Proton Pump Inhibitor Therapy Research Articles

S2343 Long-Term Omeprazole Use Causing Critical Electrolyte Derangements

Introduction: Proton-pump inhibitors (PPI) are the mainstay therapy for acid-related gastrointestinal entities. Longstanding PPI use is associated with an increased risk of adverse effects; however, clinically significant side effects, such as metabolic derangements, are rare. Here we highlight a case of critical electrolyte derangements secondary to prolonged omeprazole use. Case Description/Methods: A 61-year-old female with a history of hypertension and GERD presented with intermittent numbness for several months involving bilateral upper extremities. Exam showed no focal neurologic deficits with intact sensation and appropriate motor strength. CT head and cervical spine were unremarkable. Initial labs showed significant electrolyte derangements, including hypokalemia 3.3 mmol/L, hypocalcemia 5.7 mg/dL (0.64 mmol/L ionized), and hypomagnesemia 0.5 mg/dL. TSH, PTH, and 25-hydroxyvitamin D levels were intact (Table). EKG showed normal sinus rhythm with QTc prolongation at 542 ms. Despite aggressive intravenous repletion, her electrolytes remained suboptimal. After evaluation by endocrinology, her symptoms were thought to be secondary to PPI-induced hypomagnesemia. The patient had been taking omeprazole for nearly 20 years after evaluation by ENT for vocal cord hoarseness thought to be secondary to GERD. Patient was transitioned from PPI to an H2 blocker. She underwent EGD which showed mild gastritis with biopsies negative for Helicobacter pylori. Fortunately, her symptoms resolved after electrolyte stabilization with potassium 3.9 mmol/L, calcium 8.8 mg/dL, and magnesium 1.8 mg/dL. She was discharged on famotidine with instructions to follow up with gastroenterology. Discussion: Hypomagnesemia has become an increasingly well-recognized, albeit rare side effect of PPI use. The mechanism is thought to involve interference of TRPM6 and TRPM7 located on apical membranes of enterocytes leading to intestinal malabsorption with resulting hypomagnesemia as well as hypocalcemia and hypokalemia. Interestingly, manifestations of hypocalcemia and hypokalemia can be concealed by calcium and potassium-sparing agents, which was likely the case in our patient who was taking candesartan-hydrochlorothiazide combination therapy for hypertension. Our case demonstrates the importance of limiting chronic PPI therapy given the potential for serious consequences. Increased efforts should be aimed at deprescribing PPI therapy. Table 1. - Electrolyte derangements including hypokalemia, hypocalcemia, and hypomagnesemia, which remained suboptimal despite aggressive repletion. Electrolytes finally stabilized after switching from PPI to H2 blocker Day 0 Day 3 Day 5 Day 6 K+ (mmol/L) 3.3 3.2 3.8 3.9 Ca+2 (mg/dL) 5.7 6.6 7.8 9.5 Mg+2 (mg/dL) 0.5 1.6 1.7 1.6

S490 A Single Center Experience in the Management and Follow-Up of Patients With Esophagitis: A Retrospective Study

Introduction: Gastroesophageal reflux disease (GERD) is a chronic condition in which the reflux of gastric content into the esophagus results in symptoms and complications, such as erosive esophagitis, Barrett’s esophagus (BE), and esophageal adenocarcinoma. There are four grades of esophagitis increasing in severity from A to D. In patients with esophagitis on initial endoscopic evaluation, the current American College of Gastroenterology (ACG) guidelines recommend repeat esophagogastroduodenoscopy (EGD) after a minimum 8-week of proton pump inhibitor (PPI) therapy, to ensure healing of esophagitis and to determine the presence of BE. Our objectives were to characterize patients with esophagitis who presented to Saint Louis University Hospital (SLUH), understand practice patterns, and identify variables that predict disease progression and affect clinical outcomes. Methods: We identified 256 patients who presented to SLUH for EGD for any indication between 2012 and 2018 and were found to have endoscopic diagnosis of esophagitis. Laboratory and pathologic data were reviewed for initial and follow-up endoscopy. All categorical variables were analyzed by chi-square analysis. Analysis of variance (ANOVA) and t-tests were used for continuous data, and analysis was performed using SPSS version 27.0. Results: Out of the 256 patients who were diagnosed with esophagitis, 61 were classified as Grade A, 59 Grade B, 45 Grade C and 91 Grade D. The mean age was 59 ± 15 and the mean BMI was 27.3 ± 8. PPI prescription percentage, repeat EGD and outcomes are shown in Table. There was no statistically significant association between sex, ethnicity, smoking history, or alcohol use history and development of BE. Conclusion: Our study showed under-prescription of PPI in patients with esophagitis. Repeat EGD was only recommended for 28%, 32%, 49% and 57% of the patients with Grades A, B, C and D esophagitis, respectively. Stronger efforts should be taken to help adhere to the guidelines in prescribing acid-suppressive medications and recommending repeat EGD for patients with esophagitis. Development of esophageal cancer was the highest in those with Grade D esophagitis. Larger studies are needed to evaluate the risk of BE or dysplasia in patients with Grades A and B esophagitis and to provide additional data on rates of development of BE or esophageal cancer in the respective groups. Table 1. - Results of a single-center study on PPI prescription percentage, repeat EGD and outcomes in patients with endoscopic diagnosis of esophagitis Grade of esophagitis PPI treatment recommended Repeat EGD recommended Repeat EGD performed Barrett’s esophagus present on follow up Dysplasia present on follow up Esophageal cancer present on follow up A (N=61) 51 (84%) 17 (28%) 6 (35%) 2 (3.3%) 2 (3.3%) 1 (1.6%) B (N=59) 40 (68%) 19 (32%) 4 (21%) 3 (5.1%) 1 (1.7%) 1 (1.7%) C (N=45) 38 (84%) 22 (49%) 3 (14%) 1 (2.2%) 1 (2.2%) 1 (2.2%) D (N=91) 74 (81%) 52 (57%) 19 (37%) 8 (8.8%) 3 (3.3%) 5 (5.5%)

