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.

Recurrent abdominal pain in childhood: the functional element.

Many children report chronic abdominal pain that is severe and disruptive to normal lifestyle and schooling. Assessment and management depends on indentifying those with underlying organic disease, such as chronic infection, celiac disease or inflammatory bowel disease, but avoiding unnecessary invasive investigations. In those with a functional gut disorder, the aim of therapy is reassurance, a return to normal activity and symptom control. We address the evidence for the use of investigative and management strategies in situations where recurrent abdominal pain is likely to be a functional disorder. Epidemiological studies of European and American populations show that organic causes are uncommon, and that chronic abdominal pain is a risk factor for functional gut disorders in adulthood. There is a paucity of high quality therapeutic trials, none showing conclusive evidence of benefit. Psychological interventions, such as cognitive behavioral and family therapy are effective, reducing symptoms and improving school attendance. Asian studies suggest gastrointestinal infection, such as giardiasis, are common causes of recurrent abdominal pain, but that functional abdominal pain is also prevalent.

Ninety percent of celiac disease is being missed.

Serological screening of 5470 children age 7.5 years from a cohort of 13,971 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) suggested the prevalence of celiac disease (CD) to be at least 1%. ALSPAC is an anonymous study, and hence seropositive children could not be individually identified or undergo biopsy. Inasmuch as all children within ALSPAC suspected of having CD are referred to just 1 center, we aimed to identify children with biopsy-confirmed CD who were likely to be in this cohort and to estimate the magnitude of discrepancy between serology-positive cases and biopsy-confirmed cases. The results suggest that more than 90% of CD in children goes undiagnosed.

Effects of theophylline, choleragen and loperamide on rabbit ileal fluid and electrolyte transport in vitro.

1 The effects of theophylline and cholera toxin on water and anion movements across rabbit ileum in vitro and the reversal of these effects by the opiate action of loperamide have been investigated. Water movement across the mucosal and serosal surfaces of the tissue was measured continuously by a high resolution method. 2 Theophylline caused an increase in short circuit current and reversed the direction of net C1- movement, due mainly to a decrease in mucosal-serosal flux. It also caused a rapid, but transient, reversal in the direction of fluid movement across the mucosal surface. Fluid outflow across the serosal surface was decreased but not reversed. Cholera toxin caused a slow inhibition of water movement across both mucosal and serosal surfaces. 3 Theophylline increased the exit rate of 77Br across the mucosal surface and decreased the exit rate of 77Br across the serosal surface. Theophylline increased the exit rate of 3H-labelled mannitol across the mucosal surface. 4 Loperamide reversed the effects of theophylline and cholera toxin on water flow across the mucosal and serosal surfaces and on net transepithelial C1- flux; it also increased the rate of 77Br exit across the serosal surface of theophylline-treated tissue. These effects of loperamide could be reversed by naloxone. 5 The hydraulic conductivity, Lp of the serosal surface was measured directly by determining the osmotic flow generated by low concentrations of polyethylene glycol (mol. wt. 20,000 and 90,000). Theophylline reduced the Lp by 57%. Loperamide added to theophylline-treated tissues increased the Lp by 340%. This effect was reversed by naloxone. 6 These results indicate that modulation of intestinal smooth muscle tone affects transepithelial ion and water flows in vitro. The increase in tone induced by secretagogues increases ion and water reflux via wide shunt channels in the mucosa and thereby reduces net absorption. The increased net fluid and electrolyte absorption induced by loperamide results from the opiate-dependent inhibition of acetylcholine release from intrinsic ganglia which reduces smooth muscle tone and thereby enhances the fluid and electrolyte conductance of the submucosal layers.

Studies of water movement across the gut using oral rehydration solutions in a rat perfusion model.

