57 children with severe neurological disabilities. Parents completed a questionnaire prior to (visit 1) and 6 and 12 months (visits 2 and 3) following the gastrostomy, detailing number of chest infections requiring antibiotics and/or hospital admission. Results: Mean number of chest infections requiring antibiotics was 1.8 on visit 1 and 0.9 on visit 3. Hospital admissions for chest infections fell significantly from 0.5 to 0.09. Conclusion: This study provides no evidence for an increase in respiratory morbidity following insertion of a feeding gastrostomy in children with cerebral palsy.

Feeding the Disabled Child

Feeding difficulty and malnutrition are common in disabled children. Intake may be reduced because of anorexia, chewing and swallowing difficulties, or vomiting. Feeding is often time consuming, unpleasant, and may result in aspiration. Malnutrition may result in impaired growth and neurodevelopment, and impaired cardiorespiratory, gastrointestinal, and immune functions. Multidisciplinary assessment is recommended and should include a feeding history, oral-motor examination, and nutritional assessment. The energy requirements of most disabled children are less than those for a normal child of the same age but may be increased by spasticity, athetosis, convulsions, and recurrent infections. Micronutrient deficiencies may occur even in children receiving nutritionally complete feeds if the volume is reduced because of low energy requirements. Oral intake may be improved by a change of posture, special seating, feeding equipment, oral desensitization, mashing or pureeing of lumpy food, thickening of liquids, use of calorie supplements, and treatment of reflux/esophagitis. Non-oral feeding should be considered when oral feeding is unsafe, not enjoyable, inadequate, or very time consuming. Long-term support requires a gastrostomy. This is less obtrusive than a nasogastric tube, less likely to become displaced, less traumatic, and is associated with improved quality of life, but is also associated with significant morbidity. If there is symptomatic reflux a fundoplication may be required, but this is associated with significant mortality and substantial morbidity.