Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity.

BACKGROUND: Children with obesity are more likely to suffer gastroesophageal reflux disease, requiring acid-suppression therapy with proton pump inhibitors (PPIs) and no guidelines regarding dosing. OBJECTIVE: To prospectively evaluate lean-body-weight-based (LBW) dosing of the PPI pantoprazole for children with and without obesity. METHODS: Methods: Sixty-two children (6-17 years) received a one-time oral dose of liquid pantoprazole (1.2 mg kg-1 LBW). Plasma pantoprazole concentrations were measured at 10 time points over 8 h and pharmacokinetic (PK) profiles generated using non-compartmental techniques, in order to compare PK parameters of interest between children with and without obesity, while accounting for CYP2C19 genotype. RESULTS: Adjusted for milligram-per-kilogram total body weight (TBW) pantoprazole received, apparent drug clearance (CL/F) was reduced 50% in children with vs. without obesity (p=0.03). LBW-based dosing compensated for this reduction in CL/F (p = 0.15). CONCLUSION: To achieve comparable systemic PPI exposures for children with and without obesity, we recommend using LBW, rather than TBW-based dosing for pantoprazole.

Examination of competing diagnostic models of functional gastrointestinal disorders related to pain in children.

BACKGROUND: There have been no empirical validations of the Rome III or Rome IV criteria in children. The aim of the current study was to examine whether symptoms naturally occur in a pattern consistent with Rome III and/or Rome IV pediatric criteria for functional dyspepsia (FD) and irritable bowel syndrome (IBS). METHODS: We conducted a retrospective cohort study of 250 children, ages 8-17 years, presenting to an abdominal pain clinic with pain of at least 8 weeks duration. We evaluated patterns of gastrointestinal (GI) and non-gastrointestinal (non-GI) symptoms which had been collected in a standardized fashion as part of routine clinical care. Confirmatory factor analyses were used to compare pre-existing models of symptoms clusters, namely Rome III and Rome IV criteria for IBS and FD in children and adolescents. Factor intercorrelations also were examined to determine whether IBS symptoms and non-GI somatic complaints correlate uniquely with FD symptom clusters. KEY RESULTS: Both models demonstrated good fit with observed data [3-factor: χ2 (101, n=250)110.75, P<.05, TLI=.99, CFI=.99; 4-factor: χ2 (98, n=250)117.54, P<.05, TLI=.96, CFI=.97]. Fit indices and intercorrelations favored the more parsimonious 3-factor solution (3-factor: AIC=4654.91, BIC=4778.17; 4-factor: AIC=4757.16, BIC=4890.97) consistent with pediatric Rome III criteria that conceptualizes FD as a single diagnostic category. FD demonstrated significant overlap with IBS (.42), while non-GI-specific symptoms correlated significantly with FD (.64), but not IBS (.14) symptoms. CONCLUSIONS & INFERENCES: GI symptoms in children presenting for initial evaluation of chronic functional abdominal pain occur in a pattern consistent with Rome III and IV pediatric criteria. Rome III offers a more parsimonious model. The presence of FD symptoms is strongly, and uniquely, associated with non-GI symptoms.

Plasma ghrelin and liquid gastric emptying in children with functional dyspepsia consistent with post-prandial distress syndrome.

BACKGROUND: Adult studies indicate a role for ghrelin in functional dyspepsia (FD) mediated through ghrelin's effect on gastric emptying (GE). This study examines the relationship between ghrelin, liquid GE, and pain in children with FD. METHODS: Thirteen FD patients reporting symptoms consistent with post-prandial distress syndrome (PDS) and 17 healthy controls were enrolled. All participants received a liquid meal containing (13) C-sodium acetate. Pain severity, liquid GE utilizing exhaled (13) CO2 from the sodium acetate breath tests (ABT), plasma acyl ghrelin (AG), and des-acyl ghrelin concentrations were measured at specific intervals over 240 min following ingestion. KEY RESULTS: FD-PDS patients demonstrated lower mean baseline AG (14.8 ± 9.7 vs 27.2 ± 14.0 fmol/mL; p = 0.013), AG Cmax (24.6 ± 8.2 vs 40.5 ± 16.8 fmol/mL; p = 0.007), and AG flux (18.2 ± 7.8 vs 32.7 ± 17.3 fmol/mL; p = 0.015) than controls. The time to reach maximum exhaled (13) CO2 concentration (T max ) was longer in FD patients than controls (47.5 ± 18.5 vs 35.8 ± 11.8 min; p = 0.046). Significant relationships between ghrelin analyte ratios and ABT parameters were largely confined to control participants. CONCLUSIONS & INFERENCES: FD-PDS in children is associated with lower fasting and maximum AG concentrations, and dampened AG flux. These data suggest a possible role for altered ghrelin physiology in the pathogenesis of PDS.

