Proton Pump Inhibitor Agents Research Articles

Digestive Tract Cancer-Related Adverse Events Correlated with Proton Pump Inhibitors Use: A Pharmacovigilance Study of the FDA Adverse Event Reporting System

Background. Proton pump inhibitors (PPIs) are widely used to treat digestive system diseases. Previous studies have suggested conflicting results between PPI treatment and the risk for digestive tract cancers (DTCs). This study aimed to assess the effect of PPI use on DTCs by data mining of the FDA Adverse Event Reporting System (FAERS) database. Method. This study examined the correlations between six PPI agents and DTCs by mining the FAERS database from January 2004 to September 2021 by using OpenVigil 2.1. The reporting odds ratio (ROR) defined as the ratio between the odds of reporting a specific adverse event for one drug divided by the corresponding odds for all other drugs, with 95% confidence intervals (CIs), was used to detect statistically significant correlations between PPIs and DTCs. High-level terms (HLTs) and preferred terms (PTs) were defined by the Medical Dictionary for Regulatory Activities 24.0 (MedDRA24.0). Result. A total of 2553 DTC adverse event reports were screened, with positive signals obtained from gastric neoplasms malignant (GNM) (ROR: 1.09, 95% CI: 1.01–1.18) and bile duct neoplasms malignant (BDNM) (ROR: 1.80, 95% CI: 1.44–2.25). Esomeprazole showed the strongest signal (ROR: 1.85, 95% CI: 1.66–2.06) for GNM, while rabeprazole for BDNM (ROR: 2.94, 95% CI: 1.32–6.56), and female PPI users had a higher risk of BDNM (ROR: 2.44, 95% CI: 1.77–3.35). Among subordinate PTs, adenocarcinoma gastric and the combination of “bile duct cancer” and “cholangiocarcinoma” were highly correlated with PPI use. Conclusion. By mining the FAERS database, we provided important clues for the correlation between PPI use and DTC risk.

Time-Varying Use of Proton Pump Inhibitors and Cognitive Impairment and Dementia: A Real-World Analysis from Germany.

Time-Varying Use of Proton Pump Inhibitors and Cognitive Impairment and Dementia: A Real-World Analysis from Germany.

Management of Adult Patients with Gastrointestinal Symptoms from Food Hypersensitivity-Narrative Review.

The incidence of food hypersensitivity has increased dramatically over the years not only among children but also in adults. Adult patients are usually less suspected of food hypersensitivity symptoms since food allergies are more typical for small children, with a tendency to outgrow the condition. The aim of this article is to increase awareness of hypersensitivity to food symptoms and their diagnosis and treatment possibilities among gastroenterologists and other health care professionals dealing with this type of patient. Symptoms of many gastrointestinal disorders, especially functional, may be driven by different types of mechanisms, and food intolerance or allergy should be considered as a potential cause. This article presents the current understanding of the epidemiology, diagnosis and treatment of immune- and non-immune-mediated food-induced diseases. Diagnosis of food hypersensitivity is based mainly on medical history, different types of sensitivity tests, e.g., hydrogen breath test, specific IgE (sIgE) serum concentration, tissue eosinophil count, skin tests and oral food challenges considered as a "gold standard" for food allergy. Elimination diet and pharmacologic treatment for allergy symptoms are first-line therapies. Eosinophilic gastrointestinal diseases are often caused by non-IgE-mediated food allergies, require endoscopic biopsy samples to confirm diagnosis and proper elimination diet often combined with steroids or proton pump inhibitor agents for treatment. Mast cell activation syndrome (MCAS) derives from pathologic reaction of mast cells with increased tryptase serum level as a marker. Symptoms may occur in the digestive, respiratory, skin, neurologic and cardiovascular system. Treatment is based on histamine type 1, type 2 (H1, H2) receptor antagonists and other mast cell stabilizing agents. Carbohydrate intolerances are the most common type of food hypersensitivity in adult patients, and an elimination diet is effective for reducing symptoms. Food additives hypersensitivity remains difficult to diagnose, but use of a diet low in chemical substances alleviates symptoms and helps to diagnose the triggering factors.

Proton pump inhibitors and colorectal cancer: A systematic review.

