-
1.
Effect of food on the pharmacokinetics of YH4808, a potassium-competitive acid blocker, after single- and multiple-oral dosing in healthy subjects.
Kim, E, Kim, A, Yi, S, Kim, YK, Jang, SB, Byun, HM, Yoon, SH, Cho, JY, Jang, IJ, Yu, KS, et al
European journal of clinical pharmacology. 2018;(10):1261-1272
Abstract
PURPOSE YH4808 is a potassium-competitive acid blocker, developed for the treatment of acid-related disorders. Two clinical studies in healthy male subjects were conducted to evaluate the effect of food on the pharmacokinetics of YH4808. METHODS The first study, a randomized, three-treatment, three-period, crossover study, compared pharmacokinetics of YH4808 (300 mg) after a single dose at fed state with a standard or a high-fat meal to those at fasted state. The second study, a randomized, two-treatment, two-period, crossover study, investigated pharmacokinetics at fasted or fed state with a standard meal after twice daily dose of YH4808 (100 mg) for 7 days. Bloods for pharmacokinetic evaluation were sampled up to 48 h post-dose and 24 h post-dose at steady state, respectively. The pharmacokinetic parameters were estimated by non-compartmental method. RESULTS After single dosing, the geometric means of maximum plasma concentration increased by 1.2 and 2.1 times in the fed states with a standard meal and a high-fat meal, respectively, of that in fasted state. Corresponding values of area under the plasma concentration-time curve (AUC) from time 0 to the last measurable time point increased by 1.8 and 2.8 times, respectively. After multiple dosing, the geometric mean for 24-h AUC at steady state slightly increased in fed state by 1.1 times of that in fasted state. CONCLUSIONS As fat content of the food increased, the systemic exposure of YH4808 after single dosing increased. However, systemic exposures at steady state after multiple dosing between fasted and fed states were similar. TRIAL REGISTRATION ClinicalTrials.gov registry no.: NCT01520012.
-
2.
Toxicity of long-term use of proton pump inhibitors in children.
De Bruyne, P, Ito, S
Archives of disease in childhood. 2018;(1):78-82
Abstract
Proton pump inhibitor (PPI) use is becoming increasingly common. Although the toxicity profiles of PPIs are not well understood particularly in children, PPIs have been associated with increased risks of gastrointestinal and respiratory tract infection, vitamin B12 deficiency, hypomagnesaemia, bone fractures, and rebound hyperacidity after discontinuation. Prescribers should take into account that PPI uses pose toxicity risks, which remain to be fully characterised in infants and children.
-
3.
Thickened infant formula: What to know.
Salvatore, S, Savino, F, Singendonk, M, Tabbers, M, Benninga, MA, Staiano, A, Vandenplas, Y
Nutrition (Burbank, Los Angeles County, Calif.). 2018;:51-56
Abstract
OBJECTIVES This study aimed to provide an overview of the characteristics of thickened formulas to aid health care providers manage infants with regurgitations. METHODS The indications, properties, and efficacy of different thickening agents and thickened formulas on regurgitation and gastroesophageal reflux in infants were reviewed. PubMed and the Cochrane database were searched up to December 2016. RESULTS Based on the literature review, thickened formulas reduce regurgitation, may improve reflux-associated symptoms, and increase weight gain. However, clinical efficacy is related to the characteristics of the formula and of the infant. Commercial thickened formulas are preferred over the supplementation of standard formulas with thickener because of the better viscosity, digestibility, and nutritional balance. Rice and corn starch, carob bean gum, and soy bean polysaccharides are available as thickening agents. Hydrolyzed formulas have recently shown promising additional benefit. CONCLUSIONS Thickened formulas reduce the frequency and severity of regurgitation and are indicated in formula-fed infants with persisting symptoms despite reassurance and appropriate feeding volume intake.
-
4.
Vonoprazan: A Novel and Potent Alternative in the Treatment of Acid-Related Diseases.
Yang, X, Li, Y, Sun, Y, Zhang, M, Guo, C, Mirza, IA, Li, YQ
Digestive diseases and sciences. 2018;(2):302-311
Abstract
Although proton pump inhibitors (PPIs) have been used widely, acid-related diseases are still associated with a huge burden on the health care system. Recently, the efficacy and safety of a new acid suppressant named vonoprazan in the treatment of acid-related diseases have been evaluated by a series of studies. As a novel potassium-competitive acid blocker, vonoprazan may provide reversible acid suppression by preventing K+ from binding to gastric H+/K+-ATPase. It has been clinically used for the short-term treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease and Helicobacter pylori (H. pylori) infection in Japan. The healing rate of GERD and gastric ulcers by vonoprazan is more than 95 and 90%, respectively; also, it is effective in curing PPI-resistant GERD. It increases H. pylori eradication rate to more than 88% as part of both first-line and second-line therapy. It is also effective in the eradication of clarithromycin-resistant H. pylori strains. All of these short-term studies show vonoprazan is safe and well-tolerated. As a safe and effective acid inhibitor, vonoprazan might be a novel alternative in the treatment of acid-related diseases.