S3684 Treating Helicobacter pylori via IV Route in a Patient With Malabsorption Due to Gastric Bypass Surgery

Introduction: Helicobacter pylori (H. pylori) is checked in all patients off of proton pump inhibitor (PPI) therapy prior to Roux-en-Y surgery because of the risk for ulcers and their complications. Ulcers carry a potential for bleeding; and if located in the excluded stomach, it would not be possible to reach by scope. Over time, H. pylori has become more difficult to treat. Failed attempts at treatment are usually attributed to poor medication adherence or antibiotic resistance.1 This case highlights a patient with treatment resistant H. pylori infection after Roux-en-Y gastric bypass. Case Description/Methods: A 48-year-old female with a history of Roux-en-Y performed in 2012 due to obesity presented to clinic with ongoing abdominal pain, nausea, 18 kg weight loss, and poor oral intake. She was initially diagnosed with H. pylori in 2014, with EGD and gastric biopsies revealing chronic active gastritis with H. pylori. She reported being treated twice without eradication. Repeat EGD took place in 2020 with persistent H. pylori on biopsy. She was prescribed quadruple therapy: bismuth subcitrate potassium, metronidazole, tetracycline, and PPI. Despite this, she did not clear the infection. She was re-biopsied and tissue specimen was sent for susceptibility. Results only showed resistance to metronidazole. Based on susceptibilities, she was prescribed high dose amoxicillin three times daily and rabeprazole. Despite appropriate therapy, she tested positive once again. It became clear that the etiology of treatment resistance was secondary to malabsorption. She was ultimately treated with IV ampicillin, IV levofloxacin, and omeprazole for 10 days. Finally, her stool antigen studies returned negative. Discussion: This case describes a patient with history of gastric bypass surgery who had persistent infection with H. pylori despite completing appropriate therapies. She was treated with an oral regimen in accordance to susceptibilities without clearance, suggesting malabsorption secondary to her gastric anatomy was rendering treatment ineffective. This predicament was overcome by administering antibiotics intravenously. This case brings to light the need for further research regarding treatment of H. pylori in the setting of malabsorption, as this not clearly outlined in current guidelines or literature.

S2331 High-Potency Proton Pump Inhibitor Therapy for the Management of Chronic Hiccups

S2331 High-Potency Proton Pump Inhibitor Therapy for the Management of Chronic Hiccups

S2298 Dysphagia Lusoria Secondary to an Aberrant Left Subclavian Artery

Introduction: Dysphagia lusoria, also known as Bayford-Autenrieth dysphagia, is a rare condition with prevalence of approximately 0.5%. First reported by David Bayford in 1790, it is defined as dysphagia secondary to extrinsic compression of the esophagus as a result of congenital abnormality of the aortic arch and its branches. We report a case of Dysphagia lusoria in a patient with congenital heart syndrome. Case Description/Methods: A 36-year-old woman with history of Dysphagia lusoria secondary to an aberrant left subclavian artery (SCA), congenital heart syndrome with known right sided thoracic aorta, tricuspid atresia and stenosis, hypoplastic right ventricle, and aberrant left SCA presented to the hospital with worsening dysphagia. She reported vomiting with any solid foods and only tolerating pureed foods or liquids. She reported a history of progressive dysphagia since 2018, when she underwent an esophagogastroduodenoscopy (EGD) that showed subtle pallor in the upper esophagus concerning for partial obstruction due to aberrant subclavian artery. She also underwent a manometry that was normal. On hospital admission, she underwent an x-ray upper gastrointestinal series that showed unchanged vascular impression of the upper esophagus with mild esophageal dysmotility, consistent with her diagnosis of Dysphagia lusoria (Figure). Cardiology and vascular surgery were consulted and deemed the patient a poor surgical candidate due to her prior operations for congenital disease and fontan physiology. Management was deferred to gastroenterology, who recommended small meals and chewing well and proton pump inhibitor therapy for associated heart burn. The patient reported symptomatic improvement with dietary modification. Discussion: The most common alteration in Dysphagia lusoria is an aberrant right subclavian artery. Most patients are asymptomatic; symptoms usually include dysphagia, regurgitation, chest discomfort, weight loss, and Horner syndrome. Diagnosis is best achieved by barium esophagram, which often shows extrinsic compression above the aortic arch. EGD can further show extrinsic compression of the posterior wall of the esophagus. Mildly symptomatic patients are recommended to chew thoroughly, sip liquids, and avoid exacerbating foods. Surgical intervention with the goal of removing the aberrant vessel and reconstructing a more functional vascular system is rarely performed but reserved for severe cases. The significant risk of morbidity and mortality with surgery needs to be weighed in these patients.Figure 1.: X-ray upper gastrointestinal series showing vascular impression of the upper esophagus secondary to aberrant left subclavian artery.

