Evaluation of a psychoeducational intervention for adolescents with inflammatory bowel disease. Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure. Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial. Impact of anti-Giardia and anthelminthic treatment on infant growth and intestinal permeability in rural Bangladesh: a randomised double-blind controlled study. Polymeric versus elemental diet as primary treatment in active Crohn's disease: a randomized, double-blind trial. The effect of anorectal manometry on the outcome of treatment in severe childhood constipation: a randomized, controlled trial. Comparison of enteral nutrition and drug treatment in active Crohn's disease. Results of the European Cooperative Crohn's Disease Study. IV. Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. A randomized control study. Infliximab prevents Crohn's disease recurrence after ileal resection.
Inflammatory bowel disease (IBD), comprising Crohn's disease, ulcerative colitis, and indeterminate colitis, often has its onset in adolescence. The aim of this study was to evaluate whether a psychoeducational group intervention (aiming to enhance information seeking and giving about the disease, relaxation, social competence, and positive thinking) can strengthen the coping efforts of adolescents with IBD and have a positive effect on their Health-Related Quality of Life (HRQoL).
                Adolescent IBD patients from the Emma Children's Hospital AMC and adolescent members of the Crohn and Ulcerative Colitis Association in The Netherlands, were invited to participate in The intervention study. Using reliable and valid self-report instruments the adolescent's coping styles, feelings of competence, and HRQoL were assessed before and 6-8 months after the intervention. The parents were asked to fill in the Child Behavior Check List. Linear regression analyses were performed to test whether group participation was predictive of the outcome measures while correcting for the first measurement occasion and sex.
                Forty patients responded positively to invitation to the intervention. Eighteen adolescents, however, lived too far away to attend and served as a control group. Twenty-two children were enrolled and attended in groups of four to six children in six group sessions, supervised by two psychologists. The intervention seemed to have a positive effect on: coping (predictive control, P<0.01), feelings of competence (global self-worth, P<0.05 and physical appearance, P<0.01), and HRQoL (body image, P<0.05). These results give good reason to continue this intervention study with a larger population. Stunted growth is a serious problem for children with chronic renal failure (CRF) despite normal endogenous growth hormone secretion and normal or elevated plasma concentrations of insulin-like growth factors (IGF) I and II. Biosynthetic growth hormone (GH) was given to 20 prepubertal children (eleven boys, nine girls; mean age 9.5 years, range 4-16) with CRF and severe growth retardation in a placebo-controlled, double-blind, cross-over trial. 6 months of subcutaneous injection of GH (4 IU/m2 per day) was either preceded or followed by 6 months of placebo injection. The patients had a full examination every 3 months. Sixteen children completed the study. Height velocity improved significantly with GH therapy (p less than 0.0001) and placebo (p less than 0.04), but the GH-induced height-velocity increase exceeded that of placebo by 2.9 cm per 6 months. There was a positive relationship between prestudy height velocity and height-velocity increase. Bone maturation was not affected. GH caused a significant increase in IGF-I and a moderate increase in IGF-II plasma concentrations. The pretreatment elevation of IGF-binding protein-1 decreased by almost 50% during GH therapy, while IGF-binding protein-3 increased significantly in concentration, although this increase was significantly smaller than the GH-induced increase in IGF-I. Fructosamine, lipid, and parathyroid concentrations remained constant. Renal function deterioration did not accelerate. Impressive height-velocity increase can be achieved with GH therapy in children with CRF and growth retardation without changes in renal function. Bone maturation appears unaffected suggesting improved final height. Treatment is best started before growth retardation becomes considerable. Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn's disease are established. We investigated its efficacy in ulcerative colitis.
                We conducted a randomised placebo controlled trial of infliximab (5 mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions were given at weeks 0 and 2. Disease activity and quality of life were recorded over eight weeks of follow up. Remission was defined as an ulcerative colitis symptom score (UCSS) of < or =2 and/or Baron score of 0 at week 6. Patients not in remission were offered open label infliximab 10 mg/kg and reviewed two weeks later.
                After two weeks, there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 (13% (3/23) v 5% (1/19) (95% confidence interval (CI) -9% to 24%); p=0.74). After six weeks, remission (UCSS < or =2) rates were 39% (9/23) versus 30% (6/20) (95% CI -19 to 34%; p=0.76). The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82, Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) v 30% (6/20) (95% CI -30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was not significantly different between the groups (p=0.22 and 0.3, respectively, Mann-Whitney U test). Twenty eligible patients were given open labelled infusions. Remission was achieved in 3/11 (27%) patients initially treated with infliximab and in 1/9 (11%) patients treated with placebo.
