Chronic Proton Pump Inhibitors Research Articles

Long-Term Proton Pump Inhibitor-Acid Suppressive Treatment Can Cause Vitamin B12 Deficiency in Zollinger-Ellison Syndrome (ZES) Patients.

Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency.

Gastric Polyps in Long-Term Proton Pump Inhibitor Use: Identification of Risks and Characteristics.

Aim Estimate the prevalence of gastric polyps linked to long-term use of proton pump inhibitor (PPI), determine the various risk factors that promote this association, and identify the characteristics associated with these polyps. Methods This prospective cross-sectional study was conducted on approximately 1000 patients presenting to the Gastroenterology Endoscopic Department for upper GI endoscopy at two hospital centers in Beirut, Lebanon, over a period of 12 months from September 2021 to September 2022. The demographic and clinical data of patients who had been taking PPIs for at least one month were collected via a questionnaire. All patients with a previous Helicobacter pylori (H. pylori) infection, presence of hypergastrinemia, or a personal/family history of gastric polyps were excluded from this study. Statistical analyses were performed using SPSS 20 software. Categorical variables were compared by Fisher's exact test; p-values of less than 0.05 were considered statistically significant. Results The prevalence of gastric polyps linked to long-term PPI use was 30%. The minimum duration of daily PPI use required for the formation of polyps is around 24 months. The dosage did not play a significant role in increasing this prevalence. A significant correlation was found between chronic PPI use and factors such as sex, age range, duration, and type of PPI used. These polyps were predominantly found in females (with an OR of 2.9), increased with age, were mostly of the fundic gland type, and their size was proportionally linked to both the dosage and duration of daily PPI use. No cases of dysplasia within the fundic gland polyps (FGPs) were demonstrated in our study. Conclusion To date, there is no current data that prove an association between gastric cancer and PPI-induced FGPs. Additionally, the incidence of FGPs has increased with the widespread chronic use of PPIs. Therefore, attention should be drawn to the potential risk of dysplasia. Thus, the present study highlights the importance of limiting the prescription of PPIs to globally well-defined indications and determining the various risk factors that promote the association between gastric polyps and PPI use. This abstract was recently presented as an E-poster at the ESGE Days 2024 Congress on April 25-27, 2024, in Berlin, Germany.

Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease.

The extent of disease severity remains unclear among CYP2C19 rapid and ultra-rapid metabolizers with refractory symptoms of gastroesophageal reflux disease (GERD) on chronic proton-pump inhibitors (PPIs). To determine the impact of CYP2C19 metabolizer status in relation to chronic PPI therapy with a focus on the extent of esophageal inflammation, acid exposure, and motor function. This retrospective study included 54 patients with refractory GERD symptoms who underwent CYP2C19 genotyping for PPI metabolism, esophagogastroduodenoscopy, ambulatory pH study, and high-resolution esophageal manometry. Patients were divided into three groups: normal metabolizer (NM) group, intermediate metabolizer/poor metabolizer (IM/PM) group, and rapid metabolizer/ultra-rapid metabolizer (RM/UM) group. The Chi-square test was used to analyze categorical variables, and one-way ANOVA for comparing means. Rapid metabolizer/ultra-rapid metabolizer (RM/UM) group more frequently had either Los Angeles grade C or D GERD (7/19, 36.8% vs 1/21, 4.8%, P = 0.011) and metaplasia of the esophagus (9/19, 47.4% vs 2/21, 9.5%, P = 0.007) when compared to the NM group. RM/UM group were more frequently offered dilatation for nonobstructive dysphagia (8/19, 42.1% vs 3/21, 14.3%, P = 0.049) and more exhibited a hypotensive lower esophageal sphincter (LES) resting pressure compared to the NM group (10/19, 52.6% vs 4/21, 19%, P = 0.026). All three groups exhibited comparable DeMeester scores when PPIs were discontinued 72 hours before the ambulatory pH study. CYP2C19 RMs and UMs on chronic PPI with refractory GERD symptoms exhibited greater esophageal mucosal inflammation, as observed both endoscopically and histologically, and more were found to have hypotensive LES resting pressures and more were offered esophageal dilatation.

