Iron supplementation is frequently used in the treatment of iron deficiency anemia in the pediatric population. We describe a case of an 11-year old male who developed adverse side effects following treatment with oral ferrous sulfate tablets for 2 months. The diagnosis was made following findings of iron deposition on histology obtained during endoscopy. The iron supplementation was changed from tablet to liquid form, and repeat endoscopy 4 months following initial diagnosis showed resolution of the histologic findings of iron pill-induced gastritis.

UNASSIGNED: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicentre studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE).
UNASSIGNED: Data from patients with cirrhosis recruited at seven centres across Europe and the US were analysed. MHE was defined by the psychometric hepatic encephalopathy score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation.
UNASSIGNED: A total of 1,160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/liver transplantation. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication.
UNASSIGNED: PPI use is not associated with a higher risk of HE in patients with cirrhosis. Based on these findings, at present, a prescription should not be prohibited in case of a generally accepted indication.
UNASSIGNED: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with cirrhosis. Based on these findings, prescription of a PPI for a generally accepted indication should not be prohibited in patients with cirrhosis.

OBJECTIVE: Patients with chronic kidney disease (CKD) are at high risk for bone fractures, which are associated with high morbidity and mortality. Proton pump inhibitors (PPI) have been linked to an increased risk for fractures in the general population as well as in patients with need for hemodialysis, but studies in patients with CKD are currently missing.
METHODS: We performed a population-based observational case-control study exploring a sample of patients with CKD derived from the IQVIATM Disease Analyzer database. Patients with and without fractures were matched using the 1:1 nearest neighbor propensity score matching method. To investigate the association between PPI use and fractures, multivariable logistic regression analyses were performed adjusting for confounding factors.
RESULTS: In total, 6076 patients with and 6076 patients without fractures were matched and subsequently available for analyses. In the total cohort, PPI use was associated with an increased risk for fractures (OR 1.68; 95% CI 1.55-1.83). This association was noted for nearly all types of fractures. The strongest association between PPI use and fractures was found in patients below the age of 60 with a PPI prescription for longer than two years (OR 6.85, 95% CI 1.85-25.38). The same was true, when analyzing cumulative PPI doses. Here, patients below the age of 60 with a cumulative PPI dose above 16 000 mg (highest quartile) had the highest risk for fractures (OR 4.62, 95% CI 1.87-11.44). There was no difference between men or women regarding the association between PPI use and fractures.
CONCLUSIONS: This study provides evidence that PPI use is associated with fractures in patients with CKD. Deprescription of PPI in patients without an indication for treatment could be a modifiable risk factor to reduce fracture risk in this high-risk group.

OBJECTIVE: To evaluate the influence of proton pump inhibitor (PPI) use on COVID-19 susceptibility and severity in children.
METHODS: This retrospective, case-control study included all children ≤21 years undergoing COVID-19 polymerase chain reaction testing at a tertiary children\'s hospital between March 2020 and January 2023. The main exposure was PPI usage. The primary outcome was COVID-19 infection. The secondary outcome was COVID-19 hospitalization. Log-binomial regressions were used to examine associations between PPI use and these outcomes.
RESULTS: 116 209 patients age 8.5 ± 6.2 years underwent 234 867 COVID-19 tests. Current PPI use was associated with a decreased risk of COVID-19 test positivity compared with PPI nonuse [RR 0.85 (95% CI 0.76, 0.94), P = .002]; however, there was a significant interaction with time of testing, and an effect of PPIs was no longer seen in the final months of the study following lessening of COVID-19 precautions [RR 1.04 (95% CI 0.0.80, 1.36), P = .77]. PPI use was not associated with risk of hospitalization in patients positive for COVID-19 after adjusting for other hospitalization risk factors [RR 0.85 (95% CI 0.64, 1.13), P = .26].
CONCLUSIONS: We did not find an association between PPI use and increased COVID-19 susceptibility or severity in this pediatric sample. These results provide reassuring evidence that PPIs may not worsen COVID-19 outcomes in children.

