Receiving Proton Pump Inhibitor Therapy Research Articles

Proton-Pump Inhibitors and Risk of Bloodstream Infection without an Identifiable Source: a Hospital-Based Case-Control Study.

The association between proton-pump inhibitor (PPI) use and systemic infections caused by bacterial translocation is unclear. This study aimed to investigate whether patients receiving PPI therapy have a higher risk of bloodstream infections (BSI) without an identifiable source of infection. We conducted a hospital-based case-control study which enrolled all patients aged 20 years and older who were hospitalized in Ichinomiya Nishi Hospital with BSI confirmed by two sets of positive blood cultures in 2019. Patient data were collected from medical records, and the bacterial translocation-type (BT-type) BSI group was defined as patients with BSI without an identifiable source of infection, whereas those with a BSI from an identifiable source were assigned to the control group based on the diagnostic criteria for each infectious disease. Data from 309 patients, including 66 cases and 243 controls, were analyzed. Compared with PPI non-users, PPI users had a 2.4-fold higher risk of developing BT-type BSI after controlling for potential confounders (adjusted odds ratio: 2.41, 95% confidence interval: 1.29-4.51, P = 0.006). In conclusion, PPI use is associated with a higher risk of BSI without an identifiable source; therefore, PPI use might increase the risk of BSI secondary to bacterial translocation.

Overutilization of Proton Pump Inhibitors (PPIs) in a Community-Based Hospital: A QI Initiative

Introduction: Proton pump inhibitors (PPIs) are indicated for GERD, erosive esophagitis, and prophylactic use in patients at high risk for stress ulcerations. Long-term PPI therapy is associated with increased incidence of C. diff infections and community- and hospital-acquired pneumonia. Discontinuation of stress ulcer prophylaxis upon discharge and reevaluation of continued therapy will help reduce chronic, inappropriate treatment, which predisposes patients to adverse side effects. Aim: We sought to reform the process of inpatient PPI prescriptions based on clinical indications of therapy in order to reduce use and associated costs of PPIs by 30% over 6 months. Model for Improvement: We obtained an IRB exemption for a retrospective chart review study and collected pre-intervention data from 200 patients who had received PPI therapy between July-Aug 2022. Of these, 186 met inclusion criteria. We identified PPT overuse among all inpatient admissions, including those admitted under teaching services. Evaluating the timing of PPI initiation after admission, we found that a majority (83.8%) were started upon admission; 28.5% required PPIs throughout; and 25.2% of orders were placed within 1 day of discharge. The average duration of therapy was 3.9  2.59 days. On average, 50.5% of patients had a prior diagnosis of GERD, gastritis, or erosive esophagitis, justifying initiation of PPI therapy. However, almost a third (32.8%) met the criteria for stress ulcer prophylaxis. 17% of the cohort developed an adverse side effect, and almost 53% of patients were discharged with a new prescription for PPI. Measures: Root cause analysis revealed a lack of knowledge regarding adverse PPI effects leading to longer hospital stays. During the first PDSA, we conducted a session on “Use of PPI Inhibitors: Indications for Inpatient Prescriptions and Stress Ulcer Prophylaxis” in April 2023, educating Internal Medicine and Family Medicine resident teaching services about PPI therapy indications, contraindications, and adverse effects. Results: After our educational intervention, we collected and analyzed data from May 2023 to August 2023 and found 301 patients who met inclusion criteria. Their average age was 73.29 years. 169 patients (56%) had pre-existing diagnoses (GERD or erosive esophagitis), justifying initiation of Protonix. Of the remaining 132 without pre-existing conditions, 44 (35%) met criteria for starting stress ulcer prophylaxis. This was a 3% increase in appropriate utilization when compared to our pre-intervention data. 181 patients were discharged with a prescription for pantoprazole, of which 46 were PPI-naïve prior to admission. Conclusion: We found a decrease in inappropriate inpatient PPI administration by 3% after education. Although the post-intervention sample size was larger, the education resulted in a positive response in 1 month. The next PDSA cycle will alter the EMR order to provide only 3 orders for pantoprazole – one oral, one IV, and one for infusion, and orders will also require the selection of indication.

Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study.

Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their application is frequently not terminated. Potential adverse effects of PPI treatment could impact the outcome in case of unnecessary and, therefore, avoidable long-term continuation. We tested the hypotheses that nonindicated PPI therapy continued beyond hospital discharge is associated with increased morbidity, rehospitalization rate, and mortality. Nationwide retrospective cohort study considering critically ill patients treated on German ICUs between January, 2017, and December, 2018 with a 2-year follow-up. A total of 591,207 patient datasets of a German healthcare insurer were screened. We identified 11,576 ICU patients who received PPI therapy for the first time during their index ICU stay without having an indication for its continuation. The cohort was stratified into two groups: 1) patients without further PPI therapy and 2) patients with continuation of PPI therapy beyond 8 weeks after hospital discharge. Frequency of predescribed adverse events associated with PPI therapy, 1-year rehospitalization rate, and 2-year mortality were determined. The proportion of patients with continued PPI therapy without an objectifiable indication was 41.7% (4,825 of 11,576 patients). These patients had a 27% greater risk of pneumonia (odds ratio [OR] 1.27; 95% CI, 1.15-1.39; p < 0.001) and a 17% greater risk of cardiovascular events (OR 1.17; 95% CI, 1.08-1.26; p < 0.001). Continued PPI therapy was associated with a 34% greater risk of rehospitalization (OR 1.34; 95% CI, 1.23-1.47) and a nearly 20% greater 2-year mortality risk (hazard ratio 1.17; 95% CI, 1.08-1.27; p = 0.006). These data demonstrate that an unnecessary continuation of PPI therapy after hospital discharge may significantly impact morbidity and mortality. To avoid potentially harmful overuse of a PPIs, intensivists should ensure timely cessation of a temporarily indicated PPI therapy.

Real-World Evidence to Evaluate the Efficacy and Safety of Vonoprazan in Gastrointestinal Disorders in the Pakistani Population.

While proton pump inhibitor (PPI) therapy has proven to be effective in managing gastroesophageal reflux disease (GERD), a notable portion of patients who experience GERD symptoms may not respond to this treatment. Research suggests that roughly 30% of individuals with a presumed GERD diagnosis may continue to experience symptoms, whether partially or completely, even when receiving PPI therapy. The aim of this study was to assess the treatment of gastrointestinal diseases with a novel potassium-competitive acid blocker (P-CAB), vonoprazan, in terms of its effectiveness and safety in the Pakistani population. This prospective, multicenter, observational study was conducted in Pakistan. This study included 1,642 patients from January 2023 to August 2023, aged 18 years, with gastrointestinal disorders. All demographic data, medical history, GERD severity assessment questionnaire (GerdQ), and laboratory parameters, including stool assessment for Helicobacter pylori (H. pylori), were observed. Patients were orally treated with vonoprazan at doses of 10 mg or 20 mg, once or twice daily. Statistical analysis was done by one-way ANOVA. Out of 1,642 patients, 840 (51.2%) were males and 802 (48.8%) were females, with a mean age of 39.81±14.61 years. The mean GerdQ score at baseline was 20.37±15.87, 7.24±8.15 at the secondweek of treatment, and 3.70±6.31 at the fourth week of treatment (p<0.001). 90.74% of patients achieved H. pylori eradication. Most patients were acid regurgitation and heartburn-free for >70% of days. Most of the patients, 1,283 (78.13%), exhibited good treatment compliance. Mild adverse events were reported in 37 (2.3%) patients. The use of vonoprazan significantly reduced the likelihood of GERD by improving symptoms and was also highly effective in the elimination of H. pylori infections. Vonoprazan was generally well tolerated.

Hepatic encephalopathy with proton pump inhibitor use in post tips patients: a systematic review and meta-analysis.

Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS. We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs. no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated. The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users. Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.

Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension.

Long-term prescription of proton pump inhibitors (PPIs) in patients with cirrhosis is common practice. However, in recent years, several observational studies have reported increased complications and negative prognostic effects of PPI treatment in these patients. Judging the significance of these associations is complicated by the fact that a plausible underlying pathomechanism has not been identified so far. In the present study, we address this important issue by investigating the impact of PPI treatment on subclinical bacterial translocation from the gut into the blood stream in patients with advanced cirrhosis and portal hypertension. Indeed, we report significantly aggravated bacterial translocation in cirrhosis patients receiving PPI treatment. This finding is highly relevant, as bacterial translocation is known to promote the development of complications and impair prognosis in patients with cirrhosis. Hence, the present study could establish a plausible link between PPI treatment and adverse effects in cirrhosis.