S3707 A Cautionary Side of the Widely Prescribed: A Case of PPI-Induced AIN

Introduction: Proton pump inhibitors (PPIs) are widely prescribed for the treatment of gastric acid-related disorders. While generally well-tolerated, PPIs are not without side effects, including acute kidney injury. Here we highlight a rare case of biopsy proven PPI-induced acute interstitial nephritis (AIN). Case Description/Methods: A 54-year-old male with history of rheumatoid arthritis presented with one week history of fever, fatigue, arthralgias, and weight loss. One month prior he was admitted with upper GI bleeding due to NSAID induced peptic ulcer disease and promptly stopped NSAIDs with strict adherence to PPI therapy. He took no additional medications or supplements. On admission labs were notable for recurrent anemia without melena and new acute kidney injury, creatinine 2.32 mg/dL from baseline of 1. Given recent GI bleed patient underwent repeat EGD which showed a clean based healing antral ulcer. Recurrent anemia was attributed to renal dysfunction, which continued to worsen despite supportive care with peak creatinine 3.8 mg/dL. Urine studies were unrevealing without evidence of obstruction on imaging, but incidentally noted narrowing of the celiac artery was concerning for vasculitis related nephropathy given history of autoimmune disease. Confirmatory contrast enhanced imaging however was negative for evidence of vasculitis with negative serologies. Renal biopsy was performed which showed interstitial inflammation and tubulitis consistent with AIN. Ultimate diagnosis of PPI-induced AIN was made as he took no alternative medications which could be implicated. Patient was started on steroids with notable improvement in renal function. He was switched to an H2 receptor blocker to complete treatment of gastric ulcer and discharged on a steroid taper with complete renal recovery (Figure 1). Discussion: Initially described in 1992, PPI-induced AIN is a well-recognized albeit rare complication. It is thought to arise due to a hypersensitivity reaction, which may explain the classic presenting triad of fever, rash, and eosinophilia. However, studies have shown that this clinical triad is only present in 10% of cases thereby highlighting the difficulties of diagnosing AIN, which may ultimately require renal biopsy for definitive diagnosis. Treatment requires removal of the offending agent as well as initiation of steroids. Even with treatment, 30-70% of patients may develop chronic kidney disease. As such, it is important for clinicians to be cognizant of this potentially life altering complication of PPI.Figure 1.: Kidney biopsy showing inflammatory changes predominantly in the interstitium.

S482 Evaluating Multiple Dosing Regimens for Proton Pump Inhibitors (PPI) for the Treatment of Gastroesophageal Reflux Disease (GERD): A Systematic Review and Meta-Analysis

