Upper GI Tract

Introduction

Dysphagia is the sensation of difficulty swallowing food or liquid in the acute or chronic setting. The prevalence of dysphagia ranges based on the type and etiology but may impact up to one in six adults.^1,2 Dysphagia can cause a significant impact on a patient’s health and overall quality of life. A recent study found that only 50% of symptomatic adults seek medical care despite modifying their eating habits by either eating slowly or changing to softer foods or liquids.¹ The most common, serious complications of dysphagia include aspiration pneumonia, malnutrition, and dehydration.³ According to the Agency for Healthcare Research and Quality, dysphagia may be responsible for up to 60,000 deaths annually.³

History

The diagnosis of dysphagia begins with a thorough history. Questions about the timing, onset, progression, localization of symptoms, and types of food that are difficult to swallow are essential in differentiating oropharyngeal and esophageal dysphagia.^3,4 Further history taking must include medication and allergy review, smoking history, and review of prior radiation or surgical therapies to the head and neck.

Briefly, oropharyngeal dysphagia is difficulty initiating a swallow or passing food from the mouth or throat and can be caused by structural or functional etiologies.⁵ Clinical presentations include a sensation of food stuck in the back of the throat, coughing or choking while eating, or drooling. Structural causes include head and neck cancer, Zenker diverticulum, Killian Jamieson diverticula, prolonged intubation, or changes secondary to prior surgery or radiation.³ Functional causes may include neurologic, rheumatologic, or muscular disorders.⁶

Esophageal dysphagia refers to difficulty transporting food or liquid down the esophagus and can be caused by structural, inflammatory, or functional disorders.⁵ Patients typically localize symptoms of heartburn, regurgitation, nausea, vomiting, cough, or chest pain along the sternum or epigastric region. Alarm signs concerning for malignancy include unintentional weight loss, fevers, or night sweats.^3,7 Aside from symptoms, medication review is essential, as dysphagia is a common side effect of antipsychotics, anticholinergics, antimuscarinics, narcotics, and immunosuppressant drugs.⁸ Larger pills such as NSAIDs, antibiotics, bisphosphonates, potassium supplements, and methylxanthines can cause drug-induced esophagitis, which can initially present as dysphagia.⁸ Inflammatory causes can be elucidated by obtaining a history about allergies, tobacco use, and recent infections such as thrush or pneumonia. Patients with a history of recurrent pneumonias may be silently aspirating, a complication of dysphagia.³ Once esophageal dysphagia is clinically suspected based on history, workup can begin. 

Differentiating etiologies of esophageal dysphagia 

The next step in diagnosing esophageal dysphagia is differentiating between structural, inflammatory, or dysmotility etiology (Figure 1). 

Courtesy Tanisha Ronnie, MD, Lauren Bloomberg, MD, and Mukund Venu, MD

Patients with a structural cause typically have difficulty swallowing solids but are able to swallow liquids unless the disease progresses. Symptoms can rapidly worsen and lead to odynophagia, weight loss, and vomiting. In comparison, patients with motility disorders typically have difficulty swallowing both solids and liquids initially, and symptoms can be constant or intermittent.⁵ 

Prior to diagnostic studies, a 4-week trial of a proton pump inhibitor (PPI) is appropriate for patients with reflux symptoms who are younger than 50 with no alarm features concerning for malignancy.^7,9 If symptoms persist after a PPI trial, then an upper endoscopy (EGD) is indicated. An EGD allows for visualization of structural etiologies, obtaining biopsies to rule out inflammatory etiologies, and the option to therapeutically treat reduced luminal diameter with dilatation.¹⁰ The most common structural and inflammatory etiologies noted on EGD include strictures, webs, carcinomas, Schatzki rings, and gastroesophageal reflux or eosinophilic esophagitis.⁴

If upper endoscopy is normal and clinical suspicion for an obstructive cause remains high, barium esophagram can be utilized as an adjunctive study. Previously, barium esophagram was the initial test to distinguish between structural and motility disorders. The benefits of endoscopy over barium esophagram as the first diagnostic study include higher diagnostic yield, higher sensitivity and specificity, and lower costs.⁷ However, barium studies may be more sensitive for lower esophageal rings or extrinsic esophageal compression.3 

 

Evaluation of esophageal motility disorder

If a structural or inflammatory etiology of dysphagia is not identified, investigation for an esophageal motility disorder (EMD) is warranted. Examples of motility disorders include achalasia, ineffective esophageal motility, hypercontractility, spasticity, or esophagogastric junction outflow obstruction (EGJOO).^10,11 High-resolution esophageal manometry (HRM) remains the gold standard in diagnosis of EMD.¹² An HRM catheter utilizes 36 sensors placed two centimeters apart and is placed in the esophagus to evaluate pressure and peristalsis between the upper and lower esophageal sphincters.¹³ In 2009, the Chicago Classification System was developed to provide a diagnostic algorithm that categorizes EMD based on HRM testing, with the most recent version (4.0) being published in 2020.^12,14 Motility diagnoses are divided into two general classifications of disorders of body peristalsis and disorders of EGJ outflow. The most recent updates also include changes in swallow protocols, patient positioning, targeted symptoms, addition of impedance sensors, and consideration of supplemental testing when HRM is inconclusive based on the clinical context.¹² There are some limitations of HRM to highlight. One of the main diagnostic values used with HRM is the integrated relaxation pressure (IRP). Despite standardization, IRP measurements vary based on the recorder and patient position. A minority of patients with achalasia may have IRP that does not approach the accepted cutoff and, therefore, the EGJ is not accurately assessed on HRM.^15,16 In addition, some swallow protocols have lower sensitivity and specificity for certain motility disorders, and the test can result as inconclusive.14 In these scenarios, supplemental testing with timed barium esophagram or functional luminal imaging probe (EndoFLIP) is indicated.^10,11

Loyola University Chicago

Over the past decade, EndoFLIP has emerged as a novel diagnostic tool in evaluating EMD. EndoFLIP is usually completed during an upper endoscopy and utilizes impedance planimetry to measure cross-sectional area and esophageal distensibility and evaluate contractile patterns.¹⁶ During the procedure, a small catheter with an inflatable balloon is inserted into the esophagus with the distal end in the stomach, traversing the esophagogastric junction (EGJ). The pressure transducer has electrodes every centimeter to allow for a three-dimensional construction of the esophagus and EGJ.¹⁷ EndoFLIP has been shown to accurately measure pyloric diameter, pressure, and distensibility at certain balloon volumes.¹⁸ In addition, FLIP is being used to further identify aspects of esophageal dysmotility in patients with eosinophilic esophagitis, thought primarily to be an inflammatory disorder.¹⁹ However, limitations include minimal accessibility of EndoFLIP within clinical practice and a specific computer program needed to generate the topographic plots.²⁰ 

When used in conjunction with HRM, EndoFLIP provides complementary data that can be used to better detect major motility disorders.^15,20,21 Each study adds unique information about the different physiologic events comprising the esophageal response to distention. Overall, the benefits of EndoFLIP include expediting workup during index endoscopy, patient comfort with sedation, and real-time diagnostic data that supplement results obtained during HRM.^{10,16,20,2223}

Of note, if the diagnostic evaluation for structural, inflammatory, and motility disorders are unrevealing, investigating for atypical reflux symptoms can be pursued for patients with persistent dysphagia. Studies investigating pH, or acidity in the esophagus, in relation to symptoms, can be conducted wirelessly via a capsule fixed to the mucosa or with a nasal catheter.³

Normal workup – hypervigilance

In a subset of patients, all diagnostic testing for structural, inflammatory, or motility disorders is normal. These patients are classified as having a functional esophageal disorder. Despite normal testing, patients still have significant symptoms including epigastric pain, chest pain, globus sensation, or difficulty swallowing. It is theorized that a degree of visceral hypersensitivity between the brain-gut axis contributes to ongoing symptoms.²⁴ Studies for effective treatments are ongoing but typically include cognitive-behavioral therapy, brain-gut behavioral therapy, swallow therapy antidepressants, or short courses of proton pump inhibitors.⁹

Conclusion

In this review article, we discussed the diagnostic approach for esophageal dysphagia. Initial assessment requires a thorough history, differentiation between oropharyngeal and esophageal dysphagia, and determination of who warrants an upper endoscopy. Upper endoscopy may reveal structural or inflammatory causes of dysphagia, including strictures, masses, or esophagitis, to name a few. If a structural or inflammatory cause is ruled out, this warrants investigation for esophageal motility disorders. The current gold standard for diagnosing EMD is manometry, and supplemental studies, including EndoFLIP, barium esophagram, and pH studies, may provide complimentary data. If workup for dysphagia is normal, evaluation for esophageal hypervigilance causing increased sensitivity to normal or mild sensations may be warranted. In conclusion, the diagnosis of dysphagia is challenging and requires investigation with a systematic approach to ensure timely diagnosis and treatment

Dr. Ronnie and Dr. Bloomberg are in the department of internal medicine at Loyola University Chicago, Maywood, Ill. Dr. Venu is in the division of gastroenterology at Loyola. He is on the speakers bureau at Medtronic.

References 

1. Adkins C et al. Clin Gastroenterol Hepatol. 2020;18(9):1970-9.e2. 

2. Bhattacharyya N. Otolaryngol Head Neck Surg. 2014;151(5):765-9. 

3. McCarty EB and Chao TN. Med Clin North Am. 2021;105(5):939-54. 

4. Thiyagalingam S et al. Mayo Clin Proc. 2021;96(2):488-97. 

5. Malagelada JR et al. J Clin Gastroenterol. 2015;49(5):370-8.

6. Rommel, N and Hamdy S. Nat Rev Gastroenterol Hepatol. 2016;13(1):49-59. 

7. Liu LWC et al. J Can Assoc Gastroenterol. 2018;1(1):5-19. 

8. Schwemmle C et al. HNO. 2015;63(7):504-10. 

9. Moayyedi P et al. Am J Gastroenterol. 2017;112(7):988-1013. 

10. Triggs J and Pandolfino J. F1000Res. 2019 Aug 29. doi: 10.12688/f1000research.18900.1. 

11. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14058. 

12. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14053. 

13. Fox M et al. Neurogastroenterol Motil. 2004;16(5):533-42. 

14. Sweis R and Fox M. Curr Gastroenterol Rep. 2020;22(10):49. 

15. Carlson DA et al. Gastroenterology. 2015;149(7):1742-51. 

16. Donnan EN and Pandolfino JE. Gastroenterol Clin North Am. 2020;49(3):427-35. 

17. Carlson DA. Curr Opin Gastroenterol. 2016;32(4):310-8.
 

18. Zheng T et al. Neurogastroenterol Motil. 2022;34(10):e14386.

19. Carlson DA et al. Clin Gastroenterol Hepatol. 2022;20(8):1719-28.e3.

20. Carlson DA et al. Am J Gastroenterol. 2016;111(12):1726-35.

21. Carlson DA et al. Neurogastroenterol Motil. 2021;33(10):e14116.

22. Carlson DA et al. Gastrointest Endosc. 2019;90(6):915-923.e1.

23. Fox MR et al. Neurogastroenterol Motil. 2021;33(4):e14120.

24. Aziz Q et al. Gastroenterology. 2016 Feb 15. doi: 10.1053/j.gastro.2016.02.012.

Introduction

Dysphagia is the sensation of difficulty swallowing food or liquid in the acute or chronic setting. The prevalence of dysphagia ranges based on the type and etiology but may impact up to one in six adults.^1,2 Dysphagia can cause a significant impact on a patient’s health and overall quality of life. A recent study found that only 50% of symptomatic adults seek medical care despite modifying their eating habits by either eating slowly or changing to softer foods or liquids.¹ The most common, serious complications of dysphagia include aspiration pneumonia, malnutrition, and dehydration.³ According to the Agency for Healthcare Research and Quality, dysphagia may be responsible for up to 60,000 deaths annually.³

History

The diagnosis of dysphagia begins with a thorough history. Questions about the timing, onset, progression, localization of symptoms, and types of food that are difficult to swallow are essential in differentiating oropharyngeal and esophageal dysphagia.^3,4 Further history taking must include medication and allergy review, smoking history, and review of prior radiation or surgical therapies to the head and neck.

Briefly, oropharyngeal dysphagia is difficulty initiating a swallow or passing food from the mouth or throat and can be caused by structural or functional etiologies.⁵ Clinical presentations include a sensation of food stuck in the back of the throat, coughing or choking while eating, or drooling. Structural causes include head and neck cancer, Zenker diverticulum, Killian Jamieson diverticula, prolonged intubation, or changes secondary to prior surgery or radiation.³ Functional causes may include neurologic, rheumatologic, or muscular disorders.⁶

Esophageal dysphagia refers to difficulty transporting food or liquid down the esophagus and can be caused by structural, inflammatory, or functional disorders.⁵ Patients typically localize symptoms of heartburn, regurgitation, nausea, vomiting, cough, or chest pain along the sternum or epigastric region. Alarm signs concerning for malignancy include unintentional weight loss, fevers, or night sweats.^3,7 Aside from symptoms, medication review is essential, as dysphagia is a common side effect of antipsychotics, anticholinergics, antimuscarinics, narcotics, and immunosuppressant drugs.⁸ Larger pills such as NSAIDs, antibiotics, bisphosphonates, potassium supplements, and methylxanthines can cause drug-induced esophagitis, which can initially present as dysphagia.⁸ Inflammatory causes can be elucidated by obtaining a history about allergies, tobacco use, and recent infections such as thrush or pneumonia. Patients with a history of recurrent pneumonias may be silently aspirating, a complication of dysphagia.³ Once esophageal dysphagia is clinically suspected based on history, workup can begin. 

Differentiating etiologies of esophageal dysphagia 

The next step in diagnosing esophageal dysphagia is differentiating between structural, inflammatory, or dysmotility etiology (Figure 1). 

Courtesy Tanisha Ronnie, MD, Lauren Bloomberg, MD, and Mukund Venu, MD

Patients with a structural cause typically have difficulty swallowing solids but are able to swallow liquids unless the disease progresses. Symptoms can rapidly worsen and lead to odynophagia, weight loss, and vomiting. In comparison, patients with motility disorders typically have difficulty swallowing both solids and liquids initially, and symptoms can be constant or intermittent.⁵ 

Prior to diagnostic studies, a 4-week trial of a proton pump inhibitor (PPI) is appropriate for patients with reflux symptoms who are younger than 50 with no alarm features concerning for malignancy.^7,9 If symptoms persist after a PPI trial, then an upper endoscopy (EGD) is indicated. An EGD allows for visualization of structural etiologies, obtaining biopsies to rule out inflammatory etiologies, and the option to therapeutically treat reduced luminal diameter with dilatation.¹⁰ The most common structural and inflammatory etiologies noted on EGD include strictures, webs, carcinomas, Schatzki rings, and gastroesophageal reflux or eosinophilic esophagitis.⁴

If upper endoscopy is normal and clinical suspicion for an obstructive cause remains high, barium esophagram can be utilized as an adjunctive study. Previously, barium esophagram was the initial test to distinguish between structural and motility disorders. The benefits of endoscopy over barium esophagram as the first diagnostic study include higher diagnostic yield, higher sensitivity and specificity, and lower costs.⁷ However, barium studies may be more sensitive for lower esophageal rings or extrinsic esophageal compression.3 

 

Evaluation of esophageal motility disorder

If a structural or inflammatory etiology of dysphagia is not identified, investigation for an esophageal motility disorder (EMD) is warranted. Examples of motility disorders include achalasia, ineffective esophageal motility, hypercontractility, spasticity, or esophagogastric junction outflow obstruction (EGJOO).^10,11 High-resolution esophageal manometry (HRM) remains the gold standard in diagnosis of EMD.¹² An HRM catheter utilizes 36 sensors placed two centimeters apart and is placed in the esophagus to evaluate pressure and peristalsis between the upper and lower esophageal sphincters.¹³ In 2009, the Chicago Classification System was developed to provide a diagnostic algorithm that categorizes EMD based on HRM testing, with the most recent version (4.0) being published in 2020.^12,14 Motility diagnoses are divided into two general classifications of disorders of body peristalsis and disorders of EGJ outflow. The most recent updates also include changes in swallow protocols, patient positioning, targeted symptoms, addition of impedance sensors, and consideration of supplemental testing when HRM is inconclusive based on the clinical context.¹² There are some limitations of HRM to highlight. One of the main diagnostic values used with HRM is the integrated relaxation pressure (IRP). Despite standardization, IRP measurements vary based on the recorder and patient position. A minority of patients with achalasia may have IRP that does not approach the accepted cutoff and, therefore, the EGJ is not accurately assessed on HRM.^15,16 In addition, some swallow protocols have lower sensitivity and specificity for certain motility disorders, and the test can result as inconclusive.14 In these scenarios, supplemental testing with timed barium esophagram or functional luminal imaging probe (EndoFLIP) is indicated.^10,11

Loyola University Chicago

Over the past decade, EndoFLIP has emerged as a novel diagnostic tool in evaluating EMD. EndoFLIP is usually completed during an upper endoscopy and utilizes impedance planimetry to measure cross-sectional area and esophageal distensibility and evaluate contractile patterns.¹⁶ During the procedure, a small catheter with an inflatable balloon is inserted into the esophagus with the distal end in the stomach, traversing the esophagogastric junction (EGJ). The pressure transducer has electrodes every centimeter to allow for a three-dimensional construction of the esophagus and EGJ.¹⁷ EndoFLIP has been shown to accurately measure pyloric diameter, pressure, and distensibility at certain balloon volumes.¹⁸ In addition, FLIP is being used to further identify aspects of esophageal dysmotility in patients with eosinophilic esophagitis, thought primarily to be an inflammatory disorder.¹⁹ However, limitations include minimal accessibility of EndoFLIP within clinical practice and a specific computer program needed to generate the topographic plots.²⁰ 

When used in conjunction with HRM, EndoFLIP provides complementary data that can be used to better detect major motility disorders.^15,20,21 Each study adds unique information about the different physiologic events comprising the esophageal response to distention. Overall, the benefits of EndoFLIP include expediting workup during index endoscopy, patient comfort with sedation, and real-time diagnostic data that supplement results obtained during HRM.^{10,16,20,2223}

Of note, if the diagnostic evaluation for structural, inflammatory, and motility disorders are unrevealing, investigating for atypical reflux symptoms can be pursued for patients with persistent dysphagia. Studies investigating pH, or acidity in the esophagus, in relation to symptoms, can be conducted wirelessly via a capsule fixed to the mucosa or with a nasal catheter.³

Normal workup – hypervigilance

In a subset of patients, all diagnostic testing for structural, inflammatory, or motility disorders is normal. These patients are classified as having a functional esophageal disorder. Despite normal testing, patients still have significant symptoms including epigastric pain, chest pain, globus sensation, or difficulty swallowing. It is theorized that a degree of visceral hypersensitivity between the brain-gut axis contributes to ongoing symptoms.²⁴ Studies for effective treatments are ongoing but typically include cognitive-behavioral therapy, brain-gut behavioral therapy, swallow therapy antidepressants, or short courses of proton pump inhibitors.⁹

Conclusion

In this review article, we discussed the diagnostic approach for esophageal dysphagia. Initial assessment requires a thorough history, differentiation between oropharyngeal and esophageal dysphagia, and determination of who warrants an upper endoscopy. Upper endoscopy may reveal structural or inflammatory causes of dysphagia, including strictures, masses, or esophagitis, to name a few. If a structural or inflammatory cause is ruled out, this warrants investigation for esophageal motility disorders. The current gold standard for diagnosing EMD is manometry, and supplemental studies, including EndoFLIP, barium esophagram, and pH studies, may provide complimentary data. If workup for dysphagia is normal, evaluation for esophageal hypervigilance causing increased sensitivity to normal or mild sensations may be warranted. In conclusion, the diagnosis of dysphagia is challenging and requires investigation with a systematic approach to ensure timely diagnosis and treatment

Dr. Ronnie and Dr. Bloomberg are in the department of internal medicine at Loyola University Chicago, Maywood, Ill. Dr. Venu is in the division of gastroenterology at Loyola. He is on the speakers bureau at Medtronic.

