Trial Of Omeprazole Research Articles

Epigastric Abdominal Pain In Elite Soccer Player

Epigastric Abdominal Pain in Elite Soccer Player Richard J. Edgar, MD Crozer Sports Medicine Springfield, PA Kevin DuPrey, DO (Crozer Sports Medicine Springfield, PA David Baxter, DO Crozer Sports Medicine Springfield, PA Thomas Kaminski, PhD, ATC, FACSM University of Delaware (Sponsor) HISTORY: A 24-year-old male professional soccer player presented with acute on chronic epigastric abdominal pain worsening over the last 2 weeks prior to presentation. Associated symptoms included nausea and sour taste in mouth. Denied constitutional symptoms, vomiting, jaundice, dysphagia, chronic cough, diarrhea, constipation, hematochezia, melena, and loss of appetite. He took NSAIDs for prior knee injury, but is unsure of which medication he has taken or the doses. He failed one prior trial of Ranitidine 150 mg BID, and two prior trials of Omeprazole 40 mg BID. Patient is from Africa with recent travel to Africa prior to presentation. PHYSICAL EXAMINATION: General: No acute distress.Eyes: PERRL, EOMI, conjunctiva normal, no icterusHENT: Normocephalic, atraumatic, no mouth ulcers, normal dentition. Cardiovascular: Regular rate and rhythm, no murmursLungs: Clear to auscultation bilaterally. Abdomen: Soft, non-distended, tenderness to palpation of epigastrium, bowel sounds present, no masses, no hepatosplenomegaly. DIFFERENTIAL DIAGNOSIS:1. Gastroesophageal Reflux Disease2. Peptic Ulcer Disease3. Helicobacter Pylori Infection4. Pancreatitis 5. Strongyloides stercoralis TEST AND RESULTS:Given the persistence of symptoms despite H2-blocker/PPI treatment, the patient underwent esophagogastroduodenoscopy (EGD) after cessation of H-2 blocker and PPI for 2 weeks. The EGD showed erosive gastropathy with no bleeding and no stigmata of recent bleeding. Biopsies taken during the EGD were consistent with Helicobacter Pylori infection. FINAL/WORKING DIAGNOSIS: Helicobacter Pylori Infection with Erosive Gastropathy TREATMENT AND OUTCOMES:The patient was treated with Clarithromycin triple therapy: Amoxicillin 1000 mg BID, Clarithromycin 500 mg BID, and Omeprazole 40 mg BID for 14 days. Patient had resolution of symptoms. He continued full sport participation throughout work-up and treatment.

Annals for Educators - 16 June 2020.

Annals for Educators - 16 June 2020.

A prospective randomized controlled trial of omeprazole for preventing esophageal stricture in grade 2b and 3a corrosive esophageal injuries.

Esophageal stricture is a significant complication of grade 2b and 3a esophageal injuries and causes much patient suffering. Preventing strictures would be beneficial to patients but there are currently no proven effective drugs. This study aimed to evaluate the effect of omeprazole for preventing esophageal stricture in adults with grade 2b and 3a corrosive esophageal injuries. This study was an open single-center prospective randomized controlled trial that took place from April 2018 to January 2020. Patients were randomized to standard treatment or 80mg/day intravenously × 3days followed by 40mg/day orally for 4weeks. They were endoscoped at baseline and 4weeks post discharge. Strictures were confirmed radiologically. 20 patients were enrolled: 15 with grade 2b and five with grade 3a injuries. Standard care and omeprazole groups numbered 10 each. At 1month, seven and two patients developed strictures in the standard and omeprazole groups, respectively, p = 0.024, for a risk reduction of 71.4%. Omeprazole reduced the risk of short-term developing esophageal strictures following grade 2b and 3a corrosive esophageal injuries. Larger studies are needed to reconfirm this finding. Thai Clinical Trials Registry (TCTR) number TCTR20190504001.

The Role of Empirical Treatment with Proton Pump Inhibitor as a Diagnostic Tool in Laryngopharyngeal Reflux.