Introduction: Although once-daily dosing of PPI therapy for GERD is standard of practice, clinicians often use twice daily dosing. It remains unclear if this common practice meaningfully improves GERD symptoms of heartburn and/or regurgitation. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing for resolution of GERD, heartburn, and esophageal healing with regards to various PPI dosages and frequencies. Methods: A search of EMBASE and PubMed in October 2021 yielded 1381 unique records. Abstract/title screening and full-text review were completed by two independent reviewers, where 51 studies were included in the systematic review and 37 RCTs were included in the quantitative analysis; all included studies compared different doses within PPI. Data abstraction was performed in duplicate using Systematic Review Data Repository+, with discrepancies resolved by a third reviewer. The outcomes were resolution of GERD, heartburn, and esophageal healing within 12 weeks. Risk of bias was independently assessed using the Cochrane Risk of Bias tool (v2). Random-effects meta-analyses were conducted in Stata. Studies were excluded from quantitative review if they did not report outcomes of interest, only assessed outcomes after 12 weeks, or compared out-of-practice dosages (quarter and quadruple standard dose). Results: A total of 51 RCTs conducted across 27 countries (n=20,226 patients, 55% male, mean age 50 years) were included in the systematic review. Among 37 RCTs included in the quantitative analysis, most compared double standard dose daily vs. standard dose daily or standard dose daily vs. half standard dose daily; few studies compared daily vs. twice daily dosing. Table shows odds ratios (OR) and 95% confidence intervals (CI) for outcomes among the various dosing comparisons. For example, when compared to standard dose daily, double standard dose daily led to improved outcomes for GERD (OR 1.35, 95% CI 1.01-1.75) and esophageal healing (OR 1.62, 95% CI 1.27-2.07), but not for heartburn (OR 1.08, 95% CI 0.94-1.24) (Figure). Conclusion: Our meta-analysis revealed, in general, that increasing PPI daily dosages was associated with improved outcomes. However, few studies compared daily vs. twice daily PPI. As twice daily PPI usage is common in clinical practice, further studies are needed to determine whether twice daily dosing actually improves clinical outcomes.Figure 1.: Forest plot comparison for Standard dose, QD vs. Double Standard dose, QD in resolution of GERD symptoms (1A) and Heartburn (1B). Table 1 - Dosing Comparisons across Randomized Controlled Trials (≤12 weeks) Dosing Comparison Total Number of RCTs Total Number of Patients Outcome OR (95% Cl) Standard dose BID vs.Standard dose QD (ref) 1 202 Esophageal healing 2.34 (1.27, 4.31) * 1 202 Heartburn 3.03 (1.62, 5.68) * Double standard dose QD vs.Standard dose QD (ref) 7 2408 Esophageal healing 1.62 (1.27, 2.07) * 6 1312 GERD 1.35 (1.05, 1.75) * 5 3433 Heartburn 1.08 (0.94, 1.24) Double standard dose, BID vs.Standard dose QD (ref) 1 197 Heartburn 0.77 (0.44, 1.35) Standard dose QD vs.Half standard dose QD (ref) 9 1762 Esophageal healing 1.79 (1.44, 2.22) * 8 1718 GERD 1.42 (1.15, 1.76) * 14 3327 Heartburn 1.41 (1.17, 1.69) * Standard dose QD vs.Half standard dose BID (ref) 2 411 Esophageal healing 1.94 (1.15, 3.26) * 1 205 Heartburn 2.14 (1.19, 3.85) * Double standard dose BID vs.Double standard dose QD (ref) 1 190 Heartburn 0.90 (0.51, 1.60) 1 200 GERD 2.63 (1.30, 5.35) * Standard dose BID vs.Half standard dose BID (ref) 1 202 Esophageal Healing 0.92 (0.47, 1.79) 1 203 Heartburn 1.42 (0.74, 2.74) Half Standard dose, BID vs.Half standard dose QD (ref) 1 324 Esophageal Healing 7.43 (3.81, 14.49) * *p< 0.05.QD=daily, BID=twice daily

S709 Proton-Pump Inhibitor Infusion Misuse in the Community Hospital Setting

Introduction: Proton pump inhibitors (PPIs) are the most potent acid suppressants available. Several studies have shown that in hospitalized patients with acute upper gastrointestinal (GI) bleeding from peptic ulcer disease, high-dose PPI therapy via continuous infusion reduces the rate of high-risk bleeding lesions (active bleeding, visible vessel, adherent clot) on initial endoscopy. While the benefits of PPI infusions have been clearly described for these specific indications, they are often over-prescribed to inpatients. Our study aim was to determine the rate of misuse in a tertiary care community hospital setting. Methods: A retrospective cohort study was conducted at Lankenau Medical Center, a 370 bed community hospital. The usage of pantoprazole infusion was determined among hospitalized patients between March 1, 2018 and March 1, 2021 through review of the EPIC electronic medical record system. Appropriate candidates for pantoprazole infusion were defined as patients with hematemesis, melena, coffee-ground emesis, or hematochezia with hemodynamic instability. All other indications were categorized as inappropriate. Variables including age, sex, race, serum hemoglobin at the time of PPI infusion initiation, and antiplatelet use were collected. The rate of PPI infusion misuse was determined. Factors which significantly affected utilization of PPI infusion were determined through multivariate analysis. Results: A total of 348 pre-endoscopic PPI infusions were ordered during the three-year period. Approximately 35% of these prescriptions were ordered without an appropriate indication. The mean age of patients who were prescribed PPI infusions was 68.8 years. 48.6% were on an antiplatelet agent. The only significant variable between patients who were given a PPI infusion for an appropriate versus inappropriate indication was age, where the mean patient age was 68.8 compared to 71.1 years (p=0.04). Patient sex, race, antiplatelet use, and hemoglobin value did not significantly affect PPI infusion use. (Table) Conclusion: Pre-endoscopic PPI infusion was prescribed inappropriately in 34.8% of patients in a community hospital setting. Misuse of this drug leads to unnecessary healthcare costs and reflects poor understanding among prescribers of its appropriate clinically indicated uses. While PPIs are generally regarded as safe, misuse can increase the risk of adverse side effects. A follow-up study looking at a quality improvement intervention will follow this study. Table 1. - Characteristics and Multivariate Analysis of PPI Infusion Misuse Inappropriate PPI Infusion No Yes Total p-value n = 227 n = 121 n = 348 Age (Mean/SD) 67.6 (14.8) 71.1 (15.1) 68.8 (15.0) 0.04 Sex 0.571 Male 131 (57.7%) 66 (54.6%) 197 (56.6%) Female 96 (42.3%) 55 (45.5%) 151 (43.4%) Race 0.705 White 104 (46.0%) 59 (48.8%) 163 (47.0%) Black 112 (49.6%) 55 (45.5%) 167 (48.1%) Other 10 (4.4%) 7 (5.8%) 17 (4.9%) Ethnicity 0.12 Not Hispanic 225 (99.6%) 116 (97.5%) 341 (98.8%) Hispanic 1 (0.4%) 3 (2.5%) 4 (1.2%) Total Number of Antiplatelets 0.629 0 121 (53.3%) 58 (47.9%) 179 (51.4%) 1 70 (30.8%) 41 (33.9%) 111 (31.9%) 2 36 (15.9%) 22 (18.2%) 58 (16.7%) Antiplatelet Type (n = 169 Yes Only) Aspirin 103 (45.4%) 61 (50.4%) 164 (47.1%) 0.37 Clopidogrel 36 (15.9%) 23 (19.0%) 59 (17.0%) 0.456 Ticagrelor 4 (1.8%) 4 (3.3%) 8 (2.3%) 0.456 Prasugrel 1 (0.4%) 0 1 (0.3%) 1 Last Hemoglobin (Mean/SD, g/dl) 8.9 (2.6) 8.6 (2.9) 8.8 (2.7) 0.344 Missing Hemoglobin 19 8 27 Transfusion Units (median/IQR) 2 (0-6) 2 (0-4) 2 (0-5) 0.478