-
5.
The Epidemiology of Esophageal Adenocarcinoma.
Coleman, HG, Xie, SH, Lagergren, J
Gastroenterology. 2018;(2):390-405
Abstract
The incidence of esophageal adenocarcinoma (EAC) has increased in many Western countries and is higher in men than women. Some risk factors for EAC have been identified-mainly gastroesophageal reflux disease, Barrett's esophagus, obesity, and tobacco smoking. It is not clear whether interventions to address these factors can reduce risk of EAC, although some evidence exists for smoking cessation. Although consumption of alcohol is not associated with EAC risk, other exposures, such as physical activity, nutrition, and medication use, require further study. Genetic variants have been associated with risk for EAC, but their overall contribution is low. Studies are needed to investigate associations between risk factors and the molecular subtypes of EAC. The prognosis for patients with EAC has slightly improved, but remains poor-screening and surveillance trials of high-risk individuals are needed.
-
6.
Wireless 24, 48, and 96 Hour or Impedance or Oropharyngeal Prolonged pH Monitoring: Which Test, When, and Why for GERD?
Chae, S, Richter, JE
Current gastroenterology reports. 2018;(11):52
Abstract
PURPOSE OF REVIEW pH monitoring technologies are routinely utilized in practice to further evaluate symptoms of gastro-esophageal reflux disease and laryngopharyngeal reflux (LPR). This is a review of the recent literature of the available pH monitoring technology and creates an algorithm in the diagnostic work up of a patient with GERD or LPR. RECENT FINDINGS The catheter-free wireless pH monitor traditionally collects data for 48 h. Recent studies have found that extending to 96 h can be helpful in patients with conflicting results on the first 2 days of the study. In addition, 96 h can allow for testing both on and off of PPI therapy. The oropharyngeal monitoring device is a newer technology that is designed to aid in the diagnoses of LPR. There are limitations with this technology as there is no universal abnormal cutoff and some studies have suggested a poor correlation between multichannel intraluminal impedance-pH (MII-pH) and the oropharyngeal monitoring device. MII-pH has recently developed two additional parameters, the measurement of three 10-min nighttime periods and the post-reflux swallow-induced peristaltic wave (PSPW) index, both of which may increase accuracy of testing. Each of these technologies can provide unique data regarding acid reflux exposure in the esophagus and oropharynx. The wireless pH monitor performed off of PPI therapy can help to establish or exclude the diagnosis of GERD. For those patients with refractory symptoms on PPI, MII-pH study can be performed while on therapy and provides data regarding the response to treatment. Oropharyngeal pH monitoring is being utilized in some practices to aid in diagnosis of LPR, but the scientific validity is controversial.
-
7.
Efficacy and safety of Amla (Phyllanthus emblica L.) in non-erosive reflux disease: a double-blind, randomized, placebo-controlled clinical trial.
Karkon Varnosfaderani, S, Hashem-Dabaghian, F, Amin, G, Bozorgi, M, Heydarirad, G, Nazem, E, Nasiri Toosi, M, Mosavat, SH
Journal of integrative medicine. 2018;(2):126-131
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal complaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types: erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease (NERD). GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeconomic and therapeutic burdens to both patients and society. OBJECTIVE Due to the failure of the conventional treatments for GERD and to the traditional use of Amla (Phyllanthus emblica L.), in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD (heartburn, regurgitation and epigastralgia) for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription. MAIN OUTCOME MEASURES The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire. RESULTS Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention (P < 0.001). Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgitation severity and heartburn severity during the study period, compared with the placebo group (P < 0.001). CONCLUSION This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD. TRIAL REGISTRATION Iranian Registry of Clinical Trials IRCT2016061428469N1.
-
8.
Indications for total esophagogastric dissociation in children with gastroesophageal reflux disease.