P1116 Risk of fractures in children and adults with inflammatory bowel disease: A report from the epi-IIRN

Abstract Background Both adult and pediatric patients with inflammatory bowel disease (IBD) are at risk of osteopenia and osteoporosis, nevertheless, whether patients with IBD are subjected to a higher risk for bone fractures is debated. Thus, we aimed to assess the risk for bone fractures, osteopenia and osteoporosis in IBD vs non-IBD patients, using the epi-Israeli IBD Research Nucleus (IIRN) data. Methods Data of patients with IBD and non-IBD matched controls (approximately 3 non-IBD controls per case) were retrieved from the epi-IIRN cohort (January 2005- June 2020) that maintain data on all patients with IBD from the four Israeli HMOs. Data included demographics, osteoporosis medications, fracture data and IBD related characteristics. Patients were stratified by age group (0-17,18-49, and ≥50). Patients with known osteopenia or osteoporosis before IBD diagnosis were excluded. Results We included 32,263 patients with IBD and 89,423 non-IBD controls [48% female, 56% Crohn’s disease (CD)]. Time to first fracture was significantly shorter in female pediatric patients (p=0.01), in both female (p=0.0004) and male (p=0.003) adult and elderly patients (p&amp;lt;0.0001) (Figure 1). Time to diagnosis of osteopenia/osteoporosis in patients with IBD was significantly shorter in all age groups and genders. Rate of fractures was significantly higher in patients with IBD versus controls for all groups, and rate of osteopenia/osteoporosis was also higher in patients with IBD in all groups (Table 1). In a subgroup analysis, fracture rate did not significantly differ between CD and ulcerative colitis (UC) for all age groups, but osteopenia and osteoporosis were significantly higher in CD compared to UC in all age groups. The hazard ratio for fractures in the pediatric IBD population was 1.02 (0.88-1.16) for males and 1.17(0.95-1.44) for females, in adults 1.08 (0.99-1.16) for males and 1.12 (1.02-1.21) for females, and in the elderly 1.2 (1.08-1.32) for males and 1.19 (1.08-1.31) for females. Arthritis was significantly associated with fracture risk [HR: children 1.47 (1.15-1.88); adults 1.3 (1.17-1.44); elderly 1.19 (1.07-1.30)]. In adults and elderly, older age at diagnosis, chronic obstructive pulmonary disease, diabetes and long-term proton pump inhibitors usage were also associated with a significant increase in fracture risk. Conclusion In this large nationwide cohort, patients with IBD had significantly higher risk for bone fractures than matched controls in almost all age groups, with no difference between CD and UC. Additionally, the rate of osteopenia and osteoporosis was higher in patients with IBD, suggesting that further efforts need to be invested in bone health of this at-risk population.

Classification of gastric neuroendocrine tumors and associations with survival.