The presentations of laryngopharyngeal reflux (LPR) are diverse and include chronic hoarseness, sensation of foreign body in the throat, sore throat etc. 24h pH monitoring considered the gold standard of investigation for LPR is costly, cumbersome and not readily available at all centers. Empirical trial of Proton pump inhibitor (PPI) as a diagnostic tool after assessment by Reflux Symptom Index (RSI) and Reflux Findings Score (RFS) is a cheaper, simple and readily available alternative. The objectives of the study were to determine clinical manifestations in patients presenting with LPR and to evaluate the role of empirical treatment with PPI as a diagnostic tool in LPR. 100 patients were divided into experimental group (RSI ≥ 13 and RFS ≥ 7) and control group (RSI < 13 and RFS < 7). Omeprazole trial was given to experimental group and assessed for RSI and RFS at 04 and 08weeks. Statistical analysis was done within the group and between the groups. (1) The response rate to Omeprazole at 04 and 08weeks interval (RSI<13 and/or RFS<7) was 60% and 76% respectively. (2) The response to Omeprazole given to the experimental group with RSI≥13 and RFS≥7 was significant at 04weeks and 08weeks duration (P<0.0001). RSI and RFS are good clinical tools to assess and diagnose patients with Laryngopharyngeal reflux. Based on the clinical diagnosis an empirical trial of a proton pump inhibitor (PPI) can be given to patients for duration of 02months resulting in a good response.

Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn

BackgroundHeartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine).MethodsPatients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance–pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)–Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year.ResultsA total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P=0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, −5 to 38; P=0.17).ConclusionsAmong patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.)

Randomised, double-blind, placebo-controlled pilot trial of omeprazole in idiopathic pulmonary fibrosis

BackgroundCough is a common, disabling symptom of idiopathic pulmonary fibrosis (IPF), which may be exacerbated by acid reflux. Inhibiting gastric acid secretion could potentially reduce cough. This study aimed to...

Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)

BackgroundWorldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS. MethodsThe Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients. ResultsThe trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants. ConclusionMANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS.

All Switched Up: Abdominal Pain in a Patient With Situs Inversus Totalis

Situs Inversus Totalis (SIT) is the rare condition in which the abdominal organs and organs in the thorax lie in position that is a mirror image from their usual orientation. This condition occurs in less than 0.0001% of live births. Many with SIT are unaware of the anomaly until incidentally found on imaging or ECG. We report a case of abdominal pain that we believe to be secondary to SIT. We find this case interesting because SIT is a rare condition that is usually asymptomatic. A 35-year-old man presented to GI clinic with abdominal pain that began 8 months prior. He described it as a burning discomfort that radiated from the epigastrium to his suprapubic region. It was intermittent and associated with bloating. He reported relief with marijuana use and aloe-vera lotion. He denied associated nausea/vomiting, dysphagia/odynophagia, hematochezia/melena, or weight loss. He reported being treated for H. Pylori infection in the past, no other medical history. No previous EGD/colonoscopy. No family history of GI malignancy. Reports marijuana use and occasional cocaine use. His vital signs were unremarkable. On exam, his abdomen was soft, non-distended and non-tender in all 4 quadrants. Review of the medical records revealed previous liver ultrasound reporting SIT. Labs were unremarkable including CMP, CBC, Stool H. Pylori Ag, Hepatitis C Ab. An abdominal CT is with contrast was ordered. He was started on an empiric trial of omeprazole for symptomatic relief, and followed up in 2 months with no relief. Labs were unremarkable and imaging was notable only for SIT. He reported continued symptoms at this follow-up visit. The patient was subsequently lost to follow-up and unavailable by phone. In patients with a family history or personal history of SIT, it is important to consider the implications this may have on their presenting symptoms. This awareness can aid in the timely diagnosis of common conditions such as appendicitis, diverticulitis and biliary colic where the physical exam findings would be on the opposite side. Intestinal ischemia in SIT patients related to intestinal malrotation or mestenteric hernias is reported in the literature. Special consideration should be taken for procedural approach if abdominal interventions are required. Anatomy should not impede this, as techniques and approaches have been reported for patients with SIT requiring laparoscopic cholecystectomy, percutaneous biliary stenting, therapeutic ERCP and even liver transplantation.Figure: CT scan imaging showing situs inversus, note liver on left and stomach on right side of patient's body.

