Howden, Colin W.

ABSTRACT Background Patients with erosive oesophagitis, and those with persistent symptomatic non‐erosive gastro‐oesophageal reflux disease, require long‐term maintenance treatment with acid‐suppressing agents. Aim To evaluate the safety of vonoprazan, a potassium‐competitive acid blocker, in an integrated analysis of data from clinical trials in adults. Methods We included 14 clinical trials of vonoprazan conducted in multiple countries. Mean duration of exposure in person‐years to vonoprazan ( n = 5318) was 2068, to comparators lansoprazole ( n = 1925) or esomeprazole ( n = 86) was 751, and to placebo ( n = 779) was 59. We report adverse events, serum gastrin, and liver enzyme levels as the main outcomes. Post‐marketing safety data from December 26, 2014 (date of commercialisation in Japan) to December 25, 2023, are also provided. Results Nasopharyngitis was the only adverse event reported by at least 5.0% of patients (6.94% vonoprazan, 5.07% proton pump inhibitor (PPI), 4.49% placebo). Incidence rates per 100 person‐years for serious adverse events were 10.39 for vonoprazan, 10.65 for PPIs, and 1.69 for placebo. One patient each on vonoprazan and lansoprazole was diagnosed with gastric cancer. Mean serum gastrin levels were higher on vonoprazan than lansoprazole but normalised by 4 weeks after discontinuation. Elevated liver enzyme levels were infrequent and of low magnitude with no differences between vonoprazan and PPIs. There were four deaths; none was considered related to study drug. Conclusions Vonoprazan was well tolerated. Its safety profile from both clinical trial and post‐marketing data were consistent and comparable to that of its PPI comparators with respect to treatment‐emergent adverse events.

ABSTRACTObjectiveMost Helicobacter pylori infections are acquired during childhood. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) recently published practice guidelines for managing pediatric H. pylori infection. Before this publication, the authors conducted a survey to assess pediatric gastroenterologists' knowledge and practices regarding H. pylori.MethodsOne hundred nine of 514 NASPGHAN members completed an Internet‐based questionnaire on H. pylori infection.ResultsEighty‐two percent of respondents performed outpatient testing for H. pylori. Of these, only 31% restricted testing to children aged >5 years. Most recommended testing for H. pylori in guideline‐recommended conditions; some would not treat infected patients. Ninety‐seven percent would test for H. pylori in a child with new duodenal ulcer (DU), 79% in a child with a history of DU, and 91% in a child with new gastric ulcer. However, only 86%, 60%, and 91%, respectively, would treat H. pylori infection in those conditions. A proton pump inhibitor (PPI)‐based triple regimen was the first‐choice therapy for 78% of respondents. Correct estimates of rates of resistance to amoxicillin, clarithromycin, metronidazole, and tetracycline were 10%, 17%, 43%, and 12%, respectively. Eighty‐six percent believed there was insufficient research on H. pylori in children.ConclusionsNorth American pediatric gastroenterologists seem well informed about H. pylori infection in children despite the lack of published guidelines at the time of survey. Knowledge about antibiotic resistance rates was deficient. Most offered some outpatient testing for H. pylori and would test children with ulcer disease. However, some would not treat patients based on a positive result.

SummaryBackgroundFunctional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89–90%), postprandial fullness (75–88%), and early satiety (50–82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non‐specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive.AimTo present current management options for the treatment of FD (therapeutic gain/response rate noted when available).ResultsThe utility of Helicobacter pylori eradication for the treatment of FD is modest (6–14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7–10% therapeutic gain), histamine‐type‐2‐receptor antagonists (8–35% therapeutic gain), prokinetic agents (18–45%), tricyclic antidepressants (TCA) (response rates of 64–70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies.ConclusionsA reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori‐negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an anti‐nociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.