597 Background: The World Health Organization (WHO) classification of gastric body neuroendocrine tumors (GNETs) includes type 1 tumors characterized by hypergastrinemia and arising in a background of atrophic gastritis, type 2 tumors associated with gastrinomas, and type 3 tumors with low serum gastrin level and no background mucosal pathology. However, certain tumors remain unclassified, and the prognostic significance of these tumors is currently unknown. The purpose of this study was to better characterize GNET types and to determine associations with distant metastasis and disease-specific survival (DSS). Methods: Patients diagnosed with GNET (1986-2021) were retrospectively identified and tumors classified as type 1, 2, or 3. Unclassified tumors were reviewed for background gastric mucosal changes associated with chronic proton pump inhibitor (PPI) use. Tumors were categorized as PPI-associated if there were prominent parietal and neuroendocrine cell hyperplasia in the background mucosa, in the absence of a gastrinoma and a positive history of chronic PPI use. WHO grade was determined using mitotic index or Ki-67 proliferative index when available. Characteristics by tumor type, associations with distant metastasis at initial diagnosis, and DSS were determined using standard statistical methods. Results: Of 246 patients, 164 (66.7%) had type 1, 5 (2.0%) had type 2, 52 (21.1%) had type 3, 18 (7.3%) were PPI-associated, and 7 (2.8%) remained unclassified. Multifocal disease was more common for types 1 (56.1%) and 2 (40.0%) than type 3 (13.5%) and PPI-associated tumors (27.8%, P&lt;0.001). Patients with type 3 GNET were also less likely to have WHO grade 1 tumors (26.9%) compared to other GNETs (type 1 37.2%, type 2 40.0%, PPI-associated 50.0%, P&lt;0.001). Additionally, distant metastases at presentation occurred more frequently with type 3 (38.5%) than type 1 (1.2%), type 2 (20.0%), and PPI-associated tumors (11.1%, P&lt;0.001). GNET type (type 1 vs 3, odds ratio [OR] 0.005 [95% confidence interval [CI] 0.001-0.050; PPI-associated vs type 3, OR 0.040 [95% CI 0.004-0.45]), race (non-white vs white, OR 0.17 [95% CI 0.040-0.73]), and WHO grade (2/3 vs 1, OR 10.5 [95% CI 1.93-57.2]) were associated with distant metastasis at presentation. Five-year DSS rates were 100.0% for type 1, 59.7% (95% CI 42.7-73.2%) for type 3, and 90.9% (95% CI 50.8-98.7%) for PPI-associated (log-rank P&lt;0.001). By multivariable analysis, multifocality of primary tumors (hazard ratio [HR] 0.070 [95% CI 0.010-0.46]) and distant metastasis at diagnosis (HR 44.9, 95% CI 6.21-324.8) were independently associated with DSS, while tumor type was not (type 1 vs 3, HR 0.18 [95% CI 0.010-2.44); PPI-associated vs type 3, HR 0.13 [95% CI 0.010-1.33]). Conclusions: PPI-associated tumors may represent a distinct GNET type with intermediate outcomes compared to type 1 and type 3 tumors. However, factors other than tumor type must be considered in determining survival.

Association and Mechanisms of Proton Pump Inhibitors Use with Type-2 Diabetes Mellitus Incidence in Adults: A Systemic Review and Metaanalysis.

Proton pump inhibitors (PPIs) are an extensively prescribed class of anti-ulcer drugs. This systematic review aimed to investigate the association between PPI use and the risk of new-onset diabetes mellitus or type 2 diabetes (T2DM) incidence. A comprehensive literature search was conducted in PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov using the search terms "proton pump inhibitor," "proton pump inhibitors," "PPIs," "diabetes mellitus," and "type 2 diabetes" from inception to February 2023. Statistical analyses were performed using the "Review Manager 5.4" version, and a statistically highly significant P value <0.05 was set. This systematic review identified 12 studies (8 cohort, 1 RCT, and 3 case-control) with a total of 12, 64, 816 population, and the median age ranged from ≥18 yrs to ≤ 75 yrs. The pooled relative risk (RR) observations of a random-effects meta-analysis model showed that chronic exposure to PPI use has a significant association with T2DM risk incidence (RR, 2.44; 95% confidence interval, 1.31-4.54; I 2 = 99%, P < 0.00001). The systematic review findings of the three case-control studies also supported an association of dose-dependent and chronic use of PPIs with an incidence of T2DM among chronic users. The systematic review concludes that chronic PPI exposure increases the risk of T2DM incidence. The authors recommend the shortest possible duration of PPI use and not prescribing PPIs to high-risk prediabetics and those without a compelling indication for PPI use. Regular education to patients regarding adverse reactions with prolonged use may decrease the risk of adverse effects associated with PPIs. The authors suggest that gut dysbiosis, hypergastrinemia, hypomagnesemia, decreased pancreatic secretions and IGF-1 levels, and PXR activation associated with chronic acid suppression among chronic PPI users and the potency of PPIs might explain the association between abnormal glucose metabolism and T2DM incidence. Finally, the authors recommend further randomized controlled trials to investigate the association between PPIs and the risk of new-onset T2DM incidence.

Patients' Knowledge and Pharmacists' Practice Regarding the Long-Term Side Effects of Proton Pump Inhibitors; a Cross-sectional Study.