Luminal Clinical

<b>Luminal Clinical</b>

Oropharyngeal pH Testing Does Not Predict Response to Proton Pump Inhibitor Therapy in Patients with Laryngeal Symptoms.

Predicting response to proton pump inhibitor (PPI) therapy in patients with laryngeal symptoms is challenging. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. In this study, we aimed to investigate the prognostic potential of oropharyngeal pH monitoring to predict responsiveness to PPI therapy in patients with laryngeal symptoms. We conducted a physician-blinded prospective cohort study at a single academic institution between January 2013 and October 2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-h oropharyngeal pH monitoring, followed by an 8- to 12-week trial of omeprazole 40 mg daily. Prior to and following PPI therapy, patients completed various symptom questionnaires. The primary outcome was the association between PPI response and oropharyngeal pH metrics. PPI response was separated into three subgroups based on the post-treatment RSI score and % RSI response: non-response=RSI ≥13; partial response=post-treatment RSI <13 and change in RSI <50%; and complete response=post-treatment RSI <13 and change in RSI ≥50%. The primary analysis utilized a multinomial logistic regression controlling for the pre-treatment RSI score. A secondary analysis assessed the relationship between the change in RSI (post-pre) and oropharyngeal pH metrics via ordinary least square regression. Thirty-four patients completed the study and were included in final analysis. Symptom response to PPI therapy was as follows: 50% no response, 15% partial response, and 35% complete response. Non-responders had a higher pre-treatment RSI (P<0.01). There were no significant differences in oropharyngeal acid exposure (below pH of 4.0, 5.0, 5.5, 6.0, and RYAN scores) between responder types. The secondary analysis noted a trend between lower PPI response and a greater total percent time below pH of 5.0 (P=0.03), upright percent time below pH of 5.0 (P=0.07), and RYAN supine (corrected; P=0.03), as well as an association between PPI response and greater decreases in the Anxiety Sensitivity Inventory (P<0.01), Brief Symptom Inventory-18 (P<0.01), and Negative Affect Scale (P<0.01). Oropharyngeal pH testing did not predict laryngeal symptom response to PPI therapy. Contrary to hypothesis, our study signaled that the degree of oropharyngeal acid exposure is inversely related to PPI response. In addition, reduction in negative affect and psychological distress parallels PPI response.

Lower Oropharyngeal Acid Exposure and Higher Psychological Distress Exists Amongst Subjects With Laryngeal Symptoms and Response to PPI Therapy