References 

1. Adkins C et al. Clin Gastroenterol Hepatol. 2020;18(9):1970-9.e2. 

2. Bhattacharyya N. Otolaryngol Head Neck Surg. 2014;151(5):765-9. 

3. McCarty EB and Chao TN. Med Clin North Am. 2021;105(5):939-54. 

4. Thiyagalingam S et al. Mayo Clin Proc. 2021;96(2):488-97. 

5. Malagelada JR et al. J Clin Gastroenterol. 2015;49(5):370-8.

6. Rommel, N and Hamdy S. Nat Rev Gastroenterol Hepatol. 2016;13(1):49-59. 

7. Liu LWC et al. J Can Assoc Gastroenterol. 2018;1(1):5-19. 

8. Schwemmle C et al. HNO. 2015;63(7):504-10. 

9. Moayyedi P et al. Am J Gastroenterol. 2017;112(7):988-1013. 

10. Triggs J and Pandolfino J. F1000Res. 2019 Aug 29. doi: 10.12688/f1000research.18900.1. 

11. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14058. 

12. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14053. 

13. Fox M et al. Neurogastroenterol Motil. 2004;16(5):533-42. 

14. Sweis R and Fox M. Curr Gastroenterol Rep. 2020;22(10):49. 

15. Carlson DA et al. Gastroenterology. 2015;149(7):1742-51. 

16. Donnan EN and Pandolfino JE. Gastroenterol Clin North Am. 2020;49(3):427-35. 

17. Carlson DA. Curr Opin Gastroenterol. 2016;32(4):310-8.
 

18. Zheng T et al. Neurogastroenterol Motil. 2022;34(10):e14386.

19. Carlson DA et al. Clin Gastroenterol Hepatol. 2022;20(8):1719-28.e3.

20. Carlson DA et al. Am J Gastroenterol. 2016;111(12):1726-35.

21. Carlson DA et al. Neurogastroenterol Motil. 2021;33(10):e14116.

22. Carlson DA et al. Gastrointest Endosc. 2019;90(6):915-923.e1.

23. Fox MR et al. Neurogastroenterol Motil. 2021;33(4):e14120.

24. Aziz Q et al. Gastroenterology. 2016 Feb 15. doi: 10.1053/j.gastro.2016.02.012.

Introduction

Dysphagia is the sensation of difficulty swallowing food or liquid in the acute or chronic setting. The prevalence of dysphagia ranges based on the type and etiology but may impact up to one in six adults.^1,2 Dysphagia can cause a significant impact on a patient’s health and overall quality of life. A recent study found that only 50% of symptomatic adults seek medical care despite modifying their eating habits by either eating slowly or changing to softer foods or liquids.¹ The most common, serious complications of dysphagia include aspiration pneumonia, malnutrition, and dehydration.³ According to the Agency for Healthcare Research and Quality, dysphagia may be responsible for up to 60,000 deaths annually.³

History

The diagnosis of dysphagia begins with a thorough history. Questions about the timing, onset, progression, localization of symptoms, and types of food that are difficult to swallow are essential in differentiating oropharyngeal and esophageal dysphagia.^3,4 Further history taking must include medication and allergy review, smoking history, and review of prior radiation or surgical therapies to the head and neck.

Briefly, oropharyngeal dysphagia is difficulty initiating a swallow or passing food from the mouth or throat and can be caused by structural or functional etiologies.⁵ Clinical presentations include a sensation of food stuck in the back of the throat, coughing or choking while eating, or drooling. Structural causes include head and neck cancer, Zenker diverticulum, Killian Jamieson diverticula, prolonged intubation, or changes secondary to prior surgery or radiation.³ Functional causes may include neurologic, rheumatologic, or muscular disorders.⁶

Esophageal dysphagia refers to difficulty transporting food or liquid down the esophagus and can be caused by structural, inflammatory, or functional disorders.⁵ Patients typically localize symptoms of heartburn, regurgitation, nausea, vomiting, cough, or chest pain along the sternum or epigastric region. Alarm signs concerning for malignancy include unintentional weight loss, fevers, or night sweats.^3,7 Aside from symptoms, medication review is essential, as dysphagia is a common side effect of antipsychotics, anticholinergics, antimuscarinics, narcotics, and immunosuppressant drugs.⁸ Larger pills such as NSAIDs, antibiotics, bisphosphonates, potassium supplements, and methylxanthines can cause drug-induced esophagitis, which can initially present as dysphagia.⁸ Inflammatory causes can be elucidated by obtaining a history about allergies, tobacco use, and recent infections such as thrush or pneumonia. Patients with a history of recurrent pneumonias may be silently aspirating, a complication of dysphagia.³ Once esophageal dysphagia is clinically suspected based on history, workup can begin. 

Differentiating etiologies of esophageal dysphagia 

The next step in diagnosing esophageal dysphagia is differentiating between structural, inflammatory, or dysmotility etiology (Figure 1). 

Courtesy Tanisha Ronnie, MD, Lauren Bloomberg, MD, and Mukund Venu, MD

Patients with a structural cause typically have difficulty swallowing solids but are able to swallow liquids unless the disease progresses. Symptoms can rapidly worsen and lead to odynophagia, weight loss, and vomiting. In comparison, patients with motility disorders typically have difficulty swallowing both solids and liquids initially, and symptoms can be constant or intermittent.⁵ 

Prior to diagnostic studies, a 4-week trial of a proton pump inhibitor (PPI) is appropriate for patients with reflux symptoms who are younger than 50 with no alarm features concerning for malignancy.^7,9 If symptoms persist after a PPI trial, then an upper endoscopy (EGD) is indicated. An EGD allows for visualization of structural etiologies, obtaining biopsies to rule out inflammatory etiologies, and the option to therapeutically treat reduced luminal diameter with dilatation.¹⁰ The most common structural and inflammatory etiologies noted on EGD include strictures, webs, carcinomas, Schatzki rings, and gastroesophageal reflux or eosinophilic esophagitis.⁴

If upper endoscopy is normal and clinical suspicion for an obstructive cause remains high, barium esophagram can be utilized as an adjunctive study. Previously, barium esophagram was the initial test to distinguish between structural and motility disorders. The benefits of endoscopy over barium esophagram as the first diagnostic study include higher diagnostic yield, higher sensitivity and specificity, and lower costs.⁷ However, barium studies may be more sensitive for lower esophageal rings or extrinsic esophageal compression.3 

 

Evaluation of esophageal motility disorder

If a structural or inflammatory etiology of dysphagia is not identified, investigation for an esophageal motility disorder (EMD) is warranted. Examples of motility disorders include achalasia, ineffective esophageal motility, hypercontractility, spasticity, or esophagogastric junction outflow obstruction (EGJOO).^10,11 High-resolution esophageal manometry (HRM) remains the gold standard in diagnosis of EMD.¹² An HRM catheter utilizes 36 sensors placed two centimeters apart and is placed in the esophagus to evaluate pressure and peristalsis between the upper and lower esophageal sphincters.¹³ In 2009, the Chicago Classification System was developed to provide a diagnostic algorithm that categorizes EMD based on HRM testing, with the most recent version (4.0) being published in 2020.^12,14 Motility diagnoses are divided into two general classifications of disorders of body peristalsis and disorders of EGJ outflow. The most recent updates also include changes in swallow protocols, patient positioning, targeted symptoms, addition of impedance sensors, and consideration of supplemental testing when HRM is inconclusive based on the clinical context.¹² There are some limitations of HRM to highlight. One of the main diagnostic values used with HRM is the integrated relaxation pressure (IRP). Despite standardization, IRP measurements vary based on the recorder and patient position. A minority of patients with achalasia may have IRP that does not approach the accepted cutoff and, therefore, the EGJ is not accurately assessed on HRM.^15,16 In addition, some swallow protocols have lower sensitivity and specificity for certain motility disorders, and the test can result as inconclusive.14 In these scenarios, supplemental testing with timed barium esophagram or functional luminal imaging probe (EndoFLIP) is indicated.^10,11

Loyola University Chicago

Over the past decade, EndoFLIP has emerged as a novel diagnostic tool in evaluating EMD. EndoFLIP is usually completed during an upper endoscopy and utilizes impedance planimetry to measure cross-sectional area and esophageal distensibility and evaluate contractile patterns.¹⁶ During the procedure, a small catheter with an inflatable balloon is inserted into the esophagus with the distal end in the stomach, traversing the esophagogastric junction (EGJ). The pressure transducer has electrodes every centimeter to allow for a three-dimensional construction of the esophagus and EGJ.¹⁷ EndoFLIP has been shown to accurately measure pyloric diameter, pressure, and distensibility at certain balloon volumes.¹⁸ In addition, FLIP is being used to further identify aspects of esophageal dysmotility in patients with eosinophilic esophagitis, thought primarily to be an inflammatory disorder.¹⁹ However, limitations include minimal accessibility of EndoFLIP within clinical practice and a specific computer program needed to generate the topographic plots.²⁰ 

When used in conjunction with HRM, EndoFLIP provides complementary data that can be used to better detect major motility disorders.^15,20,21 Each study adds unique information about the different physiologic events comprising the esophageal response to distention. Overall, the benefits of EndoFLIP include expediting workup during index endoscopy, patient comfort with sedation, and real-time diagnostic data that supplement results obtained during HRM.^{10,16,20,2223}

Of note, if the diagnostic evaluation for structural, inflammatory, and motility disorders are unrevealing, investigating for atypical reflux symptoms can be pursued for patients with persistent dysphagia. Studies investigating pH, or acidity in the esophagus, in relation to symptoms, can be conducted wirelessly via a capsule fixed to the mucosa or with a nasal catheter.³

Normal workup – hypervigilance

In a subset of patients, all diagnostic testing for structural, inflammatory, or motility disorders is normal. These patients are classified as having a functional esophageal disorder. Despite normal testing, patients still have significant symptoms including epigastric pain, chest pain, globus sensation, or difficulty swallowing. It is theorized that a degree of visceral hypersensitivity between the brain-gut axis contributes to ongoing symptoms.²⁴ Studies for effective treatments are ongoing but typically include cognitive-behavioral therapy, brain-gut behavioral therapy, swallow therapy antidepressants, or short courses of proton pump inhibitors.⁹

Conclusion

In this review article, we discussed the diagnostic approach for esophageal dysphagia. Initial assessment requires a thorough history, differentiation between oropharyngeal and esophageal dysphagia, and determination of who warrants an upper endoscopy. Upper endoscopy may reveal structural or inflammatory causes of dysphagia, including strictures, masses, or esophagitis, to name a few. If a structural or inflammatory cause is ruled out, this warrants investigation for esophageal motility disorders. The current gold standard for diagnosing EMD is manometry, and supplemental studies, including EndoFLIP, barium esophagram, and pH studies, may provide complimentary data. If workup for dysphagia is normal, evaluation for esophageal hypervigilance causing increased sensitivity to normal or mild sensations may be warranted. In conclusion, the diagnosis of dysphagia is challenging and requires investigation with a systematic approach to ensure timely diagnosis and treatment

Dr. Ronnie and Dr. Bloomberg are in the department of internal medicine at Loyola University Chicago, Maywood, Ill. Dr. Venu is in the division of gastroenterology at Loyola. He is on the speakers bureau at Medtronic.

References 

1. Adkins C et al. Clin Gastroenterol Hepatol. 2020;18(9):1970-9.e2. 

2. Bhattacharyya N. Otolaryngol Head Neck Surg. 2014;151(5):765-9. 

3. McCarty EB and Chao TN. Med Clin North Am. 2021;105(5):939-54. 

4. Thiyagalingam S et al. Mayo Clin Proc. 2021;96(2):488-97. 

5. Malagelada JR et al. J Clin Gastroenterol. 2015;49(5):370-8.

6. Rommel, N and Hamdy S. Nat Rev Gastroenterol Hepatol. 2016;13(1):49-59. 

7. Liu LWC et al. J Can Assoc Gastroenterol. 2018;1(1):5-19. 

8. Schwemmle C et al. HNO. 2015;63(7):504-10. 

9. Moayyedi P et al. Am J Gastroenterol. 2017;112(7):988-1013. 

10. Triggs J and Pandolfino J. F1000Res. 2019 Aug 29. doi: 10.12688/f1000research.18900.1. 

11. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14058. 

12. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14053. 

13. Fox M et al. Neurogastroenterol Motil. 2004;16(5):533-42. 

14. Sweis R and Fox M. Curr Gastroenterol Rep. 2020;22(10):49. 

15. Carlson DA et al. Gastroenterology. 2015;149(7):1742-51. 

16. Donnan EN and Pandolfino JE. Gastroenterol Clin North Am. 2020;49(3):427-35. 

17. Carlson DA. Curr Opin Gastroenterol. 2016;32(4):310-8.
 

18. Zheng T et al. Neurogastroenterol Motil. 2022;34(10):e14386.

19. Carlson DA et al. Clin Gastroenterol Hepatol. 2022;20(8):1719-28.e3.

20. Carlson DA et al. Am J Gastroenterol. 2016;111(12):1726-35.

21. Carlson DA et al. Neurogastroenterol Motil. 2021;33(10):e14116.

22. Carlson DA et al. Gastrointest Endosc. 2019;90(6):915-923.e1.

23. Fox MR et al. Neurogastroenterol Motil. 2021;33(4):e14120.

24. Aziz Q et al. Gastroenterology. 2016 Feb 15. doi: 10.1053/j.gastro.2016.02.012.

People who have had COVID-19 have a 36% overall higher risk of developing gastrointestinal problems in the year after infection than people who have not had the illness, a large new study indicates.

The researchers estimate that, so far, SARS-CoV-2 infections have contributed to more than 6 million new cases of GI disorders in the United States and 42 million new cases worldwide.

The diagnoses more common among patients who’ve had COVID ranged from stomach upset to acute pancreatitis, say the researchers, led by Evan Xu, a data analyst at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System.

Signs and symptoms of GI problems, such as constipation and diarrhea, also were more common among patients who had had the virus, the study found.

“Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19,” the researchers write. “Post-COVID care should involve attention to gastrointestinal health and disease.”

The results were published online in Nature Communications.
 

Disease risks jump

The researchers used data from the U.S. Department of Veterans Affairs national health care databases to identify 154,068 people with confirmed COVID-19 from March 1, 2020, through Jan. 15, 2021. They used statistical modeling to compare those patients with 5.6 million patients with similar characteristics who had not been infected during the same period and an historical control group of 5.9 million patients from March 1, 2018, to Dec. 31, 2019, before the virus began to spread across the globe.

The study included hospitalized and nonhospitalized COVID patients. The majority of the study population was male, but the study included almost 1.2 million female patients.

Compared with control persons, post-COVID patients’ increased risk of a GI diagnosis and the excess disease burden at 1 year, respectively, were as follows.

• 102% for cholangitis; 0.22 per 1,000 persons
• 62% for peptic ulcer disease; 1.57 per 1,000 persons
• 54% for irritable bowel syndrome; 0.44 per 1,000 persons
• 47% for acute gastritis; 0.47 per 1,000 persons
• 46% for acute pancreatitis; 0.6 per 1,000 persons
• 36% for functional dyspepsia; 0.63 per 1,000 persons
• 35% for gastroesophageal reflux disease; 15.5 per 1,000 persons

Patients who’d had the virus were also at higher risk for GI symptoms than their COVID-free peers. Their risk was 60% higher for constipation, 58% for diarrhea, 52% for vomiting, 46% for bloating, and 44% for abdominal pain, the investigators found.

The risk of developing GI symptoms increased with COVID-19 severity and was highest for those who received intensive care because of the virus, the researchers note.

