Improving Successful Introduction after a Negative Food Challenge Test: How to Achieve the Best Result?

Oral food challenges (OFC) confirm or exclude the presence of a food allergy. The outcome can be positive (allergic symptoms), inconclusive, or negative (no symptoms). In the case of a negative OFC, parents and children are advised to introduce the challenged food allergen into their diet. However, previous studies showed difficulties in a successful introduction at home. The aim of this prospective non-randomized intervention study is to evaluate the effect of a new strategy with more guidance regarding the dietary introduction after a negative food challenge test. We compared two cohorts: an historical (retrospective) control group of 157 children, previously described, who did not receive any special advice after a negative OFC, versus a new cohort consisting of 104 children, who were guided according to our new strategy of written introduction schemes, food diaries, and several phone calls. In the historical control group, introduction was successful in 56%, partially successful in 16%, and 28% failed to introduce at home. After introduction of our new strategy, complete introduction was found in 82%, 11% had partially introduced, and only 8% failed to introduce the allergen. In conclusion, comprehensive advice and dietary recommendation after a negative OFC results in an increase in successful home introduction. Therefore, more attention, guidance, and follow-up of children and parents are desirable after a negative OFC.

[Hypoallergenic animals, fact or myth?] / Hypoallergene dieren behoren tot het rijk der fabeldieren.

Allergies to cats and dogs are common. This is a problem, since many people would like to have a pet. This is why so-called 'hypoallergenic' dogs and cats are popular. In this article, we show that the existence of these 'hypoallergenic' animals is actually a myth and that these animals are not a good option for people who are allergic to those pets. We also especially describe the negative consequences for the wellbeing of cats and dogs because of their specific external characteristics and the way in which they are bred.

Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial.

OBJECTIVE: The long-term efficacy and safety of polyethylene glycol (PEG) in constipated children are unknown, and a head-to-head comparison of the different PEG formulations is lacking. We aimed to investigate noninferiority of PEG3350 with electrolytes (PEG3350 + E) compared to PEG4000 without electrolytes (PEG4000). METHODS: In this double-blind trial, children aged 0.5 to 16 years with constipation, defined as a defecation frequency of <3 times per week, were randomized to receive either PEG3350 + E or PEG4000. Primary outcomes were change in total sum score (TSS) at week 52 compared to baseline, and dose range determination. TSS was the sum of the severity of 5 constipation symptoms rated on a 4-point scale (0-3). Noninferiority margin was a difference in TSS of ≤1.5 based on a 95%-confidence interval [CI]. Treatment success was defined as a defecation frequency of ≥3 per week with <1 episode of fecal incontinence. RESULTS: Ninety-seven subjects were included, of whom 82 completed the study. Mean reduction in TSS was -3.81 (95% CI: -4.96 to -2.65) and -3.74 (95%CI: -5.08 to -2.40), for PEG3350 + E and PEG4000, respectively. Noninferiority criteria were not met (maximum difference between groups: -1.81 to 1.68). Daily sachet use was: 0 to 2 years: 0.4 to 2.3 and 0.9 to 2.1; 2 to 4 years: 0.1 to 3.5 and 1.2 to 3.2; 4 to 8 years: 1.1 to 2.8 and 0.7 to 3.8; 8 to 16 years 0.6 to 3.7 and 1.0 to 3.7, in PEG3350 + E and PEG4000, respectively. Treatment success after 52 weeks was achieved in 50% and 45% of children, respectively (P = 0.69). Rates of adverse events were similar between groups, and no drug-related serious adverse events occurred. CONCLUSIONS: Noninferiority regarding long-term constipation-related symptoms of PEG3350 + E compared to PEG4000 was not demonstrated. However, analysis of secondary outcomes suggests similar efficacy and safety of these agents.

Interobserver variability in the interpretation of colon manometry studies in children.

