Reviews

GERD: Diagnosing and treating the burn

Cleveland Clinic Journal of Medicine. 2015 October;82(10):685-692

Author(s):

ABSTRACTGastroesophageal reflux disease (GERD) is chronic, very common, and frequently encountered in internal medicine and subspecialty clinics. It is often diagnosed on clinical grounds, but specialized testing such as endoscopy and pH monitoring may be necessary in certain patients. Although proton pump inhibitors (PPIs) are the mainstay of treatment, clinicians should be aware of their short-term and long-term side effects.

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KEY POINTS

GERD symptoms may be typical (eg, heartburn, regurgitation) or atypical (eg, cough, chest pain, hoarseness).
In patients with typical symptoms, a 6- to 8-week trial of a PPI is a reasonable and cost-effective approach to diagnosing GERD.
Endoscopy is indicated for patients who have alarm symptoms such as dysphagia, weight loss, and bleeding; it is unnecessary in patients who have typical GERD symptoms.
Ambulatory pH monitoring should be used in patients whose symptoms do not respond to a PPI and those in whom antireflux surgery is being considered.
Weight loss and head-of-bed elevation are the only lifestyle interventions that have been proven effective for GERD.
While risks of PPI use are rare, they should be discussed with patients on long-term therapy.
Symptoms that do not respond to a PPI are less likely to improve with antireflux surgery.