Background Enterocolitis due to Clostridium difficile infection (CDI) is one of the most common infectious causes of healthcare-associated diarrhea and a significant cause of morbidity and mortality among hospitalized patients. Gastroesophageal reflux disease (GERD) is notable for its high prevalence, variety of clinical presentations, and underrecognized morbidity. It is widely treated with acid suppression, both with over-the-counter and prescription medications. There are no studies evaluating the impact of GERD on CDI hospitalization. In this study, we aimed to analyze the influence of concomitant GERD on patients hospitalized for CDI enterocolitis. Methodology This was a retrospective, observational study where we extracted data from 2016 to 2020 from the National Inpatient Sample database. We included all patients hospitalized with a primary discharge diagnosis of CDI with or without a secondary diagnosis of GERD. We compared the demographics, comorbidities, and in-hospital outcomes between these two groups. Results This study identified 239,603 hospitalizations with a discharge diagnosis of CDI. Of these, 67,000 (28%) had a concurrent diagnosis of GERD. Patients with GERD had a higher prevalence of hypertension (41% vs. 35.5%, p < 0.01), hyperlipidemia (50% vs. 36.5%, p < 0.01), obesity (13.7% vs. 10.5%, p < 0.01), coronary artery disease (24.4% vs. 19.6%, p < 0.01), and chronic kidney disease (20.7% vs. 19.2%, p < 0.01). Notably, inpatient mortality was lower in CDI hospitalizations with GERD (0.66% vs. 1.46%, p < 0.01). The total hospital charge was reduced in the CDI with GERD group in comparison to the CDI without GERD group (39,599 vs. 43,589, p < 0.01). The length of hospital stay was similar between the two groups (5.3 vs. 5.4 days, p = 0.07). Regarding complications, CDI hospitalizations with GERD demonstrated lower rates of hypovolemic shock (0.5% vs. 0.73%, p = 0.06), septic shock (0.6% vs. 1.05%, p < 0.01), acute kidney injury (1.48% vs. 2.04%, p < 0.01), intestinal perforation (0.008% vs. 0.16%, p = 0.03), and lactic acidosis (0.008% vs. 0.16%, p = 0.03). Conversely, CDI patients with GERD had a higher rate of ileus (2.66% vs. 2.16%, p < 0.01). Conclusions Patients with CDI and concurrent GERD exhibited favorable in-hospital outcomes in terms of complication rates, mortality, and total hospital charges. Further research is required to comprehensively explore and validate these findings.

OBJECTIVE: Helicobacter pylori rates of eradication to common first-line regimens continue to decline globally. Prescription of the appropriate medication dosage is an important consideration, particularly in the pediatric population due to medication weight-based dosing. Limited data is available on the impact of guideline-recommended weight-based dosing on the successful eradication of H. pylori in children.
METHODS: Retrospective study of patients with histologic evidence of H. pylori from two pediatric tertiary care centers in New England. We excluded patients who were not treated or those missing eradication data. We compared the eradication rates of patients prescribed recommended weight-based dosages, duration, and frequency of treatment with those who were not.
RESULTS: One hundred forty-four patients were included. The overall eradication rate was 73.6% (106/144). All treatment regimens were properly prescribed for 14 days. There was a high rate of improper weight-based dosing: proton pump inhibitor (PPI) 31.2% (45/144), amoxicillin 31.7% (39/123), metronidazole (MET) 19.4% (12/62), clarithromycin (CLA) 23.9% (22/70), tetracycline 50% (6/12), bismuth 26.1% (6/23). When PPIs were properly weight-dosed, there was a 78.8% eradication rate that dropped to 62.2% with suboptimal dosing (p = 0.036, odds ratio [OR]: 2.26, confidence interval [CI]: 1.04-4.87). When amoxicillin was properly weight-dosed, successful eradication was achieved in 81% versus only 53.8% when improperly dosed (p = 0.002; OR: 3.64, CI: 1.58-8.37). There was no statistically significant impact on eradication rates with improper weight-based dosing of MET, CLA, tetracycline, or bismuth.
CONCLUSIONS: Proper weight-based dosing of amoxicillin and PPI is important for the successful eradication of H. pylori among children in the New England area.

