Introduction
In 1858, Dr. Rudolph Virchow, the father of comparative medicine, advocated for a collaborative approach to medicine, stating, “Between animal and human medicine there are no dividing lines—nor should there be. The object is different, but the experience obtained constitutes the basis of all medicine.” Consistent with the One Health approach, gastric acid–suppressant drugs (ASDs) have advanced significantly due to the combined efforts of both human and veterinary research. Veterinary species, for example, were pivotal in early studies evaluating ASDs and continue to provide naturally occurring models of acid-related disorders.1,2 In return, extensive multicenter human clinical trials have produced new drugs and treatment strategies widely utilized in veterinary medicine. Shared challenges in both fields, such as treatment failure and ASD overuse, underscore the need for continued collaboration.3–7
While a comparative approach is beneficial, species differences should be recognized and used to inform treatment decisions. Human acid-related disorder research heavily influences veterinary studies; for example, human guidelines for adequate gastric acid suppression are frequently used to assess ASD efficacy in veterinary species.8 However, significant species differences exist. Cats, for instance, respond differently to ASDs compared to dogs and humans,9,10 and physiologic differences between monogastrics and ruminants affect drug bioavailability.11 As a result, the advancement of ASDs in both the human and veterinary fields is dependent on a comparative, but nuanced, approach.
In this context, the following article will provide a brief comparative review on ASD efficacy, indications, and gastric pH-dependent adverse effects (AEs) in veterinary medicine with a focus on small animals. The companion Currents in One Health article by Gould et al, AJVR, October 2024, will explore gastric pH-independent effects in human and rodent models. Together, these reviews aim to not only serve as a clinical resource but also guide future research in this field.
Acid Suppression in Veterinary Medicine
Most studies in veterinary medicine assess ASD efficacy by evaluating intragastric pH rather than acid secretion. Historically, gastric pH measurement was performed with pH catheters that measured luminal gastric pH through either percutaneous, endoscopically placed gastrostomy tubes in research dogs and camelids8,12 or cannulas in ruminants.13 More recently, radiotelemetric pH capsules placed under sedation by use of standard radiography have offered a noninvasive way to continuously record intragastric pH.14,15 In humans, ASD efficacy is often evaluated by measuring the mean percentage of time that gastric pH is ≥ 3 or 4, a pH at which gastroesophageal mucosal healing is thought to be optimal. Specific treatment goals for duodenal ulceration and gastroesophageal reflux disease (GERD) are defined as maintaining an intragastric pH ≥ 3 and 4 for ≥ 75% and 67% of the day, respectively.16,17 These same goals have been used to evaluate ASDs in veterinary medicine, as species-specific treatment goals have not been determined.
The most commonly used classes of drugs that raise gastric pH include antacids, prostaglandins, and the antisecretory drugs, histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). A review of each class’s mechanism of action and application in humans is followed by a more in-depth assessment of their efficacy and use in veterinary species. Figure 1 summarizes how each drug class raises gastric pH in the context of normal gastric acid secretion.4,18
Effect of acid-suppressant drugs on parietal cell acid secretion. Stimulatory pathways are indicated by arrowhead lines with plus (+) signs. Inhibitory pathways are indicated by lines with minus (–) signs. Dashed lines indicate the major negative feedback loop controlling gastric acid production. Three major secretagogues stimulate the gastric parietal cells to produce hydrochloric acid: acetylcholine via the M3 muscarinic receptor, histamine via the histamine type 2 receptor, and gastrin via the cholecystokinin B receptor. Each stimulant acts on the parietal cell via signaling pathways involving intracellular calcium or cAMP to activate protein kinases, leading to activation of H+/K+ ATPases and gastric acid production. An increase in gastric hydrochloric acid and decrease in gastric pH stimulates the D-cell to produce somatostatin, which acts as the major negative feedback loop to decrease gastric acid secretion by reducing gastrin and histamine secretion and directly inhibiting the parietal cell. Acid-suppressant drugs utilize these pathways to decrease acid secretion. Antacids directly neutralize gastric acid, whereas prostaglandin analogs activate prostaglandin receptors on the parietal cells, effectively inhibiting signaling pathways that are responsible for acid production. Histamine H2-receptor antagonists directly inhibit histamine type 2 receptors, leading to a reduction in cAMP levels. Proton pump inhibitors directly inhibit the final pathway for acid production, the H+/K+ ATPase enzyme. Ach = Acetylcholine. CCK2R = Cholecystokinin B receptor. H2R = Histamine type 2 receptor. M3R = M3 muscarinic receptor. PG = Prostaglandin. PGER = Prostaglandin E receptor. SSTR2 = Somatostatin receptor 2. Image created with