References

Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology 1997; 112:1448–1456.
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Globale Konsensusgrupp. [The Montreal definition and classification of gastroesophageal reflux disease: a global, evidence-based consensus paper]. Z Gastroenterol 2007; 45:1125–1240. In German.
Gerson LB, Kahrilas PJ, Fass R. Insights into gastroesophageal reflux disease-associated dyspeptic symptoms. Clin Gastroenterol Hepatol 2011; 9:824–833.
Vakil NB, Traxler B, Levine D. Dysphagia in patients with erosive esophagitis: prevalence, severity, and response to proton pump inhibitor treatment. Clin Gastroenterol Hepatol 2004; 2:665–668.
Kahrilas PJ, Shaheen NJ, aezi MF, et al; American Gastroenterological Association. American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease. Gastroenterology 2008; 135:1383–1391 e1–5.
Numans ME, Lau J, de Wit NJ, Bonis PA. Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Intern Med 2004; 140:518–527.
Fass R. Empirical trials in treatment of gastroesophageal reflux disease. Dig Dis 2000; 18:20–26.
Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999; 45:172–180.
Johansson KE, Ask P, Boeryd B, Fransson SG, Tibbling L. Oesophagitis, signs of reflux, and gastric acid secretion in patients with symptoms of gastro-oesophageal reflux disease. Scand J Gastroenterol 1986; 21:837–847.
Becher A, Dent J. Systematic review: ageing and gastro-oesophageal reflux disease symptoms, oesophageal function and reflux oesophagitis. Aliment Pharmacol Ther 2011; 33:442–454.
Charbel S, Khandwala F, Vaezi MF. The role of esophageal pH monitoring in symptomatic patients on PPI therapy. Am J Gastroenterol 2005; 100:283–289.
Pandolfino JE, Richter JE, Ours T, Guardino JM, Chapman J, Kahrilas PJ. Ambulatory esophageal pH monitoring using a wireless system. Am J Gastroenterol 2003; 98:740–749.
Prakash C, Clouse RE. Value of extended recording time with wireless pH monitoring in evaluating gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2005; 3:329–334.
Hirano I, Richter JE; Practice Parameters Committee of the American College of Gastroenterology. ACG practice guidelines: esophageal reflux testing. Am J Gastroenterol 2007; 102:668–685.
Jobe BA, Richter JE, Hoppo T, et al. Preoperative diagnostic workup before antireflux surgery: an evidence and experience-based consensus of the Esophageal Diagnostic Advisory Panel. J Am Coll Surg 2013; 217:586–597.
Singh S, Richter JE, Bradley LA, Haile JM. The symptom index. Differential usefulness in suspected acid-related complaints of heartburn and chest pain. Dig Dis Sci 1993; 38:1402–1408.
Weusten BL, Roelofs JM, Akkermans LM, Van Berge-Henegouwen GP, Smout AJ. The symptom-association probability: an improved method for symptom analysis of 24-hour esophageal pH data. Gastroenterology 1994; 107:1741–1745.
Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med 2006; 166:965–971.
Hamilton JW, Boisen RJ, Yamamoto DT, Wagner JL, Reichelderfer M. Sleeping on a wedge diminishes exposure of the esophagus to refluxed acid. Dig Dis Sci 1988; 33:518–522.
Pollmann H, Zillessen E, Pohl J, et al. [Effect of elevated head position in bed in therapy of gastroesophageal reflux]. Z Gastroenterol 1996; 34(suppl 2):93–99. In German.
Stanciu C, Bennett JR. Effects of posture on gastro-oesophageal reflux. Digestion 1977; 15:104–109.
Fraser-Moodie CA, Norton B, Gornall C, Magnago S, Weale AR, Holmes GK. Weight loss has an independent beneficial effect on symptoms of gastro-oesophageal reflux in patients who are overweight. Scand J Gastroenterol 1999; 34:337–340.
Mathus-Vliegen LM, Tytgat GN. Twenty-four-hour pH measurements in morbid obesity: effects of massive overweight, weight loss and gastric distension. Eur J Gastroenterol Hepatol 1996; 8:635–640.
Ness-Jensen E, Lindam A, Lagergren J, Hveem K. Tobacco smoking cessation and improved gastroesophageal reflux: a prospective population-based cohort study: the HUNT study. Am J Gastroenterol 2014; 109:171–177.
Collings KL, Rodriguez-Stanley S, Proskin HM, Robinson M, Miner PB Jr. Clinical effectiveness of a new antacid chewing gum on heartburn and oesophageal pH control. Aliment Pharmacol Ther 2002; 16:2029–2035.
Decktor DL, Robinson M, Maton PN, Lanza FL, Gottlieb S. Effects of aluminum/magnesium hydroxide and calcium carbonate on esophageal and gastric pH in subjects with heartburn. Am J Ther 1995; 2:546–552.
Pettit M. Treatment of gastroesophageal reflux disease. Pharm World Sci 2005; 27:432–435.
Fletcher J, Wirz A, Young J, Vallance R, McColl KE. Unbuffered highly acidic gastric juice exists at the gastroesophageal junction after a meal. Gastroenterology 2001; 121:775–783.