Introduction: Predicting therapeutic response in patients with laryngopharyngeal reflux (LPR) symptoms is challenging. Consequently, patients with suspected LPR often receive empiric proton-pump inhibitor (PPI) therapy and up to 50% may not respond. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. We hypothesized that higher oropharyngeal acid burden is associated with a greater PPI response. The aims of this study were to (1) correlate oropharyngeal pH probe parameters with PPI response and (2) evaluate if alternative clinical surrogates predict PPI response. Methods: This was a physician blinded prospective cohort study conducted at a tertiary care teaching institution between 1/2013 and 10/2014. Adult subjects with laryngeal symptoms >1 month and a Reflux Symptom Index score (RSI) ≥13 off PPI therapy 2 weeks prior to study were recruited from an otolaryngology clinic. Laryngoscopy and oropharyngeal pH assessment with the Restech Dx-pH system were first performed, followed by an 8 to 12 week trial of omeprazole 40 mg once daily. Prior to, and following PPI therapy, subjects completed various symptom questionnaires [Table 1]. PPI response was defined as > mean delta RSI (difference between pre- and post-PPI therapy RSI).Table 1: Clinical variables by PPI Responder & Non-responder groupsResults: Of 34 subjects, 15 (44%) had a PPI response. Percent time of oropharyngeal pH below 5.0 did not correlate with change in RSI (Spearman's rho -0.07, P=0.7); similar trends were seen for pH < 4.0, 5.5 & 6.0. Low acid exposure ( < 1%) was significantly associated with PPI response when compared to high acid exposure (≥1%) [Figure 2]. PPI responders had higher psychological distress scores prior to treatment and a significantly greater reduction in post-treatment Brief Symptom Index, Negative Affect, and Heartburn Vigilance Scale scores. Baseline and delta GerdQ scores were significantly higher in the PPI responder group.Figure 2Conclusion: Contrary to our hypothesis, low oropharyngeal acid burden was associated with PPI symptom response, suggesting a non-acid mechanism of laryngeal symptoms in this group. PPI responders had higher psychological distress, indicating an association between cognitive affective symptoms and laryngeal complaints and supporting the placebo effect of PPI therapy. The etiology of laryngeal symptoms is undoubtedly complex, and the role of oropharyngeal pH testing to predict PPI response remains unclear.Figure 1

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.

An Unusual Referral for Epigastric Pain, Nausea, Abdominal Bloating, Diarrhea, and Weight Loss

Question: A 30-year-old woman with a past medical history of hypothyroidism presents for evaluation of epigastric discomfort, nausea without emesis, abdominal bloating, and watery, nonbloody diarrhea for 5 months. This was associated with a 15-pound weight loss. Complete blood count, liver function tests, thyroid-stimulating hormone, immunoglobulin (Ig) levels, and IgG/IgA tissue transglutaminase (tTG) were within normal limits. Stool studies for bacterial pathogens, giardia, Clostridium difficile toxin, and ova/ parasites were negative. An upper endoscopy revealed minimal antral erythema and abnormal duodenal bulb (Figure A) with a normal-appearing postbulbar duodenum (Figure B). Biopsies of the stomach, duodenal bulb, and second portion of the duodenum were obtained. What is the diagnosis? Look on page 1692 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Histology revealed a thickened subepithelial collagen band in the stomach (Figure C) and total villous blunting with an increased subepithelial collagen band in the duodenal bulb (Figure D). Conversely, the histologic appearance of the second portion of the duodenum was completely normal (Figure E). Gastric biopsies were negative for Helicobacter pylori. The diagnoses of collagenous gastritis and collagenous sprue were established. Treatment included initiation of a gluten-free diet along with a trial of omeprazole. Collagenous gastritis is an uncommon condition first described in 1989. A recent review defined 2 patient groups based on age and presentation with children and young adults presenting with anemia and abdominal pain and older adults predominantly presenting with diarrhea. In the adult group, 2 cases were associated with celiac disease, whereas an additional 5 individuals were found to have concurrent collagenous or lymphocytic colitis.1Brain O. Rajaguru C. Warren B. et al.Collagenous gastritis: reports and systematic review.Eur J Gastroenterol Hepatol. 2009; 21: 1419-1424Crossref PubMed Scopus (34) Google Scholar Various treatment approaches including acid suppression, corticosteroids, misoprostol, mesalamine, and sulfacrate were tried with mostly disappointing results; interventions therefore mainly focus on concurrent diseases such as gluten-free diet for celiac disease and budesonide for collagenous colitis.2Gopal P. McKenna B.J. The collagenous gastroenteritides: similarities and differences.Arch Pathol Lab Med. 2010; 134: 1485-1489Crossref PubMed Google Scholar Despite a sensitivity in the 90%–98% range of tTG antibodies for the detection of celiac disease, this case demonstrates that a negative IgA/IgG tTG cannot entirely exclude the diagnosis and that duodenal biopsies should still be obtained in the setting of a high clinical suspicion for celiac disease or an abnormal-appearing duodenum on endoscopy. Recent studies have also shown the importance of obtaining ≥1 biopsy from the duodenal bulb to avoid missing the diagnosis of celiac disease. In 126 patients with newly established celiac disease and 85 patients with a previous diagnosis on a gluten-free diet presenting for reevaluation, villous atrophy was limited to the duodenal bulb in 9% and 14% of cases, respectively.3Evans K.E. Aziz I. Cross S.S. et al.A prospective study of duodenal bulb biopsy in newly diagnosed and established adult celiac disease.Am J Gastroenterol. 2011; 106 (1837-1742)Crossref Scopus (84) Google Scholar