Proton Pump Inhibitors in Allergy: Benefits and Risks

Proton pump inhibitors (PPIs) are widely prescribed and are indicated for the treatment of several gastrointestinal disorders. Allergists may prescribe PPIs as a result of the coincidence of gastroesophageal reflux disease with asthma or rhinitis, or when gastroesophageal reflux disease presents as chronic cough. Furthermore, long-term, high-dose PPI therapy is a recommended option for managing eosinophilic esophagitis, resulting in histologic remission in approximately 40% of patients. Here, we discuss current recommendations for PPI use, its deescalation, and its side effect profile. We review evidence supporting the epidemiologic link between the use of acid-suppressant medication and the subsequent development of allergic disorders.

Efficacy, safety and cost-effectiveness of vonoprazan vs Proton Pump Inhibitors in reflux disorders and H. pylori eradication: A literature review.

Gastroesophageal reflux disease (GERD) is one of the most prevalent conditions worldwide and is conventionally treated by proton pump inhibitor therapy. However, around 40% of people have reported some form of resistance to this therapy. Vonoprazan has recently been approved for the treatment of GERD. Literature was searched on PubMed, Google Scholar, Embase and Medline. Inclusion criteria were 1) Human subjects; 2) papers published in English language; 3) study types that are RCTs.In pre-clinical studies, VPZ was unaffected by changes in pH, making it 1.2–2 times more potent than PPI, both in-vivo and in-vitro. In studies involving GERD, several RCTs proved higher efficacy of VPZ than conventional PPI. RCTs on patients affected by H. Pylori showed a higher efficacy than VPZ (95.8%) as compared to PPI (69.6%). In another RCT, adverse effects including diarrhea, nausea and body rash were observed in 32.7% of the people taking VPZ as compared to 40.5% of the people taking PPI. VPZ was shown to be much more cost effective as compared to PPI.This article concludes that VPZ is superior to PPI in terms of efficacy, safety and cost-effectiveness in reflux disorders and H. pylori eradication. Hence, use of vonoprazan should be preferred over conventional PPIs in these disorders. As most of the research was conducted in Japan, studies should be carried out in different regions of the world to explore if these results are extrapolated in those regions. Research is also needed to explore the efficiency of VPZ in scenarios of PPI resistance.

Real-time gastric juice analysis with EndoFaster for H. pylori diagnosis: a large, multicentre study.

Helicobacter pylori infection is the main cause of the most frequent gastroduodenal diseases. Because its prevalence is decreasing in developed countries, gastric biopsies are negative in several patients. By measuring ammonium in the gastric juice, EndoFaster allows to exclude H. pylori infection during endoscopy. This study aimed to assess the accuracy of device versions working with either 6 ml or 3 ml of gastric juice. This prospective study involved 12 endoscopic units. During endoscopy, EndoFaster testing was performed and standard five gastric biopsies were taken. The accuracy was calculated by considering histological assessment as the gold standard for H. pylori diagnosis. Gastric juice analysis was attempted in 1279 patients, but it failed in 131 (15.5%) and in 10 (2.3%), with the 6 ml and the 3 ml device, respectively (P &amp;lt; 0.001). Overall, EndoFaster detected H. pylori infection with an 86.3% sensitivity, 83.3% specificity, 52.7% positive predictive value, 96.6% negative predictive value and 83.8% accuracy. The performance was not affected either by ongoing proton pump inhibitor therapy or a previous H. pylori eradication. No significant difference in accuracy emerged between the two versions of the device. The novel version of the EndoFaster device operating with 3 ml gastric juice may be performed in virtually all patients, and it allows excluding H. pylori infection with a very high accuracy. Gastric biopsies can be avoided in a definite portion of cases without endoscopic lesions or other clinical indications.