Proton pump inhibitors (PPI) are a commonly prescribed medication, but recent evidence suggests that their long-term use may lead to several adverse events. To address this issue, our study aims to assess patient awareness and pharmacist practices in educating patients about the potential risks associated with prolonged PPI use. Two questionnaires were developed by researchers and administered in the United Arab Emirates from June to August 2021 to gather insights from patients and pharmacists about the use of PPIs, their knowledge of potential side effects, and their experiences and attitudes toward receiving education about PPI side effects. The patients' knowledge was evaluated based on their cumulative correct answers to questions related to PPI's long-term adverse effects including increased fracture risk and hypocalcemia, vitamin B12 deficiency, hypomagnesemia, and the caution of abrupt withdrawal. All statistical analyses were conducted using SPSS 25.0 software. Overall, 348 participants with a median age of 40 years participated in the survey, among them, 91 (26.14%) used various forms of PPI with 38% of users taking PPI as over-the-counter drugs. Patients had low knowledge about PPI side effects and their proper discontinuation with a median knowledge score of 0 (Interquartile range: 0-2) and only 22.2% of patients were familiar with at least three out of five asked harms. Those with lower knowledge were more likely to be Emirati compared to other nations (p=0.004) and aged over 30 years compared to their younger counterparts (p = 0.016). Few patients have obtained the relevant information from their physicians (25%) or pharmacists (7%). Inquiring 136 pharmacists, it was shown that the most common education was concerning vitamin B12 deficiency (62.5%) followed by fracture risk(58.09%) yet less than half (48%) of pharmacists instructed patients about the potential risk of hypomagnesemia. Almost all pharmacists (99%) agreed that there is a requirement for additional education on the possible harmful consequences of PPIs. The present study has established that a considerable proportion of PPI users in the UAE lack the necessary awareness about the potential adverse effects of PPI despite their extensive use in this country. The current pharmacist practice is inefficient for inculcating the potential harms of chronic PPI use and they are required to optimize their efforts to educate patients and bridge the knowledge gaps.

Association of Chronic Anti‐GERD Medication Usage and Cognitive Decline in a Racially Diverse Elderly Population

AbstractBackgroundIt is understood that early medical intervention of various diseases, like cardiovascular or gastroenterological, is a potential way to mitigate the progression of cognitive decline and dementia. However, some medications’ mechanisms of action (MOA), may alter the metabolism of foods and absorption of nutrients and inhibit neurotransmitters. The long‐term influence of chronic medication use on cognition in a racially‐diverse elderly population is unknown. As such, we aim to investigate how chronic use of specific Anti‐GERD medications (e.g., proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA’s), may be associated with global cognitive decline and cognitive functional domainsMethodUtilizing data collected from a long‐running, community‐based study, the Chicago Health and Aging project (CHAP) which started in 1993, we examined the association of anti‐GERD medication use and cognition in n = 7742, 1268 (16%) PPI users and 939 (12%) H2RA users, aged ≥65 years. This study sample consists of 63% African American (AA) participants and 60% female participants. Recruitment and data collection occurred in triennial cycles. Medication use was assessed through direct observation while neuro‐cognition was evaluated using a battery of 4‐standardized cognitive tests. Using linear mixed effects change‐point models, adjusted for age, sex, education and race, we investigated whether chronic anti‐GERD medication usage is associated with cognitive declineResultOf anti‐GERD medication users, after starting the medication, chronic use of PPI’s was associated with a faster rate of global cognitive decline β = ‐0.028 (p≤0.000), memory score β = ‐0.023 (p≤0.000) and speed score β = ‐0.012 (p≤0.034). H2RA’s were not associated with global cognition or memory score but were suggestive for speed score β = ‐0.011 (p≤0.057). In models stratified by race and separately, sex, after starting, chronic PPI use was associated with faster global cognitive decline in AA β = ‐0.030 (p≤0.000), White β = ‐0.026 (p≤0.001) and female β = ‐0.037 (p≤0.000) but not male individuals. H2RA’s were only associated with faster global cognitive decline in White individuals β = ‐0.025 (p≤0.039)ConclusionChronic use of PPI’s and H2RA’s may be associated with faster rates of global cognitive decline and memory &amp; speed scores in an elderly population. The associative results presented, demonstrate the need for further investigation into how medication usage potentially impacts cognition

Proton Pump Inhibitors and Cognitive Health: Review on Unraveling the Dementia Connection and Co-morbid Risks.