Sauter M, Curcic J, Menne D, et al. Measuring the interaction of meal and gastric secretion: a combined quantitative magnetic resonance imaging and pharmacokinetic modeling approach. Neurogastroenterol Motil 2012; 24:632–638, e272–e273.
Beaumont H, Bennink RJ, de Jong J, Boeckxstaens GE. The position of the acid pocket as a major risk factor for acidic reflux in healthy subjects and patients with GORD. Gut 2010; 59:441–451.
Tytgat GN, Simoneau G. Clinical and laboratory studies of the antacid and raft-forming properties of Rennie alginate suspension. Aliment Pharmacol Ther 2006; 23:759–765.
Chiu CT, Hsu CM, Wang CC, et al. Randomised clinical trial: sodium alginate oral suspension is non-inferior to omeprazole in the treatment of patients with non-erosive gastroesophageal disease. Aliment Pharmacol Ther 2013; 38:1054–1064.
Rohof WO, Bennink RJ, Smout AJ, Thomas E, Boeckxstaens GE. An alginate-antacid formulation localizes to the acid pocket to reduce acid reflux in patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2013; 11:1585–1591.
Khoury RM, Katz PO, Castell DO. Post-prandial ranitidine is superior to post-prandial omeprazole in control of gastric acidity in healthy volunteers. Aliment Pharmacol Ther 1999; 13:1211–1214.
Fackler WK, Ours TM, Vaezi MF, Richter JE. Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough. Gastroenterology 2002; 122:625–632.
Robinson M, Sahba B, Avner D, Jhala N, Greski-Rose PA, Jennings DE. A comparison of lansoprazole and ranitidine in the treatment of erosive oesophagitis. Multicentre Investigational Group. Aliment Pharmacol Ther 1995; 9:25–31.
Vantrappen G, Rutgeerts L, Schurmans P, Coenegrachts JL. Omeprazole (40 mg) is superior to ranitidine in short-term treatment of ulcerative reflux esophagitis. Dig Dis Sci 1988; 33:523–529.
Gralnek IM, Dulai GS, Fennerty MB, Spiegel BM. Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials. Clin Gastroenterol Hepatol 2006; 4:1452–1458.
Targownik LE, Lix LM, Leung S, Leslie WD. Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology 2010; 138:896–904.
Corley DA, Kubo A, Zhao W, Quesenberry C. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology 2010; 139:93–101.
Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013; 108:308–328.
Giuliano C, Wilhelm SM, Kale-Pradhan PB. Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis. Expert Rev Clin Pharmacol 2012; 5:337–344.
Hermos JA, Young MM, Fonda JR, Gagnon DR, Fiore LD, Lawler EV. Risk of community-acquired pneumonia in veteran patients to whom proton pump inhibitors were dispensed. Clin Infect Dis 2012; 54:33–42.
Linsky A, Gupta K, Lawler EV, Fonda JR, Hermos JA. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med 2010; 170:772–778.
Bavishi C, Dupont HL. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment Pharmacol Ther 2011; 34:1269–1281.
Bhatt DL, Cryer BL, Contant CF, et al; COGENT Investigators. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363:1909–1917.
O’Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet 2009; 374:989–997.
Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther 2012; 36:405–413.
Mittal RK, McCallum RW. Characteristics and frequency of transient relaxations of the lower esophageal sphincter in patients with reflux esophagitis. Gastroenterology 1988; 95:593–599.
Lidums I, Lehmann A, Checklin H, Dent J, Holloway RH. Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. Gastroenterology 2000; 118:7–13.
Cossentino MJ, Mann K, Armbruster SP, Lake JM, Maydonovitch C, Wong RK. Randomised clinical trial: the effect of baclofen in patients with gastro-oesophageal reflux—a randomised prospective study. Aliment Pharmacol Ther 2012; 35:1036–1044.
Richter JE. Gastroesophageal reflux disease treatment: side effects and complications of fundoplication. Clin Gastroenterol Hepatol 2013; 11:465–471.
Dickman R, Boaz M, Aizic S, Beniashvili Z, Fass R, Niv Y. Comparison of clinical characteristics of patients with gastroesophageal reflux disease who failed proton pump inhibitor therapy versus those who fully responded. J Neurogastroenterol Motil 2011; 17:387–394.
Chan WW, Chiou E, Obstein KL, Tignor AS, Whitlock TL. The efficacy of proton pump inhibitors for the treatment of asthma in adults: a meta-analysis. Arch Intern Med 2011; 171:620–629.
Chang AB, Lasserson TJ, Gaffney J, Connor FL, Garske LA. Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev 2011; 1:CD004823.
Qadeer MA, Phillips CO, Lopez AR, et al. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a meta-analysis of randomized controlled trials. Am J Gastroenterol 2006; 101:2646–2654.
Gerson LB, Mitra S, Bleker WF, Yeung P. Control of intra-oesophageal pH in patients with Barrett's oesophagus on omeprazole-sodium bicarbonate therapy. Aliment Pharmacol Ther 2012; 35:803–809.