Tanaka, Y, Tainaka, T, Uchida, H
Surgery today. 2018;(11):971-977
Abstract
Total esophagogastric dissociation (TED) is used to treat gastroesophageal reflux (GER) after failed fundoplication in neurologically impaired patients. It is now performed for some otherwise healthy patients with severe GER. In this procedure, the gastrointestinal tract is reconstructed in a non-physiological way with a Roux-en-Y esophagojejunal anastomosis and jejuno-jejunostomy. Although TED eliminates almost all GER, some patients experience late complications. In this review, we investigated the long-term outcomes after TED to determine the best indications. In total, 147 neurologically impaired patients and 28 neurologically normal patients were identified. The total rate of complications requiring re-operation was 17.2% in neurologically impaired patients and 32.1% in normal patients, both higher than the rates associated with fundoplication. Although most authors added pyloroplasty when there was a concern of gastric emptying, this sometimes caused bile reflux. Nutritional and metabolic complications, including dumping syndrome and chronic digestive malabsorption, were also reported to occur after TED. TED is an option for the treatment of neurologically impaired patients with recurrent GER after fundoplication or who are at a high risk of recurrence of GER with fundoplication. However, neurologically normal patients who have the ability to obtain nutrition orally should consider options other than TED, as postoperative complications are frequent.
-
9.
Treatment of PPI-resistant gastro-oesophageal reflux: A systematic review.
Gallusi, G, Pontone, S
Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology. 2018;(2):51-55
Abstract
BACKGROUND AND STUDY AIMS Several studies have demonstrated the superiority of proton-pump inhibitors (PPIs) in resolving erosive gastro-oesophageal reflux disease (GORD). However, this first line of treatment can fail to control symptoms in around 30% of cases, especially in the presence of non-erosive GORD. In situations where the first line of treatment fails, there is a lack of concordance regarding the best strategy to apply. This study presents a systematic review of the trials which have tested second-line treatments after PPI failure. METHODS The study was conducted according to the PRISMA statement. The systematic review included medical trials written in English which were published between 2000 and 2016 and were retrieved from PubMed and Scopus using the keywords 'PPI-resistant gastro-oesophageal reflux', 'alginate AND gastro-oesophageal reflux', 'hyaluronic acid AND gastro-oesophageal reflux', 'prokinetics AND gastro-oesophageal reflux', 'sucralfate AND gastro-oesophageal reflux' and 'baclofen AND gastro-oesophageal reflux'. RESULTS Ten randomised and non-randomised studies were included, which included 1515 patients of both sexes (mean age = 49.19 years, age range = 18-85, males = 700; 46.2%). CONCLUSIONS A personalised choice of the best treatment for PPI-resistant GORD should be based on the results of an upper endoscopy and pH/MII monitoring. For patients in situations where the first line of treatment fails, we encourage the execution of trials for testing double doses of PPIs against alternative medicaments.
-
10.
Primary laparoscopic gastrojejunostomy tubes as a feeding modality in the pediatric population.
Onwubiko, C, Weil, BR, Bairdain, S, Hall, AM, Perkins, JM, Thangarajah, H, McSweeney, ME, Smithers, CJ
Journal of pediatric surgery. 2017;(9):1421-1425
Abstract
PURPOSE Outcomes associated with primary laparoscopic gastrojejunal (GJ) tube placement in the pediatric population were evaluated. METHODS A single-institution, retrospective review examined patients undergoing laparoscopic GJ tube placement between June 2011 and December 2014. Outcomes included gastric feeding tolerance, subsequent fundoplication, complications, and mortality. RESULTS Ninety laparoscopic GJ tubes were placed. Median follow-up was 342days (interquartile range [IQR]=141-561days). Median patient age was 5months (IQR=3-11months) and weight was 5.2kg (IQR=4-8.4kg). The most common indications for placement were gastroesophageal reflux (n=85, 94.4%) and/or aspiration (n=40, 44.4%). Most common comorbidities included cardiac (n=34, 37.8%) and respiratory (n=29, 32.2%) diseases. The complication rate was 17.8%, including one case of intestinal perforation. Thirty-four (37.7%) patients transitioned to gastric feeding within 1year; time to conversion was 156days (IQR=117-210days); of those, 18.9% patients transitioned to oral feedings. A fundoplication was later performed in 4 children for persistent reflux. Mortality was 23.3% with no procedural-related deaths. CONCLUSION Primary laparoscopically placed GJ tubes are a reliable means of enteral access for pediatric patients with gastric feeding intolerance. Many of these children are successfully transitioned to gastric and/or oral feedings over time. Further studies are needed to characterize which patients are best served with a GJ tube versus alternatives such as fundoplication. LEVEL OF EVIDENCE III (treatment) TYPE OF STUDY Retrospective.