BACKGROUNDThe use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal cancer (CRC) risk. AIMTo summarize current knowledge on the relationship between PPI and CRC from basic research, epidemiological and clinical studies. METHODSThis systematic review was based on the patients, interventions, comparisons, outcome models and performed according to PRISMA guidelines. MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from inception until May 17, 2021. The initial search returned 2591 articles, of which, 28 studies met the inclusion criteria for this review. The studies were categorized as basic research studies (n = 12), epidemiological studies (n = 11), and CRC treatment studies (n = 5). The quality of the included studies was assessed using the Newcastle-Ottawa Scale or Cochrane Risk of Bias 2.0 tool depending on the study design. RESULTSData from basic research indicates that PPI do not stimulate CRC development via the trophic effect of gastrin but instead may paradoxically inhibit it. These studies also suggest that PPI may have properties beneficial for CRC treatment. PPI appear to have anti-tumor properties (omeprazole, pantoprazole), and are potential T lymphokine-activated killer cell-originated protein kinase inhibitors (pantoprazole, ilaprazole), and chemosensitizing agents (pantoprazole). However, these mechanisms have not been confirmed in human trials. Current epidemiological studies suggest that there is no causal association between PPI use and increased CRC risk. Treatment studies show that concomitant PPI and capecitabine use may reduce the efficacy of chemotherapy resulting in poorer oncological outcomes, while also suggesting that pantoprazole may have a chemosensitizing effect with the fluorouracil, leucovorin, oxaliplatin (FOLFOX) regimen.CONCLUSIONAn unexpected inhibitory effect of PPI on CRC carcinogenesis by way of several potential mechanisms is noted. This review identifies that different PPI agents may have differential effects on CRC treatment, with practical implications. Prospective studies are warranted to delineate this relationship and assess the role of individual PPI agents.

A pharmacovigilance study of association between proton pump inhibitor and dementia event based on FDA adverse event reporting system data

Proton pump inhibitor (PPI) was widely used around the world. Studies suggested conflicting results between PPI treatment and dementia event. This study examined the association between six PPI agents and dementia event by mining the US FDA Adverse Event Reporting System (FAERS) database from 2004 to 2020. We employed proportional reporting ratio (PRR) and information element (IC) methods to detect the signals of dementia relevant to PPI. We also analyzed characteristics of PPI and positive control reports, compared dementia event between long- and short-duration of PPI treatment. Finally, we identified 2396 dementia cases with PPI treatment. We did not detect significant signal between PPI and dementia event: PRR = 0.98, 95%CI 0.94 to 1.02, IC = −0.03, 95%CI − 0.17 to 0.10, even in gastroesophageal reflux disease cases: PRR = 0.65, 95%CI 0.59 to 0.72, IC = −0.62, 95%CI − 0.97 to − 0.27. No significant differences of dementia event were detected between long- and short- duration groups, the OR (95%CI) of the 3 years, 5 years and 10 years comparison were 0.70 (0.48 to 1.02), 0.72 (0.45 to 1.15) and 1.65 (0.75 to 3.63), respectively. Based on the current FAERS data mining, we discovered no association between PPI use and dementia event, even in long-term PPI therapy case.

Asthma related to gastroesophageal reflux disease: a case report and review

Asthma is a common respiratory disorder that characterized by airway hyper-reactivity and chronic inflammation. Asthma and gastroesophageal reflux disease can occur together, both can affect each other. We represent 41 years old male patient with chief complaint of asthma that preceded burning sensation on his throat and also heartburn over the last three months. Patient had visited his family doctor but his symptom still occurred. He had been experienced six episodes of these symptoms since three month ago. On physical examination there were wheezing both of his lung and prolong expiration phase. There was no abnormality on the electrocardiogram, chest X-ray and complete blood count. After administration of short acting bronchodilator and proton pump inhibitor agent, patient clinical status improved dramatically. Patient than given salmoterol fluticasone inhaler, antacid, ANT proton pump inhibitor as take-home medication. On his follow up visit to policlinic on first, fourth- and eight-week patient denied any shortness of breath and heartburn anymore. Various pathological processes play a role in the pathogenesis of GERD and Asthma. There were two theories that suggested in the mechanism that caused GERD induced Asthma, including reflux and reflex theory.

The Clinical Characteristics of Fractures in Pediatric Patients Exposed to Proton Pump Inhibitors.