Subgroup analyses found that the risks of composite gastrointestinal outcome were evident in all subgroups based on age, race, sex, obesity, smoking, cardiovascular disease, chronic kidney disease, diabetes, hyperlipidemia, and hypertension, the authors write.
 

Disease burden rises

The increased numbers of GI patients with prior SARS-CoV-2 infection are altering the burden on the health care system, senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University, St. Louis, said in an interview.

The shift may be pronounced in primary care, where GI concerns should be seen as a trigger for questions about prior SARS-CoV-2 infection, Dr. Al-Aly said.

Patients may encounter longer wait times at GI clinics or may give up on trying to schedule appointments if waits become too long, he said. They may also present to emergency departments if they can’t get an outpatient appointment, he added.

Simon C. Mathews, MD, assistant professor of medicine, division of gastroenterology, Johns Hopkins Medicine, Baltimore, told this news organization that he’s seeing increased wait times since COVID emerged.

“We know that the pandemic impacted patients’ ability and willingness to seek GI care. There continues to be a long backlog for patients who are only now getting reconnected to care. As a result, our clinics are busier than ever, and our wait times for appointments are unfortunately longer than we would like,” said Dr. Mathews, who was not involved in the research.

Abdominal pain, bloating, diarrhea, and constipation continue to be among the most common symptoms Dr. Mathews sees in clinic, he said.

Kyle Staller, MD, a Massachusetts General Brigham gastroenterologist, said in an interview that it’s important to distinguish symptoms from eventual diagnoses, which lag behind.

“Are patients attributing their symptoms to COVID, or is COVID itself creating a background of inflammation or changes in the nerves that are making these symptoms more common? My suspicion is a little bit of both,” said Dr. Staller, who is director of the Gastrointestinal Motility Laboratory at Mass General, Boston.

Although his clinic is seeing patients with the GI signs and symptoms listed in the article, “we’re not seeing as much of some of the diagnoses, like peptic ulcer disease and pancreatitis,” he said. “I wonder if those may be related to some of the consequences of being critically ill in general, rather than COVID specifically. Those diagnoses I would be more skeptical about.”
 

Duration of symptoms unclear

It’s hard to tell patients how long their GI symptoms might last after COVID, given the relatively short time researchers have had to study the virus, said Dr. Staller, who was not involved in the research.

The symptoms he’s seeing in patients after COVID mimic those of postinfectious IBS, which literature says could last for months or years, Dr. Staller said. “But they should improve over time,” he added.

Senior author Dr. Al-Aly agreed that the duration of post-COVID GI symptoms is unclear.

“What I can tell you is that even people who got SARS-CoV-2 infection from March 2020 are still coming back for GI problems,” he said.

Unlike other symptoms of long COVID, such as brain fog, gastroenterologists fortunately know how to treat the GI disorders that evolve from SARS-CoV-2 infection, said Dr. Al-Aly, who has studied the long-term effects of the virus on the brain, kidneys, heart, and other organs.

All health care providers “need to be thinking about COVID as a risk factor for all these diseases” and should ask patients about SARS-CoV-2 infection when they take their histories, he said.

The authors, Dr. Staller, and Dr. Mathews report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have had COVID-19 have a 36% overall higher risk of developing gastrointestinal problems in the year after infection than people who have not had the illness, a large new study indicates.

The researchers estimate that, so far, SARS-CoV-2 infections have contributed to more than 6 million new cases of GI disorders in the United States and 42 million new cases worldwide.

The diagnoses more common among patients who’ve had COVID ranged from stomach upset to acute pancreatitis, say the researchers, led by Evan Xu, a data analyst at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System.

Signs and symptoms of GI problems, such as constipation and diarrhea, also were more common among patients who had had the virus, the study found.

“Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19,” the researchers write. “Post-COVID care should involve attention to gastrointestinal health and disease.”

The results were published online in Nature Communications.
 

Disease risks jump

The researchers used data from the U.S. Department of Veterans Affairs national health care databases to identify 154,068 people with confirmed COVID-19 from March 1, 2020, through Jan. 15, 2021. They used statistical modeling to compare those patients with 5.6 million patients with similar characteristics who had not been infected during the same period and an historical control group of 5.9 million patients from March 1, 2018, to Dec. 31, 2019, before the virus began to spread across the globe.

The study included hospitalized and nonhospitalized COVID patients. The majority of the study population was male, but the study included almost 1.2 million female patients.

Compared with control persons, post-COVID patients’ increased risk of a GI diagnosis and the excess disease burden at 1 year, respectively, were as follows.

• 102% for cholangitis; 0.22 per 1,000 persons
• 62% for peptic ulcer disease; 1.57 per 1,000 persons
• 54% for irritable bowel syndrome; 0.44 per 1,000 persons
• 47% for acute gastritis; 0.47 per 1,000 persons
• 46% for acute pancreatitis; 0.6 per 1,000 persons
• 36% for functional dyspepsia; 0.63 per 1,000 persons
• 35% for gastroesophageal reflux disease; 15.5 per 1,000 persons

Patients who’d had the virus were also at higher risk for GI symptoms than their COVID-free peers. Their risk was 60% higher for constipation, 58% for diarrhea, 52% for vomiting, 46% for bloating, and 44% for abdominal pain, the investigators found.

The risk of developing GI symptoms increased with COVID-19 severity and was highest for those who received intensive care because of the virus, the researchers note.

Subgroup analyses found that the risks of composite gastrointestinal outcome were evident in all subgroups based on age, race, sex, obesity, smoking, cardiovascular disease, chronic kidney disease, diabetes, hyperlipidemia, and hypertension, the authors write.
 

Disease burden rises

The increased numbers of GI patients with prior SARS-CoV-2 infection are altering the burden on the health care system, senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University, St. Louis, said in an interview.

The shift may be pronounced in primary care, where GI concerns should be seen as a trigger for questions about prior SARS-CoV-2 infection, Dr. Al-Aly said.

Patients may encounter longer wait times at GI clinics or may give up on trying to schedule appointments if waits become too long, he said. They may also present to emergency departments if they can’t get an outpatient appointment, he added.

Simon C. Mathews, MD, assistant professor of medicine, division of gastroenterology, Johns Hopkins Medicine, Baltimore, told this news organization that he’s seeing increased wait times since COVID emerged.

“We know that the pandemic impacted patients’ ability and willingness to seek GI care. There continues to be a long backlog for patients who are only now getting reconnected to care. As a result, our clinics are busier than ever, and our wait times for appointments are unfortunately longer than we would like,” said Dr. Mathews, who was not involved in the research.

Abdominal pain, bloating, diarrhea, and constipation continue to be among the most common symptoms Dr. Mathews sees in clinic, he said.

Kyle Staller, MD, a Massachusetts General Brigham gastroenterologist, said in an interview that it’s important to distinguish symptoms from eventual diagnoses, which lag behind.

“Are patients attributing their symptoms to COVID, or is COVID itself creating a background of inflammation or changes in the nerves that are making these symptoms more common? My suspicion is a little bit of both,” said Dr. Staller, who is director of the Gastrointestinal Motility Laboratory at Mass General, Boston.

Although his clinic is seeing patients with the GI signs and symptoms listed in the article, “we’re not seeing as much of some of the diagnoses, like peptic ulcer disease and pancreatitis,” he said. “I wonder if those may be related to some of the consequences of being critically ill in general, rather than COVID specifically. Those diagnoses I would be more skeptical about.”
 

Duration of symptoms unclear

It’s hard to tell patients how long their GI symptoms might last after COVID, given the relatively short time researchers have had to study the virus, said Dr. Staller, who was not involved in the research.

The symptoms he’s seeing in patients after COVID mimic those of postinfectious IBS, which literature says could last for months or years, Dr. Staller said. “But they should improve over time,” he added.

Senior author Dr. Al-Aly agreed that the duration of post-COVID GI symptoms is unclear.

“What I can tell you is that even people who got SARS-CoV-2 infection from March 2020 are still coming back for GI problems,” he said.

Unlike other symptoms of long COVID, such as brain fog, gastroenterologists fortunately know how to treat the GI disorders that evolve from SARS-CoV-2 infection, said Dr. Al-Aly, who has studied the long-term effects of the virus on the brain, kidneys, heart, and other organs.

All health care providers “need to be thinking about COVID as a risk factor for all these diseases” and should ask patients about SARS-CoV-2 infection when they take their histories, he said.

The authors, Dr. Staller, and Dr. Mathews report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have had COVID-19 have a 36% overall higher risk of developing gastrointestinal problems in the year after infection than people who have not had the illness, a large new study indicates.

The researchers estimate that, so far, SARS-CoV-2 infections have contributed to more than 6 million new cases of GI disorders in the United States and 42 million new cases worldwide.

The diagnoses more common among patients who’ve had COVID ranged from stomach upset to acute pancreatitis, say the researchers, led by Evan Xu, a data analyst at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System.

Signs and symptoms of GI problems, such as constipation and diarrhea, also were more common among patients who had had the virus, the study found.

“Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19,” the researchers write. “Post-COVID care should involve attention to gastrointestinal health and disease.”

The results were published online in Nature Communications.
 

Disease risks jump

The researchers used data from the U.S. Department of Veterans Affairs national health care databases to identify 154,068 people with confirmed COVID-19 from March 1, 2020, through Jan. 15, 2021. They used statistical modeling to compare those patients with 5.6 million patients with similar characteristics who had not been infected during the same period and an historical control group of 5.9 million patients from March 1, 2018, to Dec. 31, 2019, before the virus began to spread across the globe.

The study included hospitalized and nonhospitalized COVID patients. The majority of the study population was male, but the study included almost 1.2 million female patients.

Compared with control persons, post-COVID patients’ increased risk of a GI diagnosis and the excess disease burden at 1 year, respectively, were as follows.

• 102% for cholangitis; 0.22 per 1,000 persons
• 62% for peptic ulcer disease; 1.57 per 1,000 persons
• 54% for irritable bowel syndrome; 0.44 per 1,000 persons
• 47% for acute gastritis; 0.47 per 1,000 persons
• 46% for acute pancreatitis; 0.6 per 1,000 persons
• 36% for functional dyspepsia; 0.63 per 1,000 persons
• 35% for gastroesophageal reflux disease; 15.5 per 1,000 persons

Patients who’d had the virus were also at higher risk for GI symptoms than their COVID-free peers. Their risk was 60% higher for constipation, 58% for diarrhea, 52% for vomiting, 46% for bloating, and 44% for abdominal pain, the investigators found.

The risk of developing GI symptoms increased with COVID-19 severity and was highest for those who received intensive care because of the virus, the researchers note.

Subgroup analyses found that the risks of composite gastrointestinal outcome were evident in all subgroups based on age, race, sex, obesity, smoking, cardiovascular disease, chronic kidney disease, diabetes, hyperlipidemia, and hypertension, the authors write.
 

Disease burden rises

The increased numbers of GI patients with prior SARS-CoV-2 infection are altering the burden on the health care system, senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University, St. Louis, said in an interview.

The shift may be pronounced in primary care, where GI concerns should be seen as a trigger for questions about prior SARS-CoV-2 infection, Dr. Al-Aly said.

Patients may encounter longer wait times at GI clinics or may give up on trying to schedule appointments if waits become too long, he said. They may also present to emergency departments if they can’t get an outpatient appointment, he added.

Simon C. Mathews, MD, assistant professor of medicine, division of gastroenterology, Johns Hopkins Medicine, Baltimore, told this news organization that he’s seeing increased wait times since COVID emerged.

“We know that the pandemic impacted patients’ ability and willingness to seek GI care. There continues to be a long backlog for patients who are only now getting reconnected to care. As a result, our clinics are busier than ever, and our wait times for appointments are unfortunately longer than we would like,” said Dr. Mathews, who was not involved in the research.

Abdominal pain, bloating, diarrhea, and constipation continue to be among the most common symptoms Dr. Mathews sees in clinic, he said.

Kyle Staller, MD, a Massachusetts General Brigham gastroenterologist, said in an interview that it’s important to distinguish symptoms from eventual diagnoses, which lag behind.

“Are patients attributing their symptoms to COVID, or is COVID itself creating a background of inflammation or changes in the nerves that are making these symptoms more common? My suspicion is a little bit of both,” said Dr. Staller, who is director of the Gastrointestinal Motility Laboratory at Mass General, Boston.

Although his clinic is seeing patients with the GI signs and symptoms listed in the article, “we’re not seeing as much of some of the diagnoses, like peptic ulcer disease and pancreatitis,” he said. “I wonder if those may be related to some of the consequences of being critically ill in general, rather than COVID specifically. Those diagnoses I would be more skeptical about.”
 

Duration of symptoms unclear

It’s hard to tell patients how long their GI symptoms might last after COVID, given the relatively short time researchers have had to study the virus, said Dr. Staller, who was not involved in the research.

The symptoms he’s seeing in patients after COVID mimic those of postinfectious IBS, which literature says could last for months or years, Dr. Staller said. “But they should improve over time,” he added.

Senior author Dr. Al-Aly agreed that the duration of post-COVID GI symptoms is unclear.

“What I can tell you is that even people who got SARS-CoV-2 infection from March 2020 are still coming back for GI problems,” he said.

Unlike other symptoms of long COVID, such as brain fog, gastroenterologists fortunately know how to treat the GI disorders that evolve from SARS-CoV-2 infection, said Dr. Al-Aly, who has studied the long-term effects of the virus on the brain, kidneys, heart, and other organs.

All health care providers “need to be thinking about COVID as a risk factor for all these diseases” and should ask patients about SARS-CoV-2 infection when they take their histories, he said.

The authors, Dr. Staller, and Dr. Mathews report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For adults with eosinophilic esophagitis (EoE), eliminating animal milk alone appears to be as effective for treating the disease as forgoing milk and five other foods, according to a new report.

A one-food elimination diet (1FED) led to histologic remission in 34% of patients, as determined on the basis of eosinophil count at 6 weeks, and in 40% of patients who followed a six-food elimination diet (6FED) – a nonstatistical difference, the research team wrote.

“The takeaway message is that one-food (milk) elimination is an effective treatment and a reasonable first-line treatment for EoE,” senior study author Marc Rothenberg, MD, PhD, a professor of pediatrics and director of the allergy and immunology division at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, said in an interview.

“The study was designed by the Consortium of Eosinophilic Disease Researchers (CEGIR), which includes the nation’s top institutions working with patient advocacy groups, together with the National Institutes of Health,” he said. “The group, under advice from patients, determined that it was an important question to research if one-food elimination would be effective – and how effective – compared with six-food elimination.”

The study was published in The Lancet Gastroenterology and Hepatology.
 

Studying EOE and food elimination

Previous studies have found that eliminating six common foods that trigger esophageal injury – milk, eggs, wheat, soy, fish, and nuts – can substantially reduce EoE symptoms. The 6FED has become a common approach to managing the disease.

In recent years, however, researchers have conducted small, nonrandomized studies of the less restrictive 1FED and have found some success.

In a multisite, randomized trial, Dr. Rothenberg and colleagues compared the 6FED with the 1FED among 129 adults aged 18-60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in esophageal tissue. The participants enrolled at 1 of 10 U.S. medical centers that participate in CEGIR, which is part of the NIH-funded Rare Diseases Clinical Research Network.

Between 2016 and 2019, 67 participants were assigned to the 1FED group, which eliminated only animal milk from the diet, and 62 participants were assigned to the 6FED group, which eliminated milk, eggs, wheat, soy, fish/shellfish, and peanuts/tree nuts. After following the diet for 6 weeks, participants underwent an upper endoscopy exam and esophageal tissue biopsy. The primary endpoint was the proportion of patients with histologic remission, or a peak count of less than 15 eosinophils per high-power field (eos/hpf).

If the number of eosinophils indicated that EoE was in remission, the participant exited the study. If EoE wasn’t in remission, those who were on 1FED could proceed to 6FED, and those who were on 6FED could take fluticasone propionate 880 mcg two times per day with an unrestricted diet. Both groups followed the protocols for 6 weeks and underwent another exam with tissue biopsy.

At 6 weeks, 25 patients (40%) on 6FED and 23 patients (34%) on 1FED achieved histologic remission. The difference was not statistically significant.

There were also no significant differences between the groups at stricter thresholds for partial remission, defined as peak counts of 10 eos/hpf or less and 6 eos/hpf or less. The rate of complete remission (at a peak count of ≤ 1 eos/hpf) favored 6FED, at 19% versus 6% among 1FED.

The two diets had a similar impact across several other measures, including reduction in peak eosinophil counts, reduction in EoE symptoms, and improvement in quality of life. For 6FED versus 1FED, the mean changes from baseline in the Eosinophilic Esophagitis Histology Scoring System were –0.23 versus –0.15. In addition, the mean changes in the Eosinophilic Esophagitis Endoscopic Reference Score were 1 versus –0.6, and in the Eosinophilic Esophagitis Activity Index, they were –8.2 versus –3. None of the differences were significant.

Among the patients who didn’t respond to 1FED, 21 opted to follow 6FED in the study’s second phase. Of those patients, nine (43%) attained remission after following the more restrictive diet. Among the 11 patients who didn’t initially respond to 6FED and who opted to receive fluticasone propionate, nine patients (82%) achieved remission.

“We examined a series of validated endpoints that have not previously been examined in diet trials,” Dr. Rothenberg said. “We are surprised to see that one food was equally effective as six foods.”
 

Incorporating food elimination therapy

Dr. Rothenberg and colleagues are continuing their research into EoE and food-elimination diets, with a strong focus on furthering diet therapy. In particular, the research team wants to understand how to potentially add milk – and other foods – back to the diet.

Wael Sayej, MD, associate professor of pediatrics at the University of Massachusetts Baystate Regional Campus, Springfield, has found success with the one-food elimination diet among children with EoE, he said in an interview.

In a retrospective study, Dr. Sayej and colleagues found that a one-food elimination diet was an effective first-line treatment option for pediatric patients.