Symptom Profile, Proton Pump Inhibitor Therapy, and Diagnostic Testing in Patients With Persistent Reflux-Like Symptoms: Results From a Population-Based Survey

Background: Proton pump inhibitors (PPIs) are highly effective in treating gastroesophageal reflux disease (GERD). However, persistent, troublesome reflux symptoms despite PPI use are common, and a proportion of individuals with these persistent symptoms is considered to have refractory GERD (rGERD). There are limited data on patients’ experience with persistent reflux-like symptoms to guide healthcare professionals in managing this troublesome condition. Methods: An international, population-based, online survey was conducted among adults who reported persistent reflux-like symptoms; 24 questions were posed regarding the participants’ symptoms, diagnosis, treatment, and comorbid conditions. Descriptive analyses were performed to characterize participants’ experience with diagnosis and their satisfaction with treatment. All data were self-reported. Results: Of 565 initial respondents, 283 (51%) answered the question regarding being formally diagnosed by a healthcare professional with GERD and/or rGERD. The 197 (70%) participants who answered “yes” made up the survey population. Heartburn (65%) and acid regurgitation (62%) were the most common troublesome symptoms. PPI use was reported by 145 (74%) respondents, but only 30% were satisfied with PPI therapy. The most common alternative therapies included antacid/alginates (63%), histamine H2-receptor antagonists (33%), mucosal protectants (25%), and lifestyle modifications (84%). Conclusions: In this population-based survey, nearly one-third of participants with persistent reflux-like symptoms had not received a formal diagnosis of GERD or rGERD. Although most participants diagnosed with GERD/rGERD had received PPI therapy, persistent symptoms, dissatisfaction with PPI therapy, and concerns about long-term PPI use were common. These data emphasize the need for patient input when developing management strategies for GERD and persistent reflux-like symptoms or rGERD.

Proton Pump Inhibitor Use and Risk of Gastric Cancer: Current Evidence from Epidemiological Studies and Critical Appraisal.

Simple SummaryProton pump inhibitors (PPIs) are prescribed for reducing the amount of stomach acid. PPIs increase the systemic level of gastrin, a trophic hormone, which is reported to be linked with carcinogenesis. Previous epidemiological studies have shown that the use of PPIs increase the risk of gastric cancer, questioning the safety of PPI therapy for reducing gastric acid suppression. The findings of this study show that PPI use is associated with the risk of gastric cancer (RR 1.80, 95% CI, 1.46–2.22, p < 0.001) compared with non-users. The evidence from this study suggests that clinicians should maintain heightened vigilance regarding the adverse effect of PPI therapy and weigh the long-term outcomes.Proton pump inhibitors (PPIs) are used for maintaining or improving gastric problems. Evidence from observational studies indicates that PPI therapy is associated with an increased risk of gastric cancer. However, the evidence for PPIs increasing the risk of gastric cancer is still being debated. Therefore, we aimed to investigate whether long-term PPI use is associated with an increased risk of gastric cancer. We systematically searched the relevant literature in electronic databases, including PubMed, EMBASE, Scopus, and Web of Science. The search and collection of eligible studies was between 1 January 2000 and 1 July 2021. Two independent authors were responsible for the study selection process, and they considered only observational studies that compared the risk of gastric cancer with PPI treatment. We extracted relevant information from selected studies, and assessed the quality using the Newcastle−Ottawa scale (NOS). Finally, we calculated overall risk ratios (RRs) with 95% confidence intervals (CIs) of gastric cancer in the group receiving PPI therapy and the control group. Thirteen observational studies, comprising 10,557 gastric cancer participants, were included. Compared with patients who did not take PPIs, the pooled RR for developing gastric cancer in patients receiving PPIs was 1.80 (95% CI, 1.46–2.22, p < 0.001). The overall risk of gastric cancer also increased in patients with gastroesophageal reflux disease (GERD), H. pylori treatment, and various adjusted factors. The findings were also consistent across several sensitivity analyses. PPI use is associated with an increased risk of gastric cancer in patients compared with those with no PPI treatment. The findings of this updated study could be used in making clinical decisions between physicians and patients about the initiation and continuation of PPI therapy, especially in patients at high risk of gastric cancer. Additionally, large randomized controlled trials are needed to determine whether PPIs are associated with a higher risk of gastric cancer.