There are increasing concerns regarding proton pump inhibitor (PPI) use and the risk of fractures in adults. Few studies have evaluated this risk among pediatric patients. This study examined fractures and fracture location among pediatric patients exposed to PPI compared with those without documented exposure. Encounters for patients 6 months to 15.5 years were identified between July 1, 2011 to December 31, 2015 in the Pediatric Hospital Information System database. Exclusion criteria was applied for chronic illnesses, conditions or medications predisposing to fracture. Encounters were classified as PPI encounters if a charge for PPI was documented. PPI encounters were propensity matched to non-PPI encounters. Following initial encounter, patients were evaluated over a 2-year period for hospitalizations resulting from fracture. There was a statistically significant higher rate of fractures among the PPI-exposed group (1.4% vs 1.2%, P = 0.019). Adjusting for remaining differences in sex, race, encounter type, payer, and resource intensity after matching, the difference remained statistically significant (P = 0.017) with an adjusted odds ratio (95% CI) of 1.2 (1.0--1.4). Upper extremity was the most common location for fracture; however, the PPI cohort was more likely to suffer from lower extremity, rib, and spinal fractures (P = 0.01). This study suggests an increased risk of fracture among pediatric patients taking PPI. Among patients hospitalized with a fracture, those with PPI exposure had a higher rate of lower extremity, rib, and spine fractures compared with controls. This appeared to be a class effect not related to individual PPI agent.

Evaluation of the clinical impact of concomitant acid suppression therapy in colorectal cancer patients treated with capecitabine monotherapy.

Capecitabine is an oral chemotherapeutic agent used in colorectal cancer. Two prior studies found a negative impact with the concomitant use of proton pump inhibitor agents during treatment with capecitabine in patients with early colorectal and gastroesophageal cancers. To determine if there is a clinical impact of the concomitant use of capecitabine and acid suppression therapy in patients with local and metastatic colorectal cancer. This was a single-center retrospective cohort study of adult patients with colorectal cancer on capecitabine monotherapy between 2011 and 2017. Progression-free survival (PFS) and overall survival were compared between patients on acid suppression therapy and those not on acid suppression therapy. A total of 70 patients were included. Patients on acid suppression therapy at capecitabine initiation (21%) had decreased progression-free survival versus those not on acid suppression therapy (HR 2.24, 95% CI 1.06-4.41, p = 0.035), after adjusting for disease severity and age. Acid suppression therapy use was associated with a numerical decrease in overall survival (HR 1.86, 95% CI 0.81-3.91, p = 0.14). In patients on any concomitant acid suppression therapy (25%), there was a decreased rate of progression-free survival (HR 6.21, 95% CI 2.56-14.32, p = 0.0001) but not overall survival (HR 1.64, 95% CI 0.68-3.54, p = 0.25) versus those without concomitant acid suppression therapy, after adjusting for age and disease severity. Concurrent use of acid suppression therapy and capecitabine was associated with decreased progression-free survival, and there was a trend towards decreased overall survival. Due to the demonstrated potential of decreased efficacy, concurrent use of proton pump inhibitors or histamine 2 receptor antagonists should be avoided in colorectal cancer patients on treatment with capecitabine monotherapy.

Инфекция Helicobacter pylori при длительной терапии кислотозависимых заболеваний ингибиторами протонной помпы

Aim of review. To present management approach for acid-related diseases in patients with Helicobacter pylori (H. pylori) infection, under long-term proton pump inhibitor therapy. Summary. There is no relation of gastroesophageal reflux disease (GERD) symptom severity, the pattern of relapses and treatment efficacy to the presence or absence of H. pylori infection; successful H. pylori eradication does not cause relapse of pre-existing GERD and does not induce its development. At the same time it is impossible to neglect the data on potential induction or aggravation of GERD after H. pylori eradication in separate population groups, including those in Asia. The presence of GERD could not prevent infection eradication in the presence of other indications (e.g., peptic ulcer, chronic gastritis). Monotherapy by proton pump inhibitors (PPI) in H. pylori-positive patients with GERD may lead to progression of gastric corpus atrophy that can be regarded as risk factor for stomach cancer development. H. pylori infection eradication promotes reduction of gastritis-like changes severity irrespective of maintaining of acid-suppressive treatment. The choice of specific PPI for treatment of patients with GERD and other acid-related diseases, carrying out H. pylori eradication therapy or substitution of one PPI agent to another are individualized and depend on the indications registered in the drugs administration instructions, features of its pharmacokinetics and pharmacodynamics, possible drug-to-drug interactions. Conclusion. Testing for H. pylori infection and carrying out the subsequent eradication therapy could allow to prevent progression of corpus mucosa atrophy in patients with acid-related disorders, first of all those with GERD, who received long-term PPI treatment. Estimation of duration of PPI treatment at acid-related disorders, and terms of H. pylori eradication therapy should be evaluated according to clinical guidelines and treatment protocols of these diseases taking into account age of the patient, clinical features, course of disease, presence of complications.