AIM: To measure water influx and efflux, as well as net water, sodium and potassium absorption from a range of oral rehydration solutions (ORS) in which the glucose content had been partially replaced with the amino acid leucine or with food supplements. METHODS: A series of in vivo steady-state perfusion studies in normal rat intestine. The oral rehydration solutions contained 60 or 90 mmol/L of sodium. The reference solution used was the World Health Organization (WHO) formula. RESULTS: There was a significant negative correlation between the oral rehydration solution osmolality and net water absorption (r = -0.722, P < 0.05). The highest net water absorption occurred using comminuted chicken supplemented oral rehydration solution containing 60 mmol/L sodium (P < 0.001). This oral rehydration solution also showed a significant increase in the rate of influx of water (P < 0.05) in comparison with the WHO formula containing 60 mmol/L sodium. CONCLUSION: This work provides further evidence that food-based oral rehydration solutions, including non-vegetable sources, may have a useful role to play in the management of patients with acute diarrhoea.

Effects of immediate modified feeding on infantile gastroenteritis.

BACKGROUND: Standard treatment of infants who are dehydrated as a result of acute gastroenteritis is to administer oral rehydration therapy (ORT). Traditionally, food has been withdrawn for 24-48 h, but there is no conclusive evidence that this is of any real benefit to the patient. Immediate modified feeding, in which an infant on ORT is not starved but administered a limited diet, may have benefits in the treatment of gastroenteritis, especially in children who are nutritionally compromised before they develop the illness. AIM: A pilot study was carried out to investigate the effects of giving infants suffering from acute gastroenteritis a limited modified diet in conjunction with ORT. METHOD: Infants recruited into the study by their general practitioner or by a research doctor in the hospital casualty unit of Bristol Children's Hospital were randomly allocated to receive ORT with or without immediate modified feeding. The duration of diarrhoea, weight change, and incidence of vomiting and lactose intolerance were measured in both treatment groups, and the results were compared. RESULTS: Of the infants studied, 27 received ORT and immediate modified feeding, and 32 ORT alone. The duration of diarrhoea, and incidence of vomiting or lactose intolerance were no greater in the group receiving immediate modified feeding. Patients who received ORT and immediate modified feeding appeared to gain more weight than the infants who were starved for 24-48 h, but this difference was not statistically significant. CONCLUSION: Immediate modified feeding is safe and effective, and may have nutritional advantages over traditional ORT with starvation. A similar but multicentre study using unmodified diet, i.e. child's normal diet, is being carried out by a working group of The European Society of Paediatrics, Gastroenterology and Nutrition (ESPGAN).

The use of omeprazole for resistant oesophagitis in children.

Following failure of conventional therapy for reflux oesophagitis, 15 children were treated with omeprazole 20 mg daily for a period of up to three months initially. Treatment resulted in a marked symptomatic improvement as measured by incidence of pain, vomiting, dysphagia and haematemesis. Four children failed treatment and required fundoplication. No complications from the use of omeprazole were recorded and some children have continued long-term treatment.

Psychosocial determinants of burnout in geriatric nursing.

The purpose of this study was to identify determinants of burnout using an adapted version of Kobasa's theoretical framework, considering work stressors, work support, coping strategies and hardiness. Data were collected through a questionnaire mailed to 1990 randomly selected geriatric nurses. A participation rate of 77.6% was achieved. T-test, variance analysis and multiple regression analysis were conducted. Hierarchical multiple regression analysis indicated that 49% of the variance was explained by the study variables. Hardiness and work stressors were the most important predictors of burnout. The findings are discussed in relation to Kobasa's framework, focusing on resources that reduce negative effects of geriatric work stressors. Implications for nursing practice, management, education and research are proposed.

Newer diarrheal syndromes.

Aetiological diagnosis of protracted diarrhoea remains obscure in as many as 30% of cases despite extensive investigations. A number of newer syndromes have been recognized amongst this "idiopathic group" which includes microvillous inclusion disease, "tufting" enteropathy and epithelial dysplasia, autoimmune enteropathy and "syndromic" immunodeficiency with characteristic facial abnormalities, woolly hair and intractable diarrhea. The molecular basis of some of these syndromes has been reviewed but in only a small series of patients has the functional defect been characterized. If a case is suspected the antenatal history, family history and history of consanguinity should be sought. Extra-intestinal manifestations, presence of gut or other auto-antibodies, together with phenotypic abnormalities should be looked for. Careful light and electron microscopy is done of small bowel biopsies, although microvillous inclusion disease can be usually suspected on PAS staining. Large bowel biopsy may be needed to exclude an unsuspected microscopic colitis. The prognosis of this group of conditions is poor with an overall 50-85% mortality. Although successful gut transplantation has been reported, genetic counselling may be one of the more important aspects of the clinicians' role.