OBJECTIVES: The aim of the present study was to evaluate the variability in interpretation of colon manometry (CM) in children. METHODS: Fifty-seven colon motility studies were independently reviewed by 5 observers. Each observer was required to report on the colonic motility during fasting, after administration of a meal, and after bisacodyl stimulation. They were also asked to comment whether CM study was normal or abnormal and whether in their opinion the postprandial recording provided clinically useful information. RESULTS: The median (range) agreement regarding the presence of high-amplitude propagating contractions (HAPC) was 83% (80%-92%). The interpretation of gastrocolonic response produced the most inconsistent results with median (range) agreemnet of 64% (53%-95%). The postprandial period was reported to be useful in only 3% to 24% of the studies. The median (range) agreement regarding the overall interpretation of the study being either normal or abnormal was 87% (83%-90%). CONCLUSIONS: The most easily recognizable contraction pattern during CM is the high-amplitude propagating contractions. Visual interpretation of the gastrocolonic response produces the most inconsistent results and maximum variability. Abbreviated CM studies without the postprandial period or routine calculation of the motility index to evaluate gastrocolonic response can help make colon manometries more objective and reliable.

Constipation and colonic transit times in children with morbid obesity.

OBJECTIVES: The aim of the study was to determine the frequency of functional constipation according to the Rome III criteria in children with morbid obesity and to evaluate by measuring colonic transit times (CTTs) whether decreased colonic motility is present in these children. PATIENTS AND METHODS: Ninety-one children with morbid obesity ages 8 to 18 years, entering a prospective, randomized controlled study evaluating the effect of an outpatient versus inpatient treatment program of obesity, participated. All of the children filled out a standardized questionnaire regarding their bowel habits, and CTTs were measured using radioopaque markers. Food diaries were also recorded to evaluate their diet. RESULTS: A total of 19 children (21%) had functional constipation according to the Rome III criteria, whereas 1 child had functional nonretentive fecal incontinence. Total CTT exceeded 62 hours in only 10.5% of the children with constipation, and among them, 2 had a total CTT of >100 hours. In the nonconstipated group 8.3% had a delayed CTT. Furthermore, no difference was found between the diet of children with or without constipation, specifically not with respect to fiber and fat intake. CONCLUSIONS: Our study confirms a high frequency of functional constipation in children with obesity, using the Rome III criteria. However, abnormal colonic motility, as measured by CTT, was delayed in only a minority of patients. No relation was found between constipation in these children and fiber or fat intake.

How do antegrade enemas work? Colonic motility in response to administration of normal saline solution into the proximal colon.

OBJECTIVE: The aim of the study was to evaluate the colonic motor response to the administration of normal saline into the proximal colon. PATIENTS AND METHODS: Pediatric patients undergoing colonic manometry received a saline infusion (10-20 mL/kg) in 10 minutes through the central lumen of a catheter placed into the proximal colon. We compared the number of high-amplitude propagated contractions (HAPCs), motility index, frequency and propagation of other phasic contractions in the 20 minutes before and after normal saline infusion, meal ingestion, and bisacodyl administration. RESULTS: Thirteen patients, mean age 9.4 ± 5.8 years, received the saline infusion (3 in the cecum, 8 in the hepatic flexure, and 2 in the transverse colon). In the first 20 minutes after saline infusion, the number of contractions (P = 0.005), distance of propagation of contractions (P = 0.007), frequency of contractions (P = 0.009), and motility index (P = 0.003) were significantly higher compared with baseline. Mean amplitude and number of HAPCs were not significantly different from baseline. Motility parameters after saline and after ingestion of a meal did not differ. All of the measured motility variables significantly increased after bisacodyl stimulation. Bisacodyl increased the motility index and HAPCs more than either saline infusion (P = 0.002) or meal intake (P < 0.001). CONCLUSIONS: Infusion of saline into the proximal colon is associated with an increase in colonic motility; however, at the volume and rate used in the present study it does not consistently stimulate HAPCs.

Effect of rectal distention on lower urinary tract function in children.