Effectifity and Cost Analysis of Omeprazole and Pantoprazole for Stress Related Mucosal Disease Prophylaxis in ICU

Currently, the most effective therapeutic agent as a Stress Related Mucosal Disease (SRMD) prophylaxis therapy is the group of Proton Pump Inhibitor (PPI). In Indonesia, PPI agent most commonly used is pantoprazole and omeprazole, for they are already available in the form of injection and also available in generic product. This study aimed to determine the effectiveness and the therapy cost of omeprazole and pantoprazole used as a prophylaxis agent of SRMD. This study used observational analytic method using a retrospective cohort study. The subjects were patients in ICU of Bethesda Hospital in Yogyakarta with age ≥ 18 year old who received the therapy of omeprazole or pantoprazole as a prophylaxis of SRMD during January 2012 – September 2016 who meet the inclusion and exclusion criteria. The effectivity of therapy was seen by the bleeding events. The cost was calculated based on the amount of fee required by the patient, both the use of the medicine as a prophylaxis therapy of SRMD and for the bleeding therapy of SRMD. The value of Expected Monetary Value (EMV) was then calculated using the method of Decision Tree. Subject in this study were 152 patients, in which there were 76 patients on each group therapy of pantoprazole and omeprazole. The comparison between the number of patients who did not experience bleeding between group of pantoprazole and group of omeprazole is 85.5%: 81.6% (p = 0.512). The value of EMV in the pantoprazole group is Rp. 431.490,76, while the omeprazole group is Rp. 382.042,57. There is no difference in the effectivity between pantoprazole and omeprazole as a prophylaxis of SRMD, and the cost for SRMD prophylaxis is cheaper in the omeprazole therapy than in the pantoprazole therapy.

Association Between Proton Pump Inhibitors and Microscopic Colitis.

Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC. We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis. Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included. Bibliographies from pertinent publications were reviewed for additional references. Outcome was defined as the development of biopsy-confirmed MC. A total of 19 publications were identified: 5 case control studies and 14 case reports/series (encompassing a total of 32 cases). All studies were limited by small sample sizes. Risk of MC by dose or specific PPI agent was not investigated in any of the studies. A review of the current body of evidence reveals a possible association between PPIs and MC. There is a need for large observational studies of high quality to examine the differential effect of specific PPIs and whether the magnitude of association is dose dependent. Given their widespread use, clinicians should routinely question whether patients are receiving unnecessary treatment with PPIs and discontinue therapy where appropriate.

Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review.

Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted.

Pharmacological treatment of children with gastro-oesophageal reflux.

Pharmacological treatment of children with gastro-oesophageal reflux.

Effects of Proton Pump Inhibitors andH2Receptor Antagonists on the Ileum Motility

Objectives. To investigate the effects of proton pump inhibitors (PPIs) and H2 receptor antagonists on ileum motility in rats with peritonitis and compare changes with control group rats. Methods. Peritonitis was induced by cecal ligation and puncture in 8 rats. Another of 8 rats underwent a sham operation and were accepted as controls. Twenty-four hours later after the operation, the rats were killed, and their ileum smooth muscle was excised and placed in circular muscle direction in a 10 mL organ bath. Changes in amplitude and frequency of contractions were analyzed before and after PPIs and H2 receptor blockers. Results. PPI agents decreased the motility in a dose-dependent manner in ileum in both control and intraabdominal sepsis groups. While famotidine had no significant effect on ileum motility, ranitidine and nizatidine enhanced motility in ileum in both control and intraabdominal sepsis groups. This excitatory effect of H2 receptor antagonists and inhibitor effects of PPIs were significantly high in control group when compared to the peritonitis group. The inhibitor effect of pantoprazole on ileum motility was significantly higher than the other two PPI agents. Conclusions. It was concluded that H2 receptor antagonists may be more effective than PPIs for recovering the bowel motility in the intraabdominal sepsis situation.

