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Low FODMAPs diet or usual dietary advice for the treatment of refractory gastroesophageal reflux disease: An open-labeled randomized trial.
Rivière, P, Vauquelin, B, Rolland, E, Melchior, C, Roman, S, Bruley des Varannes, S, Mion, F, Gourcerol, G, Sacher-Huvelin, S, Zerbib, F
Neurogastroenterology and motility. 2021;(9):e14181
Abstract
BACKGROUND The low FODMAPs (fermentable oligo-, di-, monosaccharides, and polyols) diet improves lower gastrointestinal symptoms. Patients suffering from proton pump inhibitor (PPI) refractory gastroesophageal reflux disease (GERD) have limited treatment options. We investigated the efficacy of a low FODMAPs diet in patients with PPI refractory GERD. METHODS This multicenter, randomized, open-label study compared the efficacy of a 4-week low FODMAPs diet and usual dietary advice (ie, low-fat diet and head of bed elevation) in patients with symptomatic PPI refractory GERD, defined by a Reflux Disease Questionnaire (RDQ) score >3 and abnormal pH-impedance monitoring on PPIs. The primary endpoint was the percentage of responders (RDQ ≤3) at the end of the diet. RESULTS Thirty-one patients (55% women, median age 45 years) were included, 16 randomized in the low FODMAPs diet group and 15 in the usual dietary advice group. Adherence to the assigned diet was good, with a significant difference in the FODMAPs intake per day between the low FODMAPs diet (2.5 g) and the usual dietary advice group (13 g) (p < 0.001). There was no difference in response rates (RDQ score ≤3) between the low FODMAPs diet (6/16, 37.5%) and usual dietary advice (3/15, 20%) groups (p = 0.43). Total RDQ score and dyspepsia subscore decreased significantly over time in both groups (p = 0.002), with no difference according to the assigned diet group (p = 0.85). CONCLUSION Low FODMAPs diet and usual dietary advice have similar but limited beneficial effects on symptoms in patients with PPI refractory GERD.
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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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Effect of Gastric Acid Suppressants on Response to a Physical Activity Intervention and Major Mobility Disability in Older Adults: Results from the Lifestyle Interventions for Elders (LIFE) Study.
Squires, PJ, Pahor, M, Manini, TM, Brown, JD
Pharmacotherapy. 2019;(8):816-826
Abstract
OBJECTIVES Proton pump inhibitors (PPIs) and histamine2 receptor antagonists (H2 RAs) are associated with pharmacologic effects that may be detrimental to mobility and response to physical activity. Mobility disability and injurious fall outcomes in PPI and H2 RA users were compared with nonusers in this secondary analysis of data from the Lifestyle Interventions for Elders (LIFE) study. METHODS Participants ages 70-89 years were randomized to a physical activity (PA) or successful aging intervention and evaluated by medication use. Confounders included baseline demographic characteristics, physical function, cognitive function, sleep quality, and acid reflux symptoms that were adjusted via propensity score weighting. Outcomes were incident and persistent major mobility disability (MMD and pMMD) and injurious falls. Weighted proportional hazard models evaluated independent and interaction effects of PPIs and H2 RAs. RESULTS No interaction was found between PPIs and H2 RAs and the PA intervention. Drug use associations were significant for H2 RAs (hazard ratio [HR] 1.74 [95% confidence interval [CI] 1.12-2.68]) and PPIs (HR 1.32 [95% CI 1.02-1.70]) compared with nonusers for pMMD. PPIs were associated with increased injurious falls compared with nonusers (HR 1.44 [95% CI 1.06-1.96]). Pooling of data from the H2 RA and PPI exposure groups showed a 26% increase in MMD (HR 1.26 [95% CI 1.07-1.48]), a 44% increase in pMMD (HR 1.44 [95% CI 1.16-1.77]), and a 48% increase in injurious falls (HR 1.48 [95% CI 1.15-1.91]) compared with nonusers. All direct comparisons between PPIs and H2 RAs were nonsignificant. CONCLUSIONS Compared with nonusers, participants using either PPIs or H2 RAs had an increased risk of MMD, pMMD, and injurious falls. It is not known if these effects are related to the individual pharmacology of each medication, reduced acid secretion, or the underlying disease state. Further study is required to determine causality.