Dementia, an international health issue distinguished by the impairment of daily functioning due to cognitive decline, currently affects more than 55 million people worldwide, with the majority residing in low-income and middle-income countries. Globally, dementia entails significant economic burdens in 2019, amounting to a cost of 1.3 trillion US dollars. Informal caregivers devote considerable hours to providing care for those affected. Dementia imposes a greater caregiving and disability-adjusted life-year burden on women. A recent study has established a correlation between prolonged Proton Pump Inhibitor (PPI) usage and dementia, in addition to other neurodegenerative conditions. PPIs are frequently prescribed to treat peptic ulcers and GERD (gastroesophageal reflux disease) by decreasing stomach acid secretion. They alleviate acid-related symptoms through the inhibition of acid-secreting H+, K+ ATPase. In a number of observational studies, cognitive decline and dementia in the elderly have been linked to the use of PPIs. The precise mechanism underlying this relationship is unknown. These drugs might also alter the pH of brain cells, resulting in the accumulation of amyloid-beta (Aβ) peptides and the development of Alzheimer's disease (AD). Despite the compelling evidence supporting the association of PPIs with dementia, the results of studies remain inconsistent. The absence of a correlation between PPI use and cognitive decline in some studies emphasizes the need for additional research. Chronic PPI use can conceal underlying conditions, including cancer, celiac disease, vitamin B12 deficiency, and renal injury, highlighting dementia risk and the need for further investigations on cognitive health.

Gitelman-Like Syndrome Associated with Seizure Secondary to Chronic Proton Pump Inhibitor Use and Alcohol Consumption: Case Report of Undetectable Magnesium

Gitelman-Like Syndrome Associated with Seizure Secondary to Chronic Proton Pump Inhibitor Use and Alcohol Consumption: Case Report of Undetectable Magnesium

Duped by dumping syndrome: non-endemic Vibrio cholerae bacteremia in an immunocompetent host with gastric bypass surgery, a case report

Extra-intestinal infection with non-O1/non-O139 strains of Vibrio cholerae (NOVC) is rare, though bacteremia and hepatobiliary manifestations have been reported. Reduced stomach acid, or hypochlorhydria, can increase risk of V. cholerae infection. We describe a 42-year-old woman with hypochlorhydria due to untreated Helicobacter pylori infection, gastric-bypass surgery, and chronic proton pump inhibitors (PPI) exposure, who developed acute diarrhoea following raw oyster consumption. Her symptoms were attributed to rapid gastric emptying (dumping syndrome) after a negative limited stool work-up. She had persistent diarrhoea, weight loss, and after 5 months was admitted with acute cholecystitis and NOVC bacteremia, requiring cholecystectomy. This is the first reported case of NOVC bacteremia and cholecystitis in a patient with gastric bypass. This case highlights the potential for NOVC biliary carriage, the role of hypochlorhydria as a risk factor for Vibrio infection, and the importance of excluding infectious diarrhoea in patients with new onset of symptoms compatible with dumping syndrome and a relevant travel history.

Knowledge, Attitude and Practices of Resident Doctors Towards use of Proton Pump Inhibitors in A Tertiary Care Hospital in Pune, India: A Cross-Sectional Survey

Background and Objectives: The most commonly prescribed drugs in healthcare systems are proton pump inhibitors (PPIs). Several studies have found that globally PPIs are frequently used without proper justification. Appropriate and updated knowledge about PPI among medical professionals is essential to enhance the rationale of PPI application. The present study with this goal was initiated to evaluate the understanding and behavioral practices toward PPI use among resident doctors in a tertiary care teaching hospital in Pune, western India. Method: A cross sectional survey using structured questionnaire. Results: The questionnaire was completed by 137 resident doctors. 82.5% of them prescribed acid-suppressing drugs for acute gastritis and other drugs in combination with them as the most common indications for the majority of their patients. These prescriptions were based on the consultant's or unit's policy, and resident doctors were not given the liberty to breach this policy. 71.5% of the respondents chose PPIs as their first choice, and 75.1% preferred the oral route. 10.2% of them claimed to have encountered a PPI-related adverse event. Despite the fact that 75.9% of the respondents preferred to prescribe PPIs for short durations, a lack of awareness about the possible risks associated with chronic PPI use was noted. 58.4% of resident doctors preferred using the step-down strategy, but 19.7% of participants were unaware of step up or step down when prescribing PPIs. The concept of drug interactions with the co-administration of PPI was also less understood by study participants. Conclusion: In the present survey study participants had less knowledge on correct indications for PPI usage as they fared PPI over any other acid-reducing medications to majority of their patients. There was also a lack of understanding of PPI adverse drug reactions, drug-drug interactions, and specific PPI administration approaches.

