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.

Interventions for growth failure in childhood Crohn's disease.

BACKGROUND: Crohn's disease in childhood is a chronic relapsing condition. Fifteen to forty per cent of children with Crohn's disease have growth retardation (Griffiths 1993a). Some treatment modalities including corticosteroids have been implicated in growth failure but it is thought mainly to be secondary to uncontrolled disease activity (Motil 1993; Markowitz 1993). Growth is fundamental to the practice of pediatrics, so by taking growth as the primary outcome measure we address issues important to both patients, their families and pediatricians. OBJECTIVES: To evaluate the effectiveness of the different modalities available for the treatment of childhood Crohn's disease with regard to the reversal of growth failure and the promotion of normal growth. SEARCH STRATEGY: Searches were made of the following databases using the Collaborative Review Group Search Strategy: EMBASE (1984-2004), MEDLINE (1966-2004), The Cochrane Central Register of Controlled Trials, The Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register and the Science Citation Index. Abstracts from the major gastrointestinal research meetings and references from published articles were also reviewed. SELECTION CRITERIA: Randomized controlled trials pertaining to children less than 18 years of age with Crohn's disease were selected. Those with growth as an outcome measure were included in the review. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of the methodological quality of each trial was independently reviewed by two reviewers. Only one good quality randomized controlled trial was included in the review and therefore no statistical analysis was possible. MAIN RESULTS: Three randomized controlled trials were identified. One was of good methodological quality (Markowitz 2000). This study looked at the use of 6-mercaptopurine (6-MP) as a steroid sparing agent. No difference in linear growth was observed between the intervention and placebo groups, although the total steroid dose received over the 18 month follow up period was reduced in the group receiving 6-MP. The two remaining randomized controlled trials (Sanderson 1987; Thomas 1993a) consider the use of enteral feeding versus corticosteroids for induction of remission, with height velocity standard deviation score at 6 months as an outcome measure. Although of less rigorous methodological quality, the results of these studies are discussed in detail in the review. In both studies height velocity standard deviation scores were significantly increased in the enteral feeding group compared with the corticosteroid group. AUTHORS' CONCLUSIONS: 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.

Inattentional blindness as a function of proximity to the focus of attention.

The effect of the distance between the center of the focus of attention and an unexpected stimulus on detection was examined in two experiments with the use of the inattentional-blindness paradigm [Mack and Rock, 1998 Inattentional Blindness (Cambridge, MA: MIT Press)]. In experiment 1, the closer a stimulus was to the center of attention, the more likely it was to be detected. Experiment 2 replicated this finding and controlled for retinal eccentricity. These results suggest that low-level stimulus characteristics (e.g. location) may play an important role in the detection of unexpected stimuli. The data are consistent with previous research on the spatial aspects of attention demonstrating that the distance to the focus of attention is a critical variable. This study demonstrates that the effect of distance is similar under conditions of inattention. Theories put forward to explain inattentional blindness should include 'early' attentional factors, as well as factors resulting from later stages of processing.

Location and attention.

A discrepancy exists in the literature concerning attention and visual localization accuracy. Prinzmetal, Amiri, Allen, and Edwards (1998), and Tsal and Bareket (1999a) found that localization accuracy increases with attention. Using an inattention paradigm, Rock, Linnett, Grant, and Mack (1992) found no difference between localization accuracy in three attention conditions: inattention, divided attention, and control. Using a similar inattention paradigm, the current study addressed this discrepancy. Subjects were instructed to perform a line judgement task, and attention for an additional location task was manipulated. In Experiment 1, location accuracy was worse in the inattention condition than in either the divided-attention or the control condition. There was no difference between the divided-attention and control conditions. Experiment 2 controlled for the possibility that improved location accuracy in the divided and control conditions was due to the expectation of performing a location response, rather than the manipulation of attention. Our results are in agreement with previous findings (Prinzmetal et al., 1998; Tsal & Bareket, 1999a) and suggest that the apparent discrepancy is due to coarse coding of the location responses in the study by Rock et al. (1992).