Efficacy of Endoscopic and Surgical Treatments for Gastroesophageal Reflux Disease: A Systematic Review and Network Meta-Analysis.

Although various endoscopic and surgical procedures are available for the treatment of gastroesophageal reflux disease (GERD), the comparative efficacy of these treatments has not been fully elucidated. This study aimed to comprehensively evaluate the efficacy of various endoscopic and surgical treatments for GERD. All relevant randomized controlled trials published through August 2021 that compared the efficacy of endoscopic and surgical GERD treatments, including radiofrequency energy delivery, endoscopic plication, reinforcement of the lower esophageal sphincter (LES), and surgical fundoplication, were searched. A network meta-analysis was performed to analyze treatment outcomes, including the requirement of proton pump inhibitor (PPI) continuation and GERD-health-related quality of life questionnaire score (GERD-HRQL). As such, 25 studies with 2854 patients were included in the analysis. Endoscopic plication, reinforcement of the LES, and surgical fundoplication were effective in reducing the requirement of PPI continuation compared to PPI therapy (pooled risk ratio (RR) (95% confidence interval [CI]): endoscopic plication, 0.34 (0.21–0.56); reinforcement of LES, 0.32 (0.16–0.63), and surgical fundoplication, 0.16 (0.06–0.42)). Radiofrequency energy delivery tended to reduce the requirement of PPI continuation compared to PPI therapy (RR (95% CI): 0.55 (0.25–1.18)). In terms of GERD-HRQL, all endoscopic and surgical treatments were superior to PPI therapy. In conclusion, all endoscopic or surgical treatments, except radiofrequency energy delivery, were effective for discontinuation of PPI medication, especially surgical fundoplication. Quality of life, measured by GERD-HRQL, also improved in patients who underwent endoscopic or surgical treatment compared to those who received PPI therapy.

Proton Pump Inhibitor Therapy Does Not Affect Prognosis of Cirrhosis Patients With Acute Decompensation and Acute-on-Chronic Liver Failure: A Single-Center Prospective Study.

Background: The aim of this study was to investigate the impact of proton pump inhibitor (PPI) therapy on complications and prognosis in cirrhosis patients with and without acute-on-chronic liver failure (ACLF).Materials and Methods: Cirrhosis patients with acute decompensation (AD) (n = 489) admitted in our center were enrolled in this prospective observational cohort study. According to treatment received, patients were identified as users or nonusers of PPI. Clinical and laboratory data, complications during hospitalization, and overall survival were recorded in all the patients.Results: Of the 489 patients, 299 (61.1%) patients received PPI therapy. The logistic regression analysis showed that age, albumin, history of previous hepatic encephalopathy (HE), and the chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score were independent risk factors for HE in patients with decompensated cirrhosis [odds ratio (OR) = 1.07, 95% CI: 1.03–1.12, p = 0.001; OR = 1.13, 95% CI: 1.04–1.24, p = 0.006; OR = 242.52, 95% CI: 40.17–1464.11, p < 0.001; and OR = 2.89, 95% CI: 2.11–3.96, p < 0.001, respectively]. Previous severe liver injury and previous bacterial infections were independent risk factors for spontaneous bacterial peritonitis (SBP) in patients with decompensated cirrhosis (OR = 3.43, 95% CI: 1.16–10.17, p = 0.026 and OR = 6.47, 95% CI: 2.29–18.29, p < 0.001, respectively). The multivariate Cox proportional hazards regression model showed that the type and dose of the PPI used were not related to 28-day and 90-day mortality in cirrhosis patients with AD or ACLF.Conclusion: PPI use does not appear to increase mortality or the risk of HE and SBP in the hospitalized cirrhosis patients with and without ACLF.