Gastroesophageal reflux disease (GERD) is a chronic and common medical problem, with up to 40% of the population experiencing its symptoms at least once per month.¹ The condition develops when the reflux of stomach contents causes troublesome symptoms or complications.²

GERD symptoms can range from heartburn and regurgitation to cough and hoarseness. While many patients’ symptoms respond to medical treatment, the diagnosis and treatment in those whose symptoms do not respond to a proton pump inhibitor (PPI) may be challenging.

This article reviews the diagnosis and treatment options for GERD.

SYMPTOMS: TYPICAL, ATYPICAL, AND ALARM

Symptoms of GERD (Table 1) can be classified as typical (heartburn and regurgitation) or atypical (cough, asthma, hoarseness, chronic laryngitis, throat-clearing, chest pain, dyspepsia, and nausea). Atypical symptoms are more likely to be due to GERD if patients also have typical symptoms and if the symptoms respond to a trial of a PPI.³

Alarm symptoms. Keep in mind that extraesophageal presentations may be multifactorial, and it may be difficult to establish that reflux, even if present, is actually the cause. While chest pain may be due to GERD, it is important to rule out cardiac chest pain before considering GERD as a cause. Similarly, dysphagia along with typical or atypical symptoms warrants investigation for potential complications such as underlying motility disorder, esophageal stricture, esophageal ring, or malignancy.⁴ Other alarm symptoms include odynophagia, bleeding, weight loss, and anemia.

DIAGNOSING GERD: RESPONSE TO A PPI IS DIAGNOSTIC

Figure 1.

Patients with typical symptoms that respond to PPI therapy need no further evaluation for a diagnosis of GERD to be made.⁵ On the other hand, further testing should be undertaken in patients with typical symptoms that do not respond to PPI therapy, in patients presenting with atypical symptoms, and in patients in whom antireflux surgery is being considered. Figure 1 shows our proposed algorithm.

Try a PPI for 6–8 weeks

Relief of heartburn and regurgitation after a 6- to 8-week course of a PPI strongly suggests GERD.⁶ However, a negative trial of a PPI does not rule out GERD, as this approach has been found to have a sensitivity of 78% and specificity of 54%.⁶

Despite this limitation, a trial of PPI therapy should be offered to patients presenting with typical symptoms and no alarm features. This approach has been found to be more cost-effective than proceeding directly to diagnostic testing.⁷