Citation: Journal of the American Veterinary Medical Association 262, 10; 10.2460/javma.24.07.0434
Antacids
Antacids (eg, calcium carbonate, aluminum hydroxide, magnesium hydroxide) neutralize gastric acid and decrease pepsinogen activation (Figure 1).19 Antacids were the first-line treatment against peptic ulcers; however, they have since been replaced by more efficacious ASDs that need less frequent dosing. They are now only recommended for mild gastroesophageal reflux and symptomatic relief from heartburn, GERD, and hyperacidity.19 In veterinary medicine, they are considered for dogs and cats with painful or erosive esophagitis or mucositis, but their use is limited by the need for frequent administration.20
Prostaglandin analogs
Misoprostol is a synthetic prostaglandin E1 analog that directly stimulates prostaglandin receptors on the parietal cells and inhibits basal and nocturnal gastric acid secretion (Figure 1). It also increases mucus and bicarbonate secretion and improves regulation of gastrointestinal (GI) mucosal blood flow and epithelial restitution.21 Misoprostol reduces endoscopic ulcers but not bleeding in human patients coadministered NSAIDs.22 However, its use is greatly reduced due to GI and abortifacient side effects.23 Among veterinary patients, misoprostol effectively reduces aspirin-induced gastric injury24 but requires frequent dosing, and there is a lack of research evaluating its protective role with other NSAIDs. Misoprostol is not effective in preventing gastric ulceration/erosion (GUE) secondary to steroid use.25,26
Histamine-2 receptor antagonists
Histamine-2 receptor antagonists inhibit the interaction of the H2 receptor on the parietal cell with histamine, the most potent secretagogue of gastric acid (Figure 1). In humans, H2RAs have largely been replaced by PPIs, which are more effective at healing ulcers, preventing GI bleeding, and providing faster healing and heartburn relief for esophagitis.27 However, H2RAs are superior for treatment of nocturnal acid breakthrough (NAB), a phenomenon in which intragastric pH is persistently < 4 for > 1 hour overnight despite PPI use.28 Therefore, H2RAs are primarily recommended as a step-down therapy for patients receiving PPIs or as an additional therapy for patients with NAB that is nonresponsive to PPIs alone.27
In dogs and cats, famotidine is the most prescribed H2RA. Cimetidine is no longer recommended, as it inhibits cytochrome P450, resulting in possible drug interactions29; decreases hepatic blood flow30; and anecdotally is less effective compared to other H2RAs. Ranitidine also does not provide adequate acid suppression via PO or IV administration to dogs or cats.8,31 Famotidine, on the other hand, initially provides excellent acid suppression in dogs, meeting clinical goals for esophagitis and ulcer treatment as defined for humans starting on day 1 of either oral (1 mg/kg, PO, q 12 h)32 or constant rate infusion (CRI) treatment (8 mg/kg/d, IV, 1-mg/kg starting bolus dose).33 Clinical goals for treatment, however, are not met with an IV bolus administration of 1 mg/kg every 12 hours alone.8,33 In cats, famotidine (1 mg/kg, PO, q 12 h) results in significant acid suppression compared to placebo but does not meet the aforementioned clinical acid-suppressing goals.10,34 Famotidine CRI appears to be safe and effective in cats on the basis of clinical experience and a single limited study35; however, further research is needed to determine its efficacy in cats. A significant limitation of famotidine is that its effect diminishes within 2 to 3 days of PO administration in humans,36 dogs,32 and cats34 and when used IV in cattle.13 The cause of H2RA tachyphylaxis is unknown, but several mechanisms have been hypothesized.37
Despite the potential for tachyphylaxis, there are specific indications for H2RA administration. Given their rapid onset of action and ability to be given with food, H2RAs can be used for immediate relief on an as-needed or short-term basis, such as for bilious vomiting or management of reflux under anesthesia.20 In addition, famotidine CRIs can benefit hospitalized patients requiring aggressive, fast acid suppression, although its efficacy after 3 days is unknown. Histamine-2 receptor antagonists could also be considered as an adjunctive therapy in animals showing signs consistent with NAB despite PPI therapy; however, tachyphylaxis can make these drugs ineffective for long-term control. Of note, combining H2RAs and PPIs does not improve gastric acid suppression15 and therefore is not recommended outside of treating NAB.