Characterization of delayed liquid gastric emptying in children by the (13)C-acetate breath test.

The (13)C-acetate breath test represents a potential alternative to conventional scintigraphy to measure liquid gastric emptying (GE). The purpose of this study was to compare the (13)C-acetate breath test to gastric scintigraphy in children with functional dyspepsia. Simultaneous assessment of GE was performed in 28 children (9-17 years of age) using a liquid test meal that was double labeled with (13)C-acetate and (99 m)Technetium. (13)CO(2) versus time profiles were fit using traditional pharmacokinetic analyses. For each subject, GE half-life [Formula: see text] determined by scintigraphy was plotted against parameters determined from the (13)C-acetate breath test. Linear regression was used to explore the associations between the tests. Complete (13)CO(2) versus time profiles were available for 25 subjects. There was no association between the scintigraphy GE T½ and the(13)CO(2) half-exhalation time. However, significant associations were observed between the gastric half-emptying time as determined by scintigraphy and two of the breath test parameters: the enrichment of (13)CO(2) present in breath samples at 60 min (DOB(60)) (r = -0.52, p = 0.01) and the area under the curve from 0 to 60 min (AUC(0-60 min)) (r = -0.54; p < 0.01). The (13)C-acetate breath test has the potential to serve as a rapid, technically simple and inexpensive means to assess liquid GE in children with functional dyspepsia and possibly serve as a pharmacodynamic surrogate in studies of prokinetic drugs in children.

Autonomic nervous system response to a solid meal and water loading in healthy children: its relation to gastric myoelectrical activity.

The aim of this study was to investigate the correlation of gastric myoelectrical and autonomic activities in healthy children. Simultaneous recordings of electrogastrography (EGG) and electrocardiogram (ECG) were performed in healthy children before and after a solid meal and water loading respectively. The autonomic activity was assessed by spectral analysis of the heart rate variability (HRV). The solid meal resulted in an increase in EGG-dominant frequency (2.92 cpm vs 3.16 cpm, P < 0.05), dominant power (46.9 dB vs 53.7 dB, P < 0.05) and percentage normal slow waves (81.9%vs 89.0%, P < 0.05), while only dominant power increased following water loading. Power in the low-frequency band of HRV (LF) was significantly increased and power in the high-frequency band of HRV (HF) significantly decreased following the solid meal. Postprandial LF was positively and HF negatively correlated with the postprandial increase in EGG-dominant power. Water loading was not associated with any significant changes in HRV parameters. These results suggest that both vagal and sympathetic pathways are involved in modulation of gastric myoelectrical activity.

Chronic stomatitis: an early sign of Crohn's disease.

The authors describe an 11-year-old boy who had persistent oral lesions that clinically mimicked first-episode herpetic stomatitis. A biopsy revealed noncaseating sterile granulomas. Investigation of the small and large bowels revealed that the child had Crohn's disease. The oral lesions responded favorably to topical steroid therapy. The authors also discuss the range of oral lesions in inflammatory bowel disease and the differential diagnoses.

Glucose response to discontinuation of parenteral nutrition in patients less than 3 years of age.

BACKGROUND: The effects of abrupt discontinuation and tapering of total parenteral nutrition (TPN) on glucose concentration were compared in patients < 3 years of age. METHODS: Serial glucose concentrations were measured over 120 minutes after abrupt discontinuation as compared with tapering (decreasing infusion rate by 50% for 1 hour before discontinuation). Serial insulin concentrations were measured after abrupt discontinuation. RESULTS: There was a significantly greater decrease in glucose concentration from baseline at 30 minutes after abrupt discontinuation as compared with tapering. Fifty-five percent (6/11) of the patients developed hypoglycemia (glucose concentration < 40 mg/dL) after abrupt discontinuation. Age, glucose infusion rate, and serum insulin concentrations were not predictive of the development of hypoglycemia. The tapering regimen did not prevent hypoglycemia, which developed in 20% (2/10). CONCLUSION: The high incidence of hypoglycemia after TPN discontinuation in children < 3 years of age requires monitoring of serum glucose concentration when initiating intermittent TPN until tolerance is documented.

C-reactive protein in acute pulmonary exacerbations of patients with cystic fibrosis.

