Prolonged Proton Pump Inhibitor Research Articles

The impact of proton pump inhibitors on brain health based on cross-sectional findings from the Rhineland Study

Reports linking proton pump inhibitors (PPIs) with cognition and dementia show conflicting results, with limited evidence on underlying biological mechanisms. However, existing studies did not investigate brain microstructure, which could provide valuable insights into early structural changes indicative of cognitive decline. Analyses were based on cross-sectional baseline data from the Rhineland Study (n = 7,465; mean age 55.3 ± 13.7 years, range 30–95 years, 56.5% women). Using multivariate linear regression, we investigated associations between PPI use and cognition and brain macro- and microstructural measures (fractional anisotropy (FA) and mean diffusivity (MD) as measures of white matter integrity). Analyses were stratified by short-term (< 3 years) and long-term (≥ 3 years) PPI use, with additional age stratification (< 65 years; ≥65 years) for cognitive outcomes. PPI users, especially younger individuals, showed poorer global cognition and working memory. Notably, younger long-term users had worse total memory. PPI use was not associated with brain volume or FA, but both short-term and long-term users showed higher MD in cognitive-related brain regions. Our findings indicate that prolonged PPI use, particularly in younger long-term users, is associated with poorer cognitive performance. Moreover, PPI users showed higher MD, indicating potential white matter integrity disruptions. Further research is needed to ascertain causality and underlying mechanisms behind PPI-related cognitive decline.

Efficacy of Bismuth Quadruple Therapy in the Treatment of Helicobacter pylori-Infected Peptic Ulcer Children in Vietnam.

The continuous increase in drug-resistant strains, the lack of novel antibiotics, and the fewer options available to combat antibiotic-resistant infections in pediatrics pose significant challenges to the eradication of Helicobacter pylori (H. pylori) in children. This study evaluated the efficacy of first-line therapy with bismuth quadruple therapy in H. pylori-positive pediatric patients with peptic ulcers. 136 patients (aged between 8 and 17 years) diagnosed with active peptic ulcers with H. pylori infection were enrolled in this study. Patients with H. pylori strain sensitive to tetracycline and metronidazole were assigned to bismuth quadruple therapy, including a proton pump inhibitor (PPI), bismuth, tetracycline, and metronidazole. Antibiotic resistance of H. pylori was analyzed by the Epsilometer test. Treatment efficacy was evaluated at 12 weeks based on H. pylori eradication and peptic ulcer healing rates. H. pylori infection status was evaluated by a 13C-urea breath test. Most isolates showed extremely high rates of resistance to commonly prescribed antibiotics used for children, including clarithromycin (97.0%) and amoxicillin (84.6%), while the low rate of resistance to levofloxacin (16.2%). The overall success rate of eradication therapy in the intention-to-treat and the per-protocol group were 86.0% and 89.3%, respectively. Peptic ulcer healing rates for total patients at 6 weeks and 12 weeks were 75.0% and 97.7%, respectively. There were no entail unpleasant adverse events, and peptic ulcer symptoms decreased steadily over time in all cases. The bismuth quadruple therapy with a 2-week PPI pretreatment and followed by prolonged PPI was highly successful in eradicating H. pylori infection and healing ulcers in pediatric patients with active peptic ulcer. This might be preferable as a first-line empiric treatment regimen for H. pylori-positive pediatric patients with peptic ulcers, especially in populations with high rates of resistance to amoxicillin and clarithromycin.

Effects of Prolonged Proton-Pump Inhibitor Use on Renal Dysfunction and Bone Fragility: A Retrospective Study.

Proton-pump inhibitor (PPI) use for management of gastroesophageal reflux disease (GERD) consists of a short-duration trial, according to guidelines. Long-term usage is appropriate under certain indications. Literature has increasingly documented an adverse effect profile of PPIs, including kidney disease and bone fragility. To investigate the rate of occurrence of osteopenia, osteoporosis, and chronic kidney disease (CKD) in patients using PPI therapy for longer than the recommended trial period of 8 weeks. Retrospective cohort analysis of a single-site primary care clinic. Patients aged 18 to 65 years with PPI prescriptions longer than 8 weeks were included. Information regarding PPI prescriptions, demographics, and medical diagnoses was collected. The search discovered 293 PPI-users and 1908 never-PPI-users. Demographics varied, with a P-value <0.05 in age, body mass index (BMI), and black population (higher in PPI group). The PPI cohort featured higher rates of osteoporosis/osteopenia and CKD (P < 0.001). The odds ratios (ORs) of diagnosis with PPI use was 2.91 (95% CI = [1.692, 4.979]) in osteoporosis/osteopenia. The OR was 1.14 (95% CI = [1.141, 2.229]) in CKD and PPI use but higher with diabetes, elevated BMI, black race, and male gender. We observed increased occurrence rates of osteoporosis, or osteopenia, and CKD in patients with prolonged PPI use. Demographics varied in age, BMI, and black race proportion. A logistic regression revealed increased likelihood of kidney disease and osteoporosis/osteopenia in association with PPI use. These results add to the evidence regarding long-term PPI use and the development of these conditions, but additional studies are needed.