                These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis. In order to test the impact of Giardia and geohelminthic infection on infant growth faltering in Bangladesh, a randomised double-blind placebo controlled intervention of 36 weeks' duration was conducted in a rural community located 40 km northwest of Dhaka. Infants aged between 3 and 15 months were randomly assigned to either anti-Giardia and anthelminthic treatment, anti-Giardia treatment only, or a control. Weight and supine length were recorded every 4 weeks. Every 12 weeks intestinal permeability (lactulose/mannitol ratio), haemoglobin, plasma albumin, alpha-1-acid glycoprotein, IgG and Giardia-specific IgM (GSIgM) and eggs of the three common geohelminths and G. intestinalis cysts were determined. Data on 222 fully compliant infants were analysed. No significant differences in intestinal permeability, biochemical or anthropometric variables were found between the intervention groups, although there were associations between improvement in small intestinal mucosal function and better weight-for-age and weight-for-height (length) Z-scores. GSIgM titres indicated high endemicity with rapid re-infection of Giardia among infants; over 95% of infants were positive throughout the study, whereas the stool examination showed very few infants with either geohelminth eggs or Giardia cysts. Enteral feeding is now an established primary therapy for active Crohn's disease. This first-double blind randomized trial was designed to compare the therapeutic efficacy of a polymeric diet (PD) with an elemental diet (ED).
                Patients with active Crohn's disease (Crohn's disease activity index [CDAI] > 150, increased bowel uptake of Tc-HMPAO-labeled leukocytes, and abnormal C-reactive protein [CRP]), were randomized to receive either an ED or a PD. The two preparations were identical except for the nitrogen source, which was amino acid based in ED and intact protein in PD. Enteral feeding was considered successful if clinical remission was achieved as defined by a final CDAI of < or = 150, a reduction in the CDAI by at least 100 points from baseline level, and a normal CRP.
                Twenty-one patients were enrolled of whom 11 were randomized to PD and 10 to ED. The two groups were comparable at entry. Clinical remission was obtained in eight (80%) patients receiving ED and six (55%) patients receiving PD, p = 0.1. The treatment failed in three and two patients in the PD and ED groups, respectively. Another two patients were intolerant to the feed (PD). Reduction in the CDAI after treatment with ED (359 +/- 67 to 112 +/- 19) was similar to that seen with PD (303 +/- 27 to 97 +/- 11). Similar changes in the CRP were also observed (16 +/- 5 to 4 +/- 1.6) and (62 +/- 20 to 9 +/- 6), respectively. Overall, enteral feeding was successful in 14 patients (63%).
                Enteral nutrition is effective in treatment of active Crohn's disease. Differences in nitrogen sources of enteral feeds are not relevant to their therapeutic efficacy, as polymeric and elemental diets are equally effective. Approximately 50% of constipated children contract rather than relax the external sphincter complex during a defecation attempt. Although biofeedback training (BF) is able to change this defecation behavior, there is no additional effect of BF to conventional treatment (CT) on clinical outcome compared with CT alone. It has been postulated that the absence of a significant difference between these 2 treatment options might be because of a therapeutic, "demystifying" effect of performing anorectal manometry in conventionally treated children, necessary to obtain basal manometric data. The objective of this prospective, controlled, randomized study was to evaluate the effect of CT with 2 anorectal manometry sessions compared with CT alone (dietary advice, diary, toilet training, oral laxatives, and enemas) on clinical outcome.
                A total of 212 constipated children (143 boys) who were visiting a referral pediatric gastroenterologic practice were randomized prospectively to CT alone (115 patients) or to CT combined with 2 manometry sessions (CTM; 97 patients). Patients were included in the study when they fulfilled at least 2 of the 4 following criteria: stool frequency fewer than 3 per week, 2 or more soiling and/or encopresis episodes per week, periodic passage of very large amounts of stool every 7 to 30 days, or a palpable rectal or abdominal fecal mass. CT comprises dietary advice, a daily diary, toilet training, and oral laxative treatment preceded by rectal disimpaction with enemas on 3 consecutive days. During both manometries, the child and the parent could watch the tracing on the computer screen. No explanation was given to either the child or the parents during the procedure. When the procedure was finished, the tracings were clarified. Successful treatment was defined as a defecation frequency of 3 or more per week and fewer than 1 soiling/encopresis episode per 2 weeks and no use of laxatives.
                Only 4 and 2 children from the CT and CTM groups showed no soiling and/or encopresis, whereas 76% and 65%, respectively, reported the periodic passage of large stools. In 26% and 30% of the patients, a rectal scybalum was found on physical examination. The success rates at 6, 26, 52, and 104 weeks' follow-up were 4%, 24%, 32%, and 43% and 7%, 22%, 30%, and 35% in the CT and CTM group, respectively. No significant difference in success percentage was observed between the 2 groups at any time of follow-up with relative risks (CT/CTM) and 95% confidence intervals, respectively, of 0.55 (0.16-1.89), 1.13 (0.67-1.89), 1.07 (0.69-1.65), and 1.23 (0.81-1.85). A significant increase in defecation frequency was observed between the first (intake) and second visits, which was sustained at all subsequent visits and stages of follow-up in both groups (not significant). Also in relation to the first visit, a significant decrease in encopresis episodes was shown and a further slow but significant decrease at 52 weeks of follow-up in both groups. The manometric data obtained from the CTM group showed a low percentage of children with normal defecation dynamics, namely 28%, which (significantly) increased to 38% at the last manometry.