“Once we get past the one-food or two-food elimination, it becomes much more difficult and cumbersome for patients to follow,” said Dr. Sayej, who is also a pediatric gastroenterologist with Baystate Health in Springfield and who wasn’t involved with the CEGIR study. “Obviously, I prefer my patients to follow a strict dairy-free diet as long-term therapy, rather than have them on a medication for the rest of their life.”

Dr. Sayej advises patients to follow the one-food elimination diet in his practice. If patients aren’t responsive, he offers options for additional dietary elimination or initiation of steroid therapy.

“The most important thing about initiating dietary elimination therapy is to take the time to educate the patient and family about the disease, the risks or complications associated with untreated disease, and the pros and cons of the treatment options,” he said.

The study was cofunded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have research, consultant, and leadership relationships with several pharmaceutical companies and organizations not related to this study. Dr. Sayej disclosed no relevant financial relationships.
 

For adults with eosinophilic esophagitis (EoE), eliminating animal milk alone appears to be as effective for treating the disease as forgoing milk and five other foods, according to a new report.

A one-food elimination diet (1FED) led to histologic remission in 34% of patients, as determined on the basis of eosinophil count at 6 weeks, and in 40% of patients who followed a six-food elimination diet (6FED) – a nonstatistical difference, the research team wrote.

“The takeaway message is that one-food (milk) elimination is an effective treatment and a reasonable first-line treatment for EoE,” senior study author Marc Rothenberg, MD, PhD, a professor of pediatrics and director of the allergy and immunology division at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, said in an interview.

“The study was designed by the Consortium of Eosinophilic Disease Researchers (CEGIR), which includes the nation’s top institutions working with patient advocacy groups, together with the National Institutes of Health,” he said. “The group, under advice from patients, determined that it was an important question to research if one-food elimination would be effective – and how effective – compared with six-food elimination.”

The study was published in The Lancet Gastroenterology and Hepatology.
 

Studying EOE and food elimination

Previous studies have found that eliminating six common foods that trigger esophageal injury – milk, eggs, wheat, soy, fish, and nuts – can substantially reduce EoE symptoms. The 6FED has become a common approach to managing the disease.

In recent years, however, researchers have conducted small, nonrandomized studies of the less restrictive 1FED and have found some success.

In a multisite, randomized trial, Dr. Rothenberg and colleagues compared the 6FED with the 1FED among 129 adults aged 18-60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in esophageal tissue. The participants enrolled at 1 of 10 U.S. medical centers that participate in CEGIR, which is part of the NIH-funded Rare Diseases Clinical Research Network.

Between 2016 and 2019, 67 participants were assigned to the 1FED group, which eliminated only animal milk from the diet, and 62 participants were assigned to the 6FED group, which eliminated milk, eggs, wheat, soy, fish/shellfish, and peanuts/tree nuts. After following the diet for 6 weeks, participants underwent an upper endoscopy exam and esophageal tissue biopsy. The primary endpoint was the proportion of patients with histologic remission, or a peak count of less than 15 eosinophils per high-power field (eos/hpf).

If the number of eosinophils indicated that EoE was in remission, the participant exited the study. If EoE wasn’t in remission, those who were on 1FED could proceed to 6FED, and those who were on 6FED could take fluticasone propionate 880 mcg two times per day with an unrestricted diet. Both groups followed the protocols for 6 weeks and underwent another exam with tissue biopsy.

At 6 weeks, 25 patients (40%) on 6FED and 23 patients (34%) on 1FED achieved histologic remission. The difference was not statistically significant.

There were also no significant differences between the groups at stricter thresholds for partial remission, defined as peak counts of 10 eos/hpf or less and 6 eos/hpf or less. The rate of complete remission (at a peak count of ≤ 1 eos/hpf) favored 6FED, at 19% versus 6% among 1FED.

The two diets had a similar impact across several other measures, including reduction in peak eosinophil counts, reduction in EoE symptoms, and improvement in quality of life. For 6FED versus 1FED, the mean changes from baseline in the Eosinophilic Esophagitis Histology Scoring System were –0.23 versus –0.15. In addition, the mean changes in the Eosinophilic Esophagitis Endoscopic Reference Score were 1 versus –0.6, and in the Eosinophilic Esophagitis Activity Index, they were –8.2 versus –3. None of the differences were significant.

Among the patients who didn’t respond to 1FED, 21 opted to follow 6FED in the study’s second phase. Of those patients, nine (43%) attained remission after following the more restrictive diet. Among the 11 patients who didn’t initially respond to 6FED and who opted to receive fluticasone propionate, nine patients (82%) achieved remission.

“We examined a series of validated endpoints that have not previously been examined in diet trials,” Dr. Rothenberg said. “We are surprised to see that one food was equally effective as six foods.”
 

Incorporating food elimination therapy

Dr. Rothenberg and colleagues are continuing their research into EoE and food-elimination diets, with a strong focus on furthering diet therapy. In particular, the research team wants to understand how to potentially add milk – and other foods – back to the diet.

Wael Sayej, MD, associate professor of pediatrics at the University of Massachusetts Baystate Regional Campus, Springfield, has found success with the one-food elimination diet among children with EoE, he said in an interview.

In a retrospective study, Dr. Sayej and colleagues found that a one-food elimination diet was an effective first-line treatment option for pediatric patients.

“Once we get past the one-food or two-food elimination, it becomes much more difficult and cumbersome for patients to follow,” said Dr. Sayej, who is also a pediatric gastroenterologist with Baystate Health in Springfield and who wasn’t involved with the CEGIR study. “Obviously, I prefer my patients to follow a strict dairy-free diet as long-term therapy, rather than have them on a medication for the rest of their life.”

Dr. Sayej advises patients to follow the one-food elimination diet in his practice. If patients aren’t responsive, he offers options for additional dietary elimination or initiation of steroid therapy.

“The most important thing about initiating dietary elimination therapy is to take the time to educate the patient and family about the disease, the risks or complications associated with untreated disease, and the pros and cons of the treatment options,” he said.

The study was cofunded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have research, consultant, and leadership relationships with several pharmaceutical companies and organizations not related to this study. Dr. Sayej disclosed no relevant financial relationships.
 

For adults with eosinophilic esophagitis (EoE), eliminating animal milk alone appears to be as effective for treating the disease as forgoing milk and five other foods, according to a new report.

A one-food elimination diet (1FED) led to histologic remission in 34% of patients, as determined on the basis of eosinophil count at 6 weeks, and in 40% of patients who followed a six-food elimination diet (6FED) – a nonstatistical difference, the research team wrote.

“The takeaway message is that one-food (milk) elimination is an effective treatment and a reasonable first-line treatment for EoE,” senior study author Marc Rothenberg, MD, PhD, a professor of pediatrics and director of the allergy and immunology division at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, said in an interview.

“The study was designed by the Consortium of Eosinophilic Disease Researchers (CEGIR), which includes the nation’s top institutions working with patient advocacy groups, together with the National Institutes of Health,” he said. “The group, under advice from patients, determined that it was an important question to research if one-food elimination would be effective – and how effective – compared with six-food elimination.”

The study was published in The Lancet Gastroenterology and Hepatology.
 

Studying EOE and food elimination

Previous studies have found that eliminating six common foods that trigger esophageal injury – milk, eggs, wheat, soy, fish, and nuts – can substantially reduce EoE symptoms. The 6FED has become a common approach to managing the disease.

In recent years, however, researchers have conducted small, nonrandomized studies of the less restrictive 1FED and have found some success.

In a multisite, randomized trial, Dr. Rothenberg and colleagues compared the 6FED with the 1FED among 129 adults aged 18-60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in esophageal tissue. The participants enrolled at 1 of 10 U.S. medical centers that participate in CEGIR, which is part of the NIH-funded Rare Diseases Clinical Research Network.

Between 2016 and 2019, 67 participants were assigned to the 1FED group, which eliminated only animal milk from the diet, and 62 participants were assigned to the 6FED group, which eliminated milk, eggs, wheat, soy, fish/shellfish, and peanuts/tree nuts. After following the diet for 6 weeks, participants underwent an upper endoscopy exam and esophageal tissue biopsy. The primary endpoint was the proportion of patients with histologic remission, or a peak count of less than 15 eosinophils per high-power field (eos/hpf).

If the number of eosinophils indicated that EoE was in remission, the participant exited the study. If EoE wasn’t in remission, those who were on 1FED could proceed to 6FED, and those who were on 6FED could take fluticasone propionate 880 mcg two times per day with an unrestricted diet. Both groups followed the protocols for 6 weeks and underwent another exam with tissue biopsy.

At 6 weeks, 25 patients (40%) on 6FED and 23 patients (34%) on 1FED achieved histologic remission. The difference was not statistically significant.

There were also no significant differences between the groups at stricter thresholds for partial remission, defined as peak counts of 10 eos/hpf or less and 6 eos/hpf or less. The rate of complete remission (at a peak count of ≤ 1 eos/hpf) favored 6FED, at 19% versus 6% among 1FED.

The two diets had a similar impact across several other measures, including reduction in peak eosinophil counts, reduction in EoE symptoms, and improvement in quality of life. For 6FED versus 1FED, the mean changes from baseline in the Eosinophilic Esophagitis Histology Scoring System were –0.23 versus –0.15. In addition, the mean changes in the Eosinophilic Esophagitis Endoscopic Reference Score were 1 versus –0.6, and in the Eosinophilic Esophagitis Activity Index, they were –8.2 versus –3. None of the differences were significant.

Among the patients who didn’t respond to 1FED, 21 opted to follow 6FED in the study’s second phase. Of those patients, nine (43%) attained remission after following the more restrictive diet. Among the 11 patients who didn’t initially respond to 6FED and who opted to receive fluticasone propionate, nine patients (82%) achieved remission.

“We examined a series of validated endpoints that have not previously been examined in diet trials,” Dr. Rothenberg said. “We are surprised to see that one food was equally effective as six foods.”
 

Incorporating food elimination therapy

Dr. Rothenberg and colleagues are continuing their research into EoE and food-elimination diets, with a strong focus on furthering diet therapy. In particular, the research team wants to understand how to potentially add milk – and other foods – back to the diet.

Wael Sayej, MD, associate professor of pediatrics at the University of Massachusetts Baystate Regional Campus, Springfield, has found success with the one-food elimination diet among children with EoE, he said in an interview.

In a retrospective study, Dr. Sayej and colleagues found that a one-food elimination diet was an effective first-line treatment option for pediatric patients.

“Once we get past the one-food or two-food elimination, it becomes much more difficult and cumbersome for patients to follow,” said Dr. Sayej, who is also a pediatric gastroenterologist with Baystate Health in Springfield and who wasn’t involved with the CEGIR study. “Obviously, I prefer my patients to follow a strict dairy-free diet as long-term therapy, rather than have them on a medication for the rest of their life.”

Dr. Sayej advises patients to follow the one-food elimination diet in his practice. If patients aren’t responsive, he offers options for additional dietary elimination or initiation of steroid therapy.

“The most important thing about initiating dietary elimination therapy is to take the time to educate the patient and family about the disease, the risks or complications associated with untreated disease, and the pros and cons of the treatment options,” he said.

The study was cofunded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have research, consultant, and leadership relationships with several pharmaceutical companies and organizations not related to this study. Dr. Sayej disclosed no relevant financial relationships.
 

The Food and Drug Administration will not act on Phathom Pharmaceutical’s vonoprazan new drug application (NDA) for erosive esophagitis or its postapproval supplement for Helicobacter pylori until the company addresses concerns over the presence of nitrosamine impurities.

The FDA approved the company’s two vonoprazan-based treatments for H. pylori infection, Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), last May.

The target action date of the company’s NDA for vonoprazan for the treatment of erosive esophagitis was Jan. 11, 2023.

In a news release, Phathom said it has received complete response letters from the FDA related to its erosive esophagitis NDA and H. pylori postapproval supplement.

Both letters address specifications and controls for a nitrosamine drug substance–related impurity, N-nitroso-vonoprazan (NVP), which was detected in the initial commercial launch materials of both products.

The FDA letters ask Phathom to provide “additional stability data to demonstrate that levels of the impurity previously found in vonoprazan drug product will remain at or below the daily acceptable intake throughout the proposed shelf life of the product,” Phathom said.

Phathom said it has conducted “extensive root cause investigations regarding the trace levels of the impurity since it was detected and has implemented mitigation measures to control the levels of NVP below the acceptable intake.”

The company expects to meet with the FDA before the end of March to discuss a resubmission plan and a timeline for the vonoprazan products.

Owing to the regulatory delays, Phathom said it no longer expects product launches for H. pylori or erosive esophagitis in the first quarter of 2023.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration will not act on Phathom Pharmaceutical’s vonoprazan new drug application (NDA) for erosive esophagitis or its postapproval supplement for Helicobacter pylori until the company addresses concerns over the presence of nitrosamine impurities.

The FDA approved the company’s two vonoprazan-based treatments for H. pylori infection, Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), last May.

The target action date of the company’s NDA for vonoprazan for the treatment of erosive esophagitis was Jan. 11, 2023.

In a news release, Phathom said it has received complete response letters from the FDA related to its erosive esophagitis NDA and H. pylori postapproval supplement.

Both letters address specifications and controls for a nitrosamine drug substance–related impurity, N-nitroso-vonoprazan (NVP), which was detected in the initial commercial launch materials of both products.

The FDA letters ask Phathom to provide “additional stability data to demonstrate that levels of the impurity previously found in vonoprazan drug product will remain at or below the daily acceptable intake throughout the proposed shelf life of the product,” Phathom said.

Phathom said it has conducted “extensive root cause investigations regarding the trace levels of the impurity since it was detected and has implemented mitigation measures to control the levels of NVP below the acceptable intake.”

The company expects to meet with the FDA before the end of March to discuss a resubmission plan and a timeline for the vonoprazan products.

Owing to the regulatory delays, Phathom said it no longer expects product launches for H. pylori or erosive esophagitis in the first quarter of 2023.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration will not act on Phathom Pharmaceutical’s vonoprazan new drug application (NDA) for erosive esophagitis or its postapproval supplement for Helicobacter pylori until the company addresses concerns over the presence of nitrosamine impurities.

The FDA approved the company’s two vonoprazan-based treatments for H. pylori infection, Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), last May.

The target action date of the company’s NDA for vonoprazan for the treatment of erosive esophagitis was Jan. 11, 2023.

In a news release, Phathom said it has received complete response letters from the FDA related to its erosive esophagitis NDA and H. pylori postapproval supplement.

Both letters address specifications and controls for a nitrosamine drug substance–related impurity, N-nitroso-vonoprazan (NVP), which was detected in the initial commercial launch materials of both products.

The FDA letters ask Phathom to provide “additional stability data to demonstrate that levels of the impurity previously found in vonoprazan drug product will remain at or below the daily acceptable intake throughout the proposed shelf life of the product,” Phathom said.

Phathom said it has conducted “extensive root cause investigations regarding the trace levels of the impurity since it was detected and has implemented mitigation measures to control the levels of NVP below the acceptable intake.”

The company expects to meet with the FDA before the end of March to discuss a resubmission plan and a timeline for the vonoprazan products.

Owing to the regulatory delays, Phathom said it no longer expects product launches for H. pylori or erosive esophagitis in the first quarter of 2023.

A version of this article first appeared on Medscape.com.

Adherence to the Seattle biopsy protocol and recommended endoscopic surveillance intervals – two established quality indicators (QIs) in Barrett esophagus (BE) – varies widely by individual endoscopist and center, an analysis of U.S. registry data shows.

“As the GI Quality Improvement Consortium (GIQuIC) registry represents the ‘best-case scenario’ for adherence, since sites and endoscopists enrolled in this quality registry are aware that their practices are being monitored, these results indicate that there is still room for improvement and better consistency,” the researchers write.

The study was published online in The American Journal of Gastroenterology.

Quality care in BE, which is a precursor to esophageal adenocarcinoma (EAC), includes adherence to the Seattle biopsy protocol for sampling the BE segment (four-quadrant biopsies every 2 cm) and to a surveillance interval of 3-5 years for patients with nondysplastic BE (NDBE).

Previous studies have found poor adherence to these two QIs, but those studies only provided overall estimates, and individual endoscopists or different sites were not taken into consideration.

Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues say their study is the first to highlight variation in adherence to these measures at the center and endoscopist levels.

The study is also the first U.S. population–based study to report the dysplasia detection rate (DDR), which is a proposed quality indicator. The findings on this metric also demonstrate marked variability across endoscopists and sites.
 

Study details

Using the nationwide GIQuIC registry, the researchers evaluated endoscopist and site-based adherence to the Seattle protocol and surveillance interval advice from January 2018 to May 2021.

Among 255 practices with 1,195 endoscopists who performed 20,155 upper endoscopies for suspected or established BE, overall adherence to the Seattle protocol was 86%, which is considerably higher than the 51% reported in a study conducted from 2002 to 2007, Dr. Kolb and colleagues note.

When researchers looked specifically at 572 endoscopists for whom there were at least 10 endoscopy records in the registry, they found high variability in adherence to the Seattle protocol (median, 93.8%; interquartile range, 18.9%).

Adherence to the Seattle protocol was also variable among 153 practices for which there were at least 20 endoscopy records (median, 90%; IQR, 20.1%).

Of the 12,100 upper endoscopies with documented NDBE, 8,517 (70.4%) had a guideline-concordant–recommended surveillance interval of 3-5 years, with variability at both the endoscopist (median, 82.4%; IQR, 36.3%) and site level (median, 77.2%; IQR, 28.9%).

Endoscopist and site adherence to the Seattle protocol and surveillance guidance generally rose along with volume of upper endoscopies performed.

The overall DDR was 3.1%; it varied among endoscopists and sites (mean, 3.3% for both).

The investigators note that the 95% confidence intervals for each provider for DDR were “highly variable” and ranged from –20% to 119.3%. Notably, increasing upper endoscopy volume had an inconsistent effect on adherence rates and DDR by endoscopists and sites.