Impact of proton pump inhibitors on the onset of gastrointestinal immune-related adverse events during immunotherapy.

The gut microbiota (GM) can influence the pathogenesis of immune-mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood. In this retrospective single-center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed). Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty-three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11-56.10, p < 0.000). This HR was confirmed after weighting for the propensity score (HR15.13 95% CI 3.22-71.03, p < 0.000). Chronic PPI use is associated with an increased risk of GI irAES.

An Emulated Clinical Trial of Deprescribing Proton Pump Inhibitors in Patients With Cirrhosis.

Proton pump inhibitors (PPI) are overused and carry harms in cirrhosis. Deprescribing is advocated but has not been trialed. We emulated a clinical trial using Medicare data. All patients were receiving chronic PPI therapy before a compensated cirrhosis diagnosis. We compared the risk death/decompensation over 3 years between continuous users and deprescribers. We find that PPI deprescription is associated with less ascites and that cumulative PPI use is associated with more ascites and encephalopathy. Ultimately, 71% of deprescribers restart PPIs. PPI deprescribing has benefits but requires ongoing support and alternative therapies for gastrointestinal symptoms.

The Effect of Proton Pump Inhibitor Use on Survival of Patients With Colorectal Cancer: A Study of a Racially Diverse Population.

Introduction Proton pump inhibitor (PPI) use is increasing in the general population. Chronic PPI use can lead to hypergastrinemia, which has been purported to increase the risk of developing colorectal cancer (CRC). Several studies have failed to report any association between PPI use and the risk of CRC. However, little is known about the effect of PPI use on CRC survival. In this retrospective analysis, we studied the effect of PPI use on CRC survival in a racially diverse population. Methods Data were abstracted for 1050 consecutive patients diagnosed with CRC from January 2007 to December 2020. The Kaplan-Meier curve was created to study the effect of PPI exposure compared to no exposure on overall survival (OS). Univariate and multivariate analyses were performed to investigate predictors of survival. Results Complete data were available for 750 patients with CRC, 52.5% were males, 22.7% were Whites, 60.1% were Asians, and 17.2% were Pacific Islanders. A total of 25.6% of patients had a history of PPI use. Moreover, 79.2% had hypertension, 68.8% had hyperlipidemia, 38.0% had diabetes mellitus, and 30.2% had kidney disease. There was no difference in median OS among PPI users compared to non-users, p value=0.4. Age, grade, and stage were predictors of inferior OS. No significant association was noticed with gender, race, comorbidities, or treatment with chemotherapy. Conclusion In this retrospective analysis of a racially diverse population of CRC patients, we found that PPI use was not associated with worse OS. Until high-quality prospective data are available, physicians should not stop PPIs that are clinically indicated.

Effect of Long-Term Proton Pump Inhibitor Use on Blood Vitamins and Minerals: A Primary Care Setting Study.

