Taher Omari

Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: A systematic review

INTRODUCTION: Use of proton-pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD) in children has increased enormously. However, effectiveness and safety of PPIs for pediatric GERD are under debate. OBJECTIVES: We performed a systematic review to determine effectiveness and safety of PPIs in children with GERD. METHODS: We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for randomized controlled trials and crossover studies investigating efficacy and safety of PPIs in children aged 0 to 18 years with GERD for reduction in GERD symptoms, gastric pH, histologic aberrations, and reported adverse events. RESULTS: Twelve studies were included with data from children aged 0–17 years. For infants, PPIs were more effective in 1 study (compared with hydrolyzed formula), not effective in 2 studies, and equally effective in 2 studies (compared with placebo) for the reduction of GERD symptoms. For children and adolescents, PPIs were equally effective (compared with alginates, ranitidine, or a different PPI dosage). For gastric acidity, in infants and children PPIs were more effective (compared with placebo, alginates, or ranitidine) in 4 studies. For reducing histologic aberrations, PPIs showed no difference (compared with ranitidine or alginates) in 3 studies. Six studies reported no differences in treatment-related adverse events (compared with placebo or a different PPI dosage). CONCLUSIONS: PPIs are not effective in reducing GERD symptoms in infants. Placebo-controlled trials in older children are lacking. Although PPIs seem to be well tolerated during short-term use, evidence supporting the safety of PPIs is lacking.

Esophageal body and lower esophageal sphincter function in healthy premature infants

BACKGROUND & AIMS Gastroesophageal reflux is a common problem in premature infants. The aim of this study was to use a novel manometric technique to measure esophageal body and lower esophageal sphincter pressures in premature infants. METHODS Micromanometric feeding assemblies (OD, < or = 2 mm) incorporating 4-9 manometric channels were used in 49 studies of 27 premature neonates. Esophageal body motility was recorded at three sites for 20 minutes after feeding. Twenty attempts (one per minute) were made to stimulate swallowing via facial stimulation (Santmyer reflex). In 32 studies lower esophageal sphincter pressures were recorded (sleeve) for 15 minutes before and after feeding. RESULTS Peristaltic motor patterns were less common than non-peristaltic motor patterns (26.6% vs. 73.4%; P < 0.0001) that comprised 31.1% synchronous, 34.6% incomplete, and 6.3% retrograde pressure waves. Reflex swallowing was elicited more frequently in neonates older than 34 weeks postconceptional age than in younger infants (33.4% vs. 20.4%; P < 0.05). Mean lower esophageal sphincter pressure was 20.5 +/- 1.7 mm Hg before and 13.7 +/- 1.3 mm Hg after feeding (P < 0.0005). CONCLUSIONS Premature infants show nonperistaltic esophageal motility that may contribute to poor clearance of refluxed material. In contrast, the lower esophageal sphincter mechanisms seem well developed.

A Method to Objectively Assess Swallow Function in Adults With Suspected Aspiration

BACKGROUND & AIMS Pharyngeal manometry and impedance provide information on swallow function. We developed a new analysis approach for assessment of aspiration risk. METHODS We studied 20 patients (30-95 years old) with suspected aspiration who were referred for videofluoroscopy, along with controls (ages 24-47 years). The pharyngeal phase of liquid bolus swallowing was recorded with manometry and impedance. Data from the first swallow of a bolus and subsequent clearing swallows were analyzed. We scored fluoroscopic evidence of aspiration and investigated a range of computationally derived functional variables. Of these, 4 stood out as having high diagnostic value: peak pressure (PeakP), pressure at nadir impedance (PNadImp), time from nadir impedance to peak pressure (TNadImp-PeakP), and the interval of impedance drop in the distal pharynx (flow interval). RESULTS During 54 liquid, first swallows and 40 clearing swallows, aspiration was observed in 35 (13 patients). Compared to those of controls, patient swallows were characterized by a lower PeakP, higher PNadImp, longer flow interval, and shorter TNadImp-PeakP. A Swallow Risk Index (SRI), designed to identify dysfunctions associated with aspiration, was developed from iterative evaluations of variables. The average first swallow SRI correlated with the average aspiration score (r = 0.846, P < .00001 for Spearman Rank Correlation). An average SRI of 15, when used as a cutoff, predicted aspiration during fluoroscopy for this cohort (κ = 1.0). CONCLUSIONS Pressure-flow variables derived from automated analysis of combined manometric/impedance measurements provide valuable diagnostic information. When combined into an SRI, these measurements are a robust predictor of aspiration.