PURPOSE: We investigated the effect of rectal distention on lower urinary tract function. MATERIALS AND METHODS: Children were assigned to a constipation and lower urinary tract symptoms group or to a lower urinary tract symptoms only group. The definition of constipation was based on pediatric Rome III criteria. Standard urodynamics were done initially and repeated during simultaneous barostat pressure controlled rectal balloon distention and after balloon deflation. We evaluated the effects of rectal balloon inflation and deflation on urodynamic parameters. Colonic transit time measurement, anorectal manometry and the Parenting Rating Scale of child behavior were also used. RESULTS: We studied 7 boys and 13 girls with a median age of 7.5 years who had constipation and lower urinary tract symptoms, and 3 boys and 3 girls with a median age of 7.5 years who had lower urinary tract symptoms only. Urodynamic patterns of response to rectal distention were inhibitory in 6 children and stimulatory in 12, and did not change in 8. In 54% of the cases balloon deflation reversed balloon inflation changes while in 46% balloon inflation changes persisted or progressed. No significant differences were noted in children with vs without constipation and no clinical symptom or diagnostic study predicted the occurrence, direction or degree of bladder responses. CONCLUSIONS: In almost 70% of children with lower urinary tract symptoms rectal distention significantly but unpredictably affected bladder capacity, sensation and overactivity regardless of whether the children had constipation, and independent of clinical features and baseline urodynamic findings. Urodynamics and management protocols for lower urinary tract symptoms that fail to recognize the effects of rectal distention may lead to unpredictable outcomes.

Magnetic resonance imaging of the lumbosacral spine in children with chronic constipation or non-retentive fecal incontinence: a prospective study.

OBJECTIVE: To determine the prevalence of lumbosacral spine (LSS) abnormalities in children with defecation disorders, intractable constipation, or non-retentive fecal incontinence (NRFI) and evaluate whether LSS abnormalities on magnetic resonance imaging (MRI) are clinically detected by neurologic examination. STUDY DESIGN: MRI of the LSS and complete neurologic examination by a pediatric neurologist blinded to the MRI results were performed in patients with intractable defecation disorders. RESULTS: Patients with intractable constipation (n = 130; 76 males; median age, 11 years; range, 6-18 years), and patients with NRFI (n = 28; 18 males; median age, 10 years; range, 7-15 years) participated. One occult spina bifida (OSB) and 3 terminal filum lipomas were found in patients with a normal neurologic examination. One patient had a terminal filum lipoma and neurologic complaints. Gluteal cleft deviation was found in 3 of 4 patients with LSS abnormalities. Neurosurgical treatment was not required in any patient during the 12-week follow-up. CONCLUSIONS: MRI showed LSS abnormalities in 3% of patients with defecation disorders and normal neurologic examination, all of whom reported symptom relief at the 12-week follow-up without neurosurgical intervention. Thus, whether or not LSS abnormalities play a role in defecation disorders remains unclear.

Rectal fecal impaction treatment in childhood constipation: enemas versus high doses oral PEG.

OBJECTIVE: We hypothesized that enemas and polyethylene glycol (PEG) would be equally effective in treating rectal fecal impaction (RFI) but enemas would be less well tolerated and colonic transit time (CTT) would improve during disimpaction. METHODS: Children (4-16 years) with functional constipation and RFI participated. One week before disimpaction, a rectal examination was performed, symptoms of constipation were recorded, and the first CTT measurement was started. If RFI was determined, then patients were assigned randomly to receive enemas once daily or PEG (1.5 g/kg per day) for 6 consecutive days. During this period, the second CTT measurement was started and a child's behavior questionnaire was administered. Successful rectal disimpaction, defecation and fecal incontinence frequencies, occurrence of abdominal pain and watery stools, CTTs (before and after disimpaction), and behavior scores were assessed. RESULTS: Ninety-five patients were eligible, of whom 90 participated (male, n = 60; mean age: 7.5 +/- 2.8 years). Forty-six patients received enemas and 44 PEG, with 5 dropouts in each group. Successful disimpaction was achieved with enemas (80%) and PEG (68%; P = .28). Fecal incontinence and watery stools were reported more frequently with PEG (P < .01), but defecation frequency (P = .64), abdominal pain (P = .33), and behavior scores were comparable between groups. CTT normalized equally (P = .85) in the 2 groups. CONCLUSION: Enemas and PEG were equally effective in treating RFI in children. Compared with enemas, PEG caused more fecal incontinence, with comparable behavior scores. The treatments should be considered equally as first-line therapy for RFI.

Health utilization and cost impact of childhood constipation in the United States.

