The duration of effect of infliximab maintenance treatment in paediatric Crohn's disease is limited.

BACKGROUND: Infliximab is effective for induction and maintenance of remission in children with moderately to severely active Crohn's disease (CD). AIM: To evaluate the long-term efficacy of infliximab treatment in paediatric CD. METHODS: In this observational, multicentre study, all paediatric CD patients in The Netherlands treated with infliximab from October 1992 to November 2009 and with minimal follow-up of 3 months since start of infliximab, were studied. RESULTS: One hundred and fifty-two CD patients [81M; median age at start of infliximab 15.0 years (IQR 13.1-16.4)] received a median number of 10.5 infliximab infusions (IQR 6-21). Median follow-up after start of infliximab was 25 months (IQR 13-40). Kaplan-Meier analysis showed that the cumulative probability of losing response to infliximab in patients who initially required repeated infusions was 13%, 40% and 50% after 1, 3 and 5 years, respectively. Seventy-four patients (49%) needed dose adjustments, with a median time to any adjustment of 6 months. CONCLUSIONS: Duration of effect of infliximab is limited as 50% of patients on infliximab maintenance treatment lose their therapeutic response after 5 years. Dose adjustments after start of infliximab are frequently needed to regain therapeutic benefit. These findings emphasise the need for effective, long-term treatment strategies for paediatric CD.

Oral rehydration solution containing a mixture of non-digestible carbohydrates in the treatment of acute diarrhea: a multicenter randomized placebo controlled study on behalf of the ESPGHAN working group on intestinal infections.

OBJECTIVE: A randomized, double-blind, placebo-controlled multicenter study to evaluate efficacy and safety of a mixture of non-digestible carbohydrates (NDC) as an adjunct to oral rehydration therapy in treatment of acute infectious diarrhea in children with mild to moderate dehydration. METHODS: 144 boys aged 1 to 36 months with diarrhea defined as three or more watery stools per day for >1 day but <5 days with mild or moderate dehydration (World Health Organization criteria) were randomly assigned to receive hypotonic oral rehydration solution (ORS) (Na 60 mmol/L, glucose 111 mmol/L) with or without a mixture of NDC (soy polysaccharide 25%, alpha-cellulose 9%, gum arabic 19%, fructooligosaccharides 18.5%, inulin 21.5%, resistant starch 7%). RESULTS: Intention-to-treat analysis did not show significant differences in mean 48 hour stool volume (ESPGHAN-ORS with NDC versus ESPGHAN-ORS, 140 +/- 124 g/kg versus 143 +/- 114 g/kg; P = 0.41). Duration of diarrhea after randomization was similar in both groups (82 +/- 39 hours versus 97 +/- 76 hours, P = 0.24). There were no significant differences in the duration of hospital stay (111 +/- 44 hours versus 126 +/- 78 hours; P = 0.3). Unscheduled intravenous rehydration was similar in both groups (21.4% versus 16.2%, P = 0.42). CONCLUSION: In boys with acute non-cholera diarrhea with mild to moderate dehydration a mixture of non-digestible carbohydrates was ineffective as an adjunct to oral rehydration therapy.

Treatment of children with cystic fibrosis: central, local or both?

UNLABELLED: Owing to a lack of longitudinal studies, the effect of centralization of care on pulmonary function and survival remains unclear. Three different levels of involvement of centralized care in the treatment of paediatric cystic fibrosis patients were compared with regard to longitudinal pulmonary function and nutritional and microbiological status in a 3-y period, and the literature was reviewed on the possible advantages and disadvantages of centralized care. The study included 105 paediatric patients attending the Cystic Fibrosis Centre between January 1997 and January 2001. Twenty-three patients were treated by local paediatricians according to the protocol of the Centre and were seen only once a year at the Centre, for an annual check-up (local care). Forty-one patients were treated at the Centre only (centralized care). The remaining 41 patients were treated in close cooperation between the Centre and local hospitals, with patients visiting the doctors alternately (shared care). The mean annual changes in pulmonary function and body mass index from all patients, as well as a microbiological survey, were reviewed. No significant differences were found between the three groups for annual changes in FEV1, FVC and body mass index, nor did the review of microbial colonization show any significant differences between the groups. Because the groups in this study were relatively small, the results might have been influenced by lack of power. CONCLUSION: In this relatively small group, no differences in pulmonary function, nutritional status or microbiological colonization between the three levels of involvement of centralized care could be found. This could signify that local paediatricians have a special role in the care for patients with cystic fibrosis, in close cooperation with the specialists at the Centre.