Over-Prescription of Acid-Suppressing Medications in Infants: How It Came About, Why It’s Wrong, and What to Do About It

It has been almost 20 years since proton pump inhibitors (PPIs) were initially shown to be effective, safe, and well-tolerated for the short-term treatment of gastroesophageal reflux disease (GERD) in children over 1 year of age 1 ; GERD diagnosed on the basis of symptoms and hard diagnostic evidence of erosive esophagitis seen at endoscopy. 2 In these studies, mostly performed in children 2 to 17 years of age, 1-3 PPIs were shown to effectively treat symptoms and erosive esophagitis that were refractory to histamine-2receptor antagonists (H2RA), buffering agents, prokinetics, and in some subjects, antireflux surgery. Subsequent to those studies with omeprazole, other PPIs were found to be similarly effective. 4-8 Efficacy and safety were also shown for maintenance of remission of chronic, relapsing erosive esophagitis in prospective studies as long as 2 years, 9 and retrospective studies as long as 11 years of use. 10 Approximately 80% 10 of children who require long-term treatment for GERD have underlying disorders that predispose them to GERD, such as neurologic impairment, repaired congenital esophageal anomalies (eg, esophageal atresia), chronic lung disease, hiatal hernia, a strong family history of GERD, Barrett’s esophagus, or esophageal adenocarcinoma, or obesity. 11 In children without these underlying disorders, GERDisusuallynotchronicorsevere, 12 andmostcommonly follows a presumed upper gastrointestinal infection with post-infectious dysmotility and delayed gastric emptying, which resolves with time. In other words, in most otherwise healthy children, GERD is not chronic. In children in whom it is, the use of PPIs has revolutionized the long-term treatment of GERD, much for the better, including allowing for significantly decreased rates of antireflux surgery in some centers. 13 In this overall context, the topic of reflux in infants (ie, 7-fold increase in PPI prescription. One of the PPIs, available in a child-friendly liquid formulation, saw a 16-fold increase in use during that 6-year period. 14 Overall, approximately 0.5% of the approximately one million infants in the study database received a PPI during their first year of life. Approximately 50% of the infants started taking a PPI before 4 months of age. 15 These data would imply that somehow the diagnosis of GERD has been missed over the past several decades or has recently become a major scourge of infants in the developed world, with acid suppressing drugs becoming a new essential food group in their own right. This change in practice has come about for several reasons, none based in medical science. There is, however, data to show that this practice does not serve our patients. Two phenomena have long been observed in otherwise healthy, thriving infants. First, many of them spit up on a daily basis—some 40% to 70%. 16,17 The developing, rapidly-growing infant takes in feeding volumes that on a per-kg basis are huge compared with older children or adults. Infants have relatively poor gastric compliance and a short esophagus; therefore, some of the large volume intake simply overflows upward, or sometimes ‘‘spills’’ (lingua Australiana) out through the mouth. This has long been recognized as physiologic reflux not reflux disease [ie, not GERD]), and it is self-resolving in approximately 95% of