References

Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology 1997; 112:1448–1456.
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Globale Konsensusgrupp. [The Montreal definition and classification of gastroesophageal reflux disease: a global, evidence-based consensus paper]. Z Gastroenterol 2007; 45:1125–1240. In German.
Gerson LB, Kahrilas PJ, Fass R. Insights into gastroesophageal reflux disease-associated dyspeptic symptoms. Clin Gastroenterol Hepatol 2011; 9:824–833.
Vakil NB, Traxler B, Levine D. Dysphagia in patients with erosive esophagitis: prevalence, severity, and response to proton pump inhibitor treatment. Clin Gastroenterol Hepatol 2004; 2:665–668.
Kahrilas PJ, Shaheen NJ, aezi MF, et al; American Gastroenterological Association. American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease. Gastroenterology 2008; 135:1383–1391 e1–5.
Numans ME, Lau J, de Wit NJ, Bonis PA. Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Intern Med 2004; 140:518–527.
Fass R. Empirical trials in treatment of gastroesophageal reflux disease. Dig Dis 2000; 18:20–26.
Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999; 45:172–180.
Johansson KE, Ask P, Boeryd B, Fransson SG, Tibbling L. Oesophagitis, signs of reflux, and gastric acid secretion in patients with symptoms of gastro-oesophageal reflux disease. Scand J Gastroenterol 1986; 21:837–847.
Becher A, Dent J. Systematic review: ageing and gastro-oesophageal reflux disease symptoms, oesophageal function and reflux oesophagitis. Aliment Pharmacol Ther 2011; 33:442–454.
Charbel S, Khandwala F, Vaezi MF. The role of esophageal pH monitoring in symptomatic patients on PPI therapy. Am J Gastroenterol 2005; 100:283–289.
Pandolfino JE, Richter JE, Ours T, Guardino JM, Chapman J, Kahrilas PJ. Ambulatory esophageal pH monitoring using a wireless system. Am J Gastroenterol 2003; 98:740–749.
Prakash C, Clouse RE. Value of extended recording time with wireless pH monitoring in evaluating gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2005; 3:329–334.
Hirano I, Richter JE; Practice Parameters Committee of the American College of Gastroenterology. ACG practice guidelines: esophageal reflux testing. Am J Gastroenterol 2007; 102:668–685.
Jobe BA, Richter JE, Hoppo T, et al. Preoperative diagnostic workup before antireflux surgery: an evidence and experience-based consensus of the Esophageal Diagnostic Advisory Panel. J Am Coll Surg 2013; 217:586–597.
Singh S, Richter JE, Bradley LA, Haile JM. The symptom index. Differential usefulness in suspected acid-related complaints of heartburn and chest pain. Dig Dis Sci 1993; 38:1402–1408.
Weusten BL, Roelofs JM, Akkermans LM, Van Berge-Henegouwen GP, Smout AJ. The symptom-association probability: an improved method for symptom analysis of 24-hour esophageal pH data. Gastroenterology 1994; 107:1741–1745.
Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med 2006; 166:965–971.
Hamilton JW, Boisen RJ, Yamamoto DT, Wagner JL, Reichelderfer M. Sleeping on a wedge diminishes exposure of the esophagus to refluxed acid. Dig Dis Sci 1988; 33:518–522.
Pollmann H, Zillessen E, Pohl J, et al. [Effect of elevated head position in bed in therapy of gastroesophageal reflux]. Z Gastroenterol 1996; 34(suppl 2):93–99. In German.
Stanciu C, Bennett JR. Effects of posture on gastro-oesophageal reflux. Digestion 1977; 15:104–109.
Fraser-Moodie CA, Norton B, Gornall C, Magnago S, Weale AR, Holmes GK. Weight loss has an independent beneficial effect on symptoms of gastro-oesophageal reflux in patients who are overweight. Scand J Gastroenterol 1999; 34:337–340.
Mathus-Vliegen LM, Tytgat GN. Twenty-four-hour pH measurements in morbid obesity: effects of massive overweight, weight loss and gastric distension. Eur J Gastroenterol Hepatol 1996; 8:635–640.
Ness-Jensen E, Lindam A, Lagergren J, Hveem K. Tobacco smoking cessation and improved gastroesophageal reflux: a prospective population-based cohort study: the HUNT study. Am J Gastroenterol 2014; 109:171–177.
Collings KL, Rodriguez-Stanley S, Proskin HM, Robinson M, Miner PB Jr. Clinical effectiveness of a new antacid chewing gum on heartburn and oesophageal pH control. Aliment Pharmacol Ther 2002; 16:2029–2035.
Decktor DL, Robinson M, Maton PN, Lanza FL, Gottlieb S. Effects of aluminum/magnesium hydroxide and calcium carbonate on esophageal and gastric pH in subjects with heartburn. Am J Ther 1995; 2:546–552.
Pettit M. Treatment of gastroesophageal reflux disease. Pharm World Sci 2005; 27:432–435.
Fletcher J, Wirz A, Young J, Vallance R, McColl KE. Unbuffered highly acidic gastric juice exists at the gastroesophageal junction after a meal. Gastroenterology 2001; 121:775–783.
Sauter M, Curcic J, Menne D, et al. Measuring the interaction of meal and gastric secretion: a combined quantitative magnetic resonance imaging and pharmacokinetic modeling approach. Neurogastroenterol Motil 2012; 24:632–638, e272–e273.
