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Oral esomeprazole in Japanese pediatric patients with gastric acid-related disease: Safety, efficacy, and pharmacokinetics.
Shimizu, T, Nakayama, Y, Ishii, E, Ida, S, Satou, T, Tokuhara, D, Arai, K, Nii, M, Rydholm, H, Yajima, T, et al
Pediatrics international : official journal of the Japan Pediatric Society. 2019;(1):87-95
Abstract
BACKGROUND Proton pump inhibitors (PPI) are widely used for the treatment of gastric acid-related disease, but they are not approved for use in children in Japan. To assess the safety, pharmacokinetics, pharmacodynamics, and efficacy (gastrointestinal symptom improvement) of PPI in Japanese pediatric patients with gastric acid-related disease, we conducted an 8 week, open-label, parallel-group, multicenter, phase I/III study of once-daily oral esomeprazole use. METHODS Japanese children, aged 1-14 years with gastric acid-related disease, were stratified by weight and age into five groups (10 patients/group) to receive esomeprazole as granules for suspension (10 mg) or capsules (10 mg or 20 mg) once daily. RESULTS Esomeprazole was absorbed and eliminated rapidly in all groups, with a median time to reach maximum plasma concentration of 1.47-1.75 h, an arithmetic mean terminal elimination half-life of 0.80-1.37 h, and a weight-correlated apparent total body clearance of 0.216-0.343 L/h/kg. Area under the plasma concentration-time curve during a dosage interval and maximum plasma drug concentration were generally higher in groups given a higher dose (20 mg) or with a lower age/weight, but also in patients identified as poor metabolizers on cytochrome P450 2C19 genotype. Most patients who had any upper gastrointestinal symptoms at baseline were asymptomatic at the end of the study. Thirty-three patients (66%) reported ≥1 adverse events, including three patients who reported serious adverse events not judged to be causally related to esomeprazole. CONCLUSIONS Oral esomeprazole, at 10 mg or 20 mg once daily, had a similar safety, efficacy, and pharmacokinetic profile in Japanese pediatric patients to that previously seen in adults and Caucasian children.
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Comparison of tube feeding in stroke patients: Nasogastric tube feeding versus oroesophageal tube feeding-A pilot study.
Park, JW, Park, KD, Kim, TH, Lee, JY, Lim, OK, Lee, JK, Choi, C
Medicine. 2019;(30):e16472
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Abstract
BACKGROUNDS Patients with central nervous system injuries present with dysphagia and may require non-oral feeding methods, like percutaneous endoscopic gastrostomy, nasogastric (NG) tube, or oroesophageal (OE) tube. The prevalence of pneumonia in patients with gastroesophageal reflux (GER) is significantly higher than that in patients without GER. We aimed to determine the most appropriate tube feeding with low risk of GER by comparing the results of 24-hour pH monitoring studies in patients who were administered 2 types of feeding: NG tube and OE tube. METHODS In this pilot study, 6 stroke patients underwent 24-hour esophageal pH monitoring during NG tube feeding and OE tube feeding, sequentially. Parameters collected included acid exposure time, mean esophageal pH, number of reflux episode, time of bolus reflux for both total 24-hour pH study data and postprandial data, and deMeester composite score. RESULTS Total acid reflux time (minutes) decreased more with OE tube feeding than that with NG tube feeding in the total 24-hour pH study. The number of reflux episodes decreased in both total and postprandial data with OE tube feeding versus NG tube feeding (P < .05). There were no significant differences in mean esophageal pH and total time of bolus reflux between the 2 groups. CONCLUSIONS Although we could not definitively conclude that OE tube feeding decreased the severity of GER compared with NG tube feeding, there were significant differences in 4 out of 9 parameters. OE tube can be a substitute for NG tube in patients with dysphagia after stroke leading to GER disease.
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The Influence of Proton Pump Inhibitors on the Fecal Microbiome of Infants with Gastroesophageal Reflux-A Prospective Longitudinal Interventional Study.