Efficacy and Safety of Domperidone in Combination with Proton Pump Inhibitors in Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are also commonly prescribed to treat GERD. Domperidone, a well-known antiemetic, is an example of a prokinetic agent. It is a dopaminergic blocker that increases lower oesophagus sphincter pressure and activates gastric motility. We carried out a systematic review and meta-analysis to explore the benefits of domperidone in addition to PPI therapy for GERD. We searched for publications comparing PPI plus domperidone to PPI monotherapy in terms of symptom improvement in GERD (until 21 April 2022) on PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, WHO’s International Clinical Studies Registry Platform, and ClinicalTrials.gov without restricting date, language, or study design. The protocol was registered in PROSPERO (CRD42021242076). This meta-analysis incorporated 11 studies with a total of 841 participants (419 in the PPI plus domperidone group and 422 in the PPI monotherapy group). The combination of a PPI and domperidone resulted in a significant reduction in global GERD symptoms. Adverse events associated with PPI plus domperidone treatment were similar to those associated with PPI monotherapy. In conclusion, the combination of domperidone and a PPI is generally safe and effective in treating GERD as compared with that of PPI alone.

Oxygen desaturation in a transgender man: initial concerns and recommendations regarding the practice of chest binding: a case report

BackgroundOver 1.4 million US adults identify as transgender when gender identity differs from the sex assigned at birth [1]. Although transgender patients face adverse health outcomes, they remain an understudied population [2]. A 2017 study surveyed 411 practicing clinicians and found that 80% had been involved in treating a transgender patient, but 80.6% had never received training on transgender care [3]. The purpose of this report is to describe prolonged desaturation in one case of a transgender patient who wore a chest binder intraoperatively owing to a lack of preoperative recognition.Case presentationA 19-year-old transgender male of African-American descent with anxiety and class 3 obesity presented for an esophagogastroduodenoscopy to evaluate a 2-year history of upper abdominal pain unresponsive to proton pump inhibitor therapy, with a plan for monitored anesthesia care. His medications included sertraline, pantoprazole, zolpidem, ergocalciferol, leuprolide, and testosterone cypionate. Preoperatively, the patient was instructed to remove all clothing and to don a patient gown while in the bathroom. The attending anesthesiologist then conducted the interview and examination in the preoperative holding area. The patient was induced with 250 mg of propofol, and reassuring respirations were noted by capnography. Respirations and oxygen saturation remained stable upon insertion of the endoscope. Four minutes later, the patient’s oxygen saturation rapidly decreased to 50% and end-tidal capnography was lost. The endoscope was removed, and the patient was given 200 mg of propofol and 20 mg succinylcholine. His oxygen saturation recovered to 80% and 100% after 2 and 5 minutes, respectively, of ventilation with 100% inspired oxygen. No further oxygen desaturation was noted throughout the procedure, and the patient was closely monitored for signs of respiratory difficulty during an uneventful postoperative course. After full emergence, it was revealed that the patient had been wearing a chest binder throughout the operative procedure. The patient was counseled on the necessity to communicate the presence of this accessory prior to all future procedures.ConclusionIn the clinical narrative, a healthy patient was observed to have prolonged oxygen desaturation after induction of anesthesia. Laryngospasm was suspected clinically owing to the sudden absence of end-tidal carbon dioxide. Prolonged oxygen desaturation despite appropriate interventions suggests the contribution of additional factors. We speculate that the presence of a chest binder intraoperatively predisposed the patient to more rapid oxygen desaturation less responsive to typical therapy. A chest binder would introduce mechanical restriction to the patient’s breathing owing to its inherent design to compress. Although the patient was asked to remove all clothing, specific instructions were not provided regarding the removal of a chest binder. The presence of chest binding was also absent in the electronic health record, despite the documented presence of the patient’s preferred gender, hormonal therapy regimen, and medical history. Ultimately, this case reflects the gap between practitioner knowledge and hospital guidelines and the practices of transgender patients. In reviewing existing literature and the potential for atelectasis with external compression, we would consider that patients refrain from chest binding for 12–24 hours before surgical procedures, resume no sooner than 24 hours after ambulation, and participate in diagnostic incentive spirometry pre- and postoperatively.

Management of Dysplastic Barrett's Esophagus and Early Esophageal Adenocarcinoma.

While patients with Barrett's esophagus without dysplasia may benefit from endoscopic surveillance, those with low-grade dysplasia may be managed with either endoscopic surveillance or endoscopic eradication. Patients with Barrett's esophagus with high-grade dysplasia and/or intramucosal adenocarcinoma will generally require endoscopic eradication therapy. The management of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma is predominantly endoscopic, with multiple effective methods available for the resection of raised neoplasia and ablation of flat neoplasia. High-dose proton-pump inhibitor therapy is advised during the treatment of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma. After the endoscopic eradication of Barrett's esophagus and associated neoplasia, surveillance is required for the diagnosis and retreatment of recurrence or progression.