Gastroesophageal reflux in children.

Gastroesophageal reflux (GOR) is a major cause of morbidity and failure to thrive particularly in neurologically impaired children. Clinical manifestations of GOR in children range from regurgitation, food refusal, irritability, failure to thrive, hematemesis, wheezing and aspiration pneumonia, apnoea and apparent life threatening events in infants to clinically silent reflux. Although, no one test is always best to diagnose GOR, 24 hour esophageal pH monitoring remains the 'gold standard' for diagnosis. Barium radiography is useful for the diagnosis of associated anatomical abnormalities and endoscopy enables a histological diagnosis of esophagitis. Therapy for gastroesophageal reflux disease is now well established. Proper positioning of the baby and thickening of feeds is beneficial in uncomplicated GOR. Prokinetic agents like cisapride should be tried if dietary management and antacids are ineffective. Metoclopramide or domperidone may be tried in neurologically impaired children. H2-receptor antagonists are indicated in GOR complicated by esophagitis. Ranitidine is regarded to be more potent. Cimetidine has additional spectrum of adverse effects and sufficient information is not available on famotidine. Omeprazole has been shown to be effective in treating GOR-esophagitis resistant to H2 antagonist therapy even in high risk patients.

Mechanisms of action of loperamide.

The beneficial effect of loperamide in some children with severe protracted diarrhoea which persisted when nil by mouth, made us suspect that loperamide may have an antisecretory action. Using a steady-state perfusion technique in rat jejunum we showed that loperamide inhibits cholera toxin induced secretion of water, sodium and chloride (p less than 0.001). This antisecretory action was blocked by naloxone and not mediated via an effect on tissue cyclic AMP level or adenylate cyclase activity. More recently we have studied the effect of loperamide on secretion of water in the rat jejunum induced by other agents with differing mechanisms of action. The first set of observations suggest that loperamide's antisecretory effect is mediated via opiate receptors either distal to, or separate from the adenylate cyclase/cyclic AMP pathway. Our more recent studies support the notion that loperamide has an effect on specific transport systems rather than non-specific passive diffusional processes.

[Systems for the delivery of health care]. / Les systèmes de prestation des soins.

Re-examining the role of the nurse, the authors remind us of the importance of understanding how our system of health care has evolved, as well as what it holds for the future. Presenting an historical overview of the past 50 years, they discuss concepts related to moving the profession forward and suggest the decade ahead offers key opportunities.

[Validation of a model of psychosocial determinants of occupational health of geriatric nurses]. / Validation d'un modèle de déterminants psychosociaux de la santé au travail de l'infirmière en gériatrie.

The purpose of this study was to verify a model of relationships between psychosocial factors and health for 8066 francophone nurses working in geriatric care in Québec. A random sample of 1990 subjects was drawn and a participation rate of 77.9% and 55% was obtained for the two-time study taken twelve months apart. Based on the theory of Maddi and Kobasa (1984), the model was reproduced for the two-time periods with the aid of structural equations. The analyses showed that three variables exert a direct influence on psychological distress: professional burnout, occupational stressors and hardiness. Also, variables have a direct effect on burnout: listed in order of importance, these are hardiness, occupational stressors, work support, active strategies of coping and employment status. In dealing with the work stressors, the nurses who are hardy make use of active strategies of coping and look for support form their colleagues. The results of the study help to better understand the psychological and social resources that best favor adaptation of working women in highly demanding work environments. The fallout of the study converges towards the quality of life of helping professionals and towards the cost and quality of health and social services.