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1.
The pharmacotherapeutic management of gastroesophageal reflux disease (GERD).
Chapelle, N, Ben Ghezala, I, Barkun, A, Bardou, M
Expert opinion on pharmacotherapy. 2021;(2):219-227
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a very common worldwide condition, affecting about 15-20% of the whole population, and representing a major burden for health-care systems. Because of its frequency, health physicians - family doctors as well as specialists - should be aware of the different pharmacotherapeutic approaches in managing GERD, according to disease severity. AREAS COVERED Authors summarize the pharmacological management of GERD in adults, present the different pharmaceutical classes, and review the evidence on efficacy for each treatment according to the most common clinical scenarios: non-erosive gastroesophageal reflux disease (NERD), erosive esophagitis (EE), and proton-pump inhibitor (PPI) refractory GERD. They also provide an overview of treatments under development. EXPERT OPINION To date, PPIs remain the most effective treatment option for both NERD and EE. However, Potassium-Competitive Acid blockers (PCAB) may be considered, with at least similar efficacy in Asian populations. Preliminary data suggest that PCABs could be superior to classic PPIs in patients with severe EE, and may also be of particular interest in the management of PPI-refractory GERD patients. Their definitive role in GERD management, however, still remains to be determined based on properly designed and conducted randomized clinical trials.
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2.
Safety considerations when managing gastro-esophageal reflux disease in infants.
Simon, M, Levy, EI, Vandenplas, Y
Expert opinion on drug safety. 2021;(1):37-49
Abstract
Introduction: Gastro-esophageal reflux disease (GERD) in infants is worldwide diagnosed with increasing frequency, resulting in an increasing number of infants exposed to treatment. In this review, we focus on the safety of therapeutic options. Areas covered: English articles were searched from 1990 until May 2020 in PubMed and Google Scholar. Evidence suggests that non-pharmacological treatment is often effective and safe. Guidelines restrict pharmacological treatment to acid-suppressive medication, which is associated with adverse effects, often related to gastro-intestinal dysbiosis and consequences of the latter. Aluminum-free alginates have some efficacy and are not associated with relevant adverse effects. Especially in infants, GERD is often nonacid related. Prokinetics are not recommended because of lack of efficacy and numerous adverse effects. Expert opinion: Pediatric trials are underpowered regarding adverse effects. The number of infants exposed to anti-secretory agents is increasing worldwide, often without indication. Informing healthcare providers about adverse effects of acid-secretory medication may contribute to a more rational use. Acid inhibiting agents such as alginates are a drug class associated with limited efficacy and devoid of serious adverse effects. Regarding prokinetics, the risk of adverse effects outweighs the benefit. Reassurance of parents and nutritional management of GERD in infants is effective and safe.
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3.
Extraesophageal syndrome of gastroesophageal reflux: relationships with lung disease and transplantation outcome.
Chan, WW, Ahuja, N, Fisichella, PM, Gavini, S, Rangan, V, Vela, MF
Annals of the New York Academy of Sciences. 2020;(1):95-105
Abstract
Gastroesophageal reflux disease (GERD) is prevalent and may be associated with both esophageal and extraesophageal syndromes, which include various pulmonary conditions. GERD may lead to pulmonary complications through the "reflux" (aspiration) or "reflex" (refluxate-triggered, vagally mediated airway spasm) mechanisms. While GERD may cause or worsen pulmonary disorders, changes in respiratory mechanics due to lung disease may also increase reflux. Typical esophageal symptoms are frequently absent and objective assessment with reflux monitoring is often needed for diagnosis. Impedance monitoring should be considered in addition to traditional pH study due to the involvement of both acidic and weakly acidic/nonacidic reflux. Antireflux therapy may improve outcomes of some pulmonary complications of GERD, although careful selection of a candidate is paramount to successful outcomes. Further research is needed to identify the optimal testing strategy and patient phenotypes that would benefit from antireflux therapy to improve pulmonary outcomes.
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4.
Eosinophilic Esophagitis: Update on Diagnosis and Treatment in Pediatric Patients.
Rossetti, D, Isoldi, S, Oliva, S
Paediatric drugs. 2020;(4):343-356
Abstract
Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder characterized by symptomatic esophageal dysfunction and an eosinophil-predominant inflammation of the esophagus. EoE arises from interaction between genetic and environmental factors. In pediatric patients, clinical manifestations vary depending on age, from a gastroesophageal reflux disease (GERD)-like condition to severe dysphagic symptoms. Upper endoscopy is considered the gold standard for diagnosis and monitoring of EoE; however, significant efforts are underway to identify noninvasive diagnostic tools and biomarkers to avoid repetitive invasive procedures. Therapeutic first-line options currently available for EoE are elimination diets, proton pump inhibitors (PPIs), and steroids. The aim of treatment is to improve clinical symptoms while obtaining mucosal healing and avoiding long-term complications. Dietary treatment options comprise different empiric diets or an exclusively amino acid formula. Despite the efficacy of diets, compliance is often challenging. PPIs and topical steroids represent the main pharmacological options for EoE, and both can induce and maintain remission. Topical steroids have been reported as more effective, but data on long-term safety remain insufficient for both these and PPIs. Endoscopic dilations are currently reserved for severe untreated fibrostenotic disease unresponsive to medical therapies. Several biologic agents are available but not yet approved for EoE.
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5.
HISTORICAL PERSPECTIVE OF GASTROESOPHAGEAL REFLUX DISEASE CLINICAL TREATMENT.
Zaterka, S, Marion, SB, Roveda, F, Perrotti, MA, Chinzon, D
Arquivos de gastroenterologia. 2019;(2):202-208
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases. GERD generates significant impairment in patients' quality of life and it is associated to relevant medical resources utilization. A better understanding of GERD pathophysiology in the past five decades has favored the evolution of therapeutic strategies from non-drug interventions and antacids to more efficacious and safer alternatives. OBJECTIVE To summarize data about the historical evolution of GERD management in Brazil, focusing on medical therapy and addressing evidence on efficacy and safety of drug classes currently recommended. METHODS A narrative review was conducted by systematizing information about discoveries on GERD pathophysiology. We also addressed efficacy and safety of medications currently used to reduce symptoms and improve endoscopic healing of esophageal lesions. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating GERD outcomes positively impacted by proton pump inhibitors (PPIs), the first choice of pharmacotherapy for the disease. RESULTS The chronological development of therapeutic measures for GERD in Brazil evolved from lifestyle interventions with relative poor effect on symptoms related to esophageal acid exposure, particularly heartburn, to effective and safe pharmacological interventions such as histamine H2-receptor antagonists and PPIs. In the present days, some drug classes play a minor role in disease management, namely prokinetics and antacids, due to their reduced efficacy and relevant safety concerns (particularly with prokinetics). The main challenge for prescribers and researchers seems to be finding long-acting acid suppressants strategies able to ameliorate patients' symptoms and quality of life, thereafter, reducing medical resource consumption. The dual delayed-release PPI dexlansoprazole seems to respond for some of the limitations other PPIs have. CONCLUSION Recognizing the historical evolution of GERD management can help care providers to better understand therapeutic options for their patients, as well as focus on unmet needs that deserve further attention. PPIs are still the first choice therapy, with good evidence in favor of their efficacy, despite some safety concerns. However, as with any medical intervention, it is recommended to prescribe PPIs for patients with clear indication, using adequate dosing and monitoring for adverse events.
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6.
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.
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7.
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.
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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.
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9.
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.
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10.
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.