Castellani, C, Singer, G, Kashofer, K, Huber-Zeyringer, A, Flucher, C, Kaiser, M, Till, H
Frontiers in cellular and infection microbiology. 2017;:444
Abstract
Proton pump inhibitors (PPIs) are the standard therapy for gastroesophageal reflux disease. In adults, PPI treatment is associated with Clostridium difficile infections (CDI). In contrast to adults the microbiome of infants develops from sterility at birth toward an adult-like profile in the first years of life. The effect of PPIs on this developing microbiome has never been studied. The aim of the present study was to determine the effect of oral PPIs on the fecal microbiome in infants with gastroesophageal reflux disease (GERD). In this prospective longitudinal study 12 infants with proven GERD received oral PPIs for a mean period of 18 weeks (range 8-44). Stool samples were collected before ("before PPI") and 4 weeks after initiation of PPI therapy ("on PPI"). A third sample was obtained 4 weeks after PPI discontinuation ("after PPI"). The fecal microbiome was determined by NGS based 16S rDNA sequencing. This trial was registered with clinicaltrials.gov (NCT02359604). In a comparison of "before PPI" and "on PPI" neither α- nor β-diversity changed significantly. On the genus level, however, the relative abundances showed a decrease of Lactobacillus and Stenotrophomonas and an increase of Haemophilus. After PPI therapy there was a significant increase of α- and β-diversity. Additionally, the relative abundances of the phyla Firmicutes, Bacteroidetes, and Proteobacteria were significantly changed and correlated to patients' age and the introduction of solid foods. PPI treatment has only minor effects on the fecal microbiome. After discontinuation of PPI treatment the fecal microbiome correlated to patients' age and nutrition.
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Vonoprazan treatment improves gastrointestinal symptoms in patients with gastroesophageal reflux disease.
Shinozaki, S, Osawa, H, Hayashi, Y, Sakamoto, H, Miura, Y, Lefor, AK, Yamamoto, H
The Kaohsiung journal of medical sciences. 2017;(12):616-622
Abstract
The effects of vonoprazan, a new potassium-competitive acid blocker, on gastroesophageal reflux disease (GERD) symptom are not fully elucidated. The aim of this study is to determine the effect of vonoprazan on GERD and associated gastrointestinal symptoms. We retrospectively reviewed 88 Helicobacter pylori negative patients with GERD treated with vonoprazan 10 mg daily. Symptoms were evaluated using the Izumo scale, which reflects quality of life related to various abdominal symptoms. The rates of improvement and resolution of GERD symptoms were 86% (76/88) and 57% (50/88), respectively. Improvement and resolution in patients with erosive esophagitis was higher than in those with non-erosive reflux disease (91% vs 83%, p = 0.260 and 71% vs 47%, p = 0.025, respectively). We attempted to identify factors which predict the effects of vonoprazan. Multivariate analysis identified advanced age (≥60-year-old) (odds ratio [OR] 7.281, 95% confidence interval [CI] 2.056-25.776, p = 0.002), obesity (BMI ≥ 24) (OR 3.342, 95%CI 1.124-9.940, p = 0.030) and erosive esophagitis (OR 4.368, 95%CI 1.281-14.895, p = 0.018) as positive predictors of resolution of GERD symptoms. Alcohol use (OR 0.131, 95%CI 0.027-0.632, p = 0.011) and history of H. pylori eradication (OR 0.171, 95%CI 0.041-0.718, p = 0.015) were identified as negative predictors. Vonoprazan also improved epigastric pain (73%), postprandial distress (60%), constipation (58%) and diarrhea (52%) in patients with GERD. In conclusion, vonoprazan 10 mg daily is effective in improving GERD symptoms. Advanced age, obesity, erosive esophagitis, alcohol use and history of H. pylori eradication influence the resolution of GERD symptoms. Treatment with vonoprazan favorably affects gastrointestinal symptoms in patients with GERD.
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Esophageal microbiome in eosinophilic esophagitis.
Harris, JK, Fang, R, Wagner, BD, Choe, HN, Kelly, CJ, Schroeder, S, Moore, W, Stevens, MJ, Yeckes, A, Amsden, K, et al
PloS one. 2015;(5):e0128346
Abstract
OBJECTIVE The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis. DESIGN In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease. RESULTS Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects. CONCLUSIONS Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.
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Mucosal impedance discriminates GERD from non-GERD conditions.