2. As a Gastroenterologist; Supportive Situation for Concomitant Treatment with PPI and Anti-Platelet Drug

Clopidogrel, an anti-platelet drug, is converted to its active metabolite by cytochrome P450 (CYP) enzymes such as CYP2C19. Clopidogrel users with decreased CYP2C19 function, especially CYP2C19 poor metabolizers, have been reported to exhibit less inhibition of platelet aggregation and increased cardiovascular (CV) events. As metabolism of proton pump inhibitors (PPIs) involves CYP2C19, a hypothesis that competition by PPIs may interfere with clopidogrel-induced anti-platelet action is raised. Although a retrospective cohort study suggested that clopidogrel users prescribed PPIs had increased risks of CV events, a prospective randomized trial of omeprazole vs. placebo showed no difference in CV events. Therefore, the current evidence does not justify the conclusion that PPIs decrease the clinical efficacy of clopidogrel, and further study is required to clarify this discrepancy. Combination therapy of clopidogrel and aspirin causes the development of gastric mucosal injury and gastrointestinal bleeding, which is sometimes lethal. Therefore, current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a PPI to reduce gastrointestinal mucosal injury and bleeding. Physicians should consider the possibility of increased CV risk and gastrointestinal bleeding by concomitant clopidogrel plus aspirin treatment, and select the appropriate treatment for patients with cardiovascular diseases upon considering the benefit and risk.

Pancreatic Acinar Metaplasia (PAM) in the Distal Esophagus - Is it a Variant of Pancreatic Heterotopia or an Under Reported Histological Finding?

Purpose: Introduction: PAM consists of nests or lobules of pancreatic acinar cells which are characterized by the presence of fine acidophilic granules in the apical cytoplasm and prominent basophilia of the basal portion of the cells. They contain exocrine pancreatic markers such as lipase, trypsinogen, and pancreatic alpha-amylase. Pancreatic heterotopia (PH) (pancreatic rest) is distinguished from PAM by the presence of ductal elements, pancreatic stroma or well defined islets. We report a case of PAM above the gastro esophageal junction (GEJ) and present a brief review of the literature. Case: A 77 year old woman with known GERD for more than 10 years underwent a follow up EGD for refractory symptoms. Patient had a known history of acoustic neuroma treated with resection and radiotherapy, and hyper plastic colon polyps. The current EGD showed a small hiatus hernia and irregular Z line, a fundic gland polyp, and erythematous gastropathy. Biopsies of the distal esophagus showed gastric mucosa with ectopic pancreatic tissue and adjacent inflammation. There was no evidence of BE or H. Pylori gastritis. Discussion: Out of 644 patients who underwent EGD Johansson et al identified PAM above GEJ in 40 (6%), below GEJ in 67 (10%) and both above and below GEJ in 14 (2%). Female gender, H. Pylori infection and GERD were associated with PAM above the GEJ. Focal PAM was found in 11 of 350 (3.14%) biopsies of Barrett's mucosa from 120 patients with BE enrolled in a clinical efficacy trial of omeprazole versus ranitidine for treatment of GERD. Another study by Popiolek et al examined GEJ specimens from 69 young adults and children and found that PAM was present in 16% of the study population and was not associated with BE. The data suggested that PAM at the GEJ develops independently of inflammation and was felt to be a congenital. In contrast, anecdotal reports of heterotopic pancreas (commonly recognized as pancreatic rest) causing abdominal pain, acute pancreatititis, GI bleeding, gastric perforation, gastric outlet obstruction, obstructive jaundice, intussuception, pseudocyst formation, and rarely adenocarcinoma have been described. The presence of PAM above GEJ is likely congenital and may have no clinical relevance or malignant potential. However it remains a distinct and common histological finding and may be underreported in clinical practice.

Case 2: Making a diagnosis: Lest we forget the family

An 11-year-old girl was referred to the paediatric gastroenterology service with symptoms of hoarse voice, central chest discomfort with a frequent acidic taste in the mouth, and mild epigastric pain. An assessment by an otolaryngologist revealed congestion and small nodules on her vocal cords. A diagnosis of gastroesophageal reflux disease (GERD) had been entertained. The patient was otherwise well without any vomiting, dysphagia, alteration in stool pattern or weight loss. Her history was unremarkable, with normal growth and development. During history taking in the outpatient clinic, it was inquired as to whether anyone else in the family had similar problems. The mother reported that her husband had severe, chronic GERD requiring a fundoplication. The physical examination of the patient was normal. She was prescribed ranitidine and a follow-up was arranged. When the patient was seen two months later, there was little improvement in her symptoms. A trial of omeprazole was initiated. A lack of response led to an increase in the dose of the medication, but that was also of no avail. An upper gastrointestinal endoscopy was performed to look for reflux esophagitis or eosinophilic esophagitis. On endoscopy, the esophagus and stomach appeared normal. Inspection of the duodenum revealed the unexpected diagnosis.