The investigators saw no correlation between overall DDR and Seattle protocol adherence among sites and only weak but statistically significant negative correlation between DDR and Seattle protocol adherence among individual endoscopists.
 

Practical approaches to improvement

The researchers say their observations from the GIQuIC database “most accurately represent the real-world experience in Barrett’s endoscopy.”

The results can serve as a “benchmark for quality initiatives and intervention trials aimed at improving outcomes for patients with BE,” they say.

Improving adherence to key QI measures and ensuring more consistent clinical behavior across practice groups and endoscopists are “critical first steps” to ensure high-quality BE care, Dr. Kolb and colleagues say.

To that end, they encourage professional societies to emphasize these metrics to their members and to streamline the reporting systems for QIs within the electronic health records used across various practice settings.

Avenues to improve examination quality may include educational interventions, such as online learning platforms that teach dysplasia detection or that highlight best practices, they add. These educational tools should be easy to use and should emphasize quality improvement measures.

“Future efforts are warranted to identify and extinguish predictors of this variability and to determine whether these interventions can improve DDR and adherence rates to QIs among endoscopists doing these examinations with the goal to improve EAC outcomes,” they conclude.

The study had no financial support. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adherence to the Seattle biopsy protocol and recommended endoscopic surveillance intervals – two established quality indicators (QIs) in Barrett esophagus (BE) – varies widely by individual endoscopist and center, an analysis of U.S. registry data shows.

“As the GI Quality Improvement Consortium (GIQuIC) registry represents the ‘best-case scenario’ for adherence, since sites and endoscopists enrolled in this quality registry are aware that their practices are being monitored, these results indicate that there is still room for improvement and better consistency,” the researchers write.

The study was published online in The American Journal of Gastroenterology.

Quality care in BE, which is a precursor to esophageal adenocarcinoma (EAC), includes adherence to the Seattle biopsy protocol for sampling the BE segment (four-quadrant biopsies every 2 cm) and to a surveillance interval of 3-5 years for patients with nondysplastic BE (NDBE).

Previous studies have found poor adherence to these two QIs, but those studies only provided overall estimates, and individual endoscopists or different sites were not taken into consideration.

Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues say their study is the first to highlight variation in adherence to these measures at the center and endoscopist levels.

The study is also the first U.S. population–based study to report the dysplasia detection rate (DDR), which is a proposed quality indicator. The findings on this metric also demonstrate marked variability across endoscopists and sites.
 

Study details

Using the nationwide GIQuIC registry, the researchers evaluated endoscopist and site-based adherence to the Seattle protocol and surveillance interval advice from January 2018 to May 2021.

Among 255 practices with 1,195 endoscopists who performed 20,155 upper endoscopies for suspected or established BE, overall adherence to the Seattle protocol was 86%, which is considerably higher than the 51% reported in a study conducted from 2002 to 2007, Dr. Kolb and colleagues note.

When researchers looked specifically at 572 endoscopists for whom there were at least 10 endoscopy records in the registry, they found high variability in adherence to the Seattle protocol (median, 93.8%; interquartile range, 18.9%).

Adherence to the Seattle protocol was also variable among 153 practices for which there were at least 20 endoscopy records (median, 90%; IQR, 20.1%).

Of the 12,100 upper endoscopies with documented NDBE, 8,517 (70.4%) had a guideline-concordant–recommended surveillance interval of 3-5 years, with variability at both the endoscopist (median, 82.4%; IQR, 36.3%) and site level (median, 77.2%; IQR, 28.9%).

Endoscopist and site adherence to the Seattle protocol and surveillance guidance generally rose along with volume of upper endoscopies performed.

The overall DDR was 3.1%; it varied among endoscopists and sites (mean, 3.3% for both).

The investigators note that the 95% confidence intervals for each provider for DDR were “highly variable” and ranged from –20% to 119.3%. Notably, increasing upper endoscopy volume had an inconsistent effect on adherence rates and DDR by endoscopists and sites.

The investigators saw no correlation between overall DDR and Seattle protocol adherence among sites and only weak but statistically significant negative correlation between DDR and Seattle protocol adherence among individual endoscopists.
 

Practical approaches to improvement

The researchers say their observations from the GIQuIC database “most accurately represent the real-world experience in Barrett’s endoscopy.”

The results can serve as a “benchmark for quality initiatives and intervention trials aimed at improving outcomes for patients with BE,” they say.

Improving adherence to key QI measures and ensuring more consistent clinical behavior across practice groups and endoscopists are “critical first steps” to ensure high-quality BE care, Dr. Kolb and colleagues say.

To that end, they encourage professional societies to emphasize these metrics to their members and to streamline the reporting systems for QIs within the electronic health records used across various practice settings.

Avenues to improve examination quality may include educational interventions, such as online learning platforms that teach dysplasia detection or that highlight best practices, they add. These educational tools should be easy to use and should emphasize quality improvement measures.

“Future efforts are warranted to identify and extinguish predictors of this variability and to determine whether these interventions can improve DDR and adherence rates to QIs among endoscopists doing these examinations with the goal to improve EAC outcomes,” they conclude.

The study had no financial support. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adherence to the Seattle biopsy protocol and recommended endoscopic surveillance intervals – two established quality indicators (QIs) in Barrett esophagus (BE) – varies widely by individual endoscopist and center, an analysis of U.S. registry data shows.

“As the GI Quality Improvement Consortium (GIQuIC) registry represents the ‘best-case scenario’ for adherence, since sites and endoscopists enrolled in this quality registry are aware that their practices are being monitored, these results indicate that there is still room for improvement and better consistency,” the researchers write.

The study was published online in The American Journal of Gastroenterology.

Quality care in BE, which is a precursor to esophageal adenocarcinoma (EAC), includes adherence to the Seattle biopsy protocol for sampling the BE segment (four-quadrant biopsies every 2 cm) and to a surveillance interval of 3-5 years for patients with nondysplastic BE (NDBE).

Previous studies have found poor adherence to these two QIs, but those studies only provided overall estimates, and individual endoscopists or different sites were not taken into consideration.

Jennifer Kolb, MD, with the University of California, Los Angeles, and colleagues say their study is the first to highlight variation in adherence to these measures at the center and endoscopist levels.

The study is also the first U.S. population–based study to report the dysplasia detection rate (DDR), which is a proposed quality indicator. The findings on this metric also demonstrate marked variability across endoscopists and sites.
 

Study details

Using the nationwide GIQuIC registry, the researchers evaluated endoscopist and site-based adherence to the Seattle protocol and surveillance interval advice from January 2018 to May 2021.

Among 255 practices with 1,195 endoscopists who performed 20,155 upper endoscopies for suspected or established BE, overall adherence to the Seattle protocol was 86%, which is considerably higher than the 51% reported in a study conducted from 2002 to 2007, Dr. Kolb and colleagues note.

When researchers looked specifically at 572 endoscopists for whom there were at least 10 endoscopy records in the registry, they found high variability in adherence to the Seattle protocol (median, 93.8%; interquartile range, 18.9%).

Adherence to the Seattle protocol was also variable among 153 practices for which there were at least 20 endoscopy records (median, 90%; IQR, 20.1%).

Of the 12,100 upper endoscopies with documented NDBE, 8,517 (70.4%) had a guideline-concordant–recommended surveillance interval of 3-5 years, with variability at both the endoscopist (median, 82.4%; IQR, 36.3%) and site level (median, 77.2%; IQR, 28.9%).

Endoscopist and site adherence to the Seattle protocol and surveillance guidance generally rose along with volume of upper endoscopies performed.

The overall DDR was 3.1%; it varied among endoscopists and sites (mean, 3.3% for both).

The investigators note that the 95% confidence intervals for each provider for DDR were “highly variable” and ranged from –20% to 119.3%. Notably, increasing upper endoscopy volume had an inconsistent effect on adherence rates and DDR by endoscopists and sites.

The investigators saw no correlation between overall DDR and Seattle protocol adherence among sites and only weak but statistically significant negative correlation between DDR and Seattle protocol adherence among individual endoscopists.
 

Practical approaches to improvement

The researchers say their observations from the GIQuIC database “most accurately represent the real-world experience in Barrett’s endoscopy.”

The results can serve as a “benchmark for quality initiatives and intervention trials aimed at improving outcomes for patients with BE,” they say.

Improving adherence to key QI measures and ensuring more consistent clinical behavior across practice groups and endoscopists are “critical first steps” to ensure high-quality BE care, Dr. Kolb and colleagues say.

To that end, they encourage professional societies to emphasize these metrics to their members and to streamline the reporting systems for QIs within the electronic health records used across various practice settings.

Avenues to improve examination quality may include educational interventions, such as online learning platforms that teach dysplasia detection or that highlight best practices, they add. These educational tools should be easy to use and should emphasize quality improvement measures.

“Future efforts are warranted to identify and extinguish predictors of this variability and to determine whether these interventions can improve DDR and adherence rates to QIs among endoscopists doing these examinations with the goal to improve EAC outcomes,” they conclude.

The study had no financial support. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The available evidence suggests that proton pump inhibitors (PPIs) do not cause gastric cancer, researchers say.

A new study could help resolve a controversy over one of the most serious side effects attributed to the widely used medications.

“Our findings are reassuring, especially to all those patients who have an indication for long-term PPI use and need persistent and effective gastric acid suppression to prevent serious health consequences,” said Daniele Piovani, MSc, PhD, an assistant professor of medical statistics at Humanitas University, Milan, in an email to this news organization.

Previous studies did not take into account the probability that the diseases for which the medications were prescribed might have caused the cancer, Dr. Piovani and colleagues write in Alimentary Pharmacology and Therapeutics.

Researchers have worried about the potential of PPIs to cause cancer after finding that they are associated with enterochromaffin-like cells, gastric atrophy, and changes in gut microbiota and gastric mucosal immunology.

Observational studies and meta-analyses showed a link between PPIs and an increased risk for gastric cancer.

“However, the underlying conditions for which PPIs are prescribed are associated with gastric cancer,” said Dr. Piovani. “This may result in an apparent association between PPIs and gastric cancer.”

Another potential confounding factor is that as-yet undiagnosed cancer might also cause symptoms that are treated with PPIs. Patient behavior also may play a role, she noted.

“Let’s imagine a patient with peptic ulcer who takes PPIs,” said Dr. Piovani. “He may not only have peptic ulcer but also be a heavy smoker. He may drink much more alcohol, have a different dietary pattern, be more likely to be exposed to high levels of stress, etc. in respect to a control [patient] who does not have peptic ulcer and does not take PPIs.”
 

Comparing two drug classes

More recent studies have compared people taking PPIs to people taking histamine-2 receptor antagonists (H2RAs). H2RAs are often used to treat the same conditions as PPIs, but they are not as strongly linked to hypergastrinemia and are not associated with gastric atrophy, so they might serve as good comparators.

Since results of these studies have been conflicting, Dr. Piovani and colleagues attempted to weigh them together in a systematic review and meta-analysis. They identified two randomized clinical trials and 12 observational studies with a total of over 6 million patients.

One randomized controlled trial involved Helicobacter pylori–negative patients with bleeding ulcers. Researchers assigned 138 to 20 mg daily rabeprazole (a PPI) and 132 to 40 mg famotidine (an H2RA). After a year, no cancer occurred.

The other randomized controlled trial involved H. pylori–negative patients with idiopathic peptic ulcers. Investigators assigned 114 to 30 mg lansoprazole (another PPI) and 114 to 40 mg famotidine. In 2 years, one patient receiving famotidine developed cancer.

The researchers found several methodological problems with these trials. One flaw is that the study periods were not long enough to accurately measure what effects the medications might have on gastric cancers, which are a rare outcome, they note. The evidence from these studies was so weak they could not draw conclusions from the results, the investigators conclude.

Pooling data from the 11 observational trials they were able to combine, the researchers found that PPI users had a one-third higher random relative risk of cancer than H2RA users (95% confidence interval, 1.11-1.59). However, these studies were heterogenous, and five of them did not adjust for age and sex, as well as other potentially confounding covariates.

The remaining six observational studies adjusted for age, sex, and at least two other covariates that could affect the risk for gastric cancer. These studies had a total of 2.5 million patients and 7,372 gastric cancers. Combined, these studies showed an RR of gastric cancer in PPI users, compared with H2RA users of 1.07, which was not statistically significant (95% CI, 0.97-1.19).

The researchers found no clear evidence of a dose-response or of an increased risk with longer-term use of PPIs.
 

Findings support practice guidance

“I found this relatively reassuring,” Mark Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare, Murray, Utah, told this news organization.

PPIs do dramatically increase the pH of the stomach, stimulating the stomach to try to compensate in a process that can sometimes give rise to tumors, Dr. Lewis said. But these tumors appear to be benign.

Other concerns about PPI use, such as reduction in bone density, remain under investigation, he said.

Some H2RA blockers might actually pose a greater cancer risk than PPIs, said Dr. Lewis, and many clinicians seem to favor PPIs. “I have seen a huge sea change where most patients are on PPIs. And I would say that H2RA blockers are older and increasingly the exception in terms of usage, not the rule.”

The investigators note that observational studies by their nature cannot prove cause and effect, but because gastric cancer is so rare, a randomized controlled trial of PPIs versus H2RAs that is large enough to be definitive may not be feasible.

They conclude that their findings support the American Gastroenterological Association recommendation that “the decision to discontinue PPIs should be based solely on the lack of an indication for use and not because of concern for PPI-associated adverse effects.”

Dr. Piovani and Dr. Lewis report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The available evidence suggests that proton pump inhibitors (PPIs) do not cause gastric cancer, researchers say.

A new study could help resolve a controversy over one of the most serious side effects attributed to the widely used medications.

“Our findings are reassuring, especially to all those patients who have an indication for long-term PPI use and need persistent and effective gastric acid suppression to prevent serious health consequences,” said Daniele Piovani, MSc, PhD, an assistant professor of medical statistics at Humanitas University, Milan, in an email to this news organization.

Previous studies did not take into account the probability that the diseases for which the medications were prescribed might have caused the cancer, Dr. Piovani and colleagues write in Alimentary Pharmacology and Therapeutics.

Researchers have worried about the potential of PPIs to cause cancer after finding that they are associated with enterochromaffin-like cells, gastric atrophy, and changes in gut microbiota and gastric mucosal immunology.

Observational studies and meta-analyses showed a link between PPIs and an increased risk for gastric cancer.

“However, the underlying conditions for which PPIs are prescribed are associated with gastric cancer,” said Dr. Piovani. “This may result in an apparent association between PPIs and gastric cancer.”

Another potential confounding factor is that as-yet undiagnosed cancer might also cause symptoms that are treated with PPIs. Patient behavior also may play a role, she noted.

“Let’s imagine a patient with peptic ulcer who takes PPIs,” said Dr. Piovani. “He may not only have peptic ulcer but also be a heavy smoker. He may drink much more alcohol, have a different dietary pattern, be more likely to be exposed to high levels of stress, etc. in respect to a control [patient] who does not have peptic ulcer and does not take PPIs.”
 

Comparing two drug classes

More recent studies have compared people taking PPIs to people taking histamine-2 receptor antagonists (H2RAs). H2RAs are often used to treat the same conditions as PPIs, but they are not as strongly linked to hypergastrinemia and are not associated with gastric atrophy, so they might serve as good comparators.

Since results of these studies have been conflicting, Dr. Piovani and colleagues attempted to weigh them together in a systematic review and meta-analysis. They identified two randomized clinical trials and 12 observational studies with a total of over 6 million patients.

One randomized controlled trial involved Helicobacter pylori–negative patients with bleeding ulcers. Researchers assigned 138 to 20 mg daily rabeprazole (a PPI) and 132 to 40 mg famotidine (an H2RA). After a year, no cancer occurred.

The other randomized controlled trial involved H. pylori–negative patients with idiopathic peptic ulcers. Investigators assigned 114 to 30 mg lansoprazole (another PPI) and 114 to 40 mg famotidine. In 2 years, one patient receiving famotidine developed cancer.

The researchers found several methodological problems with these trials. One flaw is that the study periods were not long enough to accurately measure what effects the medications might have on gastric cancers, which are a rare outcome, they note. The evidence from these studies was so weak they could not draw conclusions from the results, the investigators conclude.

Pooling data from the 11 observational trials they were able to combine, the researchers found that PPI users had a one-third higher random relative risk of cancer than H2RA users (95% confidence interval, 1.11-1.59). However, these studies were heterogenous, and five of them did not adjust for age and sex, as well as other potentially confounding covariates.

The remaining six observational studies adjusted for age, sex, and at least two other covariates that could affect the risk for gastric cancer. These studies had a total of 2.5 million patients and 7,372 gastric cancers. Combined, these studies showed an RR of gastric cancer in PPI users, compared with H2RA users of 1.07, which was not statistically significant (95% CI, 0.97-1.19).

The researchers found no clear evidence of a dose-response or of an increased risk with longer-term use of PPIs.
 

Findings support practice guidance

“I found this relatively reassuring,” Mark Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare, Murray, Utah, told this news organization.

PPIs do dramatically increase the pH of the stomach, stimulating the stomach to try to compensate in a process that can sometimes give rise to tumors, Dr. Lewis said. But these tumors appear to be benign.

Other concerns about PPI use, such as reduction in bone density, remain under investigation, he said.

Some H2RA blockers might actually pose a greater cancer risk than PPIs, said Dr. Lewis, and many clinicians seem to favor PPIs. “I have seen a huge sea change where most patients are on PPIs. And I would say that H2RA blockers are older and increasingly the exception in terms of usage, not the rule.”

The investigators note that observational studies by their nature cannot prove cause and effect, but because gastric cancer is so rare, a randomized controlled trial of PPIs versus H2RAs that is large enough to be definitive may not be feasible.

They conclude that their findings support the American Gastroenterological Association recommendation that “the decision to discontinue PPIs should be based solely on the lack of an indication for use and not because of concern for PPI-associated adverse effects.”