Ates, F, Yuksel, ES, Higginbotham, T, Slaughter, JC, Mabary, J, Kavitt, RT, Garrett, CG, Francis, D, Vaezi, MF
Gastroenterology. 2015;(2):334-43
Abstract
BACKGROUND & AIMS Current diagnostic tests for gastroesophageal reflux disease (GERD) are suboptimal and do not accurately and reliably measure chronicity of reflux. A minimally invasive device has been developed to assess esophageal mucosal impedance (MI) as a marker of chronic reflux. We performed a prospective longitudinal study to investigate MI patterns in patients with GERD and common nonreflux conditions, to assess MI patterns before and after treatment with proton pump inhibitors and to compare the performance of MI and wireless pH tests. METHODS We evaluated MI in 61 patients with erosive esophagitis, 81 with nonerosive but pH-abnormal GERD, 93 without GERD, 18 with achalasia, and 15 with eosinophilic esophagitis. MI was measured at the site of esophagitis and at 2, 5, and 10 cm above the squamocolumnar junction in all participants. MI was measured before and after acid suppressive therapy, and findings were compared with those from wireless pH monitoring. RESULTS MI values were significantly lower in patients with GERD (erosive esophagitis or nonerosive but pH-abnormal GERD) or eosinophilic esophagitis than in patients without GERD or patients with achalasia (P < .001). The pattern of MI in patients with GERD differed from that in patients without GERD or patients with eosinophilic esophagitis; patients with GERD had low MI closer to the squamocolumnar junction, and values increased axially along the esophagus. These patterns normalized with acid suppressive therapy. MI patterns identified patients with esophagitis with higher levels of specificity (95%) and positive predictive values (96%) than wireless pH monitoring (64% and 40%, respectively). CONCLUSIONS Based on a prospective study using a prototype device, measurements of MI detect GERD with higher levels of specificity and positive predictive values than wireless pH monitoring. Clinical Trials.gov, Number: NCT01556919.
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Electrical stimulation therapy of the lower oesophageal sphincter for refractory gastro-oesophageal reflux disease - interim results of an international multicentre trial.
Kappelle, WF, Bredenoord, AJ, Conchillo, JM, Ruurda, JP, Bouvy, ND, van Berge Henegouwen, MI, Chiu, PW, Booth, M, Hani, A, Reddy, DN, et al
Alimentary pharmacology & therapeutics. 2015;(5):614-25
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Abstract
BACKGROUND A previous single-centre study showed that lower oesophageal sphincter electrical stimulation therapy (LES-EST) in gastro-oesophageal reflux disease (GERD) patients improves reflux symptoms and decreases oesophageal acid exposure. AIM: To evaluate safety and efficacy of LES-EST in GERD patients with incomplete response to proton pump inhibitors (PPIs) in a prospective, international, multicentre, open-label study. METHODS GERD patients, partially responsive to PPIs, received LES-EST. GERD health-related quality of life (GERD-HRQL), daily symptom diaries, quality of life scores, oesophageal acid exposure, and LES resting and residual pressure were measured before and after initiation of LES-EST. Stimulation sessions were optimised based on residual symptoms and oesophageal acid exposure. RESULTS Forty-four patients were enrolled and 6-month data from 41 patients are available. Hiatal repair was performed in 16 patients. One device-related, one procedure-related and one unrelated severe adverse event were reported. GERD-HRQL improved from 31.0 (IQR 26.2-36.8) off-PPI and 16.5 (IQR 9.0-22.8) on-PPI to 4 (IQR 1-8) at 3-month and 5 (IQR 3-9) at 6-month follow-up (P < 0.0001 vs. on- and off-PPI). Oesophageal acid exposure (pH < 4.0) improved from 10.0% (IQR 7.5-12.9) to 3.8% (IQR 1.9-12.3) at 3 months (P = 0.0027) and 4.4% (IQR 2.2-7.2) at 6 months (P < 0.0001). CONCLUSIONS These interim results show an acceptable safety record of LES-EST to date, combined with good short-term efficacy in GERD patients who are partially responsive to PPI therapy. A remarkable reduction in regurgitation symptoms, without the risk of intervention-requiring dysphagia may prove to be an advantage compared with other anti-reflux procedures. ClinicalTrials.gov Identifier: NCT01574339.
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Can multichannel intraluminal pH-impedance monitoring be limited to 3 hours? Comparison between ambulatory 24-hour and post-prandial 3-hour recording.
Gourcerol, G, Verin, E, Leroi, AM, Ducrotté, P
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 2014;(8):732-6
Abstract
Esophageal multichannel intraluminal pH-impedance recording (MII) is now a valid technique for determining the acidic, liquid, gas or mixed nature of gastroesophageal reflux episodes. However, some recordings may stop prematurely due to technical reasons or poor patient tolerance of the probe. Therefore, we questioned whether analysis of post-prandial 3-hour recording could predict the results obtained in ambulatory 24-hour recording. Fifty patients with symptoms of gastroesophageal reflux disease were investigated. For each patient, post-prandial 3-hour MII was recorded after a test meal, then followed by ambulatory 21-hour MII. Correlation between the total number of liquid reflux events in the 3-hour and 24-hour recordings was elevated (R=0.71; P<0.001), with better correlation for acid (R=0.80; P<0.001) and weak acid reflux (R=0.56; P<0.001) than non-acid reflux (R=0.44; P<0.01). Sensitivity and specificity of 3-hour recording in detecting elevated liquid reflux over 24 hours (id>75reflux/24 h) were 49% and 100%, respectively, for 8 or less liquid/mixed reflux events per 3 hours, and 78% and 88%, respectively for 15 or more liquid/mixed reflux events per 3 hours. The sensitivity and specificity of symptom association probability (SAP) calculated over 3 hours were 56% and 91%, respectively. In conclusion, we identified relevant indicators on the 3-hour post-prandial recording likely to give accurate prediction of absence or presence of gastroesophageal reflux disease from 24-hour MII recording.