OBJECTIVE: To estimate the total health care utilization and costs for children with constipation in the United States. STUDY DESIGN: We analyzed data from 2 consecutive years (2003 and 2004) of the Medical Expenditure Panel Survey (MEPS), a nationally representative household survey. We identified children who either had been reported as constipated by their parents or had received a prescription for laxatives in a given year. Outcome measures were service utilization and expenditures. RESULTS: The MEPS database included a total of 21 778 children age 0 to 18 years, representing 158 million children nationally. An estimated 1.7 million US children (1.1%) reported constipation in the 2-year period. No differences with respect to age, sex, race, and socioeconomic status were found between the children with constipation and those without constipation. The children with constipation used more health services than children without constipation, resulting in significantly higher costs: $3430/year vs $1099/year. This amounts to an additional cost for children with constipation of $3.9 billion/year. CONCLUSIONS: This study demonstrates that childhood constipation has a significant impact on the use and cost of medical care services. The estimated cost per year is 3 times than that in children without constipation, which likely is an underestimate of the actual burden of childhood constipation.

Tegaserod use in children: a single-center experience.

BACKGROUND: Tegaserod is increasingly prescribed by pediatric gastroenterologists even though there are few published data concerning its use in children. The aim of this study was to describe the authors' experience with tegaserod in children. PATIENTS AND METHODS: Patients treated with tegaserod from 2004 through 2006 were included in this study. Defecation and fecal incontinence frequency and global assessment of relief of symptoms were assessed. RESULTS: Seventy-two patients (44 girls) ranging in age from 1.1 to 18.3 years constitute the patient sample of this report. The median age was 10 years and the median follow-up after initiation of tegaserod treatment was 11.3 months (range 2.3-45.2 months). Indications to prescribe tegaserod were constipation (58%) and a variety of other conditions including functional dyspepsia or inflammatory bowel disease (42%). Defecation frequency increased after tegaserod use (1 vs 7/week, P < 0.001) and presence of fecal incontinence decreased (47% vs 23%, P < 0.001) in the constipation group. Parents rated relief of constipation as moderate or significant in 71% of cases in the constipation group. In the group with other indications to start tegaserod therapy, moderate or significant relief of abdominal pain and bloating was noted in 64% and 68% of patients, respectively. The median dose of tegaserod prescribed was 0.22 mg x kg x day (range 0.05-0.87 mg x kg(-1) x day(-1)). Adverse events were observed in 32% of the patients. The most common side effects were self-limiting diarrhea (20%) and abdominal pain (8%). Only one patient discontinued tegaserod because of side effects; this patient experienced pain at his cecostomy site. CONCLUSIONS: Tegaserod seems to relieve a variety of functional gastrointestinal symptoms in children. Further randomized controlled studies are needed to support the specific pediatric target of prescribing tegaserod.

The role of a probiotics mixture in the treatment of childhood constipation: a pilot study.

BACKGROUND: Inconsistent data exist about the efficacy of probiotics in the treatment of constipation. Several studies in adults with constipation showed positive effects of probiotics on constipation. Inconsistent data exist regarding the effect of a single probiotic strain in constipated children. The aim of this pilot study was to determine the effect of a mixture of probiotics containing bifidobacteria and lactobacilli in the treatment of childhood constipation. METHODS: Children aged 4-16 years with constipation as defined by the Rome III criteria were eligible for the study. During a 4 week period, children received a daily mix of 4 x 109 colony forming units of a probiotic mixture (Ecologic(R)Relief) containing Bifidobacteria (B.) bifidum, B. infantis, B. longum, Lactobacilli (L.) casei, L. plantarum and L. rhamnosus. Primary outcome measures were frequency of bowel movements (BMs) per week and stool consistency. Secondary outcome measures were number of faecal incontinence episodes per week, abdominal pain and side effects. RESULTS: Twenty children, 50% male, median age 8 (range 4-16) were included. The frequency of BMs per week increased from 2.0 (1.0-5.0) to 4.2 (0.0-16.0) in week 2 (p = 0.10) and 3.8 (2.1-7.0) in week 4 (p = 0.13). In 12 children presenting with <3 BMs/week, BMs per week increased significantly from 1.0 (0.0-2.0) to 3.0 (0.0-7.0) in week 2 (p = 0.01) and 3.0 (0.0-10.0) in week 4 (p = 0.01). The stool consistency was reported as hard in 7 children at baseline, in 4 children at week 2 (p = 0.23) and in 6 children after 4 weeks of treatment (p = 1.00). A significant decrease in number of faecal incontinence episodes per week was found in the entire group: 4.0 (0.0-35.0) to 1.5 (0.0-14.0) in week 2 (p = 0.01) and 0.3 (0.0-7.0) in week 4 (p = 0.001). The presence of abdominal pain decreased significantly from 45% to 25% in week 2 (p = 0.04) and 20% at week 4 (p = 0.006). No side effects were reported. CONCLUSION: This pilot study shows that a mixture of probiotics, has positive effects on symptoms of constipation. To confirm these findings, a large randomised placebo controlled trial is required.