Case 1: Vesicular rash in an infant

Afive-month-old term male infant was referred by his family doctor for evaluation of a vesicular rash. The mother first noticed several clusters of vesicles on the baby’s chest five days before presentation. In the subsequent four days, new adjacent vesicles erupted on the chest with clear discharge. He had slightly decreased appetite but normal voiding and stools, with no accompanying fever. A review of the infant’s systems was otherwise unremarkable. The baby was born to a 32-year-old Pakistani-Canadian woman who remained in Pakistan during her pregnancy. Antenatal screening for HIV, hepatitis B and syphilis was negative, and a rubella immunoglobulin G test was positive. The baby was born at 39 weeks’ gestational age by spontaneous vaginal delivery with no perinatal complications. The birth weight was 3.2 kg and the baby was discharged home on the second day of life with a normal physical examination. He had received his two- and four-month routine immunizations uneventfully. There was no family history of immunodeficiency or recurrent infections. A physical examination revealed a thriving, afebrile and well-appearing infant. Multiple crops of vesicles on an erythematous base were present on both the anterior and posterior right hemithorax (Figure 1). There were no satellite lesions. One further detail on history suggested the diagnosis. Case 2: Making a diagnosis: Lest we forget the family A n 11-year-old girl was referred to the paediatric gastroenterology service with symptoms of hoarse voice, central chest discomfort with a frequent acidic taste in the mouth, and mild epigastric pain. An assessment by an otolaryngologist revealed congestion and small nodules on her vocal cords. A diagnosis of gastroesophageal reflux disease (GERD) had been entertained. The patient was otherwise well without any vomiting, dysphagia, alteration in stool pattern or weight loss. Her history was unremarkable, with normal growth and development. During history taking in the outpatient clinic, it was inquired as to whether anyone else in the family had similar problems. The mother reported that her husband had severe, chronic GERD requiring a fundoplication. The physical examination of the patient was normal. She was prescribed ranitidine and a follow-up was arranged. When the patient was seen two months later, there was little improvement in her symptoms. A trial of omeprazole was initiated. A lack of response led to an increase in the dose of the medication, but that was also of no avail. An upper gastrointestinal endoscopy was performed to look for reflux esophagitis or eosinophilic esophagitis. On endoscopy, the esophagus and stomach appeared normal. Inspection of the duodenum revealed the unexpected diagnosis. CliniCian’s Corner