Pantoprazole: a proton pump inhibitor with oral and intravenous formulations

Proton pump inhibitors (PPI) are a significant part of therapy for most acid-related diseases including gastroesophageal reflux disease, peptic ulcer disease and acute gastrointestinal bleeding. Pantoprazole is one of several available proton pump inhibitor agents and provides dose-dependent control of gastric acid secretion. Pantoprazole has indications in gastroesophageal reflux disease and peptic ulcer disease, along with indications as co-therapy in the eradication of Helicobacter pylori infection and in the control of the acid secretion associated with the Zollinger–Ellison syndrome, as well as in NSAID ulcer prevention. Pantoprazole is available in both oral and intravenous formulations. It is effective across all age groups, although only indicated in adults (and adolescents in Europe). It has been approved for use in over 100 countries and has been used for over 13 years. Pantoprazole has an excellent safety profile and a low potential for drug–drug interactions. While still widely prescribed, pantoprazole and the other branded proton pump inhibitors are under considerable market pressure from the less expensive but similarly effective generic and over-the-counter formulations of omeprazole.

Gastrointestinal Stromal Tumors: A Rare Neoplasm Presenting with Gastrointestinal Bleeding

Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal (GI) tract that arise from primitive mesenchymal cells. GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. GISTs are known with myoid, neural or mixed features of differentiation. Clinical findings are gastrointestinal bleeding, abdominal pain, and weight loss. GISTs express a heterogeneous clinical course not easily predicted. The histologic features that correlate best with development of recurrence and metastasis are mitotic activity, tumor size and the presence of tumor necrosis and most recently, mutation in the c-kit gene. Some authors specifically use the term GIST to refer to only those mesenchymal tumors that express CD117, whereas others believe that the diagnosis can be made in the absence of CD117 positivity based on clinical and morphologic features. Surgical resection remains the treatment of choice, since chemotherapy and radiation are ineffective. Long-term follow-up is imperative and recurrence rates are high. We report the case of a 60 years old female patient who presented with intermittent melena, chronic dyspepsia, and anemia. Upper digestive tract endoscopy showed a submucosal tumor, broad-based, centrally ulcerated, projection of >5 cm in the gastric corpus-antral wall as the cause of the upper gastrointestinal bleeding. Endoscopic biopsies were negative for neoplastic changes. After triple eradication therapy of Helicobacter pylori and treatment continued with proton pump inhibitor agent, the patient underwent distal gastrectomy with Billroth-I reconstruction. Histopatological studies on the surgical resection specimen revealed a GIST of smooth muscle with spindle cell, no evidence of mitotic activity but of uncertain biological behavior. One year after surgery the patient is was improved with no signs of residual malignancy. However, metastases were found later in the liver in the next two year. Keywords: GIST, stromal tumor, surgery, C-kit

The Extent of Abuse of Proton Pump Inhibitor Therapy and Its Potential Consequences for the Patient and Impact on Health Care Costs

Purpose: Proton Pump Inhibitor (PPI) agents are relatively safe and highly effective in offering symptomatic relief in patients with GERD, as part of triple therapy for H. Pylori and as gastric protective agents during NSAID therapy. A prescription for a PPI is often initially given without much thought on its need and renewed with much less scrutiny for months. Aim: To evaluate the extent of abuse of PPI therapy in a medical clinic of a teaching institution. To analyze the financial impact of the abusive use of PPI therapy. Methods: A chart review of 500 consecutive patients was conducted for the number of prescriptions for any one of the PPI agents (Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole and Rabeprazole) and for their indication or the lack of it. Patients receiving PPI therapy were classified into three groups –Group 1– those who had a valid indication, Group 2– those who had a questionable indication (the Gray Zone – patients with nausea, vomiting, decreased appetite, abdominal pain of unknown etiology, viral/candida esophagitis, chronic dry cough) and Group 3– those who had no indication or even had achlorhydria. Results: Total number of patients on a PPI = 131 (26%)/500 The misuse of PPI therapy is anywhere between 15% to 42% (15% + 27%) (See Table 1)Table 1: GROUP RESULTS.Cost Analysis: The cost of therapy in: Group 3 = 20 patients X $4.94/day*=$36,062.00/year Group 2 =35 patients X $4.94/day*=$63,108.50/year Group 1 is not calculated since it was medically indicated. (*Mean cost of the available PPIs used once-daily. Prices from Walgreens.com effective 6/14/06). Conclusions: Once PPI therapy is initiated, for any reason, it is seldom discontinued. The financial impact on healthcare is substantial due to the high cost of PPI therapy. Potential side effects of PPI therapy, including increased susceptibility to C. Difficile colitis, Community Acquired Pneumonia, Vit. B12 malabsorption and Acute Interstitial Nephritis (AIN), are rarely assessed because of the feeling that PPIs are safe. Patients may be spending their limited resources on PPI therapy at the expense of other life saving medications.