                Anorectal manometry combined with CT compared with CT alone did not result in higher success rates in chronically constipated children. Therefore, anorectal manometry has no additional demystifying or educational effect on clinical outcome in chronically constipated children. This observation together with the observation in the current and previous studies that no correlation was found between (achievement of) normal defecation dynamics and success and that no relation was observed between volume of urge or critical volume and success leaves no diagnostic or therapeutic role for anorectal manometry in chronic constipated children, except its use as a diagnostic test to exclude Hirschsprung's disease. A simple CT is successful in 30% of severely constipated children who are referred to a tertiary hospital, underscoring the importance of long-lasting and adequate laxative treatment. This study compared the effect of enteral nutrition as the sole therapy of active Crohn's disease with drug treatment. Patients with active Crohn's disease (Crohn's Disease Activity Index greater than 200) were randomized to receive either enteral nutrition with a liquid oligopeptide diet (n = 55) or a combination of 6-methylprednisolone, 48 mg daily, subsequently tapered, and sulfasalazine, 3 g daily (n = 52). The two groups were not different with respect to age, sex, body weight, location of disease, or treatment before the study. The severity of disease was similar at the beginning of the study in both groups [Crohn's Disease Activity Index (mean +/- SEM), 323 +/- 12 vs. 316 +/- 11]. Remission was defined as a decrease of the initial Crohn's Disease Activity Index by 40% or at least 100 points. Twenty-nine patients in the diet group and 41 patients in the drug group reached remission within 6 weeks of therapy (chi 2 test, P less than 0.01). The median elapsed time to remission was 30.7 days in the diet group compared with 8.2 days in the drug group (Mantel Cox, P less than 0.01). To determine whether one of these treatments was more beneficial for a subgroup of patients, the effectiveness of both treatments was analyzed separately in patients with very severe disease (initial Crohn's Disease Activity Index greater than 300) and less severe disease (initial Crohn's Disease Activity Index less than 300), and in patients with different disease location. However, no influence of initial disease activity or disease location on the effect of either treatment could be shown. These data show that enteral nutrition is less effective than a combination of 6-methylprednisolone and sulfasalazine in treating active Crohn's disease. The association between severe nutritional depletion and chronic obstructive pulmonary disease (COPD) has long been recognized. A potential therapeutic benefit to nutritional support was previously suggested by us in a pilot investigation. Subsequent studies have reported conflicting results regarding the role of nutritional therapy in this clinical population. We report a randomized controlled study of nutritional therapy in underweight patients with COPD that combines an initial inpatient investigation (controlled nutritional support) with a prolonged outpatient follow-up interval. Provision of adequate calorie and protein support, adjusted to metabolic requirements, resulted in weight gain (intervention = +2.4 kg versus control -0.5 kg), improved handgrip strength (intervention = +5.5 kg-force versus control -6.0 kg-force), expiratory muscle strength (intervention = +14.9 cm H2O versus control -9.2 cm H2O), and walking distance (intervention = +429 feet versus control -1.0 foot). Inspiratory muscle strength was also improved (intervention = +11.4 cm H2O versus control +4.8 cm H2O) although this did not quite reach statistical significance. We conclude that provision of adequate nutrient supply under controlled conditions results in significant clinical improvements in the COPD patient population. However, the intervention is costly, time-intensive, and of limited therapeutic magnitude. More detailed work of alternative outpatient strategies combined with additional rehabilitative measures is indicated to delineate the full therapeutic potential of nutritional support for this clinical population. Crohn's disease commonly recurs after intestinal resection. We evaluated whether the administration of infliximab after resective intestinal surgery for Crohn's disease reduces postoperative recurrence.
                We randomly assigned 24 patients with Crohn's disease who had undergone ileocolonic resection to receive intravenous infliximab (5 mg/kg), administered within 4 weeks of surgery and continued for 1 year, or placebo. The primary end point was the proportion of patients with endoscopic recurrence at 1 year. Secondary end points were clinical recurrence and remission and histologic recurrence.
                The rate of endoscopic recurrence at 1 year was significantly lower in the infliximab group (1 of 11 patients; 9.1%) compared with the placebo group (11 of 13 patients; 84.6%) (P = .0006). There was a nonsignificant higher proportion of patients in clinical remission in the infliximab group (8 of 10; 80.0%) compared with the placebo group (7 of 13; 53.8%) (P = .38). The histologic recurrence rate at 1 year was significantly lower in the infliximab group (3 of 11 patients; 27.3%) compared with the placebo group (11 of 13 patients; 84.6%) (P = .01). The occurrence of adverse events was similar between the placebo and infliximab groups, and none occurred in the immediate postoperative period.
                Administration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn's disease.
In addition to these randomized controlled trials, a body of lower quality evidence does exist relevant to two other important interventions; the use of supplemental enteral nutrition (Morin 1980; Belli 1988; Israel 1995) and the judicious use of surgical interventions in pre-pubertal children with refractory disease (Alperstein 1985; Lipson 1990; McLain 1990). Newer treatments, such as infliximab, are now becoming more widely used and may offer advantages in promoting growth. These effects are as yet unstudied. This review highlights the need for large, multi centre studies of the different treatment options in paediatric Crohn's disease and the importance of standardised measurements of growth, such as height velocity standard deviation scores and height standard deviation scores as outcome measures.