Dr. Piovani and Dr. Lewis report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The available evidence suggests that proton pump inhibitors (PPIs) do not cause gastric cancer, researchers say.

A new study could help resolve a controversy over one of the most serious side effects attributed to the widely used medications.

“Our findings are reassuring, especially to all those patients who have an indication for long-term PPI use and need persistent and effective gastric acid suppression to prevent serious health consequences,” said Daniele Piovani, MSc, PhD, an assistant professor of medical statistics at Humanitas University, Milan, in an email to this news organization.

Previous studies did not take into account the probability that the diseases for which the medications were prescribed might have caused the cancer, Dr. Piovani and colleagues write in Alimentary Pharmacology and Therapeutics.

Researchers have worried about the potential of PPIs to cause cancer after finding that they are associated with enterochromaffin-like cells, gastric atrophy, and changes in gut microbiota and gastric mucosal immunology.

Observational studies and meta-analyses showed a link between PPIs and an increased risk for gastric cancer.

“However, the underlying conditions for which PPIs are prescribed are associated with gastric cancer,” said Dr. Piovani. “This may result in an apparent association between PPIs and gastric cancer.”

Another potential confounding factor is that as-yet undiagnosed cancer might also cause symptoms that are treated with PPIs. Patient behavior also may play a role, she noted.

“Let’s imagine a patient with peptic ulcer who takes PPIs,” said Dr. Piovani. “He may not only have peptic ulcer but also be a heavy smoker. He may drink much more alcohol, have a different dietary pattern, be more likely to be exposed to high levels of stress, etc. in respect to a control [patient] who does not have peptic ulcer and does not take PPIs.”
 

Comparing two drug classes

More recent studies have compared people taking PPIs to people taking histamine-2 receptor antagonists (H2RAs). H2RAs are often used to treat the same conditions as PPIs, but they are not as strongly linked to hypergastrinemia and are not associated with gastric atrophy, so they might serve as good comparators.

Since results of these studies have been conflicting, Dr. Piovani and colleagues attempted to weigh them together in a systematic review and meta-analysis. They identified two randomized clinical trials and 12 observational studies with a total of over 6 million patients.

One randomized controlled trial involved Helicobacter pylori–negative patients with bleeding ulcers. Researchers assigned 138 to 20 mg daily rabeprazole (a PPI) and 132 to 40 mg famotidine (an H2RA). After a year, no cancer occurred.

The other randomized controlled trial involved H. pylori–negative patients with idiopathic peptic ulcers. Investigators assigned 114 to 30 mg lansoprazole (another PPI) and 114 to 40 mg famotidine. In 2 years, one patient receiving famotidine developed cancer.

The researchers found several methodological problems with these trials. One flaw is that the study periods were not long enough to accurately measure what effects the medications might have on gastric cancers, which are a rare outcome, they note. The evidence from these studies was so weak they could not draw conclusions from the results, the investigators conclude.

Pooling data from the 11 observational trials they were able to combine, the researchers found that PPI users had a one-third higher random relative risk of cancer than H2RA users (95% confidence interval, 1.11-1.59). However, these studies were heterogenous, and five of them did not adjust for age and sex, as well as other potentially confounding covariates.

The remaining six observational studies adjusted for age, sex, and at least two other covariates that could affect the risk for gastric cancer. These studies had a total of 2.5 million patients and 7,372 gastric cancers. Combined, these studies showed an RR of gastric cancer in PPI users, compared with H2RA users of 1.07, which was not statistically significant (95% CI, 0.97-1.19).

The researchers found no clear evidence of a dose-response or of an increased risk with longer-term use of PPIs.
 

Findings support practice guidance

“I found this relatively reassuring,” Mark Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare, Murray, Utah, told this news organization.

PPIs do dramatically increase the pH of the stomach, stimulating the stomach to try to compensate in a process that can sometimes give rise to tumors, Dr. Lewis said. But these tumors appear to be benign.

Other concerns about PPI use, such as reduction in bone density, remain under investigation, he said.

Some H2RA blockers might actually pose a greater cancer risk than PPIs, said Dr. Lewis, and many clinicians seem to favor PPIs. “I have seen a huge sea change where most patients are on PPIs. And I would say that H2RA blockers are older and increasingly the exception in terms of usage, not the rule.”

The investigators note that observational studies by their nature cannot prove cause and effect, but because gastric cancer is so rare, a randomized controlled trial of PPIs versus H2RAs that is large enough to be definitive may not be feasible.

They conclude that their findings support the American Gastroenterological Association recommendation that “the decision to discontinue PPIs should be based solely on the lack of an indication for use and not because of concern for PPI-associated adverse effects.”

Dr. Piovani and Dr. Lewis report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among people with type 2 diabetes who self-reported regularly using a proton pump inhibitor (PPI), the incidence of cardiovascular disease (CVD) events as well as all-cause death was significantly increased in a study of more than 19,000 people with type 2 diabetes in a prospective U.K. database.

During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease, compared with nonuse of a PPI, after full adjustment for potential confounding variables.

The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in MI, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.

PPIs are a medication class widely used in both over-the-counter and prescription formulations to reduce acid production in the stomach and to treat gastroesophageal reflux disease and other acid-related disorders. The PPI class includes such widely used agents as esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).

The analyses in this report, which used data collected in the UK Biobank, are “rigorous,” and the findings of “a modest elevation of CVD risk are consistent with a growing number of observational studies in populations with and without diabetes,” commented Mary R. Rooney, PhD, an epidemiologist at Johns Hopkins University, Baltimore, who focuses on diabetes and cardiovascular diseases.
 

Prior observational reports

For example, a report from a prospective, observational study of more than 4300 U.S. residents published in 2021 that Dr. Rooney coauthored documented that cumulative PPI exposure for more than 5 years was significantly linked with a twofold increase in the rate of CVD events, compared with people who did not use a PPI. (This analysis did not examine a possible effect of diabetes status.)

And in a separate prospective, observational study of more than 1,000 Australians with type 2 diabetes, initiation of PPI treatment was significantly linked with a 3.6-fold increased incidence of CVD events, compared with PPI nonuse.

However, Dr. Rooney cautioned that the role of PPI use in raising CVD events “is still an unresolved question. It is too soon to tell if PPI use in people with diabetes should trigger additional caution.” Findings are needed from prospective, randomized trials to determine more definitively whether PPIs play a causal role in the incidence of CVD events, she said in an interview.

U.S. practice often results in unwarranted prolongation of PPI treatment, said the authors of an editorial that accompanied the 2021 report by Dr. Rooney and coauthors.
 

Long-term PPI use threatens harm

“The practice of initiating stress ulcer prophylaxis [by administering a PPI] in critical care is common,” wrote the authors of the 2021 editorial, Nitin Malik, MD, and William S. Weintraub, MD. “Although it is data driven and well intentioned, the possibility of causing harm – if it is continued on a long-term basis after resolution of the acute illness – is palpable.”

The new analyses using UK Biobank data included 19,229 adults with type 2 diabetes and no preexisting coronary artery disease, MI, heart failure, or stroke. The cohort included 15,954 people (83%) who did not report using a PPI and 3,275 who currently used PPIs regularly. Study limitations include self-report as the only verification of PPI use and lack of information on type of PPI, dose size, or use duration.

The findings remained consistent in several sensitivity analyses, including a propensity score–matched analysis and after further adjustment for use of histamine₂ receptor antagonists, a drug class with indications similar to those for PPIs.

The authors of the report speculated that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.

The study received no commercial funding. The authors and Dr. Rooney disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among people with type 2 diabetes who self-reported regularly using a proton pump inhibitor (PPI), the incidence of cardiovascular disease (CVD) events as well as all-cause death was significantly increased in a study of more than 19,000 people with type 2 diabetes in a prospective U.K. database.

During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease, compared with nonuse of a PPI, after full adjustment for potential confounding variables.

The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in MI, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.

PPIs are a medication class widely used in both over-the-counter and prescription formulations to reduce acid production in the stomach and to treat gastroesophageal reflux disease and other acid-related disorders. The PPI class includes such widely used agents as esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).

The analyses in this report, which used data collected in the UK Biobank, are “rigorous,” and the findings of “a modest elevation of CVD risk are consistent with a growing number of observational studies in populations with and without diabetes,” commented Mary R. Rooney, PhD, an epidemiologist at Johns Hopkins University, Baltimore, who focuses on diabetes and cardiovascular diseases.
 

Prior observational reports

For example, a report from a prospective, observational study of more than 4300 U.S. residents published in 2021 that Dr. Rooney coauthored documented that cumulative PPI exposure for more than 5 years was significantly linked with a twofold increase in the rate of CVD events, compared with people who did not use a PPI. (This analysis did not examine a possible effect of diabetes status.)

And in a separate prospective, observational study of more than 1,000 Australians with type 2 diabetes, initiation of PPI treatment was significantly linked with a 3.6-fold increased incidence of CVD events, compared with PPI nonuse.

However, Dr. Rooney cautioned that the role of PPI use in raising CVD events “is still an unresolved question. It is too soon to tell if PPI use in people with diabetes should trigger additional caution.” Findings are needed from prospective, randomized trials to determine more definitively whether PPIs play a causal role in the incidence of CVD events, she said in an interview.

U.S. practice often results in unwarranted prolongation of PPI treatment, said the authors of an editorial that accompanied the 2021 report by Dr. Rooney and coauthors.
 

Long-term PPI use threatens harm

“The practice of initiating stress ulcer prophylaxis [by administering a PPI] in critical care is common,” wrote the authors of the 2021 editorial, Nitin Malik, MD, and William S. Weintraub, MD. “Although it is data driven and well intentioned, the possibility of causing harm – if it is continued on a long-term basis after resolution of the acute illness – is palpable.”

The new analyses using UK Biobank data included 19,229 adults with type 2 diabetes and no preexisting coronary artery disease, MI, heart failure, or stroke. The cohort included 15,954 people (83%) who did not report using a PPI and 3,275 who currently used PPIs regularly. Study limitations include self-report as the only verification of PPI use and lack of information on type of PPI, dose size, or use duration.

The findings remained consistent in several sensitivity analyses, including a propensity score–matched analysis and after further adjustment for use of histamine₂ receptor antagonists, a drug class with indications similar to those for PPIs.

The authors of the report speculated that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.

The study received no commercial funding. The authors and Dr. Rooney disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among people with type 2 diabetes who self-reported regularly using a proton pump inhibitor (PPI), the incidence of cardiovascular disease (CVD) events as well as all-cause death was significantly increased in a study of more than 19,000 people with type 2 diabetes in a prospective U.K. database.

During median follow-up of about 11 years, regular use of a PPI by people with type 2 diabetes was significantly linked with a 27% relative increase in the incidence of coronary artery disease, compared with nonuse of a PPI, after full adjustment for potential confounding variables.

The results also show PPI use was significantly linked after full adjustment with a 34% relative increase in MI, a 35% relative increase in heart failure, and a 30% relative increase in all-cause death, say a team of Chinese researchers in a recent report in the Journal of Clinical Endocrinology and Metabolism.

PPIs are a medication class widely used in both over-the-counter and prescription formulations to reduce acid production in the stomach and to treat gastroesophageal reflux disease and other acid-related disorders. The PPI class includes such widely used agents as esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).

The analyses in this report, which used data collected in the UK Biobank, are “rigorous,” and the findings of “a modest elevation of CVD risk are consistent with a growing number of observational studies in populations with and without diabetes,” commented Mary R. Rooney, PhD, an epidemiologist at Johns Hopkins University, Baltimore, who focuses on diabetes and cardiovascular diseases.
 

Prior observational reports

For example, a report from a prospective, observational study of more than 4300 U.S. residents published in 2021 that Dr. Rooney coauthored documented that cumulative PPI exposure for more than 5 years was significantly linked with a twofold increase in the rate of CVD events, compared with people who did not use a PPI. (This analysis did not examine a possible effect of diabetes status.)

And in a separate prospective, observational study of more than 1,000 Australians with type 2 diabetes, initiation of PPI treatment was significantly linked with a 3.6-fold increased incidence of CVD events, compared with PPI nonuse.

However, Dr. Rooney cautioned that the role of PPI use in raising CVD events “is still an unresolved question. It is too soon to tell if PPI use in people with diabetes should trigger additional caution.” Findings are needed from prospective, randomized trials to determine more definitively whether PPIs play a causal role in the incidence of CVD events, she said in an interview.

U.S. practice often results in unwarranted prolongation of PPI treatment, said the authors of an editorial that accompanied the 2021 report by Dr. Rooney and coauthors.
 

Long-term PPI use threatens harm

“The practice of initiating stress ulcer prophylaxis [by administering a PPI] in critical care is common,” wrote the authors of the 2021 editorial, Nitin Malik, MD, and William S. Weintraub, MD. “Although it is data driven and well intentioned, the possibility of causing harm – if it is continued on a long-term basis after resolution of the acute illness – is palpable.”

The new analyses using UK Biobank data included 19,229 adults with type 2 diabetes and no preexisting coronary artery disease, MI, heart failure, or stroke. The cohort included 15,954 people (83%) who did not report using a PPI and 3,275 who currently used PPIs regularly. Study limitations include self-report as the only verification of PPI use and lack of information on type of PPI, dose size, or use duration.

The findings remained consistent in several sensitivity analyses, including a propensity score–matched analysis and after further adjustment for use of histamine₂ receptor antagonists, a drug class with indications similar to those for PPIs.

The authors of the report speculated that mechanisms that might link PPI use and increased CVD and mortality risk could include changes to the gut microbiota and possible interactions between PPIs and antiplatelet agents.

The study received no commercial funding. The authors and Dr. Rooney disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Clinicians should conduct regular, structured follow-up on treatments for eosinophilic esophagitis (EoE), according to an expert panel.

“Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings,” wrote Ulrike von Arnim, MD, from University Hospital Magdeburg (Germany), and an international team of colleagues in Clinical Gastroenterology and Hepatology.

Although medicine and diet can control EoE, there is presently no cure, and long-term management is needed to prevent recurrence and long-term effects such as esophageal remodeling, fibrosis, and stricture, the researchers said. Yet they could find no evidence-based recommendations for clinical monitoring of the condition.

With the participation of The International Gastrointestinal Eosinophil Researchers (TIGER) and the European Consortium for Eosinophilic Diseases of the GI Tract (EUREOS), they assembled a team of 18 gastroenterologists, pathologists, and allergists from the United States and Western Europe with expertise in the condition.

Almost all panelists had more than 10 years of subspecialty EoE care and more than five relevant research publications. All were members of TIGER or EUREOS. The panel met by video conferencing and responded to surveys to develop a consensus about why, by what means, and when to monitor patients with EoE.

The group reached 75% or greater agreement on 11 statements on these subjects.

Regular follow-ups are needed because they enable clinicians to detect whether treatments have stopped working, improve therapy adherence, and introduce patients to any new treatments that become available, while preventing gaps in care that can worsen outcomes, the group wrote.

Symptoms don’t give a precise indication of esophageal healing and shouldn’t be the sole measure for disease activity, the experts wrote. They recommended other approaches to monitoring, including biopsies. They also endorse the Endoscopic Reference Score as an outcome measure.

The panel recommended noninvasive tissue sampling, mentioning the esophageal string test and the Cytosponge as examples, but called for more research on these two techniques.

Blood markers, oral swabs, breath condensates, and stool and urine samples are not recommended as approaches for monitoring EoE, they wrote.

The optimal interval to measure the efficacy of a therapy is more difficult to decide, the panel noted.

“The clinician’s decision should take into account the clinical severity of the disease, estimated risk of imminent subsequent food impaction, presence of stenosis, as well as mode of action and reported outcome of the chosen medical, dietary, or mechanical treatment,” they wrote. Intervals from 6 to 24 weeks may be appropriate.

For diets and topical corticosteroids, they agreed on an interval of 8-12 weeks to confirm remission but say a longer time might be preferred for slower-acting therapies, such as monoclonal antibodies.

The panel had the most trouble reaching a consensus on how often to follow up on patients whose disease is in remission or is stable. They settled on 12 to 24 months after the last endoscopy. Any longer than 2 years risks missing increased disease activity, they wrote.

This follow-up should include assessment of symptoms and a gastrointestinal endoscopy in cases of relapse or suspected stricture, as well as when treatment modification is being considered or when assessment of histological activity is desired, the panel recommended.

Almost all the panelists disclosed financial relationships with pharmaceutical or medical device companies.

A version of this article first appeared on Medscape.com.

Clinicians should conduct regular, structured follow-up on treatments for eosinophilic esophagitis (EoE), according to an expert panel.

“Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings,” wrote Ulrike von Arnim, MD, from University Hospital Magdeburg (Germany), and an international team of colleagues in Clinical Gastroenterology and Hepatology.

Although medicine and diet can control EoE, there is presently no cure, and long-term management is needed to prevent recurrence and long-term effects such as esophageal remodeling, fibrosis, and stricture, the researchers said. Yet they could find no evidence-based recommendations for clinical monitoring of the condition.

With the participation of The International Gastrointestinal Eosinophil Researchers (TIGER) and the European Consortium for Eosinophilic Diseases of the GI Tract (EUREOS), they assembled a team of 18 gastroenterologists, pathologists, and allergists from the United States and Western Europe with expertise in the condition.

Almost all panelists had more than 10 years of subspecialty EoE care and more than five relevant research publications. All were members of TIGER or EUREOS. The panel met by video conferencing and responded to surveys to develop a consensus about why, by what means, and when to monitor patients with EoE.

The group reached 75% or greater agreement on 11 statements on these subjects.

Regular follow-ups are needed because they enable clinicians to detect whether treatments have stopped working, improve therapy adherence, and introduce patients to any new treatments that become available, while preventing gaps in care that can worsen outcomes, the group wrote.