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Effect of lateral positioning on gastroesophageal reflux (GER) and underlying mechanisms in GER disease (GERD) patients and healthy controls.
Loots, C, Smits, M, Omari, T, Bennink, R, Benninga, M, van Wijk, M
Neurogastroenterology and motility. 2013;(3):222-9, e161-2
Abstract
BACKGROUND Posture has been shown to influence the number of transient lower esophageal sphincter relaxation (TLESRs) and gastroesophageal reflux (GER), however, the physiology explaining the influence of right lateral position (RLP), and left lateral position (LLP) is not clear. The aim of this study was to determine the influence of RLP and LLP on TLESRs and GERD after a meal in GER disease (GERD) patients and healthy controls (HC) while monitoring gastric distension and emptying. METHODS Ten GERD patients and 10 HC were studied for 90 min (30 min test meal infusion, 30 min postprandial in either RLP or LLP (randomly assigned) and 30 min in alternate position). The study was repeated on a separate day in reverse position order. TLESRs, GER, and gastric emptying rate were recorded using manometry, multichannel intraluminal impedance, and (13) C-octanoate breath tests. Gastric distension was visualized by five serial gastric volume scintigraphy scans during the first 30 min. KEY RESULTS Gastroesophageal reflux, (GER) disease patients had increased numbers of TLESRs in RLP compared to LLP in the first postprandial hour [5 (4-14) and 4.5 (2-6), respectively, P = 0.046] whereas the number of TLESRs was not different in RLP and LLP [4 (2-4) and 4 (3-6), respectively, P = 0.7] in HC. Numbers of GER increased similar to TLESRs in GERD patients. In GERD patients, gastric emptying reached peak (13)CO(2) excretion faster and proximal gastric distension was more pronounced. CONCLUSIONS & INFERENCES In GERD patients, TLESRs, GER, distension of proximal stomach, and gastric emptying are increased in RLP compared to LLP. This effect is not seen in HC.
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Use of direct, endoscopic-guided measurements of mucosal impedance in diagnosis of gastroesophageal reflux disease.
Saritas Yuksel, E, Higginbotham, T, Slaughter, JC, Mabary, J, Kavitt, RT, Garrett, CG, Vaezi, MF
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2012;(10):1110-6
Abstract
BACKGROUND & AIMS Diagnostic tests for gastroesophageal reflux disease (GERD) are constrained because measurements are made at a single time point, so the long-term effects on the mucosa cannot be determined. We developed a minimally invasive system to assess changes in esophageal mucosal impedance (MI), a marker of reflux. We measured the extent of changes in MI along the esophagus and show that the device to assess MI can be used to diagnose patients with GERD. METHODS A single-channel MI catheter composed of a unique sensor array was designed to easily traverse the working channel of an upper endoscope. We performed a prospective longitudinal study of patients with erosive esophagitis (n = 19), nonerosive but pH-positive GERD (n = 23), and those without GERD (n = 27). MI was measured at the site of esophagitis as well as 2, 5, and 10 cm above the squamocolumnar junction. The MI values were compared among groups, at different levels along the esophageal axis. RESULTS Median MI values were significantly lower at the site of erosive mucosa (811 Ω; range, 621-1272 Ω) than other nonerosive regions (3723 Ω; range, 2421-4671 Ω; P = .001), and were significantly lower at 2 cm above the squamocolumnar junction in patients with GERD (2096 Ω; range, 1415-2808 Ω), compared with those without GERD (3607 Ω; range, 1973-4238 Ω; P = .008). There was a significant and graded increase in MI along the axis of the distal to proximal esophagus in patients with GERD that was not observed in individuals without reflux (P = .004). CONCLUSIONS Measurements of MI along the esophagus can be used to identify patients with GERD. ClinicalTrials.gov, number NCT01194323.