041 Clopidogrel and proton pump inhibitors: can near patient testing help to inform dual prescription?

Clopidogrel is relatively contraindicated in patients at risk of gastrointestinal bleeding. To reduce this risk, proton-pump inhibitors (PPI) which are often co-prescribed. Many PPIs undergo hepatic metabolism by the cytochrome (CYP) P450 isoenzymes, thus CYP P450-metabolised drugs, including clopidogrel become vulnerable to drug-drug interaction. Gilard et al first highlighted the negative impact of PPIs, on the pharmacodynamic response to clopidogrel in the randomised, double-blind Omeprazole CLopidogrel Aspirin (OCLA) trial. A randomised trial of omeprazole and pantoprazole conducted by Cuisset et al also demonstrated that after 1 month, patients receiving pantoprazole had significantly better platelet response to clopidogrel than those receiving omeprazole. Population-based studies have suggested that concomitant use of PPI with clopidogrel results in significantly increased risk of adverse outcomes. Anxieties brought on by such studies have been largely allayed by the recently presented results of the COGENT trial. This major randomised controlled trial, comparing clopidogrel with omeprazole vs clopidogrel alone demonstrated no difference in the risk of cardiovascular events between groups. We assessed the impact of PPI co-prescription on clopidogrel response using a verified near patient test, prospectively in 269 patients (mean age 63±11, 85 female) admitted with high risk ACS (characterised by electrocardiographic changes of ischaemia and/or raised troponin I). Loading and maintenance of clopidogrel was as per contemporary UK practice. Eighty-eight patients were prescribed a PPI concomitantly as in-patients. Platelet response to clopidogrel in whole blood samples, taken at the time of angiography, was assessed using a VerifyNow analyser (Accumetrics, California, US). Of the 269 patients recruited, 151 (56%) proceeded to PCI, 40 (15%) underwent coronary artery bypass grafting (CABG), 78 (29%) were treated medically. The clinical endpoint was adverse clinical events (ACE) at 18 months (death, MI, repeat revascularisation, CABG, stroke or unplanned cardiovascular hospitalisation). Co-administration of PPI and clopidogrel was associated with significantly reduced clopidogrel P2Y12 activity (p=0.022) (Abstract 41 Figure 1a) but not clinical outcome (ACE, p=0.123, Abstract 41 Figure 1b). Groups were well matched for age, gender, body mass index, current smoking, presence of diabetes and hyperlipidaemia. More patients in the PPI group had suffered a previous MI (36% vs 20%, p=0.007) and had received previous PCI treatment (20% vs 8%, p=0.005). As near patient tests of clopidogrel activity find their position in the care of patients with ischaemic heart disease, physicians may wish to use this technology to test patients at high risk of stent thrombosis who are also taking medications which pose a risk of inhibiting platelet clopidogrel response.

11 Month-Old Twins With Food Avoidance

Maggie and Lily are 11 month-old twins who are brought by their parents to the Developmental-Behavioral Pediatric Clinic for a life-long history of feeding difficulties. The twins are this couple's first children. Their mother is tearful as she recounts a stressful pregnancy complicated by pre-term labor beginning at 24 weeks gestation with strict bed rest for the remainder of the pregnancy. The twins were delivered at 35 weeks gestation by Caesarian Section. Lily weighed 5 lbs 11 oz; Maggie was small-for-gestational age with a birth weight of 3 lbs 13 oz. Maggie required oxygen with nasal prongs for only a few hours after birth. She remained in the Neonatal Intensive Care Unit (NICU) with initial nasogastric tube feeding; she was advanced to bottle feeding prior to discharge. Both Maggie and Lily were slow to initiate and sustain formula feeding. They required over 1 hour to consume 2 ounces of formula and "tire easily". At 1 month of age, Maggie resisted feedings by crying and arching her back. By 5 months of age, both children cried at the sight of the bottle and tried to push it away. However, they never lost weight. Maggie was treated with intermittent naso-gastric tube feeding at 5-6 months of age in order to gain adequate weight. At 11 months of age, both girls continued to resist feeding, but their mother was able to "get in" 24 ounces each day of a 31-calorie/ounce formula "with a lot of work". Dad observed that his wife's entire day revolved around getting the twins to eat and that became a significant stress for her as well as on their relationship. The children had a gastroenterology evaluation including an upper gastrointestinal series, pH probe and gastro-duodenal endoscopy with biopsies. All studies were normal. Trials of omeprazole, metoclopramide and thickened feeds did not improve their feeding problem. They are currently not on any medications. They have not had a history of vomiting, diarrhea, or diaphoresis with feeds, and they have experienced only 1 mild upper respiratory infection. One or two soft bowel movements occur each day. Developmentally, they are on track for their age. The parents report that they can pull up to a stand and cruise, use a pincer grasps, and speak "mama" discriminately. A review of their growth charts reveal that their weight is consistently between the 10-25% percentiles; weight is currently at the 25% percentile. Head circumference and height are between the 25-50% percentiles.