Subnormal response of plasma glucose concentration to glucagon despite adequate glycogenolysis: the importance of kinetic measurements.

The plasma glucose concentration response to a glucagon bolus is considered an important diagnostic tool in hypoglycemia of unknown origin. The response of plasma glucose concentration to glucagon can however also be misleading in the differential diagnosis. In a 3-week-old male infant suffering recurrent severe preprandial hypoglycemia and dependent on continuous i.v. glucose infusion, extensive diagnostic screening including a liver biopsy did not lead to a diagnosis. Based on an insufficient glycemic response (twice) to a glucagon bolus, a disorder of glycogenolysis was suspected. Glucose production and gluconeogenesis were measured (glycogenolysis calculated) during diminishing i.v. glucose infusion and after a glucagon bolus. Reducing glucose infusion resulted in a steep increase in glycogenolysis and gluconeogenesis, maintaining total glucose turnover (production plus infusion) constant at +/-9 mg x kg(-1) x min(-1) (+/-60% gluconeogenesis, +/-40% glycogenolysis). Plasma glucose concentration however decreased from 4.9 mmol/l to 3.4 mmol/l. Glucagon increased glucose production by 50% but resulted in only a minor increase in glucose concentration. Conclusion. As glucose concentration depends on the balance between glucose production and utilization (uptake), facilitated glucose uptake rather than impaired glycogenolysis explains the hypoglycemic episodes in this patient. A subnormal response of plasma glucose to glucagon therefore does not necessarily imply a disturbance in glycogenolysis. In cases of hypoglycemia of unknown origin, measurement of glucose kinetics with stable isotopes is indicated.

[Choice of therapy for children with acute gastroenteritis in Norway]. / Terapivalg ved akutt gastroenteritt hos barn i Norge.

BACKGROUND: Acute gastroenteritis is a common and potentially lethal condition in children worldwide. Recommendations for oral rehydration therapy have been issued by paediatric societies both in the USA and Europe. In 1998, The European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) initiated a multicentre study to determine how current practice corresponds with these recommendations. MATERIAL AND METHODS: Paediatricians and general practitioners in 29 European countries responded to a questionnaire regarding oral rehydration therapy of a six months old infant. RESULTS: In Norway, 55 physicians responded. Neither paediatricians nor general practitioners seem to be familiar with all the ESPGHAN recommendations. There is a lack of knowledge about the advantages of fast rehydration and subsequent early reintroduction of a normal diet. Many physicians also wrongly believe that secondary lactose intolerance is a common complication. INTERPRETATION: The recommendations do not seem to be well implemented among health professionals. It is necessary to educate health-care workers at all levels in order to improve treatment of acute diarrhoea in children.

Management of acute gastroenteritis in Europe and the impact of the new recommendations: a multicenter study. The Working Group on acute Diarrhoea of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.