OBJECTIVE: To determine whether proton pump inhibitor (PPI) exposure is associated with an increased risk of developing eosinophilic esophagitis (EoE) in children with esophageal atresia (EA).
METHODS: A retrospective chart review of children with EA from January 1, 2005 to December 31, 2020 was undertaken at Sydney Children\'s Hospital Randwick. Children with EA and EoE (cases) were matched (1:2) to children with only EA (controls) to compare PPI exposure. Other early-life factors such as infantile antibiotic exposure and personal or family history of atopy were also analyzed using simple and multivariable logistic regression.
RESULTS: Of 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EoE and EA received PPI for significantly higher durations (p = .018) and at significantly higher cumulative doses (p = .017) than controls. Food allergy (adjusted odds ratio [aOR], 7.317; 95% confidence interval [CI], 2.244-23.742), family history of atopy (aOR, 3.504; 95% CI, 1.268-9.682), and infantile antibiotic exposure (aOR, 1.040; 95% CI, 1.006-1.075) were also significantly associated with an increased risk of developing EoE in the EA cohort.
CONCLUSIONS: Prolonged duration and high cumulative dose of PPI exposure were significantly associated with subsequent EoE development in children with EA. Food allergy, family history of atopy, and infantile antibiotic exposure in EA were also significantly associated with an increased risk of EoE development.

Proton pump inhibitor (PPI) treatment is responsible for substantial gastrin elevation secondary to reduced intragastric acidity. Due to the increasing global prevalence of PPI users, concerns have been raised about the clinical significance of continuous gastrin elevation and its potential long-term side effects. Hypergastrinemia secondary to PPIs has trophic effects on gastric mucosa, leading to enterochromaffin-like cell hyperplasia and gastric (fundic) polyp formation, and it is believed to provoke acid rebound following PPI withdrawal that induces PPI overutilization. Previous studies have found higher gastrin release following PPI therapy in females compared with males, and sex differences have also been demonstrated in pharmacokinetic parameters and dose requirements for acid reflux. It is conceivable that females might be at increased risk of PPI overuse, because they often receive higher milligram-per-kilogram doses. The prevalence of PPI use is more common among females, and the female sex is a risk factor for adverse drug reactions. This non-systematic review outlines the current knowledge of the impact of biological sex on the response to PPIs. The aim is to highlight the female sex as a potential risk factor that could be a step toward precision medicine and should be considered in future research on the response to PPI treatment.

Erosive esophagitis (EE) is a severe form of gastroesophageal reflux disease commonly treated with proton pump inhibitors (PPIs). The aim of this retrospective, observational cohort study was to describe the characteristics and healthcare burden of patients with EE.
We identified adults in the USA with an EE diagnosis between January  1, 2016 and February 28, 2019 in a linked dataset containing electronic health records (EHR) from the Veradigm Network EHR and claims data from Komodo Health. Patients were required to have 1 year of baseline data and 3 years of follow-up data. Patients were stratified by the number of PPI lines of therapy (LOT) during the 4-year study period. We descriptively captured patient characteristics and treatment patterns, along with all-cause and EE-related healthcare utilization and costs.
Among the 158,347 qualifying adults with EE, 71,958 (45.4%) had 1 PPI LOT, 14,985 (9.5%) had 2 LOTs, 15,129 (9.6%) had 3+ LOTs, and 56,275 (35.5%) did not fill a PPI prescription. Omeprazole and pantoprazole comprised more than 70% of any LOT, with patients commonly switching between the two. Mean (standard deviation) annualized all-cause and EE-related healthcare costs in the follow-up period were $16,853 ($70,507) and $523 ($3659), respectively. Both all-cause and EE-related healthcare costs increased with LOTs.
Patients with EE are commonly treated with prescription PPIs; however, 19.0% of patients cycled through multiple PPIs. Higher PPI use was associated with a higher comorbidity burden and higher healthcare costs compared to 0 PPI use.