C-reactive protein (CRP) concentrations were evaluated in 9 cystic fibrosis (CF) patients with acute pulmonary exacerbations and 14 patients with acute exacerbations of asthma without any symptoms of an acute infection. CRP concentrations were serially evaluated over the course of therapy in CF patients and compared with pulmonary function tests (PFTs) and clinical scores. CF patients were treated with aerosolized bronchodilators, intravenous fluids, and chest physiotherapy for 48 hours. Intravenous antibiotic therapy was added after 48 hours. Initial CRP concentrations differed significantly between patients with CF and those with asthma. CRP concentrations were elevated in 7 of 9 CF patients versus 3 of 14 asthma patients (P < 0.02). In CF patients, CRP concentrations did not correlate with PFTs (except on day 0) or clinical scores. Frequently PFTs and clinical scores continued to improve after CRP levels had reached their lowest concentrations. CRP concentrations decreased only after the addition of antibiotic therapy.

Grasp biopsy, suction biopsy, and clinical history in the evaluation of esophagitis in infants 0-6 months of age.

Fifty-three infants 0-6 months of age with abnormal 24-h intraesophageal pH monitoring were evaluated by esophageal suction biopsies and endoscopic grasp biopsies. Histologic esophagitis was present in 30% of the infants. Of the infants with esophagitis, 88% were accurately identified by suction biopsy, and 75% were accurately identified by endoscopic grasp biopsy. Suction biopsy alone was not significantly different from combined grasp and suction biopsy, while differences between grasp biopsy and combined biopsy approached significance (p = 0.051). Twelve clinical symptoms and 21 intraesophageal pH monitoring parameters were evaluated for their ability to predict esophagitis, and none were found to be useful. We conclude that endoscopic esophageal biopsy, while more costly, offers no advantage over suction biopsy for the detection of esophagitis in young infants.

Esophagitis and modified Bernstein tests in infants with apparent life-threatening events.

OBJECTIVE: The current study was undertaken to determine the prevalence of abnormal intraesophageal pH monitoring, esophagitis, and oxygen desaturation after experimental esophageal acidification (modified Bernstein test) in patients with apparent life-threatening events (ALTEs). METHODS: Fifty patients admitted to the hospital with ALTEs were evaluated. Patients underwent 24-hour intraesophageal pH monitoring, esophageal suction biopsies, and modified Bernstein tests to document oxygen desaturation during experimental esophageal acidification. RESULTS: Abnormal pH monitoring was present in 82%, esophagitis in 16%, and oxygen desaturation of at least 5% with experimental esophageal acidification in 22% of the patients. Esophagitis was present in only 3 of 11 patients with oxygen desaturation, which was not different from those patients without oxygen desaturation. Clinical history was not predictive of oxygen desaturation during experimental acidification except that patients with a history of an ALTE while awake were more likely to demonstrate oxygen desaturation with acid. CONCLUSION: We conclude that 1) the prevalence of oxygen desaturation with experimental acidification in infants with ALTEs is significant and warrants further evaluation; 2) esophagitis is not a necessary predisposing condition to esophageal acid sensitivity in infants with ALTEs; and 3) ALTEs while awake are frequently associated with a positive modified Bernstein test.

Abbreviated esophageal pH monitoring as an indication for fundoplication in children.

Intraesophageal pH recordings from 40 patients with abnormal studies who underwent fundoplication during a 1-year period were evaluated. Scores were recalculated for the first 12, 16, and 20 hours, respectively. Five of the recordings were for less than 24 hours, but were grossly abnormal and mathematically could not have normalized at 24 hours. The percentage of studies which were normal at 12, 16, and 20 hours were 20%, 15%, and 0%, respectively. One fifth of the patients would have been denied a fundoplication based on 12-hour results. In addition, 75 consecutive pH recordings were evaluated prospectively. Total scores were determined for the first 12, 16, and 20 hours with accuracies of 85%, 93%, and 92%, respectively. The sensitivity of 12-hour monitoring was only 78%. All abbreviated studies had a low rate of false positives; however, any false positives may be significant when used to determine the need for an operation. Abbreviated studies were associated with high false-negative rates (up to 52% for the 12-hour studies) for the calculated mean duration of sleep reflux, a parameter that has been found to be useful in identifying patients with respiratory symptoms secondary to gastroesophageal reflux. The use of abbreviated pH monitoring is discouraged.

Comparison of methods of assessing 24-hour intraesophageal pH recordings in children.