GASTROPROTECTION IN PATIENTS ON ANTITHROMBOTIC THERAPY: A QUALITY IMPROVEMENT STUDY

GASTROPROTECTION IN PATIENTS ON ANTITHROMBOTIC THERAPY: A QUALITY IMPROVEMENT STUDY

Long-term proton pump inhibitor use is a risk factor for mortality in patients hospitalized for COVID-19

Background and aimThe aim of this study is to evaluate whether the long-term (≥4 weeks) use of proton pump inhibitors (PPIs) is a risk factor for intubation requirement and mortality in patients hospitalized for COVID-19.Materials and methods In this multicentric retrospective study, a total of 382 adult patients (≥18 years of age) with confirmed COVID-19 who were hospitalized for treatment were enrolled. The patients were divided into two groups according to the periods during which they used PPIs: the first group included patients who were not on PPI treatment, and the second group included those who have used PPIs for more than 4 weeksResultsThe study participants were grouped according to their PPI usage history over the last 6 months. In total, 291 patients did not use any type of PPI over the last 6 months, and 91 patients used PPIs for more than 4 weeks. Older age (HR: 1.047, 95% CI: 1.026–1.068), current smoking (HR: 2.590, 95% CI: 1.334–5.025), and PPI therapy for more than 4 weeks (HR: 1.83, 95% CI: 1.06–2.41) were found to be independent risk factors for mortalityConclusionThe results obtained in this study show that using PPIs for more than 4 weeks is associated with negative outcomes for patients with COVID-19. Patients receiving PPI therapy should be evaluated more carefully if they are hospitalized for COVID-19 treatment.

Sporadic fundic gland polyps with dysplasia or carcinoma: Clinical and endoscopic characteristics.

Fundic gland polyps (FGPs) are the most common gastric polyps and have been regarded as benign lesions with little malignant potential, except in the setting of familial adenomatous polyposis. However, in recent years, the prevalence of FGPs has been increasing along with the widespread and frequent use of proton pump inhibitors (PPIs). To date, several cases of FGPs with dysplasia or carcinoma (FGPD/CAs) have been reported. In this review, we evaluated the clinical and endoscopic characteristics of sporadic FGPD/CAs. Majority of the patients with sporadic FGPD/CAs were middle-aged women receiving PPI therapy and without Helicobacter pylori (H. pylori) infection. Majority of the sporadic FGPD/ CAs occurred in the body of the stomach and were sessile and small with a mean size of 5.4 mm. The sporadic FGPs with carcinoma showed redness, irregular surface structure, depression, or erosion during white light observation and irregular microvessels on the lesion surface during magnifying narrow-band imaging. In addition, sporadic FGPs, even with dysplasia, are likely to progress to cancer slowly. Therefore, frequent endoscopy is not required for patients with sporadic FGPs. However, histopathological evaluation is necessary if endoscopic findings different from ordinary FGPs are observed, regardless of their size. In the future, the prevalence of FGPs is expected to further increase along with the widespread and frequent use of PPIs and decreasing infection rate of H. pylori. Currently, it is unclear whether FGPD/CAs will also increase in the same way as FGPs. However, the trends of these lesions warrant further attention in the future.

Clinical features and therapeutic responses to proton pump inhibitor in patients with severe reflux esophagitis: A multicenter prospective observational study.

Background and AimIn patients with severe erosive reflux disease (ERD; Los Angeles classification grade C/D) who do not undergo endoscopic examination, insufficient strength and duration of proton pump inhibitor (PPI) therapy may lead to complications such as esophageal bleeding and stenosis. Therefore, to provide a safe and effective treatment for gastroesophageal reflux disease (GERD), we investigated the clinical features of patients with severe ERD and their responses to PPI therapy.MethodsPatients with GERD symptoms received PPI therapy for 4 weeks after endoscopic examination. The patients completed the Gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test questionnaire before and 2 or 4 weeks after PPI treatment. Patient characteristics, presence/absence of coexisting atrophic gastritis (AG) and hiatus hernia (HH), and responses to PPI therapy were compared in patients with GERD among three groups (nonerosive reflux disease, mild ERD [grade A/B], and severe ERD).ResultsThe severe ERD group had a significantly higher proportion of males, higher body mass index, and longer duration of GERD morbidity. Furthermore, the severe ERD group also had a significantly lower incidence of coexisting AG and higher incidence of HH. There was no difference in the severity of GERD before PPI treatment among the three groups. Unexpectedly, the response to PPI therapy was the best in the severe ERD group.ConclusionSufficient strength and period of PPI therapy are required, even if the symptoms show early improvement, when treating GERD patients without performing endoscopy, considering the possibility of severe ERD.