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Evaluation of the effect on patient parameters of not monitoring gastric residual volume in intensive care patients on a mechanical ventilator receiving enteral feeding: A randomized clinical trial.
Ozen, N, Tosun, N, Yamanel, L, Altintas, ND, Kilciler, G, Ozen, V
Journal of critical care. 2016;:137-44
Abstract
PURPOSE This study aimed to evaluate the effects of not measuring gastric residual volume (GRV) in intensive care patients on a mechanical ventilator and receiving enteral feeding on the feeding intolerance, gastroesophageal reflux (GER) risk, and nutritional adequacy. METHODS This randomized clinical study was performed in 2 medical intensive care units of 2 university hospitals in Ankara, Turkey. The patients were randomized into 2 groups. In the group with GRV monitoring, GRV was measured 3 times a day, and the GRV threshold was accepted as 250 mL. In addition, 24-hour pH monitoring was used in this group to assess the risk of GER. In the group without GRV monitoring, GRV was not measured. The patients were followed-up for 5 days. RESULTS The feeding targets were reached more quickly in the group without GRV monitoring (n = 26) with no increase in the complication rate (P < .05). No significant relationship was found between GRV and GER in the group with GRV monitoring (n = 25) (P > .05). CONCLUSION The discrepancies in GRV measurement make it unreliable for monitoring feeding intolerance and GER. The use of GRV measurements may therefore be discontinued as part of the standard care protocol in medical intensive care units.
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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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[Value of a new thickened formula in infants with regurgitations].
Chevallier, B, Fournier, V, Logre, B, Beck, L, Ceccato, F, Hui Bon Hoa, G, Lachambre, E, Van Egroo, LD, Sznajder, M
Archives de pediatrie : organe officiel de la Societe francaise de pediatrie. 2009;(4):343-52
Abstract
OBJECTIVES The purpose of this open multicenter study was to evaluate the value of a new starch-thickened formula in infants with regurgitations in ambulatory pediatric practice. POPULATION AND METHODS The study population comprised full-term infants with an age at inclusion of 1-90 days, who were bottle-fed and presented regurgitations. The formula tested was an infant formula-thickened with starch (2g/100mL). The primary endpoint was the frequency of bottles regurgitated, expressed in percentage of meals per day after 15 days of feeding with the preparation studied. Secondary endpoints were the assessment of regurgitations using the Vandenplas' score, as well as the daily increase in weight, height, and cranial circumference, overall and gastrointestinal tolerance, and formula acceptability. RESULTS Sixty-four infants presenting regurgitation were included. The frequency of bottles regurgitated estimated at 80.3% at inclusion significantly decreased at D3, D15, and D30 to 40.1, 40.2 and 37.2% (P<0.0001), respectively. Thirty percent of infants did not present regurgitations at all at D30. Similarly, a significant decrease in the Vandenplas' score was observed from 1.9 at D0 to 0.9 at D30 (P<0.0001). Infant growth was similar to the French and European growth curves. CONCLUSION The results showed rapid and lasting improvement in decreasing the frequency of feeding-bottles regurgitated by 50% from the first 3 days of using this new starch-thickened formula (2g/100mL). These satisfying results encourage the use of the tested formula in cases of infant regurgitation, in line with the European Society of Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommendations.
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Oral pantoprazole in the form of granules or tablets are pharmacodynamically equivalent in suppressing acid output in patients with gastro-oesophageal reflux disease and a history of erosive oesophagitis.