Novel and alternative therapies for childhood constipation.

Constipation is a worldwide problem that affects many children. Treatment of constipation is largely based on clinical experience rather than on evidence-based controlled clinical trials. Stool softeners and cathartic agents in combination with behavioral interventions constitute the programs most commonly used to facilitate painless and frequent defecation. Long-term treatment is needed for most patients, and approximately 30% of children beyond puberty continue to struggle with symptoms of constipation, such as infrequent, painful evacuation of stools and fecal incontinence. Not surprisingly, chronicity of these bowel complaints may cause significant interference with the child's emotional growth and development. Development of new therapeutic strategies is necessary in order to treat these challenging patients more effectively. This review provides an overview of novel and alternative therapies, such as new drugs, surgery, and probiotics, that are being proposed for the treatment of childhood chronic constipation.

Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality.

CONTEXT: Adequate adrenal function is pivotal to survive meningococcal sepsis. OBJECTIVES: The objective of the study was to evaluate adrenocortical function in meningococcal disease. DESIGN: This was an observational cohort study. SETTING: The study was conducted at a university-affiliated pediatric intensive care unit. PATIENTS: Sixty children with meningococcal sepsis or septic shock participated in the study. MAIN OUTCOME MEASURES: The differences in adrenal function between nonsurvivors (n = 8), shock survivors (n = 43), and sepsis survivors (n = 9) on pediatric intensive care unit admission were measured. RESULTS: Nonsurvivors had significantly lower median cortisol to ACTH ratio than shock survivors and sepsis survivors. Because cortisol binding globulin and albumin levels did not significantly differ among the groups, bioavailable cortisol levels were also significantly lower in nonsurvivors than sepsis survivors. Nonsurvivors had significantly lower cortisol to 11-deoxycortisol ratios but not lower 11-deoxycortisol to 17-hydroxyprogesterone ratios than survivors. Using multiple regression analysis, decreased cortisol to ACTH ratio was significantly related to higher IL-6 levels and intubation with etomidate (one single bolus), whereas decreased cortisol to 11-deoxycortisol ratio was significantly related only to intubation with etomidate. Aldosterone levels tended to be higher in nonsurvivors than shock survivors, whereas plasma renin activity did not significantly differ. CONCLUSIONS: Our study shows that the most severely ill children with septic shock had signs of adrenal insufficiency. Bioavailable cortisol levels were not more informative on adrenal function than total cortisol levels. Besides disease severity, one single bolus of etomidate during intubation was related to decreased adrenal function and 11beta-hydroxylase activity. Decreased adrenal function was not related to decreased 21-hydroxylase activity. Based on our results, it seems of vital importance to take considerable caution using etomidate and consider combining its administration with glucocorticoids during intubation of children with septic shock.

What does the measurement of whole-body fatty acid rate of appearance in plasma by using a fatty acid tracer really mean?

We evaluated the validity of using a single fatty acid tracer to assess total plasma long-chain free fatty acid (FFA) kinetics and the relationship between the rate of appearance (R(a)) of fatty acids in plasma and the fatty acid composition of adipose tissue triglyceride (TG). A mixture of [(13)C]-labeled myristate, palmitate, stearate, oleate, and linoleate was infused in healthy men during basal conditions and during conditions that stimulate (epinephrine infusion) and inhibit (insulin infusion) lipolysis of adipose tissue TGs. Calculated total FFA, R(a) based on palmitate, oleate, or linoleate tracers, was within 15% of the measured sum of the individual fatty acid R(a) under all conditions, whereas stearate and myristate tracers consistently underestimated and overestimated total FFA R(a), respectively. The fatty acid R(a) profile closely matched the fatty acid profile of subcutaneous adipose tissue TGs during epinephrine infusion, but not during basal conditions and insulin infusion. Our data support the common practice of using labeled palmitate or oleate as fatty acid tracers for assessing total plasma FFA kinetics and suggest that a source of lipids other than adipose tissue TG release fatty acids into the systemic circulation.