Pre-endoscopic intravenous proton pump inhibitors therapy for upper gastrointestinal bleeding: A prospective, multicentre study

Background/AimThe indiscriminate use of high-dose, proton pump inhibitor (PPI) infusion in non-variceal upper gastrointestinal bleeding (UGIB) patients to reduce the rate of peptic ulcers with high-risk stigmata (HRS) has been questioned. We evaluated the prevalence of HRS on peptic ulcer and non-ulcer lesions in patients receiving or not receiving pre-endoscopic PPI therapy. MethodsData of consecutive UGIB patients observed in 50 Italian centres were analysed. The prevalence of both HRS on peptic ulcers and active bleeding on non-ulcer lesions between patients treated or not treated with PPI were compared. Multivariate analysis was performed. ResultsA total of 1,792 (69.8%) out of 2,566 patients received PPI therapy. Prevalence of HRS on ulcers was 51.8% and 53.4% (P = 0.58) in treated and not treated patients, respectively, and the rate of endoscopic therapy did not differ between groups. Prevalence of non-ulcer bleeding lesions was higher in patients treated than in those not treated with PPI (18.7% vs 10.6%; P = 0.023). At multivariate analysis, PPI therapy (OR: 1.16, 95% CI = 0.82–1.64; P = 0.4) was not an independent factor affecting HRS prevalence, which was inversely correlated with timing to endoscopy (OR: 0.85, 95% CI = 0.76–0.95; P = 0.005). ConclusionsOur data failed to detect a significant role of pre-endoscopic PPI therapy in decreasing prevalence of HRS and need for endoscopic treatment in bleeding patients with either peptic ulcer or non-ulcer lesions.

Proton pump inhibitors reduce phlebotomy burden in patients with HFE-related hemochromatosis: a systematic review and meta-analysis.

Proton pump inhibitors (PPIs) may reduce iron absorption and serum ferritin levels in patients with homeostatic iron regulator (HFE)-related hemochromatosis, reducing the need for frequent phlebotomies. Our study aimed to perform for the first time a meta-analysis of existing observational and randomized controlled studies to ascertain the overall effect of PPI use in patients with HFE-related hemochromatosis. Studies in adults reporting the outcomes of PPIs use in hereditary hemochromatosis patients from Medline, Embase, Scopus and Google Scholar databases from inception to December 2019 were systematically searched. The study outcomes were the serum ferritin levels and annual requirement for phlebotomies. Pooled mean difference, and 95% confidence intervals (CIs) were obtained by the random-effects model. Forrest plots were constructed to show the summary pooled estimate. Heterogeneity was assessed by using I2 measure of inconsistency. Following an initial search of 202 manuscripts, a total of three studies involving 68 patients with hemochromatosis (34 in the PPIs group and 34 in the placebo or non-PPI group) were included. A minimum duration of PPI use was 1 year. Patients who received PPIs therapy did not have a statistically significant lower serum ferritin levels (mean difference: -18.86, 95% CI: -60.44, 22.72, P = 0.37, I2 = 88%) but required significantly less sessions of phlebotomies annually (mean difference: -3.10, 95% CI: -4.46, -3.08, P < 0.00001, I2 = 93%). No publication bias was found on Egger (P = 0.94) or Begg (P = 0.98) tests. PPIs can be used as an adjuvant therapy to reduce phlebotomy burden in patients with HFE-related hemochromatosis.

SAT-121 Secretin Stimulation Test in a Patient Receiving Proton PUMP Inhibitor Therapy- to Do or Not to Do?