Hogan, D, Pratha, V, Riff, D, Ducker, S, Schwartz, H, Soffer, E, Wang, W, Rath, N, Comer, GM
Alimentary pharmacology & therapeutics. 2007;(2):249-56
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Abstract
AIM: To demonstrate the pharmacodynamic comparability between oral 40 mg pantoprazole delayed-release granules and tablets. METHODS This was a multicentre, randomized, open-label, 2-period, 2-sequence, 9-week crossover study in patients aged 18-65 years with gastro-oesophageal reflux disease and documented erosive oesophagitis. The primary endpoint was a comparison of the inhibition of pentagastrin-stimulated maximum acid output (MAO) at steady state after once daily dosing for 1 week and 23 h after the last dose of pantoprazole granules and tablets. Basal acid output was measured prior to MAO. Standard safety evaluations were performed. The one-sided t-test was used to test the null hypothesis that granules - 1.2 x tablet ≥ 0 against the alternative hypothesis that this difference was <0 for both MAO and basal acid output values. RESULTS Sixty patients completed the study. The mean MAO values were 7.11 +/- 4.98 and 7.29 +/- 4.77 mmol/h, while the mean basal acid output values were 0.74 +/- 0.91 and 0.58 +/- 0.63 mmol/h for the granules and tablets, respectively. The two formulations were shown statistically to be pharmacodynamically equivalent in suppressing MAO (P = 0.006), safe and well tolerated. CONCLUSION Patients with gastro-oesophageal reflux disease who are unable to swallow the tablet may safely be prescribed the pantoprazole sodium granules.
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Pharmacokinetics and tolerability of rabeprazole sodium in subjects aged 12 to 16 years with gastroesophageal reflux disease: an open-label, single- and multiple-dose study.
James, L, Walson, P, Lomax, K, Kao, R, Varughese, S, Reyes, J, ,
Clinical therapeutics. 2007;(9):2082-92
Abstract
OBJECTIVE This study was conducted to characterize the pharmacokinetic and safety profile of rabeprazole sodium tablets in children and adolescents with gastroesophageal reflux disease (GERD). METHODS This was a multicenter, open-label, single- and multiple-dose study in subjects aged 12 to 16 years with GERD. Subjects were stratified by age (12-<14 years and 14-16 years) and were randomized to receive oral rabeprazole 10 or 20 mg/d over 5 or 7 days (to accommodate weekends). The pharmacokinetic parameters calculated included C(max), T(max), AUC, t(1/2), and apparent oral clearance (day 5/7 only). Blood samples for pharmacokinetic determinations were obtained on study days 1, 2, and 5 (or 7) and at discharge on day 6 (or 8). Safety assessments, including adverse events (AEs), were performed at all study visits. RESULTS Twenty-four subjects were enrolled in the study (12 in each dose group); they were predominantly white, had a mean age of 14.2 years, and had a mean body mass index of 24.3 kg/m(2) (the 90th percentile for adolescents of this age in the United States). Mean age and weight did not differ significantly between the 2 dose groups. On day 1, C(max) was significantly greater in the rabeprazole 20-mg group compared with the rabeprazole 10-mg group (P = 0.024); on day 5/7, both AUC and C(max) were significantly greater in the rabeprazole 20-mg group compared with the rabeprazole 10-mg group (P = 0.005 and P = 0.007, respectively). Within-period comparisons for both groups indicated that the AUC and C(max) for rabeprazole and its thioether metabolite did not differ significantly from day 1 to day 5/7. In addition, the T(max) and t(1/2) were relatively unchanged from day 1 to day 5/7 in both dose groups. Treatment-emergent signs and symptoms occurred in 11 subjects, 6 in the 10-mg group and 5 in the 20-mg group. The most frequently reported AEs were headache and nausea (16.7% and 8.3%, respectively). No statistically significant differences were observed between dose groups in terms of the number of subjects with AEs. CONCLUSIONS Rabeprazole 10 and 20 mg were well tolerated in these children and adolescents with GERD. The results of the pharmacokinetic analyses of single and multiple oral doses indicated no apparent accumulation of rabeprazole or its thioether metabolite with the 10-mg dose. There was, however, a suggestion of accumulation with multiple dosing of rabeprazole 20 mg, which requires confirmation in larger studies.