Proton pump inhibitors (eg, omeprazole, pantoprazole, esomeprazole, lansoprazole) directly inhibit the H+/K+ ATPase enzyme responsible for gastric acid secretion (Figure 1). Proton pump inhibitors start as prodrugs that become protonated and trapped in the acidic environment of the parietal cell. They subsequently form disulfide bonds with and inactivate H+/K+ ATPase. Proton pump inhibitors are considered first-line therapy in humans with upper GI bleeding or esophagitis.27,38 Among PPIs, esomeprazole is the most effective for mucosal erosion healing in erosive esophagitis and heartburn relief39 and is first-line treatment for GERD.40
Proton pump inhibitors
Proton pump inhibitors also provide excellent acid suppression in veterinary species. In dogs, PO omeprazole results in greater acid suppression compared to PO or IV H2RA administration.8,10,31,41 In addition, PO omeprazole is more effective for the treatment of exercise-induced gastric lesions in dogs compared to famotidine.42 In humans, acid suppression is typically given once a day to start. However, in dogs, omeprazole must be administered twice daily to meet the goals defined for acid suppression in humans.8,41,43 Multiple formulations, including omeprazole capsules, oral tablets, reformulated paste, suspension, and fractionated tablets, have been evaluated,8,10,41,43 and all provide superior acid suppression compared to H2RAs. Intramuscular injection of a long-acting omeprazole can also provide acid suppression for 5 to 7 days.44 One disadvantage of PPIs is that, unlike H2RAs, some may take up to 5 days to reach peak effect,9,45 although their effect is generally at least comparable to H2RAs by day 2.8 In situations where fast acid suppression is needed, esomeprazole at 0.5 to 1 mg/kg IV every 12 hours provides similar acid suppression to a famotidine CRI on day 1 of treatment in dogs and outperforms pantoprazole.46,47 Oral esomeprazole also provides excellent acid suppression (1 mg/kg, PO, q 12-24 h), but time to maximal efficacy is unknown in dogs.48 In cats, twice-daily PO omeprazole is also superior to H2RAs but fails to meet human treatment goals for esophagitis or ulceration, although specific treatment goals for cats are unknown.10,31 Esomeprazole appears to be highly effective in cats though, with some cats achieving the human treatment goal for duodenal ulceration by day 4 (1 mg/kg, PO, q 12 h).9 Dexlansoprazole and lansoprazole should not be used in cats, as they are less efficacious than other PPIs.9 Among large animals, PPIs are also the preferred ASD. Oral omeprazole once a day effectively prevents gastric ulcers in racehorses49 and is the treatment of choice for equine gastric ulcer syndrome.50 In adult ruminants, PO omeprazole is not bioavailable,12,51 but parenteral pantoprazole (2 mg/kg, SC, q 24 h and 1 mg/kg, IV, q 24 h)12 in alpacas and esomeprazole in sheep (1 mg/kg, IV)11 significantly increase gastric pH.
In summary, PPIs are first-line therapy in dogs and cats for the treatment of acid-related GUE.4 While both omeprazole and esomeprazole are excellent oral options, esomeprazole offers the benefit of once-daily administration when medicating is difficult or compliance is questionable, although some dogs require twice-daily administration.52 Twice-daily PO esomeprazole in cats may represent a superior option for acid suppression,9 but a direct comparison study to omeprazole is needed. In critically ill patients for which fast, aggressive acid suppression is needed, IV esomeprazole or famotidine CRI are suitable options for rapid, effective suppression.
Indications for Acid Suppression
Conditions with strong indication for acid suppression
Acid-suppressant drugs are commonly misused, with some human studies estimating that 25% to 70% of PPI prescriptions are not appropriate.53 In veterinary medicine, 68.5% of dogs and 60.9% of cats at tertiary referral centers were prescribed ASDs without an appropriate indication.3,5 Of note, in some populations, inappropriate prescription has persisted despite the publication of consensus guidelines on rational use of gastroprotectants.6 However, in others, inappropriate prescriptions have substantially decreased.54 As described later in this article, PPI use might not be benign, and thus it is important to identify conditions for which acid suppression is and is not indicated.