Introduction:Complications of gastrinoma cause increase in mortality in patients with MEN syndrome. There are concerns that secretin stimulation test (SST) can produce false positive results in the setting of proton pump inhibitor (PPI) use. However, withholding the PPI treatment in a patient with severe peptic ulcer disease can be potentially unsafe. There is also a theoretical concern that abrupt withdrawal of PPI will cause a surge in gastrin. Here we discuss a case where SST yielded impressive results despite the use of PPI.Case report:78 y.o. Caucasian male presented in December 2018 with chronic nausea, vomiting, diarrhea of 5-year duration. Further evaluation showed severe esophagitis with strictures, multiple gastric and duodenal ulcers and he was initiated on PPI. He also had h/o hyperparathyroidism diagnosed 2 years ago s/p parathyroidectomy (2 of 4 parathyroid glands removed) and one kidney stone in his late 20s and early 70s. He had no family history of any endocrine issues. Physical examination was unremarkable. Labs were significant for gastrin levels (nl <100 pg/mL) of 375 pg/mL in 6/2016 and 219 pg/mL in 11/2018. SST was performed on 12/22/2018 which showed gastrin levels as follows: -10 min=405 pg/mL, - 5 min=404 pg/mL, + 2 min=3201 pg/mL, + 5 min=3439 pg/m, +10 min=2445 pg/mL, +20 min=1218 pg/mL, +30 min=578 pg/mL. He was diagnosed with gastrinoma based on the SST results. Genetic testing did not show any pathogenic sequence variants or deletions/duplications identified in MEN-1; CASR; CDC73; CDKN1B or RET. Given history of hyperparathyroidism and gastrinoma, he was clinically diagnosed with MEN1 syndrome. Ga-68 DOTATATE scan in May 2019 revealed focal radiotracer avidity in the tail the pancreas suspicious for neuroendocrine tumor and multiple radiotracer avid retroperitoneal and abdominal lymph nodes. Focal radiotracer avid lesion was also noted in the sacrum suspicious for osseous metastatic disease. He was started on lantreotide monthly injections in July 2019. Gastrin level decreased to 94 pg/mL 1 week after first injection, however later increased to 304 pg/ml 1 week after third dose of lantreotide. Surgical options are also being explored.Conclusion:An increase in more than 120pg/mL over basal gastrin level within 10 min in SST is consistent with a diagnosis of gastrinoma. Our patient demonstrated an impressive increase in gastrin level with SST while on PPI therapy. Pertinent diagnostic information was successfully obtained without increasing the risk of complications that can occur by withdrawal of PPI therapy.

Proton-pump inhibitor use and the development of new ischemic heart disease in non-cardiac chest pain patients.

The growing reports regarding cardiac-related adverse events of chronic proton-pump inhibitors (PPI) treatment, a mainstay therapy of non-cardiac chest pain (NCCP), have raised concerns about alteration of the natural course in NCCP patients using PPI. We aimed to determine if NCCP patients receiving PPI have a higher risk of developing ischemic heart disease (IHD) compared to those not receiving PPI therapy. Three groups of NCCP patients were included; PPI, histamine-2 receptor antagonist (H2RA), and no antireflux treatment. Diagnosis of NCCP had to precede diagnosis of IHD by at least 30days, and in those receiving antireflux treatment at 30days after starting the medication. Data analysis was corrected for 6 known confounding factors for IHD including hyperlipidemia, hypertension, obesity, smoking status, male gender, and diabetes mellitus. Of the patients on PPI or H2RA, 1280 and 250, respectively, developed IHD. Patients on PPI therapy displayed an increased odd of developing ischemic heart disease compared to patients never placed on therapy (OR 1.14, 95% CI 1.03-1.25, P-value .0093). Patients placed on H2RA therapy did not show a statistically significant change in risk compared to patients who were not placed on therapy (OR 0.90, 95% CI 0.77-1.06, P-value .2049). Number needed to harm in the PPI and H2RA groups was 17 and 45, respectively. PPIs confer a statistically significant, but marginal effect on the risk of IHD development in NCCP patients. Thus, PPI use in NCCP only minimally alters the overall benign natural course of the disease.