Prolonged intraesophageal pH recording, an important test in the evaluation of children with suspected gastroesophageal reflux (GER) disease, may be performed and evaluated by markedly different methodologies. Twenty-four-hour intraesophageal pH recordings from 67 consecutive infants were evaluated by three scoring methods: early postprandial, late postprandial, and total recording. In addition, the scoring methods were evaluated for their ability to identify 20 infants with clinically defined GER-induced acute life-threatening events (ALTEs). There were significant positive correlations between each pair of scoring systems (early postprandial with late postprandial, early postprandial with total recording, and late postprandial with total recording). However, our data indicate that the three methods identify different groups of patients. The early and late postprandial methods disagreed in designating "normal" versus "abnormal" in approximately 20% of patients. The total recording method was more likely to label patients as normal than either of the other methods; it yielded normal results in approximately one half of patients abnormal by either the early or the late postprandial methods. Patients with GER-induced ALTEs were identified by the early postprandial method in 90% of cases, the late postprandial method in 95% of cases, and the total recording method in only 45% of cases. By applying three different scoring methods to the same 24-h intraesophageal pH recording, we demonstrated less-than-perfect correlation among the methods. Long-term follow-up is needed to determine if these differences are of clinical significance. We feel that effort should be directed toward standardizing the approach to intraesophageal pH monitoring in infants.

Accuracy and reproducibility of 12-h esophageal pH monitoring.

Seventy-five consecutive 24-h intraesophageal pH recordings performed according to the methods of Jolley et al. were evaluated. Total scores and the mean duration of sleep reflux (ZMD) were calculated for the first and the last 12 h, respectively, and compared to each other, as well as to the full 24-h recording. The accuracy of the first and last 12 h in predicting whether the 24-h study was abnormal was 85% and 87%, respectively. The accuracy in predicting whether the ZMD for the 24-h study was abnormal was 73% and 83%, respectively, with an overall 39% false-negative rate. The 12-h study reproducibility was 72% for the total score and 56% for the ZMD. Since the original standards were determined from 18- to 24-h recordings, the test was restandardized based on 12-h recordings from patients with normal 24-h studies. Restandardization did not improve the accuracy or reproducibility. The high false-negative rate for the ZMD and the poor reproducibility cast serious doubt on the utility of 12-h pH recordings, especially in patients with respiratory symptoms.

Nutrition education strategies for work-site wellness: evaluation of a graduate course targeted to work-site wellness majors.

A course incorporating concepts of wellness with nutrition intervention strategies was developed and targeted to graduate students in the health education and wellness program. Pretest/final test evaluations of course participants indicated significant increases in students' nutrition knowledge and confidence in their ability to perform tasks identified in the course objectives. By offering courses for future wellness professionals that emphasize nutrition education strategies and resource selection, the number and quality of nutrition-related programs offered at work sites might increase.

Cholelithiasis. Clinical characteristics in children. Case analysis and literature review.

Thirty-five cases of cholelithiasis diagnosed at a children's hospital over a 7.5-year period are reviewed and compared to 693 cases of pediatric gallstones reported in the literature. Symptomatology and associated medical history are more important in diagnosing cholelithiasis than are laboratory tests. Hemolytic disease is the most common associated condition in our series (46%) as well as in the literature (30%), but the frequency of the various associated conditions varies with age. Isolated gallstone disease does occur, particularly in the young infant. Jaundice is the most common symptom in children less than 1 year of age, being present in greater than 90 percent of symptomatic patients previously reported. Overall, the most common symptom in our series is vomiting (60%). Right upper quadrant pain in the absence of vomiting does not appear to be significant, as this occurred in only one patient (3%) in our series.

Bilirubinuria: an early indicator of gallbladder hydrops associated with Kawasaki disease.

We report four cases of gallbladder hydrops associated with Kawasaki disease diagnosed over a 7.5 year period. Despite varying clinical presentations, all four of these patients had the common finding of bilirubinuria prior to clinical symptoms or at the time of admission. Review of 40 other cases of Kawasaki disease without evidence of hydrops over this time period revealed that urinalysis had been performed in each and bilirubinuria was present in only one case. Bilirubinuria appears to be an early indicator of hydrops in these patients.

Characteristic features of neonatal sepsis due to Haemophilus influenzae.

The number of cases of neonatal Haemophilus influenzae sepsis reported in the literature has increased. The predominant serotypes (80%) involved in neonates appear to be non-type b whereas in older infants type b is responsible for the great majority of cases. It appears that most cases of neonatal H. influenzae sepsis begin before or at the time of delivery, as the disease is strongly associated with early postnatal onset (83%), prematurity (83%), and a variety of maternal complications (44%). The mortality rate is 55.5% overall but 90% among babies born at less than or equal to 30 weeks of gestation.