Long-term proton pump inhibitor (PPI) use is frequently encountered in primary care. Its effect on micronutrient absorption is known, as vitamin B12, calcium or vitamin D insufficiency may occur in such patients. We recruited patients using a PPI (pantoprazole) for >12 months. The control group was represented by subjects attending the general practitioner not taking any PPI in the last 12 months. We excluded subjects using nutritional supplements or with diseases interfering with micronutrient blood levels. All subjects underwent blood sampling with full blood count, iron, ferritin, vitamin D, calcium, sodium, potassium, phosphate, zinc and folate. We recruited 66 subjects: 30 in the PPI group and 36 in the control group. Long-term pantoprazole users had lower red blood cell count but similar hemoglobin. We did not find any significant difference in blood iron, ferritin, vitamin B12 and folate. Vitamin D deficit was observed more frequently in the PPI group (100%) than in controls (30%, p < 0.001), with blood levels lower in pantoprazole consumers. No differences in calcium, sodium and magnesium were observed. Pantoprazole users had lower phosphate levels than controls. Finally, a non-significant trend for zinc deficiency was found in PPI users. Our study confirms that chronic PPI users may encounter alterations in some micronutrients involved in bone mineral homeostasis. The effect on zinc levels deserves further investigation.

Assessment of small intestinal bacterial overgrowth and methane production in patients on chronic proton-pump inhibitor treatment: prevalence and role of rifaximin in its management in primary care.

Although proton pump inhibitor (PPI) drugs have considered able to induce small intestinal bacterial overgrowth (SIBO), no data are so far available from primary care (PC). We assessed the prevalence of SIBO and methane (CH<inf>4</inf>) production consequent to chronic PPI therapy using Lactulose Breath Test (LBT). Secondary aim was to explore the possible role of rifaximin in treating PPI-induced SIBO patients. One hundred twenty-five gastroesophageal reflux disease patients, constantly treated with PPI for at least 6 months and undergoing to LBT, were retrospectively assessed. An age-matched control population (control) of 100 patients, which had not used PPI in the last 6 months, was also enrolled. In the PPI group, SIBO positive patients and CH<inf>4</inf> producers were treated with rifaximin 1200 mg/daily for 14 days and re-checked with LBT one month after the end of treatment. The area under the curve (AUC) before and after treatment was also calculated for both SIBO positive patients and CH<inf>4</inf> producers. In the PPI group, SIBO prevalence was significantly higher vs. controls (38/125 [30.4%] vs. 27/100 [27%], P<0.05). 77/125 (61.6%) PPI patients were found to be CH<inf>4</inf> producers vs. 21/100 (21%) controls (P<0.05). Among SIBO patients in the PPI group, 34 (89.4%) were also CH<inf>4</inf> producers vs. 17/27 (63%) controls (P<0.05). After treatment, LBT resulted negative in 15/22 SIBO patients (68.1%) (P<0.05) and in 18/34 CH<inf>4</inf> producers (52.9%) (P<0.05). At the AUC analysis, an overall reduction of 54.2% for H<inf>2</inf> in SIBO patients and of 47.7% for CH<inf>4</inf> was assessed after rifaximin treatment (P<0.05). Our data showed that chronic use of PPI could be able to increase the prevalence of SIBO and to shift the intestinal microbial composition towards a CH4-producing flora. rifaximin could represent a useful therapeutical option for PPI-induced SIBO and for modulating CH4-producing flora.

Current management of gastro-oesophageal reflux disease-treatment costs, safety profile, and effectiveness: a narrative review.

The purpose of this study was to review the current management of gastro-oesophageal reflux disease (GORD), including treatment costs, safety profile and effectiveness. A literature review was performed of randomized-controlled trials, systematic reviews, Cochrane reports and National/Societal guidelines of the medical, endoscopic and surgical management of GORD. Proton pump inhibitor (PPI) prescribing patterns and expenditure were reviewed in different countries, including Australia, Canada, New Zealand, UK and USA. Proton pump inhibitors (PPIs) are primarily indicated for control of GORD, Helicobacter pylori eradication (combined with antibiotics), preventing NSAID-induced gastrointestinal bleeding and treating peptic ulcer disease. There is widespread overprescribing of PPIs in Western and Eastern nations in terms of indication and duration, with substantial expense for national health providers. Despite a favourable short-term safety profile, there are observational associations of adverse effects with long-term PPIs. These include nutrient malabsorption, enteric infections and cardiovascular events. The prevalence of PPI use makes their long-term safety profile clinically relevant. Cost-benefit, symptom control and quality-of-life outcomes favour laparoscopic fundoplication rather than chronic PPI treatment. Laparoscopic fundoplication in long-term management of PPI-responsive GORD is supported by SAGES, NICE and ACG, and PPI-refractory GORD by AGA and SAGES guidelines. The importance of establishing a definitive diagnosis prior to invasive management is emphasized, especially in PPI-refractory heartburn. We examined evidence-based guidelines for PPI prescribing and deprescribing in primary care and hospital settings and the need for PPI stewardship and education of health professionals. This narrative review presents the advantages and disadvantages of surgical, endoscopic and medical management of GORD, which may assist in shared decision making and treatment choice in individual patients.This paper was presented (GS020) at the 88th RACS Annual Scientific Conference, 6-10 May, 2019.