The US FDA recommends PPI treatment for humans with erosive esophagitis, GERD, pathological hypersecretory conditions (Zollinger-Ellison syndrome), gastric and duodenal ulcers, NSAID drug prophylaxis for patients at high risk of GI bleeding, and Helicobacter pylori infection.55 There are strong data supporting its efficacy in controlling reflux disease and esophagitis, as approximately 70% to 80% of patients with erosive reflux disease and 60% of patients with nonerosive reflux disease achieve symptomatic relief with PPI treatment.27 Studies also support their efficacy in treating GUE; multiple studies show that IV PPI therapy 72 hours after endoscopic hemostatic therapy results in a significant reduction in further bleeding, surgery, and mortality.38
Based on the 2018 American College of Veterinary Internal Medicine consensus statement on gastroprotectant use for dogs and cats, indications include esophagitis, gastroesophageal reflux, and GUE.4 While veterinary medicine lacks controlled studies evaluating the effect of PPIs on esophagitis and reflux, multiple studies have shown that PPI administration prior to anesthesia significantly raises esophageal and gastric pH,56,57 which may help prevent acid- and pepsin-related injury secondary to reflux. Acid-suppressant drugs are also recommended for treatment of GUE. Risk factors for GUE in dogs include NSAID or glucocorticoid use, GI neoplasia, gastrinoma, and GI mechanical disease (foreign bodies, gastric dilatation and volvulus).58 In cats, GUE is uncommon but most commonly caused by neoplasia.59 Other conditions reported in cats with GUE include a history of NSAID use, inflammatory bowel disease, hypovolemic shock, and parasitic infections.59
Prophylactic administration of ASDs to prevent stress-related mucosal damage in working or competing animals is controversial but reasonable to consider when lesions might be contributing to illness. In humans, GI bleeding is common in long-distance runners,60 and in 1 study,61 35% to 48% of dogs competing in the Iditarod had GUE or hemorrhage. Labrador Retrievers trained for explosive detection also have substantial gastric disease after 5 days of sustained exercise,62 and working breeds are more likely to have GUE than mixed-breed dogs.58 Among dogs in the Iditarod, omeprazole administered daily is effective at decreasing the severity and prevalence of gastric lesions.42
Conditions for which further research is needed
There are several diseases for which ASDs can be considered but further research is needed. One such condition is mast cell disease. Humans with mastocytosis are at higher risk of developing peptic ulcers, likely secondary to high circulating histamine concentrations triggering hyperacidity, and H2RAs and PPIs are often recommended to treat GI signs.63 Dogs with mast cell disease also have evidence of GI ulceration,64 and H2RAs are often recommended when systemic signs are present, when tumors are manipulated, or in situations where degranulation is likely to occur, such as radiation therapy.65 Further research is needed to evaluate whether these agents help these dogs and whether hyperacidity is present in this condition (the companion Currents in One Health article by Gould et al, AJVR, October 2024, presents additional information).
An additional disease of concern is immune-mediated thrombocytopenia (ITP), which commonly presents with GI bleeding.66 In humans, PPIs are considered in acute, major GI bleeding in patients with ITP.67 In a study68 evaluating dogs with ITP, treatment with gastroprotectants did not improve the probability of surviving to discharge, but other factors, such as its relationship to transfusion number or visit cost, were not evaluated. One variable limiting ASD success in this condition is that a pH > 6 is necessary for platelet aggregation,69 a goal that is often unobtainable with standard doses of PPIs.41 Only 2 dogs achieved a mean pH of 6 for 50% of the day on day 1 or 2 of treatment with esomeprazole at 1 mg/kg IV every 12 hours (Kuhl et al, unpublished data, 2020). While the 2018 consensus statement on gastroprotectant use does not support ASD treatment in ITP, the 2024 consensus statement on ITP states that they can be considered when melena is suspected.70 In these scenarios, more efficacious ASDs such as esomeprazole should be considered and monitoring for benefit is advised.