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Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study.
Levy, J, Hayes, C, Kern, J, Harris, J, Flores, A, Hyams, J, Murray, R, Tolia, V
Journal of pediatric gastroenterology and nutrition. 2001;(4):458-63
Abstract
BACKGROUND Major concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to make cisapride available only through a limited access program. Concerns have grown despite the fact that most instances of prolonged QTc and other ventricular arrhythmias occurred while the drug was used concomitantly with contraindicated drugs. This study sought to analyze electrocardiograms (ECGs) from a multicenter pediatric study and to identify abnormalities in QTc interval associated with cisapride use. METHODS Children between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical therapy for at least 6 weeks. In 49 subjects, ECGs obtained before and after randomization to receive 0.2 mg/kg dose three times daily or placebo were reviewed independently and blindly by two pediatric cardiologists. Placebo and active drug groups were compared for QTc and for change in QTc from baseline values after 3 to 8 weeks of treatment. RESULTS Mean QTc among patients taking the drug was 408+/-18 ms. None was higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2+/-20 ms. CONCLUSIONS In our study group of children without underlying cardiac disease or electrolyte imbalance, cisapride was found to have no significant effect on cardiac electrical function compared with placebo. These results are consistent with the drug's record of exceedingly infrequent cardiac events. Because the availability of this prokinetic is threatened, its safety and the safety and efficacy of alternative treatment options (including surgery) should be studied further.
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Effectiveness and costs of omeprazole vs ranitidine for treatment of symptomatic gastroesophageal reflux disease in primary care clinics in West Virginia.
Kaplan-Machlis, B, Spiegler, GE, Zodet, MW, Revicki, DA
Archives of family medicine. 2000;(7):624-30
Abstract
OBJECTIVE To compare clinical, health-related quality of life (HRQL), and medical cost outcomes in patients with symptomatic gastroesophageal reflux disease (GERD) receiving omeprazole sodium or ranitidine hydrochloride treatment. METHODS A multicenter, randomized, open-label, medical effectiveness trial conducted in 5 university-based family medicine clinics. Two hundred sixty-eight patients with GERD were recruited and randomly assigned to omeprazole sodium, 20 mg once daily, or ranitidine hydrochloride, 150 mg twice daily, for up to 6 months. Main outcome assessments included the Gastrointestinal Symptom Rating Scale (GSRS) Reflux score, Psychological General Well-Being Index, and Short-Form-36 Health Survey administered at baseline and 2, 4, 12, and 24 weeks. Medical resource use and cost data were collected. RESULTS More omeprazole-treated patients reported improved heartburn resolution at 2 weeks (49.0% vs 33.3%; P=.007) and 4 weeks (58.6% vs 35.0%; P<.001) compared with ranitidine-treated patients. The GSRS Reflux scores across 3 months showed overall differences between omeprazole (mean, 2.67) and ranitidine (mean, 2.95) groups (P=.04). Mean total 6-month medical costs were $915 lower ($8371 vs $9286; P=.64), and no difference in mean outpatient medical costs ($1198 vs $1158; P=.76) were observed in the omeprazole group compared with the ranitidine group. A post hoc secondary analysis showed that, at 12 and 24 weeks, patients treated with omeprazole for 8 weeks or more reported greater heartburn resolution (ie, 24 [43%] of 56 patients at both intervals) than patients treated with ranitidine for 8 weeks or more (12 [24%] and 13 [26%] of 50 patients, respectively; P=.001). CONCLUSIONS Ranitidine and omeprazole were both effective at improving heartburn symptoms; however, omeprazole provided greater resolution of heartburn symptoms at 2 and 4 weeks. Despite omeprazole's higher acquisition cost, there were no significant differences in total or outpatient costs between groups.