Gastroesophageal Reflux in the Preterm Neonate

After completing this article, readers should be able to: 1. Describe the epidemiology and pathophysiology of gastroesophageal reflux (GER) in preterm neonates. 2. Delineate the associations of GER with apnea, chronic lung disease, behavior, and growth of preterm infants. 3. Review the investigations used to evaluate GER in preterm infants. 4. Describe nonpharmacologic and pharmacologic therapies for GER. Gastroesophageal reflux (GER) is a normal physiologic event occurring across the age spectrum. It may contribute to a variety of disorders, including esophagitis, feeding problems, and airway disease in all age groups. (1) A large number of symptoms and signs have been purported to be caused by GER despite a lack of data showing a clear association between a specific symptom and GER. In preterm infants, empiric therapy often is administered using agents of unproven efficacy and safety to treat symptoms that likely are unrelated to GER. In a survey on management practices for GER in preterm infants, common treatment strategies included positioning (98%) and slopes (96%), histamine 2 (H 2) receptor antagonists (100%), feed thickeners (98%), antacids (96%), prokinetics (79%), proton pump inhibitors (PPIs) (65%), and dopamine receptor antagonists (53%). (2)(3) The safety, efficacy, and appropriate dosing recommendations for most medical therapies remain uncertain in neonates. In this review, we attempt to summarize the current literature regarding physiology, pathophysiology, and diagnostic and management strategies for GER pertinent to the neonate, with an emphasis on the preterm infant. GER describes the retrograde movement of stomach contents (air or feeding, liquid or semisolid, acid or alkaline, enzymes or bile salts) into the esophagus. GER disease (GERD) occurs when GER causes symptoms or signs such as pain, poor weight gain, esophagitis, hematemesis, and airway symptoms, including apnea, aspiration, recurrent pneumonia, chronic lung disease (CLD), or large airway inflammation. However, any of these symptoms or signs …

On-demand proton pump inhibitor therapy in patients with gastro-oesophageal reflux disease

On-demand therapy is an established modality in long-term therapy with histamine-2-receptor antagonists, in cases of mild non-erosive gastro-oesophageal reflux disease. In the literature, only a few studies have specifically addressed the problem of proton pump inhibitors on-demand treatment. The evidence, so far, available suggests that this might be an effective modality of long-term treatment in the majority of patients with non-erosive gastro-oesophageal reflux disease. This treatment modality appears to be the most cost-effective and the best tolerated medical regimen for gastro-oesophageal reflux disease. It also seems to be able to restore the impairment of health-related quality of life due to gastro-oesophageal reflux disease symptoms. Although the current standard of care for patients with non-erosive gastro-oesophageal reflux disease is maintenance therapy with daily administration of a proton pump inhibitor agent, on-demand therapy, with the same drug, may be a reasonable long-term choice. The ideal proton pump inhibitors for such treatment will be those with a more rapid onset of action, more profound acid inhibition, more predictable therapeutic effect and less drug-drug interactions. Newer proton pump inhibitors, like esomeprazole, the S-chiral isomer of omeprazole, are promising drugs for on-demand treatment of gastro-oesophageal reflux disease.

Interactions between H. pylori infection, gastric acid secretion and anti-secretory therapy.

There is evidence of a two-way interaction between gastric acid secretion and H. pylori-associated gastritis. Gastric acid secretion influences the density of H. pylori colonisation, its distribution within the stomach and the severity of the mucosal inflammatory response to the infection. In addition, H. pylori gastritis alters gastric acid secretion. In subjects with a predominant antral gastritis, it increases acid secretion predisposing to duodenal ulcer, whereas in others with predominant body gastritis, acid secretion is impaired and the subjects have an increased risk of gastric cancer. The two-way interaction between acid secretion and H. pylori gastritis is observed when H. pylori-positive subjects are treated with proton pump inhibitor agents. The inhibition of acid secretion induces a body gastritis and this inflammation of the body mucosa inhibits acid secretion thus augmenting the anti-secretory effect of the drug. In this article, we discuss the interaction between gastric acid secretion and H. pylori gastritis and its importance in determining disease outcome.