Effect of omeprazole on acid gastroesophageal reflux and gastric acidity in preterm infants with pathological acid reflux.

Introduction: Proton pump inhibitor (PPI) therapy is increasingly being used to treat premature infants with gastroesophageal reflux disease (GERD); however, the efficacy of PPI on acid production in this population has yet to be assessed in this patient group. The aim of this study was to determine the effect of 0.7 mg/kg/d omeprazole on gastric acidity and acid gastroesophageal reflux in preterm infants with reflux symptoms and pathological acid reflux on 24-h pH probe. Methods: A randomized, double blind, placebo-controlled, crossover design trial of omeprazole therapy was performed in 10 preterm infants (34–40 weeks postmenstrual age). Infants were given omeprazole for 7 d and then placebo for 7 d in randomized order. Twenty-four-hour esophageal and gastric pH monitoring was performed on days 7 and 14 of the trial. Results: Compared to placebo, omeprazole therapy significantly reduced gastric acidity (%time pH <4, 54% vs 14%, P < 0.0005), esophageal acid exposure (%time pH <4, 19% vs 5%, P < 0.01) and number of acid GER episodes (119 vs 60 episodes, P < 0.05). Conclusions: Omeprazole is effective in reducing esophageal acid exposure in premature infants with pathological acid reflux on 24-h pH probe; however, the far more complex issues of safety and efficacy have yet to be addressed.

Role of the multichannel intraluminal impedance technique in infants and children

Recently, multichannel intraluminal impedance (MII) was added to the repertoire of tests available to study esophageal (patho)physiology in children. MII has since been used in 2 major areas. First, it has been used as a diagnostic test for gastroesophageal reflux disease (GERD). The main advantage over traditional pH monitoring is its ability to detect both acid and nonacid gastroesophageal reflux (GER) and to discern between liquid and gas GER. Although feasible with multiple pH sensors, the MII technique routinely detects the proximal extent of a GER episode. When a pH sensor is added to the MII-catheter, important information about the acidity of a GER event can be gathered. The second area in which the role of MII has been investigated is that of esophageal function testing. Manometry classically reveals information about esophageal pressure patterns and sphincter function, but does not inform us about bolus flow. MII not only detects the presence of esophageal flow but also adds information on the direction of flow, duration of bolus presence, completeness of bolus clearance, and composition of a bolus. The combination of MII with manometry enables determination of the relationship between esophageal pressures and flow and, therefore, enhances evaluation of esophageal function in terms of assessment of mechanisms of esophageal volume clearance. In addition, this technique will improve our understanding of (patho)physiological mechanisms in pediatric GERD and other esophageal motility disorders.

Determination of in vivo absorption, metabolism, and transport of drugs by the human intestinal wall and liver with a novel perfusion technique

The contribution of the gastrointestinal tract in comparison with the liver for the low and variable bioavailability of orally administered drugs is still poorly understood. Here we report on a new intestinal perfusion technique for the direct assessment of absorption, metabolism, and transport of drugs by the intestinal wall.

A Novel Method for the Nonradiological Assessment of Ineffective Swallowing

OBJECTIVES:This validation study evaluates a new manometry impedance-based approach for the objective assessment of pharyngeal function relevant to postswallow bolus residue.METHODS:We studied 23 adult and pediatric dysphagic patients who were all referred for a videofluoroscopy, and compared these patients with 10 adult controls. The pharyngeal phase of swallowing of semisolid boluses was recorded with manometry and impedance. Fluoroscopic evidence of postswallow bolus residue was scored. Pharyngeal pressure impedance profiles were analyzed. Computational algorithms measured peak pressure (Peak P), pressure at nadir impedance (PNadImp), time from nadir impedance to PeakP (PNadImp–PeakP), the duration of impedance drop in the distal pharynx (flow interval), upper esophaghageal sphincter (UES) relaxation interval (UES-RI), nadir UES pressure (NadUESP), UES intrabolus pressure (UES-IBP), and UES resistance. A swallow risk index (SRI) was derived by the formula: SRI=(FI × PNadImp)/(PeakP × (TNadImp-PeakP+1)) × 100.RESULTS:In all, 76 patient swallows (35 with residue) and 39 control swallows (12 with residue) were analyzed. Different functional variables were found to be altered in relation to residue. In both controls and patients, flow interval was longer in relation to residue. In controls, but not patients, residue was associated with an increased PNadImp (suggestive of increased pharyngeal IBP). Controls with residue had increased UES-IBP, NadUESP, and UES resistance compared with patients with residue. Residue in patients was related to a prolonged UES-RI. The SRI was elevated in relation to residue in both controls and patients and an average SRI of 9 was optimally predictive of residue (sensitivity 75% and specificity 80%).CONCLUSIONS:We present novel findings in control subjects and dysphagic patients showing that combined manometry and impedance recordings can be objectively analyzed to derive pressure-flow variables that are altered in relation to the bolus residual and can be combined to predict ineffective pharyngeal swallowing.