Symptoms don’t give a precise indication of esophageal healing and shouldn’t be the sole measure for disease activity, the experts wrote. They recommended other approaches to monitoring, including biopsies. They also endorse the Endoscopic Reference Score as an outcome measure.

The panel recommended noninvasive tissue sampling, mentioning the esophageal string test and the Cytosponge as examples, but called for more research on these two techniques.

Blood markers, oral swabs, breath condensates, and stool and urine samples are not recommended as approaches for monitoring EoE, they wrote.

The optimal interval to measure the efficacy of a therapy is more difficult to decide, the panel noted.

“The clinician’s decision should take into account the clinical severity of the disease, estimated risk of imminent subsequent food impaction, presence of stenosis, as well as mode of action and reported outcome of the chosen medical, dietary, or mechanical treatment,” they wrote. Intervals from 6 to 24 weeks may be appropriate.

For diets and topical corticosteroids, they agreed on an interval of 8-12 weeks to confirm remission but say a longer time might be preferred for slower-acting therapies, such as monoclonal antibodies.

The panel had the most trouble reaching a consensus on how often to follow up on patients whose disease is in remission or is stable. They settled on 12 to 24 months after the last endoscopy. Any longer than 2 years risks missing increased disease activity, they wrote.

This follow-up should include assessment of symptoms and a gastrointestinal endoscopy in cases of relapse or suspected stricture, as well as when treatment modification is being considered or when assessment of histological activity is desired, the panel recommended.

Almost all the panelists disclosed financial relationships with pharmaceutical or medical device companies.

A version of this article first appeared on Medscape.com.

Clinicians should conduct regular, structured follow-up on treatments for eosinophilic esophagitis (EoE), according to an expert panel.

“Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings,” wrote Ulrike von Arnim, MD, from University Hospital Magdeburg (Germany), and an international team of colleagues in Clinical Gastroenterology and Hepatology.

Although medicine and diet can control EoE, there is presently no cure, and long-term management is needed to prevent recurrence and long-term effects such as esophageal remodeling, fibrosis, and stricture, the researchers said. Yet they could find no evidence-based recommendations for clinical monitoring of the condition.

With the participation of The International Gastrointestinal Eosinophil Researchers (TIGER) and the European Consortium for Eosinophilic Diseases of the GI Tract (EUREOS), they assembled a team of 18 gastroenterologists, pathologists, and allergists from the United States and Western Europe with expertise in the condition.

Almost all panelists had more than 10 years of subspecialty EoE care and more than five relevant research publications. All were members of TIGER or EUREOS. The panel met by video conferencing and responded to surveys to develop a consensus about why, by what means, and when to monitor patients with EoE.

The group reached 75% or greater agreement on 11 statements on these subjects.

Regular follow-ups are needed because they enable clinicians to detect whether treatments have stopped working, improve therapy adherence, and introduce patients to any new treatments that become available, while preventing gaps in care that can worsen outcomes, the group wrote.

Symptoms don’t give a precise indication of esophageal healing and shouldn’t be the sole measure for disease activity, the experts wrote. They recommended other approaches to monitoring, including biopsies. They also endorse the Endoscopic Reference Score as an outcome measure.

The panel recommended noninvasive tissue sampling, mentioning the esophageal string test and the Cytosponge as examples, but called for more research on these two techniques.

Blood markers, oral swabs, breath condensates, and stool and urine samples are not recommended as approaches for monitoring EoE, they wrote.

The optimal interval to measure the efficacy of a therapy is more difficult to decide, the panel noted.

“The clinician’s decision should take into account the clinical severity of the disease, estimated risk of imminent subsequent food impaction, presence of stenosis, as well as mode of action and reported outcome of the chosen medical, dietary, or mechanical treatment,” they wrote. Intervals from 6 to 24 weeks may be appropriate.

For diets and topical corticosteroids, they agreed on an interval of 8-12 weeks to confirm remission but say a longer time might be preferred for slower-acting therapies, such as monoclonal antibodies.

The panel had the most trouble reaching a consensus on how often to follow up on patients whose disease is in remission or is stable. They settled on 12 to 24 months after the last endoscopy. Any longer than 2 years risks missing increased disease activity, they wrote.

This follow-up should include assessment of symptoms and a gastrointestinal endoscopy in cases of relapse or suspected stricture, as well as when treatment modification is being considered or when assessment of histological activity is desired, the panel recommended.

Almost all the panelists disclosed financial relationships with pharmaceutical or medical device companies.

A version of this article first appeared on Medscape.com.

Nearly half of patients discharged from a hospital had inappropriate proton pump inhibitor (PPI) prescriptions, suggests a retrospective analysis of an Israeli health care database that showed no improvements in prescribing patterns over time.

The research was published online in the journal Digestive and Liver Disease.

First author Orly Sneh-Arbib, MD, division of gastroenterology and liver disease, Clalit Health Services, Talpiot, Jerusalem, said in an interview that she and her co-authors were “very surprised” that the rates of inappropriate prescribing remained so high, especially as they had discussed the adverse effects of the drugs numerous times during departmental meetings.

She believes that, for many clinicians, handing out a prescription for PPIs has become a habit, with the thought being: “Just take this; it’s like a vitamin.”

In the paper, the researchers write, “Undoubtedly, more action is needed to raise physicians’ knowledge and attention to the subject while providing automated and standardized technology-based tools to reduce inappropriate PPI use using an acceptable algorithm.”

For the study, Dr. Sneh-Arbib and her colleagues developed an algorithm to assess inappropriate PPI prescribing in almost 4,000 internal medicine patients. To try to limit future overprescribing, their algorithm is now included in the clinical records system.

Consequently, every time a clinician tries to prescribe a PPI, they have to confirm that there is a valid indication for doing so, with the aim of adding an “extra step in the process,” Dr. Sneh-Arbib said.
 

Clear but complex PPI indications

There are a small, well-defined number of indications for long-term PPI use, the authors write. The indications include prior upper gastrointestinal bleeding, maintenance treatment after healing of erosive esophagitis, Barrett’s esophagus, the use of nonsteroidal anti-inflammatory drugs or antiplatelet agents in patients with increased bleeding risk, and maintenance therapy for symptom control in patients with gastroesophageal reflux disease.

The authors also note that the “appropriateness of PPIs is complex,” with multiple factors to consider for long-term PPI use, including complex drug combinations and medical history.

But having seen patients in their 30s prescribed PPIs “just because of taking steroids or aspirin,” Dr. Sneh-Arbib said she wanted to investigate further.

To examine the rate of inappropriate long-term PPI prescription on discharge from internal medicine departments, the team conducted a retrospective analysis of adults admitted to their institution for the first 6 months of 2014 and the first 6 months of 2017.

They included all patients prescribed PPIs on discharge with a recommendation for long-term use and excluded those who were transferred between departments or who had a hospital stay longer than 3 months.

Information on age, gender, ethnicity, socioeconomic status, current and past diagnoses including all relevant gastrointestinal diagnoses, Charlson comorbidity index, and medications on admission and discharge were recorded.
 

Guidelines for use of PPIs

To assess inappropriate PPI prescribing, the team searched for published recommendations on long-term use, Dr. Sneh-Arbib said. They developed an algorithm based on the U.K. National Institute for Health and Care Excellence (NICE) clinical guideline, “Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management.”

The guideline is “not perfect,” Dr. Sneh-Arbib said, but it was suitable. The team then randomly chose 100 patients from their records to validate the resulting algorithm, finding an accuracy of 96%.

The full analysis included 3,982 patients, of whom 74% were aged 65 years or older, and 50.8% were women. PPIs were first prescribed before hospital admission in 92.4% of cases.

The researchers found that the overall rate of inappropriate PPI prescriptions was 44.3%, a figure that was stable between the two the study periods. In 2014, the rate of inappropriate use was 43.2%, and it was 45.6% in 2017, a nonsignificant difference.

Inappropriate PPIs were higher (68.1%) in patients younger than 65 years, compared with those aged 65 years and older (36%).

The researchers analyzed factors associated with inappropriate PPIs, first excluding 448 patients with clear gastrointestinal indications.

In the majority of cases, the inappropriate PPI prescriptions occurred in patients who were not taking dual antiplatelet treatment (89.4%), in younger patients who were taking aspirin only (8.6%), and in patients receiving a single antiplatelet agent other than aspirin (1.9%), according to multivariate analysis.

Overall, 42.4% of patients classified as inappropriate PPI use were not using aspirin, nonsteroidal anti-inflammatory drugs, antiplatelets, antiaggregants, anticoagulants, or steroids, the researchers found.

They also note that most patients in the study (92.3%) had received PPIs before admission, prescribed by their general practitioner or during a previous hospitalization. This raises concerns about unneeded continuation of the drugs and lack of review by clinicians, they write.
 

PPI deprescribing

Approached for comment, Adrienna Jirik, MD, a gastroenterologist at the Cleveland Clinic, told this news organization that “PPI overprescription is a common problem worldwide, with the United States being no exception.”

They are “one of the most prescribed medications in the world, with several formulations readily available as an over-the-counter medication,” she added.

Dr. Jirik, who was not involved with the study, said that the algorithm used is “on par with the United States clinical practice guidelines for PPI use” and a “great start to initiate an encounter with a patient on PPIs in the outpatient setting to review the indications and to de-escalate and deprescribe therapy.”

Indeed, the American Gastroenterological Association recently published a clinical practice update on deprescribing PPIs.

“It may be useful to incorporate a version of this algorithm as a ‘hard stop’ on some outpatient EMR [electronic medical record] templates to remind providers to address this issue prior to closing an encounter,” Dr. Jirik added.

She noted, however, that tackling any medication reconciliation is a very important but difficult and time-consuming task.

“Education is definitely key for both primary and subspecialty providers,” Dr. Jirik said. “If patients have been on a long-term PPI, the inpatient provider can suggest a plan for de-escalation based on practice guidelines and arrange proper outpatient follow-up for eventual deprescribing.”

No funding was declared. The authors and Dr. Jirik report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nearly half of patients discharged from a hospital had inappropriate proton pump inhibitor (PPI) prescriptions, suggests a retrospective analysis of an Israeli health care database that showed no improvements in prescribing patterns over time.

The research was published online in the journal Digestive and Liver Disease.

First author Orly Sneh-Arbib, MD, division of gastroenterology and liver disease, Clalit Health Services, Talpiot, Jerusalem, said in an interview that she and her co-authors were “very surprised” that the rates of inappropriate prescribing remained so high, especially as they had discussed the adverse effects of the drugs numerous times during departmental meetings.

She believes that, for many clinicians, handing out a prescription for PPIs has become a habit, with the thought being: “Just take this; it’s like a vitamin.”

In the paper, the researchers write, “Undoubtedly, more action is needed to raise physicians’ knowledge and attention to the subject while providing automated and standardized technology-based tools to reduce inappropriate PPI use using an acceptable algorithm.”

For the study, Dr. Sneh-Arbib and her colleagues developed an algorithm to assess inappropriate PPI prescribing in almost 4,000 internal medicine patients. To try to limit future overprescribing, their algorithm is now included in the clinical records system.

Consequently, every time a clinician tries to prescribe a PPI, they have to confirm that there is a valid indication for doing so, with the aim of adding an “extra step in the process,” Dr. Sneh-Arbib said.
 

Clear but complex PPI indications

There are a small, well-defined number of indications for long-term PPI use, the authors write. The indications include prior upper gastrointestinal bleeding, maintenance treatment after healing of erosive esophagitis, Barrett’s esophagus, the use of nonsteroidal anti-inflammatory drugs or antiplatelet agents in patients with increased bleeding risk, and maintenance therapy for symptom control in patients with gastroesophageal reflux disease.

The authors also note that the “appropriateness of PPIs is complex,” with multiple factors to consider for long-term PPI use, including complex drug combinations and medical history.

But having seen patients in their 30s prescribed PPIs “just because of taking steroids or aspirin,” Dr. Sneh-Arbib said she wanted to investigate further.

To examine the rate of inappropriate long-term PPI prescription on discharge from internal medicine departments, the team conducted a retrospective analysis of adults admitted to their institution for the first 6 months of 2014 and the first 6 months of 2017.

They included all patients prescribed PPIs on discharge with a recommendation for long-term use and excluded those who were transferred between departments or who had a hospital stay longer than 3 months.

Information on age, gender, ethnicity, socioeconomic status, current and past diagnoses including all relevant gastrointestinal diagnoses, Charlson comorbidity index, and medications on admission and discharge were recorded.
 

Guidelines for use of PPIs

To assess inappropriate PPI prescribing, the team searched for published recommendations on long-term use, Dr. Sneh-Arbib said. They developed an algorithm based on the U.K. National Institute for Health and Care Excellence (NICE) clinical guideline, “Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management.”

The guideline is “not perfect,” Dr. Sneh-Arbib said, but it was suitable. The team then randomly chose 100 patients from their records to validate the resulting algorithm, finding an accuracy of 96%.

The full analysis included 3,982 patients, of whom 74% were aged 65 years or older, and 50.8% were women. PPIs were first prescribed before hospital admission in 92.4% of cases.

The researchers found that the overall rate of inappropriate PPI prescriptions was 44.3%, a figure that was stable between the two the study periods. In 2014, the rate of inappropriate use was 43.2%, and it was 45.6% in 2017, a nonsignificant difference.

Inappropriate PPIs were higher (68.1%) in patients younger than 65 years, compared with those aged 65 years and older (36%).

The researchers analyzed factors associated with inappropriate PPIs, first excluding 448 patients with clear gastrointestinal indications.

In the majority of cases, the inappropriate PPI prescriptions occurred in patients who were not taking dual antiplatelet treatment (89.4%), in younger patients who were taking aspirin only (8.6%), and in patients receiving a single antiplatelet agent other than aspirin (1.9%), according to multivariate analysis.

Overall, 42.4% of patients classified as inappropriate PPI use were not using aspirin, nonsteroidal anti-inflammatory drugs, antiplatelets, antiaggregants, anticoagulants, or steroids, the researchers found.

They also note that most patients in the study (92.3%) had received PPIs before admission, prescribed by their general practitioner or during a previous hospitalization. This raises concerns about unneeded continuation of the drugs and lack of review by clinicians, they write.
 

PPI deprescribing

Approached for comment, Adrienna Jirik, MD, a gastroenterologist at the Cleveland Clinic, told this news organization that “PPI overprescription is a common problem worldwide, with the United States being no exception.”

They are “one of the most prescribed medications in the world, with several formulations readily available as an over-the-counter medication,” she added.

Dr. Jirik, who was not involved with the study, said that the algorithm used is “on par with the United States clinical practice guidelines for PPI use” and a “great start to initiate an encounter with a patient on PPIs in the outpatient setting to review the indications and to de-escalate and deprescribe therapy.”

Indeed, the American Gastroenterological Association recently published a clinical practice update on deprescribing PPIs.

“It may be useful to incorporate a version of this algorithm as a ‘hard stop’ on some outpatient EMR [electronic medical record] templates to remind providers to address this issue prior to closing an encounter,” Dr. Jirik added.

She noted, however, that tackling any medication reconciliation is a very important but difficult and time-consuming task.

“Education is definitely key for both primary and subspecialty providers,” Dr. Jirik said. “If patients have been on a long-term PPI, the inpatient provider can suggest a plan for de-escalation based on practice guidelines and arrange proper outpatient follow-up for eventual deprescribing.”

No funding was declared. The authors and Dr. Jirik report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nearly half of patients discharged from a hospital had inappropriate proton pump inhibitor (PPI) prescriptions, suggests a retrospective analysis of an Israeli health care database that showed no improvements in prescribing patterns over time.

The research was published online in the journal Digestive and Liver Disease.

First author Orly Sneh-Arbib, MD, division of gastroenterology and liver disease, Clalit Health Services, Talpiot, Jerusalem, said in an interview that she and her co-authors were “very surprised” that the rates of inappropriate prescribing remained so high, especially as they had discussed the adverse effects of the drugs numerous times during departmental meetings.

She believes that, for many clinicians, handing out a prescription for PPIs has become a habit, with the thought being: “Just take this; it’s like a vitamin.”

In the paper, the researchers write, “Undoubtedly, more action is needed to raise physicians’ knowledge and attention to the subject while providing automated and standardized technology-based tools to reduce inappropriate PPI use using an acceptable algorithm.”

For the study, Dr. Sneh-Arbib and her colleagues developed an algorithm to assess inappropriate PPI prescribing in almost 4,000 internal medicine patients. To try to limit future overprescribing, their algorithm is now included in the clinical records system.

Consequently, every time a clinician tries to prescribe a PPI, they have to confirm that there is a valid indication for doing so, with the aim of adding an “extra step in the process,” Dr. Sneh-Arbib said.
 

Clear but complex PPI indications

There are a small, well-defined number of indications for long-term PPI use, the authors write. The indications include prior upper gastrointestinal bleeding, maintenance treatment after healing of erosive esophagitis, Barrett’s esophagus, the use of nonsteroidal anti-inflammatory drugs or antiplatelet agents in patients with increased bleeding risk, and maintenance therapy for symptom control in patients with gastroesophageal reflux disease.

The authors also note that the “appropriateness of PPIs is complex,” with multiple factors to consider for long-term PPI use, including complex drug combinations and medical history.

But having seen patients in their 30s prescribed PPIs “just because of taking steroids or aspirin,” Dr. Sneh-Arbib said she wanted to investigate further.

To examine the rate of inappropriate long-term PPI prescription on discharge from internal medicine departments, the team conducted a retrospective analysis of adults admitted to their institution for the first 6 months of 2014 and the first 6 months of 2017.

They included all patients prescribed PPIs on discharge with a recommendation for long-term use and excluded those who were transferred between departments or who had a hospital stay longer than 3 months.

Information on age, gender, ethnicity, socioeconomic status, current and past diagnoses including all relevant gastrointestinal diagnoses, Charlson comorbidity index, and medications on admission and discharge were recorded.
 