The role of hepatic disease in the development of GUE and use of PPIs in dogs with hepatic disease is also deserving of additional research. In humans with cirrhosis, GI bleeding is common and likely secondary to factors such as esophageal variceal bleeding and portal hypertensive gastropathy.71 While PPIs are frequently prescribed to patients with cirrhosis,72 their use is often inappropriate, as they do not prevent bleeding from gastroesophageal varices or portal hypertensive gastropathy.72,73 In addition, PPI use may not be benign in these patients and has been associated with an increased risk of infection and encephalopathy.74 In dogs, it is unknown whether hepatic disease predisposes to GUE. One retrospective study75 of 43 dogs found that hepatic disease was the second most common condition reported in dogs with GUE. Two additional studies found that 9 of 40 dogs with hepatic disease had endoscopic evidence of erosion or ulcer76 and 17% of 51 dogs with intrahepatic portosystemic shunts (PSS) had GUE.77 Neither study had a control group however, and in the single prospective study58 completed with a control group, hepatic disease was not associated with GUE. Unlike humans, esophageal varices are also uncommon in dogs and not commonly associated with bleeding.78 While 1 study77 reported that lifelong ASD therapy in dogs with intrahepatic PSS decreased deaths due to GI bleeding from 50% to 4%, it is unclear why and how PPIs benefit dogs with intrahepatic PSS. The 2018 consensus guidelines do not support prophylactic use of ASDs in animals with hepatic disease that is not associated with GI bleeding. However, further research is needed to determine whether ASDs provide benefit for GI bleeding secondary to hepatic disease.
Conditions for which acid suppression is not indicated
There are multiple conditions for which, per the American College of Veterinary Internal Medicine consensus, ASDs are not recommended due to lack of evidence of a demonstratable benefit at the time of publication. These conditions include nonerosive gastritis, pancreatitis, presence of noninflammatory Helicobacter colonization, and chronic kidney disease.4 In addition, despite the high prevalence of mucosal bleeding in dogs with acute thoracolumbar intervertebral disc extrusion, ASDs should not be used preventatively in this disease, as they do not reduce GI complications.79 Furthermore, ASDs should not be used prophylactically with NSAIDs in patients without other risk factors for GI bleeding. Piroxicam in combination with omeprazole or famotidine is associated with increased GI AEs80 and induces fecal dysbiosis.81 Previous studies also show no benefit of using prophylactic omeprazole (0.7 mg/kg, PO, q 24 h) or misoprostol to reduce GUE with concurrent glucocorticoid administration.25 Although clinical consequences of GI bleeding were not observed, 1 study82 using a more appropriate dosage of omeprazole (1 mg/kg, PO, q 12 h) found that total mucosal lesion scores on endoscopy and invasive erosions were lower for dogs receiving prednisone and omeprazole compared to prednisone alone. As a result, it may be reasonable to consider prophylactic use of PPIs with steroids if a patient is at high risk of ulceration, has evidence of clinically significant bleeding, or has a history of ulceration with steroids; otherwise, prophylactic use should be avoided.
Short-term AEs
Human research has revealed several short- and long-term AEs associated with the use of acid-neutralizing drugs or ASDs. In veterinary medicine, research has primarily focused on short-term AEs. The most common AE of aluminum-containing antacids is constipation, but aluminum and magnesium accumulation can occur in animals with renal disease.4,83 Side effects associated with prostaglandin analogs, including GI complications and abortion, limit their use. Misoprostol should be avoided in pregnant animals. Histamine-2 receptor antagonists are also excreted renally and should be dose reduced in dogs with advanced kidney disease; otherwise, these drugs have a good safety profile.84
Short-term AEs of PPIs have been more thoroughly studied in veterinary medicine and reveal that PPIs are not only associated with vomiting and diarrhea8,79,85,86 but can also cause dysbiosis.87 In humans, PPIs are associated with dysbiosis and increased risk of enteric infections such as Clostridioides difficile.88 Dogs receiving a 15-day course of omeprazole also have a significant change in their gut and fecal microbiome.89 In addition, dogs that receive carprofen with omeprazole have higher dysbiosis indices and decreased short-chain fatty acid–producing bacteria compared to dogs receiving carprofen alone.81 While 1 study87 did not identify significant fecal microbiome changes associated with esomeprazole use in dogs, it was likely underpowered to identify this change. Dysbiosis may present clinically, as dogs that receive gastroprotectants (famotidine, omeprazole) with piroxicam experience significantly more severe GI AEs compared to dogs given piroxicam alone.80 Horses receiving omeprazole with phenylbutazone also have an increased risk of GI complications.90 Cats show a mild but transient change in their microbiome associated with omeprazole use,91 but more research is needed with greater sample sizes. Further research is also needed to determine how to ameliorate these effects, as 1 study87 with concurrent probiotic administration failed to show a benefit in decreasing PPI-induced AEs. However, anecdotally, lower dosages of these medications with subsequent small increases to the therapeutic dose or different drugs within the same class can be trialed.