Addition of pH-Impedance Monitoring to Standard pH Monitoring Increases the Yield of Symptom Association Analysis in Infants and Children with Gastroesophageal Reflux

OBJECTIVE To assess the additional yield of combined multichannel intraluminal pH-impedance (pH-MII) monitoring compared with standard pH monitoring on gastroesophageal reflux (GER) symptom associations in infants and children. STUDY DESIGN In 80 patients, 24-hour ambulatory pH-MII monitoring was performed. Tracings were analyzed with established pH-MII criteria. Symptoms of regurgitation and belching were excluded from analysis, because these were considered to be a direct consequence of GER. Standard GER-symptom correlation indices were calculated with: 1) standard pH monitoring; 2) MII detection of liquid and mixed bolus GER; 3) MII detection of all bolus GER (liquid, mixed, and gas); 4) pH-MII detection of all GER, including pH-only GER. RESULTS Fifty patients (21 children) were included. MII detection of all bolus GER yielded a significantly greater number of patients who were symptom-positive, 36 (72%) compared with 25 (50%) with standard pH-monitoring (P = .04). A positive symptom association was observed in 8 of 10 (80%) patients with pathological esophageal acid exposure and 28 of 40 (70%) patients with negative pH-findings. CONCLUSIONS A high proportion of patients with normal esophageal acid exposure had a positive symptom association on pH-MII monitoring. Including all MII-detected bolus GER and excluding pH-only GER for analysis optimizes the yield of GER-symptom associations in infants and children.

Intraluminal micromanometry: an evaluation of the dynamic performance of micro‐extrusions and sleeve sensors

Conventional manometric techniques are unsuitable for studies in premature infants and small laboratory animals. We have therefore developed silicone rubber 5‐lumen and 10‐lumen micromanometric extrusions with an o.d. 2.0 mm and lumina of 0.35 mm i.d. This study evaluates the suitability of micro‐extrusions for intraluminal perfusion manometry.

Reproducibility and Agreement of Pharyngeal Automated Impedance Manometry With Videofluoroscopy

BACKGROUND & AIMS Automated impedance manometry analysis (AIM) measures swallow function variables that define bolus timing, intrabolus pressure, contractile vigor, and bolus presence; these are combined to derive a swallow risk index (SRI) that is correlated with pharyngeal dysfunction and aspiration. We assessed intra-rater and inter-rater reproducibility of AIM analysis-derived variables; the diagnostic accuracy of AIM-based criteria for detecting aspiration was determined by using expertly scored videofluoroscopy as the standard. METHODS Data on 50 bolus swallows of 10 mL each were randomly selected from a database of swallows that were simultaneously recorded with impedance, manometry, and videofluoroscopy. Data were divided into 5 subgroups of 10 swallows for analysis: 10 dysphagic liquid, 10 dysphagic liquid with aspiration, 10 dysphagic semisolid, 10 control liquid, and 10 control semisolid. Repeat analyses were performed by 10 observers with varying levels of expertise in manometry by using purpose-designed software (AIMplot). Swallow videos were scored by 4 experts by using the penetration-aspiration scale (PAS) score. Reproducibility of calculation of swallow function variables and the SRI and PAS was assessed by using intraclass correlation coefficient (ICC). The majority consensus of expert PAS scores was used to dichotomously define aspiration (consensus PAS >3). Observer analyses were compared by Cohen κ statistical analysis. RESULTS The intra-rater and inter-rater reproducibility of swallow function variables was high (SRI mean intra-rater ICC, 0.97 and mean inter-rater ICC, 0.91). SRI >15-20 was optimal for detecting the presence of aspiration during liquid bolus swallows with an almost perfect agreement with expert scoring of videofluoroscopy (κ > 0.8). CONCLUSIONS AIM analysis has high intra-rater and inter-rater reproducibility, and among observers of varying expertise, SRI predicts the presence of aspiration.