Evaluation of Accuracy and Feasibility of a New-Generation Ultra-Rapid Urease Test for Detection of Helicobacter pylori Infection

Helicobacter pylori (Hp) infection can be diagnosed by invasive and noninvasive methods, and, among the former, Rapid Urease Tests (RUTs) are an important option. Accuracy and rapidity of results are fundamental for RUTs. The aim of the study is to prospectively evaluate the sensitivity, specificity and time to positivity of a new-generation ultra-rapid urease test (iNatal duo test) for Hp detection and compare the results with other available RUTs [CLO Test (Campylobacter-Like Organism Test), CP Test (Campylobacter pylori Test) and Pronto Dry]. Gastric biopsies were taken in consecutive patients undergoing upper endoscopy: two in the antrum and two in the body for histology, and one in the antrum and one in the body for each RUT. RUTs were read at 1, 5, 15, 30 and 60 min, 3 h and 24 h after biopsy insertion into the reagent. Histology was considered as “gold standard”. The performance of the tests was evaluated in patients not taking proton pump inhibitors (PPI) (n = 924) by calculation of sensitivity, specificity and positive and negative predictive value. Agreement rate (κ) for every RUT and histology was calculated and compared. The performance of the iNatal duo test was also tested in a subgroup of patients taking PPI (n = 198). Hp was positive in 225/924 patients (24.3%) not taking PPIs and in 56/198 (28.3%) who were taking PPIs. The iNatal duo test was more sensitive than the other RUTs for detecting Hp at every time point. The sensitivity at 5 min was 96.2% in patients not taking PPIs and 92.2% in patients taking PPIs. κ with histology was higher for the iNatal duo test than any other RUT (at 30 min: iNatal duo 0.99, CLO 0.60, CP 0.78, Pronto 0.85, at 15 min: iNatal duo 0.99, CLO 0.46, CP 0.63, Pronto 0.71). In a prospective study, the iNatal duo test demonstrated high accuracy and rapidity for Hp detection, both in patients with and without PPI therapy. This new generation of ultra-rapid urease test could be useful for the rapid and correct management of patients undergoing upper GI endoscopy for suspected Hp infection.

Chronic Proton-Pump Inhibitor Therapy and Fracture Risk in Women Aged Between 50 and 65 years: A Retrospective Case-Control Study.

IntroductionChronic proton-pump inhibitor (PPI) prescription is on the rise in the last decade with an increased prevalence in the elderly population. For most patients, this class of drugs is the primary treatment for various diseases. Even though PPIs are generally safe, long-term use has been associated with multiple adverse effects like bone fractures. The extent of the association between PPI and fracture is still unclear in women aged between 50 and 65 years. Besides, many other variables and risk factors must be accounted for in the analysis of this relation.MethodsThis is a retrospective case-control study looking at women 50-65 years of age who presented to Genesys Health for a low-impact fall. Data were extracted from electronic medical records and fracture outcomes; PPI therapy exposure and duration were determined. Chi-square analysis was performed to determine the association between chronic PPI therapy and fracture outcome and independently analyzed for major risk factors of osteoporosis, including smoking, low body mass index, and cancer.ResultsPatients in the chronic PPI therapy group were found to have a decreased fracture outcome overall in each subcategory of risk factors. When adjusting for all risk factors, there was a significant but weak association between chronic PPI therapy and increased fracture outcome.ConclusionWith different results from previous studies, this study sheds new light on this debate. More studies need to be carried out to determine the association between chronic PPI therapy and fracture outcomes in postmenopausal women.

Transient adrenal insufficiency following treatment of rheumatoid arthritis with intramuscular methylprednisolone acetate

An 82-year-old woman presented with dizziness, a fall, and pubic fractures. She had resting severe hypertension, with marked orthostatic hypotension. She was recently diagnosed with cyclic citrullinated peptide (+) rheumatoid arthritis. She had received 120 mg intramuscular methylprednisolone (Depo-Medrone®) eight months prior, and a second dose a day preceding hospitalisation. Two days into the admission, her Glasgow coma scale (GCS) score dropped acutely from 15/15 (E4;V5;M6) to 3/15 (E1;V1;M1). The initial differential diagnoses were: an acute stroke (a total anterior circulation syndrome-TACS or brainstem stroke), opiate toxicity (fracture pains), and possible unwitnessed seizure (in a post-ictal state). Urgent computerised tomography (CT) brain was unremarkable. She had an acute-on-chronic hyponatraemia (nadir 121 mmol/L) while on long-term proton pump inhibitor therapy, and hyperkalaemia (peak 5.8 mmol/L). Initial management included intravenous (IV) naloxone, fluids and diazepam with poor clinical response. Due to persistent low GCS, the admitting team were concerned about a potentially guarded prognosis. However, based on the history of recent high dose steroid injections, plus the evolving clinical picture and abnormal biochemistry, empirical treatment was started (IV hydrocortisone 100 mg QDS and 0.9% saline infusion) for possible adrenal insufficiency. An ‘add-on’ request for random serum cortisol was made to her admission bloods, and returned low (33 nmol/L). With treatment, her GCS improved rapidly from 3/15 to 15/15. A subsequent planned short synacthen test was abnormal (cortisol level pre-synacthen 100; 30min post-synacthen 340), suggestive of adrenal insufficiency. Following consultation with endocrinology, she was maintained on oral hydrocortisone 10 mg (am)/5 mg(teatime) with sustained clinical improvement.