BACKGROUND: Oral omeprazole is the accepted treatment for equine squamous gastric disease (ESGD); however, it is not universally effective. Esomeprazole results in more consistent and pronounced acid suppression in men and is more effective than omeprazole in the treatment of oesophageal and gastric disease. Pharmacodynamic and pilot clinical studies have indicated esomeprazole might also be more effective than omeprazole in horses.
OBJECTIVE: To compare the efficacy and safety of oral esomeprazole and omeprazole pastes in the treatment of ESGD and, where present, concurrent equine glandular gastric disease (EGGD).
METHODS: Randomised, single-blinded controlled trial.
METHODS: Horses presenting with grade ≥2 ESGD lesions were randomly allocated to receive 4 mg/kg of either a buffered esomeprazole or omeprazole paste orally once daily for 28 days before gastroscopy being repeated within a further 3 days. Videos and images were anonymised and subsequently graded blind by one researcher. The severity of ESGD (and EGGD) lesions before and after treatment, and thereby treatment responses, were compared using univariable logistic regression.
RESULTS: A higher proportion of horses had ESGD healing in response to esomeprazole treatment (63/74, 85%) than with omeprazole treatment (43/73, 59%) (odds ratio [OR]: 4.00, 95% confidence interval [CI]: 1.81, 8.82, p = 0.001). In a subset of horses that had concurrent EGGD, a greater proportion of the horses treated with esomeprazole had lesions ≤grade 1 (esomeprazole 28/51, 55%; omeprazole 6/24, 25%; OR: 3.65, 95% CI: 1.25, 10.71, p = 0.02) Using grade 0 as the benchmark for EGGD healing, the difference remained significant (OR: 4.44, 95% CI: 1.33, 14.85, p = 0.02).
CONCLUSIONS: It may not be possible to extrapolate these results to other populations with different signalment or management.
CONCLUSIONS: Oral-buffered esomeprazole was a more effective treatment for ESGD (and concurrent EGGD) than oral-buffered omeprazole.
UNASSIGNED: Oral verabreichtes Omeprazol ist die akzeptierte Behandlungsform von Equine Squamous Gastric Disease (ESGD); allerdings ist es nicht universell effektiv. Esomeprazol resultiert in konsistenterer und ausgeprägter Säuresuppression beim Menschen und ist effektiver als Omeprazol in der Behandlung von Ösophageal‐ und Magenerkrankungen. Pharmakodynamische und klinische Pilotstudien ließen erkennen, dass Esomeprazol auch bei der Behandlung von Pferden effektiver ist als Omeprazol.
UNASSIGNED: Vergleich der Effektivität und Sicherheit oraler Esomeprazol‐ und Omeprazolpasten bei der Behandlung ESGD, und, falls vorhanden, zeitgleich auftretendem Equine Glandular Gastric Disease (EGGD).
METHODS: Randomisierte, einfach verblindete Fallkontrollstudie.
METHODS: Pferde mit Grad ≥2 ESGD Läsionen wurden zufällig einer Behandlung mit 4 mg/kg gepufferter Esomeprazol‐ oder Omeprazolpaste zugewiesen, oral verabreicht SID für 28 Tage bevor eine Gastroscopie innerhalb weiterer 3 Tage wiederholt wurde. Videos und Bilder wurden anonymisiert und anschließend von einem geblendeten Autor gradiert. Der Schweregrad der ESGD (und EGGD) Läsionen vor und nach Behandlung, und damit Ansprechen auf die Behandlung, wurden mithilfe der univariablen logistischen Regression verglichen.
UNASSIGNED: Ein größerer Anteil an Pferden zeigte ESGD‐Abheilung als Reaktion auf die Behandlung mit Esomeprazol (63/74, 85%) im Vergleich zu der Behandlung mit Omeprazol (43/73, 59%; OR:4.00, 95%CI:1.81, 8.82, p = 0.001). Ein größerer Anteil einer Teilmenge der Pferde mit simultanem EGGD, welche mit Esomeprazol behandelt wurden, hatte Läsionen ≤ Grad 1 (Esomeprazol 28/51, 55%; Omeprazol 6/24, 25%; OR: 3.65, 95%CI: 1.25, 10.71, p = 0.02). Wenn Grad 0 als Bezugsgröße für EGGD‐Abheilung verwendet wurde, blieb der Unterschied signifikant (OR: 4.44, 95%CI: 1.33, 14.85, p = 0.02). HAUPTEINSCHRÄNKUNGEN: Es ist möglicherweise nicht möglich, diese Resultate auf andere Populationen mit abweichendem Signalement oder Management zu extrapolieren.
UNASSIGNED: Die orale Verabreichung von gepuffertem Esomeprazol war effektiver für die Behandlung von ESGD (und zeitgleich auftretendem EGGD) als die orale Verabreichung von gepuffertem Omeprazol.