Guidelines for use of PPIs

To assess inappropriate PPI prescribing, the team searched for published recommendations on long-term use, Dr. Sneh-Arbib said. They developed an algorithm based on the U.K. National Institute for Health and Care Excellence (NICE) clinical guideline, “Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management.”

The guideline is “not perfect,” Dr. Sneh-Arbib said, but it was suitable. The team then randomly chose 100 patients from their records to validate the resulting algorithm, finding an accuracy of 96%.

The full analysis included 3,982 patients, of whom 74% were aged 65 years or older, and 50.8% were women. PPIs were first prescribed before hospital admission in 92.4% of cases.

The researchers found that the overall rate of inappropriate PPI prescriptions was 44.3%, a figure that was stable between the two the study periods. In 2014, the rate of inappropriate use was 43.2%, and it was 45.6% in 2017, a nonsignificant difference.

Inappropriate PPIs were higher (68.1%) in patients younger than 65 years, compared with those aged 65 years and older (36%).

The researchers analyzed factors associated with inappropriate PPIs, first excluding 448 patients with clear gastrointestinal indications.

In the majority of cases, the inappropriate PPI prescriptions occurred in patients who were not taking dual antiplatelet treatment (89.4%), in younger patients who were taking aspirin only (8.6%), and in patients receiving a single antiplatelet agent other than aspirin (1.9%), according to multivariate analysis.

Overall, 42.4% of patients classified as inappropriate PPI use were not using aspirin, nonsteroidal anti-inflammatory drugs, antiplatelets, antiaggregants, anticoagulants, or steroids, the researchers found.

They also note that most patients in the study (92.3%) had received PPIs before admission, prescribed by their general practitioner or during a previous hospitalization. This raises concerns about unneeded continuation of the drugs and lack of review by clinicians, they write.
 

PPI deprescribing

Approached for comment, Adrienna Jirik, MD, a gastroenterologist at the Cleveland Clinic, told this news organization that “PPI overprescription is a common problem worldwide, with the United States being no exception.”

They are “one of the most prescribed medications in the world, with several formulations readily available as an over-the-counter medication,” she added.

Dr. Jirik, who was not involved with the study, said that the algorithm used is “on par with the United States clinical practice guidelines for PPI use” and a “great start to initiate an encounter with a patient on PPIs in the outpatient setting to review the indications and to de-escalate and deprescribe therapy.”

Indeed, the American Gastroenterological Association recently published a clinical practice update on deprescribing PPIs.

“It may be useful to incorporate a version of this algorithm as a ‘hard stop’ on some outpatient EMR [electronic medical record] templates to remind providers to address this issue prior to closing an encounter,” Dr. Jirik added.

She noted, however, that tackling any medication reconciliation is a very important but difficult and time-consuming task.

“Education is definitely key for both primary and subspecialty providers,” Dr. Jirik said. “If patients have been on a long-term PPI, the inpatient provider can suggest a plan for de-escalation based on practice guidelines and arrange proper outpatient follow-up for eventual deprescribing.”

No funding was declared. The authors and Dr. Jirik report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New research suggests that body mass index (BMI) may influence response to topical corticosteroid (tCS) therapy for eosinophilic esophagitis (EoE).

The higher the patient’s BMI level, the lower the individual’s response to tCS therapy from a symptomatic, endoscopic, and histologic perspective, researchers observed in a retrospective study.

Because there are few clinical predictors of response to topical steroids, clinicians may want to consider BMI in their treatment algorithm and when discussing therapeutic treatment options with patients with EoE, the investigators write in an article published online in Clinical Gastroenterology and Hepatology.

For EoE, current guidelines recommend the use of proton-pump inhibitor (PPI) therapy, topical steroids, and dietary elimination. In addition, the biologic dupilumab (Dupixent) was recently approved in the United States for EoE.

Determining what therapy patients with EoE will respond best to remains a challenge, and obesity’s role in treatment response has been unclear.

To investigate the effect patients’ weight might have on tCS therapy, Evan Dellon, MD, MPH, and colleagues at the University of North Carolina School of Medicine, Chapel Hill, reviewed cases involving 296 adults and adolescents aged 14 years and older who had received topical steroids for EoE.

Baseline characteristics were similar, although heartburn was more common among the 68 patients with obesity than among the non-obese patients (59% vs. 37%; P = .001), and the rate of hiatal hernias detected endoscopically was higher among the patients with obesity (22% vs. 11%; P = .02).

Following tCS treatment, peak eosinophil counts were higher for patients with obesity, compared with non-obese patients (36.1 vs. 21.5; P = .003).

Histologic response was significantly higher in non-obese patients, compared with patients with obesity, at less than 15 eosinophils per high-power field (eos/hpf: 61% vs. 47%; P = .049) and less than or equal to 6 eos/hpf (54% vs. 38%; P = .02).

Among the non-obese patients with EoE, global endoscopic response to tCS was significantly greater than among the patients with obesity (76% vs. 59%; P = .006).

In additon, among non-obese patients, the post-treatment EoE-Endoscopic Reference Score (2.4 vs. 3.2; P = .01) and the endoscopic severity score were significantly lower (2.0 vs. 2.4; P = .05).

Global symptomatic response to tCS was seen in 84% of non-obese patients, versus only 67% of those with obesity (P = .03).

On multivariate analysis, increasing BMI was independently associated with decreased histologic response after accounting for age, heartburn, dilation, and hiatal hernia.

This relationship persisted whether BMI was assessed as a continuous variable (adjusted odds ratio, 0.93 for each unit increase in BMI), as non-obese versus obese (aOR 0.38), as overweight versus normal weight (aOR 0.46), or obese versus normal weight (aOR 0.26).
 

Different treatment algorithm?

The results remained generally similar when patients were stratified by PPI response status and by continued use of PPIs.

The investigators note that in their cohort, only five patients responded to PPI therapy; all were non-obese. It’s possible, they note, that patients with a higher BMI may benefit from dual PPI/tCS treatment initially, but this strategy would require prospective assessment.

As for the mechanism behind obesity’s apparent negative impact on tCS therapy, the researchers say the low-grade systemic inflammatory state of obesity may make tCS therapy less effective, but they add that studies are needed to pinpoint the exact mechanism.

The study suggests that “a clinician can now add another epidemiologic risk factor for potential poor response to treatment for EoE, specifically steroids,” Philip Katz, MD, professor of medicine, division of gastroenterology and hepatology, Weill Cornell Medicine, New York, said in an interview when reached for comment.

However, it is “difficult, if not impossible, to discern from a retrospective study like this why higher BMI would be a risk factor for poor response,” said Dr. Katz, who was not affiliated with the study.

“The main potential clinical message here is that people who are overweight with EoE perhaps need to be looked at differently and might require a different treatment algorithm or treatment approach than a person who is ideal body weight,” Dr. Katz added.

Also commenting for this article, Shreya Chablaney, MD, a gastroenterologist at NYU Langone Health’s Center for Esophageal Health and clinical instructor at NYU Grossman School of Medicine, noted that predictors of patient response to various treatment options for EoE are not well understood and that more robust data are needed to guide appropriate patient selection when considering them.

“Though this is a relatively small, single-center, retrospective study, it shows an interesting finding, that high BMI is independently associated with a decrease in histologic, symptomatic, and endoscopic response to topical steroids, even when controlling for heartburn and the presence of a hiatal hernia,” she said.

“While these findings may not yet affect current management, it highlights the need for more prospective research to see if dosing adjustment, type of topical steroid, or alternative therapy altogether should be considered in patients who are obese,” Dr. Chablaney said.

Support for the study was provided by the National Institutes of Health. Dr. Dellon is a consultant for Abbott, AbbVie, Adare/ Ellodi, Aimmune, Akesobio, ALK, Allakos, Amgen, Arena, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eurpaxia, Ferring, GSK, Gossamer Bio, Invea, Landos, LucidDx, Morphic, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, and Target RWE. Dr. Katz is a consultant for Phathom Pharmaceuticals and Sebella Pharmaceuticals and serves on an advisory board for AstraZeneca. Dr. Chablaney reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New research suggests that body mass index (BMI) may influence response to topical corticosteroid (tCS) therapy for eosinophilic esophagitis (EoE).

The higher the patient’s BMI level, the lower the individual’s response to tCS therapy from a symptomatic, endoscopic, and histologic perspective, researchers observed in a retrospective study.

Because there are few clinical predictors of response to topical steroids, clinicians may want to consider BMI in their treatment algorithm and when discussing therapeutic treatment options with patients with EoE, the investigators write in an article published online in Clinical Gastroenterology and Hepatology.

For EoE, current guidelines recommend the use of proton-pump inhibitor (PPI) therapy, topical steroids, and dietary elimination. In addition, the biologic dupilumab (Dupixent) was recently approved in the United States for EoE.

Determining what therapy patients with EoE will respond best to remains a challenge, and obesity’s role in treatment response has been unclear.

To investigate the effect patients’ weight might have on tCS therapy, Evan Dellon, MD, MPH, and colleagues at the University of North Carolina School of Medicine, Chapel Hill, reviewed cases involving 296 adults and adolescents aged 14 years and older who had received topical steroids for EoE.

Baseline characteristics were similar, although heartburn was more common among the 68 patients with obesity than among the non-obese patients (59% vs. 37%; P = .001), and the rate of hiatal hernias detected endoscopically was higher among the patients with obesity (22% vs. 11%; P = .02).

Following tCS treatment, peak eosinophil counts were higher for patients with obesity, compared with non-obese patients (36.1 vs. 21.5; P = .003).

Histologic response was significantly higher in non-obese patients, compared with patients with obesity, at less than 15 eosinophils per high-power field (eos/hpf: 61% vs. 47%; P = .049) and less than or equal to 6 eos/hpf (54% vs. 38%; P = .02).

Among the non-obese patients with EoE, global endoscopic response to tCS was significantly greater than among the patients with obesity (76% vs. 59%; P = .006).

In additon, among non-obese patients, the post-treatment EoE-Endoscopic Reference Score (2.4 vs. 3.2; P = .01) and the endoscopic severity score were significantly lower (2.0 vs. 2.4; P = .05).

Global symptomatic response to tCS was seen in 84% of non-obese patients, versus only 67% of those with obesity (P = .03).

On multivariate analysis, increasing BMI was independently associated with decreased histologic response after accounting for age, heartburn, dilation, and hiatal hernia.

This relationship persisted whether BMI was assessed as a continuous variable (adjusted odds ratio, 0.93 for each unit increase in BMI), as non-obese versus obese (aOR 0.38), as overweight versus normal weight (aOR 0.46), or obese versus normal weight (aOR 0.26).
 

Different treatment algorithm?

The results remained generally similar when patients were stratified by PPI response status and by continued use of PPIs.

The investigators note that in their cohort, only five patients responded to PPI therapy; all were non-obese. It’s possible, they note, that patients with a higher BMI may benefit from dual PPI/tCS treatment initially, but this strategy would require prospective assessment.

As for the mechanism behind obesity’s apparent negative impact on tCS therapy, the researchers say the low-grade systemic inflammatory state of obesity may make tCS therapy less effective, but they add that studies are needed to pinpoint the exact mechanism.

The study suggests that “a clinician can now add another epidemiologic risk factor for potential poor response to treatment for EoE, specifically steroids,” Philip Katz, MD, professor of medicine, division of gastroenterology and hepatology, Weill Cornell Medicine, New York, said in an interview when reached for comment.

However, it is “difficult, if not impossible, to discern from a retrospective study like this why higher BMI would be a risk factor for poor response,” said Dr. Katz, who was not affiliated with the study.

“The main potential clinical message here is that people who are overweight with EoE perhaps need to be looked at differently and might require a different treatment algorithm or treatment approach than a person who is ideal body weight,” Dr. Katz added.

Also commenting for this article, Shreya Chablaney, MD, a gastroenterologist at NYU Langone Health’s Center for Esophageal Health and clinical instructor at NYU Grossman School of Medicine, noted that predictors of patient response to various treatment options for EoE are not well understood and that more robust data are needed to guide appropriate patient selection when considering them.

“Though this is a relatively small, single-center, retrospective study, it shows an interesting finding, that high BMI is independently associated with a decrease in histologic, symptomatic, and endoscopic response to topical steroids, even when controlling for heartburn and the presence of a hiatal hernia,” she said.

“While these findings may not yet affect current management, it highlights the need for more prospective research to see if dosing adjustment, type of topical steroid, or alternative therapy altogether should be considered in patients who are obese,” Dr. Chablaney said.

Support for the study was provided by the National Institutes of Health. Dr. Dellon is a consultant for Abbott, AbbVie, Adare/ Ellodi, Aimmune, Akesobio, ALK, Allakos, Amgen, Arena, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eurpaxia, Ferring, GSK, Gossamer Bio, Invea, Landos, LucidDx, Morphic, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, and Target RWE. Dr. Katz is a consultant for Phathom Pharmaceuticals and Sebella Pharmaceuticals and serves on an advisory board for AstraZeneca. Dr. Chablaney reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New research suggests that body mass index (BMI) may influence response to topical corticosteroid (tCS) therapy for eosinophilic esophagitis (EoE).

The higher the patient’s BMI level, the lower the individual’s response to tCS therapy from a symptomatic, endoscopic, and histologic perspective, researchers observed in a retrospective study.

Because there are few clinical predictors of response to topical steroids, clinicians may want to consider BMI in their treatment algorithm and when discussing therapeutic treatment options with patients with EoE, the investigators write in an article published online in Clinical Gastroenterology and Hepatology.

For EoE, current guidelines recommend the use of proton-pump inhibitor (PPI) therapy, topical steroids, and dietary elimination. In addition, the biologic dupilumab (Dupixent) was recently approved in the United States for EoE.

Determining what therapy patients with EoE will respond best to remains a challenge, and obesity’s role in treatment response has been unclear.

To investigate the effect patients’ weight might have on tCS therapy, Evan Dellon, MD, MPH, and colleagues at the University of North Carolina School of Medicine, Chapel Hill, reviewed cases involving 296 adults and adolescents aged 14 years and older who had received topical steroids for EoE.

Baseline characteristics were similar, although heartburn was more common among the 68 patients with obesity than among the non-obese patients (59% vs. 37%; P = .001), and the rate of hiatal hernias detected endoscopically was higher among the patients with obesity (22% vs. 11%; P = .02).

Following tCS treatment, peak eosinophil counts were higher for patients with obesity, compared with non-obese patients (36.1 vs. 21.5; P = .003).

Histologic response was significantly higher in non-obese patients, compared with patients with obesity, at less than 15 eosinophils per high-power field (eos/hpf: 61% vs. 47%; P = .049) and less than or equal to 6 eos/hpf (54% vs. 38%; P = .02).

Among the non-obese patients with EoE, global endoscopic response to tCS was significantly greater than among the patients with obesity (76% vs. 59%; P = .006).

In additon, among non-obese patients, the post-treatment EoE-Endoscopic Reference Score (2.4 vs. 3.2; P = .01) and the endoscopic severity score were significantly lower (2.0 vs. 2.4; P = .05).

Global symptomatic response to tCS was seen in 84% of non-obese patients, versus only 67% of those with obesity (P = .03).

On multivariate analysis, increasing BMI was independently associated with decreased histologic response after accounting for age, heartburn, dilation, and hiatal hernia.

This relationship persisted whether BMI was assessed as a continuous variable (adjusted odds ratio, 0.93 for each unit increase in BMI), as non-obese versus obese (aOR 0.38), as overweight versus normal weight (aOR 0.46), or obese versus normal weight (aOR 0.26).
 

Different treatment algorithm?

The results remained generally similar when patients were stratified by PPI response status and by continued use of PPIs.

The investigators note that in their cohort, only five patients responded to PPI therapy; all were non-obese. It’s possible, they note, that patients with a higher BMI may benefit from dual PPI/tCS treatment initially, but this strategy would require prospective assessment.

As for the mechanism behind obesity’s apparent negative impact on tCS therapy, the researchers say the low-grade systemic inflammatory state of obesity may make tCS therapy less effective, but they add that studies are needed to pinpoint the exact mechanism.

The study suggests that “a clinician can now add another epidemiologic risk factor for potential poor response to treatment for EoE, specifically steroids,” Philip Katz, MD, professor of medicine, division of gastroenterology and hepatology, Weill Cornell Medicine, New York, said in an interview when reached for comment.

However, it is “difficult, if not impossible, to discern from a retrospective study like this why higher BMI would be a risk factor for poor response,” said Dr. Katz, who was not affiliated with the study.

“The main potential clinical message here is that people who are overweight with EoE perhaps need to be looked at differently and might require a different treatment algorithm or treatment approach than a person who is ideal body weight,” Dr. Katz added.

Also commenting for this article, Shreya Chablaney, MD, a gastroenterologist at NYU Langone Health’s Center for Esophageal Health and clinical instructor at NYU Grossman School of Medicine, noted that predictors of patient response to various treatment options for EoE are not well understood and that more robust data are needed to guide appropriate patient selection when considering them.

“Though this is a relatively small, single-center, retrospective study, it shows an interesting finding, that high BMI is independently associated with a decrease in histologic, symptomatic, and endoscopic response to topical steroids, even when controlling for heartburn and the presence of a hiatal hernia,” she said.

“While these findings may not yet affect current management, it highlights the need for more prospective research to see if dosing adjustment, type of topical steroid, or alternative therapy altogether should be considered in patients who are obese,” Dr. Chablaney said.

Support for the study was provided by the National Institutes of Health. Dr. Dellon is a consultant for Abbott, AbbVie, Adare/ Ellodi, Aimmune, Akesobio, ALK, Allakos, Amgen, Arena, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eurpaxia, Ferring, GSK, Gossamer Bio, Invea, Landos, LucidDx, Morphic, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, and Target RWE. Dr. Katz is a consultant for Phathom Pharmaceuticals and Sebella Pharmaceuticals and serves on an advisory board for AstraZeneca. Dr. Chablaney reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.