A Randomized Clinical Trial of Proton Pump Inhibitors Combined with Traditional Chinese Medicine in the Treatment of Laryngopharyngeal Reflux Disease

Background: To explore whether combined with TCM based on classical proton pump inhibitors (PPIs) therapy can achieve better efficacy for patients with laryngopharyngeal reflux disease. Methods: There were 150 laryngopharyngeal reflux patients enrolled and divided into three groups randomly, with 50 cases in each group. Patients in group A were treated with the proton pump inhibitor (PPI) lansoprazole. Patients in group B were treated with lansoprazole combined with Banxia Houpu decoction, and patients in group C were treated with acupuncture treatments and a combination of Chinese and Western medicine. The reflux symptom index (RSI), reflux finding score (RFS), and quality of life (36-item short form health survey questionnaire) were assessed before and 4 and 8 weeks after treatment. Results: The RSI and RFS scores of the three groups were significantly reduced after treatment (P &lt; 0.001). In group B and C, they were lower than in group A at 8 weeks (P &lt; 0.01). The SF-36 score of 3 groups increased after treatment. At both 4 and 8 weeks (P &lt; 0.001), and patients in groups B and C scored higher than patients in group A (P &lt; 0.001). The total effective rate of group B and group C was higher than that of group A (P &lt; 0.05). Conclusion: All three treatments have therapeutic effects on the disease, but the efficacy of a PPI alone is not as good as the combined treatments' efficacies. Moreover, PPI combined with Banxia Houpu decoction and/or acupuncture treatment substantially affects life improvement.

Proton Pump Inhibitors Use and Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Retrospective Cohort Analysis.

BackgroundSince their introduction in the early 1980s, proton pump inhibitors (PPIs) have been used worldwide for a broad range of indications. Unfortunately, however, PPIs have become overly prescribed by healthcare providers, sometimes in the absence of clear indications. Although PPIs were initially presumed to have an excellent safety profile, emerging studies have shed light on the association between their long-term use and a myriad of side effects, including the possibility of an increased risk of spontaneous bacterial peritonitis (SBP). Data available to date regarding the association between PPI use and SBP development in cirrhotic patients is conflicting. While some observational studies provide no association between PPI use in cirrhotic patients and an increased risk of SBP development, many others support this association. As a result of the conflicting conclusions from case controls, cohorts, and meta-analyses, we aimed to carry out this retrospective cohort analysis of data from cirrhotic patients included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Our aim was to evaluate for a possible association between PPIs use and the risk of SBP development in cirrhotic patients and to compare the prevalence of SBP development between cirrhotic patients who were actively using PPIs and those who were not.MethodsA retrospective cohort analysis with chart review was conducted on patients with cirrhosis who were included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Using this database, records were reviewed between December 2017 and 2020. Included patients were adults aged 30 to 79 years with a Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnosis of liver cirrhosis. Included patients with a SNOMED-CT diagnosis of liver cirrhosis were divided into two groups: the first group included all cirrhotic patients who did not use PPIs and the second group included all cirrhotic patients who were on PPIs at home.ResultsIn our analysis, SBP occurred in 1.7% (1,860 patients) of the included cirrhotic patients whether they were actively taking PPIs or not. Among the 40,670 cirrhotic patients who were on PPIs at home, 1,350 (3.3%) patients developed SBP. On multivariate analysis, PPI use was the strongest predictor for SBP in cirrhotic patients (odds ratio (OR) = 4.24; 95% confidence interval (CI): 3.83 - 4.7, P value < 0.0001), with cirrhotic patients taking PPIs being 4.24 more likely to develop SBP than those not on PPIs. In addition, PPI use, history of bleeding varices, age, race, and gender were found to be independent predicting factors for SBP, in descending order of importance.ConclusionsOur retrospective cohort analysis has shown that the use of PPIs in patients with liver cirrhosis is an independent predicting risk factor for SBP development. It solidified the argument that cirrhotic patients receiving this form of therapy seem to have a higher risk of developing SBP. In the setting of the emerging evidence that PPIs might impose health risks in cirrhotic patients, further studies are needed to settle the current debate between supporters and opponents of this proposition. In addition, future studies may help clarify the relationship between the occurrence of SBP in cirrhotic patients and the type, dose, and duration of PPIs used. We recommend that unless it is clearly indicated, PPI therapy should be avoided or administered with caution in patients with cirrhosis.

Potassium-competitive acid blockers and gastroesophageal reflux disease.

Proton pump inhibitors (PPIs), the most commonly used antisecretory medi-cations in the management of reflux illness, virtually eliminate elective surgery for ulcer disease, and relegate anti-reflux surgery to patients with gastroesophageal reflux disease (GERD) who are inadequately managed by medical therapy. However, PPI medications still leave some therapeutic demands of GERD unmet. Furthermore, up to 40%-55% of daily PPI users have chronic symptoms, due to PPI refractoriness. Potassium-competitive acid blockers (P-CABs) transcend many of the problems and limits of PPIs, delivering quick, powerful, and extended acid suppression and allowing for treatment of numerous unmet needs. Recently, it has become clear that compromised mucosal integrity plays a role in the etiology of GERD. As a result, esophageal mucosal protection has emerged as a novel and potential treatment approach. An increasing body of research demonstrates that when P-CABs are used as primary drugs or add-on drugs (to regular treatment), they provide a considerable extra benefit, particularly in alleviating symptoms that do not respond to PPI therapy.