BACKGROUND: The European Society for Paediatric Gasteroenterology, Hepatology and Nutrition (ESPGHAN) issued two sets of recommendations for the treatment of infants with acute gastroenteritis (1992, 1997). The purpose of this multicentre study performed in 29 European countries was to determine how closely current treatment compares with the ESPGHAN recommendations. METHODS: The outline of the study was based on a questionnaire that addressed the management of a 6-month-old infant with acute gastroenteritis complicated by mild to moderate dehydration. National coordinators circulated the questionnaire to randomly selected primary care physicians and to hospital-based paediatricians. RESULTS: A total of 2997 questionnaires were returned, of which 1768 were from Western Europe (WE) and 1229 from Central and Eastern Europe (CEE). Eighty-four percent of responding physicians said they would follow the ESPGHAN recommendation to use oral rehydration solution (ORS) for rehydration, with 66% using an ORS containing 60 mmol/l sodium ORS. Only 16% (WE 15%, CEE 19%) would follow the guidelines and use rapid oral rehydration over 3 to 4 hours. Forty-five percent would rehydrate infants in a 3- to 6-hour period (WE 35%, CEE 60%), and 17% (WE 23%, CEE 9%) would extend the rehydration period to 12 to 24 hours. ESPGHAN recommendation of rapid reintroduction of normal feeding after 3 to 4 hours of oral rehydration would be followed by only 21% of responding physicians, and only 43% (WE 46%, CEE 38%) would start feeding with full-strength formula. However, the guideline about continuation of breast-feeding is widely followed (total 77%; WE 78%, CEE 75%). Thirty-six percent (WE 45%, CEE 23%) use a lactose-containing formula after successful oral rehydration. Contrary to the ESPGHAN guideline 35% (WE 30%, CEE 42%) would use a lactose-free formula and 19% (WE 12%, CEE 28%) a lactose and cow's milk protein-free formula. Only 37% (WE 30%, CEE 46%) of responding physicians would follow the recommendation to use ORS to replace ongoing losses from watery diarrhoea. CONCLUSIONS: The results of the survey suggest that with the exception of recommending ORS for rehydration and continuation of breast-feeding during diarrhoea, a minority of responding European physicians follow the ESPGHAN guidelines for optimal management of children with acute gastroenteritis.

[Cisapride treatment for children with gastro-esophageal reflux]. / Gebruik van cisapride bij kinderen met gastro-oesofageale reflux.

The prokinetic drug cisapride is widely used for treating gastro-oesophageal reflux in infants and children. As in the Netherlands it is not officially registered for use in these age groups, prescribing doctors have problems obtaining adequate information on proper use and side effects. In the treatment of pediatric gastro-oesophageal reflux with cisapride the major recommendations include not to exceed the maximum dose of 0.2 mg/kg four times daily, to avoid comedication with imidazoles and macrolides and to check the QTc interval in patients with known risk factors for QTc prolongation.

The small intestinal fructose transporters: site of dietary perception and evidence for diurnal and fructose sensitive control elements.

To obtain an insight into the mechanisms responsible for GLUT5 diurnality and fructose responsiveness, rats were gavaged at 9:00 AM or 6:00 PM with 1 g of fructose in the presence or absence of cycloheximide. After 4 h of fructose exposure, GLUT5 mRNA and protein levels increased 2-3.5-fold above the natural diurnal levels of expression. In situ hybridization and immunochemical analysis of GLUT5 mRNA and protein demonstrated that both diurnality and fructose responsiveness was confined to mature enterocytes. The protein synthesis inhibitor, cycloheximide, blunted the diurnal and fructose driven increase in GLUT5 mRNA expression in the morning, but had minimal effect on the pattern of expression in the evening. This differential sensitivity of intestinal GLUT5 mRNA to de novo protein synthesis may reflect the increasing presence of diurnal and fructose sensitive control factors during the day. Following vehicle gavage, Cycloheximide was more effective in reducing GLUT5 protein expression levels in the morning when compared to the evening. These data suggest that the turnover of GLUT5 protein may be diurnally influenced.

[A child with puzzling complaints--does he have a disease?]. / Een kind met onbegrepen klachten--heeft het wel een ziekte?

Two children were presented to the physician with serious, long-lasting and unexplained complaints. The first was a girl aged four years with diarrhoea, vomiting and subfebrile temperature, the other was a boy aged almost 1 year with sudden spells of cyanosis and tachycardia. The mothers were found to falsify and fabricate the illness of their children: Münchausen syndrome by proxy. As a consequence of this behaviour, the children underwent extensive and sometimes invasive diagnostic investigations and treatment for their puzzling illness. A number of alarm signals associated with the condition, the parent and the child may help the physician to recognize and diagnose this syndrome at an early stage. Confrontation of the mother with the incriminating findings must take place under carefully prepared circumstances. The syndrome is related to the mothers' need for medical attention in order to retain a certain psychological balance. The fathers often have a passive role in the family life.