Use of proton pump inhibitor may be associated with progression of cerebral small vessel disease.

Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases. However, recent studies have shown that chronic PPI use is associated with the progression of endothelial senescence and cerebrovascular diseases. We hypothesized that PPI users might be vulnerable to fast progression of cerebral small vessel disease (SVD) with cumulative effects. Four hundred and eleven patients, who underwent brain magnetic resonance imaging, more than twice between January 2010 and December 2016 were screened. Patients aged < 50 years, and those who had concomitant diseases that might affect the progression of cerebral SVD were excluded. Baseline characteristics were collected. We evaluated the severity of SVD using the Fazekas score, the number of cerebral microbleeds (CMBs), and assessed the progression of SVD or CMBs based on the cumulative dose of PPIs. Among the included patients (N = 137), 39 were PPI ever-users. Univariate Cox regression analysis showed that PPI use was independently associated with the progression of Fazekas score only in the deep white matter hyperintensities (WMH) (hazard ratio [HR] 2.891, 95% confidence interval [CI] 1.210-6.906, P = 0.017). In multivariate Cox regression analysis, long-term PPI use was associated with a progression of Fazekas score in the deep WMH (HR 3.453, 95% CI 1.027-9.475, P = 0.045). However, PPI use was not associated with the progression of CMB. The present study results suggest that long-term use of PPIs is associated with the progression of deep cerebral WMH. Further research is needed using a large number of patients to validate this relationship.

Prevalence, Clinical Characteristics, and Treatment Response in Patients with Post Cricoid Inlet Patch—A Descriptive Retrospective Study

Abstract Objectives The aim of this study was to determine the incidence of post cricoid inlet patch (PC-IP) and to assess the clinical characteristics, pathological features, and treatment response. Materials and Methods A retrospective cross-sectional study was conducted from April 2016 to April 2021 in the tertiary gastroenterology unit of urban India. All patients with symptoms of globus sensation, chronic cough, heartburn, hoarseness, throat pain, dysphagia, and acid regurgitation after a thorough clinical examination underwent esophagogastroduodenoscopy by experienced endoscopists including biopsy. Sociodemographic data, symptoms and its duration, previous hospital visits, and chronic proton pump inhibitor (PPI) use were noted during the study. Results Three-thousand two-hundred fifty upper gastrointestinal endoscopies were performed during the study period. The prevalence of PC-IP was 2.7%, comprising 36.3% males and rest females. Mean age was 36.2 ± 17years. The most common symptom among these patients was globus sensation (81.8%) followed by acid regurgitation (75%), dyspepsia (64.7%), dysphagia (48.8%), throat pain (29.54%), chronic cough (22.72%), hoarseness (22.72%), and others (6.81%). Mean diameter of PC-IP was 1.5 ± 0.5 cm, more than one patch was found in 23.76% of patients. Histopathological examination showed heterotrophic gastric mucosa in 77.27%, out of which 38.23% had oxyntic type, 44.11% had mucoid type, and the rest had mixed cell type. On median follow-up after 20 months, 68.18% of patient had persistent symptoms, 77.27% were PPI responsive, and 22.73% were PPI refractory. On follow-up, 38.63% of patients had a repeat endoscopic procedure and biopsy (20.45%); none showed any changes in size or dysplasia. Conclusion Prevalence of PC-IP could be higher than the estimated. Careful examination of upper esophagus and use of narrow band imaging will increase the possibility of identifying IP. Those symptomatic patients need treatment with PPI, sometimes for long term. Ablative therapy with radiofrequency or argon plasma coagulation needs further clarification.