An underexplored area in veterinary medicine is the interaction of select types of PPIs (eg, omeprazole, esomeprazole, lansoprazole) with antiplatelet or antifungal drugs (eg, clopidogrel, various antifungals), due to epigenetic variation in the cytochrome 2C19. This interaction is well documented in humans.92–94 Decreased drug absorption of iron, mycophenolate, tyrosine kinase inhibitors, factor Xa inhibitors, and other drugs that require an acidic gastric environment for activation has also been observed in humans.92,93,95 Limited research has explored these interactions in veterinary medicine. One study96 evaluated the effect of clopidogrel and omeprazole on platelet function in normal dogs and found no significant difference in platelet function when dogs received clopidogrel and omeprazole versus clopidogrel alone. Further research on drug interactions involving PPIs in veterinary medicine is greatly needed.
Long-term AEs
Sequelae reported in humans receiving chronic PPI therapy include vitamin and mineral deficiencies (eg, vitamins B12 and C, iron, calcium, and magnesium), increased risk of pathological factures secondary to decreased bone mineral content and density, and secondary respiratory infections.97 Known mechanisms of action responsible for these effects predominantly include vitamin and mineral malabsorption secondary to increased elevated GI pH and bacterial overgrowth from a chronic reduction in “healthy” gastric acidity.
Few studies have evaluated long-term AEs in dogs or cats receiving ASDs. No changes in blood vitamin B12, magnesium, or bone mineral density or content as assessed via dual energy X-ray absorptiometry scans were appreciated in cats receiving 60 days of PO omeprazole therapy compared to crossover placebo therapy.14 Similarly, significant hypocobalaminemia was not documented in dogs following 60 days of PO omeprazole therapy.98 However, hypergastrinemia has been reported in dogs, cats, and horses receiving PPI therapy.14,98,99 In addition, in 1 study14 evaluating long-term omeprazole use in cats, 2 of 6 cats had intragastric pH monitoring performed at the time of omeprazole cessation and both experienced rebound gastric hyperacidity. In humans, rebound acid hypersecretion, defined as an increase in gastric acid secretion above pretreatment levels, occurs after abrupt cessation following just 8 weeks of PPI therapy and results in worsened heartburn, acid regurgitation, and dyspepsia.100 It is suspected that proton-pump inhibition results in compensatory gastrin release, leading to hypertrophy of enterochromaffin-like cells and increased gastric acid secretion once PPI therapy is discontinued. As a result of these findings, current guidelines recommend tapering of PPI therapy by 50% per week after 3 to 4 weeks of treatment. In humans, hypergastrinemia is also associated with parietal cell protrusions, and long-term PPI use is associated with an up to 4-fold increase in risk of fundic gland polyps.101 A dog treated with PO omeprazole for over 4 years developed fundic gland polyps that resolved after omeprazole discontinuation and steroid treatment.102
Conclusion
Both human and veterinary research have been critical for shaping current recommendations for ASDs in companion animals. On the basis of this research, PPIs have superior acid-suppressant effects and are indicated for esophagitis or GUE treatment. However, there is a strong need for additional research into ASD recommendations for cats and in specific disease conditions, such as mast cell and hepatic disease. Given that there should be “no dividing lines” between human and veterinary medicine, the veterinary field should look to the human field to understand novel drugs for refractory disease, long-term AEs and risks of PPIs, and other mechanisms in which PPIs may have desired or undesired consequences outside of their effects on gastric pH. A review of these pH-independent effects and their implications for the veterinary field are discussed in the companion Currents in One Health article by Gould et al, AJVR, October 2024.
Acknowledgments
None reported.
Disclosures
Dr. Tolbert is on the scientific advisory board for TriviumVet, a veterinary healthcare company that has an acid-suppressant drug marketed for dogs in Europe.
No AI-assisted technologies were used in the generation of this manuscript.
Funding
The authors have nothing to disclose.
ORCID
M. Tolbert https://orcid.org/0000-0001-8725-9530
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