Beaumont H, Bennink RJ, de Jong J, Boeckxstaens GE. The position of the acid pocket as a major risk factor for acidic reflux in healthy subjects and patients with GORD. Gut 2010; 59:441–451.
Tytgat GN, Simoneau G. Clinical and laboratory studies of the antacid and raft-forming properties of Rennie alginate suspension. Aliment Pharmacol Ther 2006; 23:759–765.
Chiu CT, Hsu CM, Wang CC, et al. Randomised clinical trial: sodium alginate oral suspension is non-inferior to omeprazole in the treatment of patients with non-erosive gastroesophageal disease. Aliment Pharmacol Ther 2013; 38:1054–1064.
Rohof WO, Bennink RJ, Smout AJ, Thomas E, Boeckxstaens GE. An alginate-antacid formulation localizes to the acid pocket to reduce acid reflux in patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2013; 11:1585–1591.
Khoury RM, Katz PO, Castell DO. Post-prandial ranitidine is superior to post-prandial omeprazole in control of gastric acidity in healthy volunteers. Aliment Pharmacol Ther 1999; 13:1211–1214.
Fackler WK, Ours TM, Vaezi MF, Richter JE. Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough. Gastroenterology 2002; 122:625–632.
Robinson M, Sahba B, Avner D, Jhala N, Greski-Rose PA, Jennings DE. A comparison of lansoprazole and ranitidine in the treatment of erosive oesophagitis. Multicentre Investigational Group. Aliment Pharmacol Ther 1995; 9:25–31.
Vantrappen G, Rutgeerts L, Schurmans P, Coenegrachts JL. Omeprazole (40 mg) is superior to ranitidine in short-term treatment of ulcerative reflux esophagitis. Dig Dis Sci 1988; 33:523–529.
Gralnek IM, Dulai GS, Fennerty MB, Spiegel BM. Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials. Clin Gastroenterol Hepatol 2006; 4:1452–1458.
Targownik LE, Lix LM, Leung S, Leslie WD. Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology 2010; 138:896–904.
Corley DA, Kubo A, Zhao W, Quesenberry C. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology 2010; 139:93–101.
Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013; 108:308–328.
Giuliano C, Wilhelm SM, Kale-Pradhan PB. Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis. Expert Rev Clin Pharmacol 2012; 5:337–344.
Hermos JA, Young MM, Fonda JR, Gagnon DR, Fiore LD, Lawler EV. Risk of community-acquired pneumonia in veteran patients to whom proton pump inhibitors were dispensed. Clin Infect Dis 2012; 54:33–42.
Linsky A, Gupta K, Lawler EV, Fonda JR, Hermos JA. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med 2010; 170:772–778.
Bavishi C, Dupont HL. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment Pharmacol Ther 2011; 34:1269–1281.
Bhatt DL, Cryer BL, Contant CF, et al; COGENT Investigators. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363:1909–1917.
O’Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet 2009; 374:989–997.
Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther 2012; 36:405–413.
Mittal RK, McCallum RW. Characteristics and frequency of transient relaxations of the lower esophageal sphincter in patients with reflux esophagitis. Gastroenterology 1988; 95:593–599.
Lidums I, Lehmann A, Checklin H, Dent J, Holloway RH. Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. Gastroenterology 2000; 118:7–13.
Cossentino MJ, Mann K, Armbruster SP, Lake JM, Maydonovitch C, Wong RK. Randomised clinical trial: the effect of baclofen in patients with gastro-oesophageal reflux—a randomised prospective study. Aliment Pharmacol Ther 2012; 35:1036–1044.
Richter JE. Gastroesophageal reflux disease treatment: side effects and complications of fundoplication. Clin Gastroenterol Hepatol 2013; 11:465–471.
Dickman R, Boaz M, Aizic S, Beniashvili Z, Fass R, Niv Y. Comparison of clinical characteristics of patients with gastroesophageal reflux disease who failed proton pump inhibitor therapy versus those who fully responded. J Neurogastroenterol Motil 2011; 17:387–394.
Chan WW, Chiou E, Obstein KL, Tignor AS, Whitlock TL. The efficacy of proton pump inhibitors for the treatment of asthma in adults: a meta-analysis. Arch Intern Med 2011; 171:620–629.
Chang AB, Lasserson TJ, Gaffney J, Connor FL, Garske LA. Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev 2011; 1:CD004823.
Qadeer MA, Phillips CO, Lopez AR, et al. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a meta-analysis of randomized controlled trials. Am J Gastroenterol 2006; 101:2646–2654.
Gerson LB, Mitra S, Bleker WF, Yeung P. Control of intra-oesophageal pH in patients with Barrett's oesophagus on omeprazole-sodium bicarbonate therapy. Aliment Pharmacol Ther 2012; 35:803–809.

An unusual cause of vitamin B12 and iron deficiency

GERD: Diagnosing and treating the burn

References

SYMPTOMS: TYPICAL, ATYPICAL, AND ALARM

DIAGNOSING GERD: RESPONSE TO A PPI IS DIAGNOSTIC

Try a PPI for 6–8 weeks

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