Upper Endoscopy in Patients with Extra-Oesophageal Reflux Symptoms: A Multicentre Study

Background: There are no evidence-based recommendations for performing upper gastrointestinal endoscopy (UGIE) in patients with extra-oesophageal symptoms of gastro-oesophageal reflux disease (GORD). However, UGIEs are often performed in clinical practice in these patients. We aimed to assess the prevalence of gastro-oesophageal lesions in patients with atypical GORD symptoms. Methods: Patients complaining of at least one extra-oesophageal GORD symptom and undergoing UGIE in seven centres were prospectively enrolled. Clinically relevant lesions (Barrett’s oesophagus, erosive oesophagitis, gastric precancerous conditions, peptic ulcer, cancer, and H. pylori infection) were statistically compared between groups regarding GORD symptoms (atypical vs. both typical and atypical), type of atypical symptoms, age, and presence of hiatal hernia. Results: Two hundred eleven patients were enrolled (male/female: 74/137; mean age: 55.5 ± 14.7 years). Barrett’s oesophagus was detected in 4 (1.9%), erosive oesophagitis in 12 (5.7%), gastric precancerous conditions in 22 (10.4%), and H. pylori infection in 38 (18%) patients. Prevalence of clinically relevant lesions was lower in patients with only atypical GORD symptoms (28.6 vs. 42.5%; p = 0.046; χ² test), in patients ≤50 years (20 vs. 44.8%; p = 0.004; χ² test), and in those in ongoing proton pump inhibitor (PPI) therapy (21.1 vs. 40.2%; p = 0.01; χ² test). No clinically relevant lesions were detected in patients ≤50 years, without alarm symptoms, and receiving PPI therapy. Hiatal hernia was diagnosed in only 6 patients with cardiologic and in 41 patients with ear-nose-throat symptoms (11.3 vs. 35.1%; p = 0.03; χ² test). Conclusions: Clinically relevant lesions are uncommon among young (≤50 years) patients with extra-oesophageal GORD symptoms. Hiatal hernia is not more prevalent in patients with cardiologic symptoms and suspicion of GORD. The usefulness of UGIE in these patients is questionable.

Association Between Acute Gastroenteritis and Continuous Use of Proton Pump Inhibitors During Winter Periods of Highest Circulation of Enteric Viruses

An increased risk of acute bacterial enteric infections has been reported among patients receiving proton pump inhibitor (PPI) therapy. The risk of acute gastroenteritis (AGE) of viral origin associated with continuous PPI exposure has been less studied. To investigate the association between continuous PPI therapy and AGE occurrence during winter epidemic periods when the circulation of enteric viruses is the highest. A matched cohort study was performed using a prospectively collected drug dispensing database from a large panel of community pharmacies in continental France. All patients recorded in the database during the 2015 to 2016 winter season, with documented age, sex, and use of an identifiable regular panel pharmacy, were eligible for the study. Each patient exposed to continuous PPI therapy was matched to 3 unexposed patients, according to year of birth, sex, and identifiable regular panel pharmacy. Analyses were performed between January 2017 and December 2018. Continuous PPI use during the 2015 to 2016 AGE winter epidemic. The occurrence of at least 1 AGE episode during the 2015 to 2016 AGE winter epidemic was the main outcome. Episodes of AGE were identified using a previously validated algorithm based on drug dispensing data. Relative risks of AGE were estimated using a multivariable log-binomial model adjusted for age, sex, and treatments for chronic conditions. There were 233 596 patients receiving PPI therapy (median [interquartile range] age, 71 [62-81] years; 55.8% female) and 626 887 matched patients not receiving PPI therapy (median [interquartile range] age, 70 [61-80] years; 56.3% female) included in the analyses. At least 1 AGE epidemic episode was identified in 3131 patients (1.3%) receiving PPI therapy and in 4327 patients (0.7%) not receiving PPI therapy. The adjusted relative risk of AGE for those receiving PPI therapy was 1.81 (95% CI, 1.72-1.90) for all ages considered, 1.66 (95% CI, 1.54-1.80) among those aged 45 to 64 years, 2.19 (95% CI, 1.98-2.42) among those aged 65 to 74 years, and 1.98 (95% CI, 1.82-2.15) among those aged 75 years and older. Continuous PPI therapy was associated with an increased risk of developing AGE during periods of highest circulation of enteric viruses. These findings support the hypothesis that PPI use is associated with an increased risk of enteric viral infections.