Proton Pump Inhibitors. Investigating Their Role in Small Intestinal Bacterial Overgrowth

Proton pump inhibitors (PPIs) are widely used medications known for their effectiveness in reducing gastric acid production and their overall safety profile. Despite being valued for these properties, concerns have been raised regarding potential adverse effects associated with their long-term use. Various studies indicate a higher prevalence of small intestinal bacterial overgrowth (SIBO) in patients on prolonged PPI therapy, with symptoms ranging from bloating and diarrhea to malabsorption and nutrient deficiencies. Diagnosing SIBO primarily involves non-invasive breath tests that measure hydrogen and methane levels produced by bacterial fermentation after ingesting a carbohydrate substrate, such as lactulose or glucose. Direct aspiration and culture of small intestinal fluid offer a more definitive diagnosis but are invasive and less commonly performed. Treatment of SIBO focuses on reducing bacterial overgrowth by using antibiotics.This review aims to inform clinicians about the possible risks of PPI therapy and the importance of suspecting SIBO in patients with nonspecific gastrointestinal symptoms.

Compared to histamine-2 receptor antagonist, proton pump inhibitor induces stronger oral-to-gut microbial transmission and gut microbiome alterations: a randomised controlled trial

ObjectiveWe aim to compare the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the gut microbiota through longitudinal analysis.DesignHealthy volunteers were randomly assigned to receive either...

Bone mineral changes in young adult females on short-term proton pump inhibitor: A retrospective cohort study

Background/Aim: Proton pump inhibitors (PPIs), despite being the most prescribed medications today, have generated controversy due to their potential impact on bone metabolism. Numerous studies have emphasized the potential of prolonged PPI use to reduce bone mineral density, thereby increasing the risk of bone fractures among elderly and young individuals. However, the precise impact of PPI usage for 1 year or less on bone mineral density in young adults remains incompletely understood. Method: In this retrospective cohort study, we conducted a comprehensive review of all dual x-ray bone densitometric examinations conducted on females under 40 years old at our tertiary care center between 2010 and 2014. Among the initial 685 patients assessed, 117 samples met the predefined inclusion criteria and were consequently enrolled in the study. Subsequently, the enrolled cases were categorized into three distinct groups: Group 1 (n=46), which received PPI treatment for less than six months; Group 2 (n=31), which received PPIs for a duration ranging from 6 to 12 months; and Group 3 (n=40), comprising individuals with no history of PPI use, thus serving as the control group. Comprehensive baseline descriptive data, encompassing bone mineral density, t-scores, and z-scores, were meticulously compared among the three groups mentioned above. Results: The overall mean age of the study population was 32.84 (5.27) years, with an age range spanning from 20 to 40 years. No statistically significant differences in age were discerned among the three groups. Similarly, the groups exhibited no significant body mass index (BMI) variations. Noteworthy findings emerged after examining the effects of PPI usage on bone mineral density, z-scores, and t-scores across the three groups. Specifically, the data suggested that PPIs might influence t-scores (Group 1: -0.48 (0.77); Group 2: -1.25 (0.86); Group 3: -0.33 (0.78)), yielding an F-value of 13.28 for (2.116), signifying statistical significance at P&lt;0.001. Moreover, the observed mean square error (MSE) was 64, while the effect size (eta²) was 0.19. Subsequent post-hoc Tukey tests indicated a significant distinction in the T-score of Group 2 compared to the other two groups. Furthermore, the analysis of z-scores (Group 1: 0.46 (0.79); Group 2: -1.27 (0.76); Group 3: -0.35 (0.86)) revealed a similar trend, with an F-value of 13.21 for (2.116) and a P-value below 0.001. The corresponding MSE was 0.65, and the eta² stood at 0.19. Additional post-hoc Tukey tests indicated that the Z-score of Group 2 significantly diverged from the other groups. However, it is noteworthy that both t and z-scores for Group 1 and Group 3 did not exhibit statistically significant differences. Conclusion: Prolonged use of PPIs for durations surpassing 6 months may potentially reduce bone mineral density among young adults. Nevertheless, this observed impact does not attain clinically significant levels of osteopenia. Conversely, using PPIs for periods under 6 months did not significantly affect bone mineral density.

Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence.

Background: Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. Methods: First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. Results: Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. Conclusions: Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.

Safety of Proton Pump Inhibitors in Pediatric Population: A Systematic Review.

Objective. Commonly recommended drugs for adults and children include proton pump inhibitors (PPIs), proven effective for treating peptic diseases like stomach ulcers, GERD, and Helicobacter pylori infections in children over 1-year-old. Yet, prolonged PPI use carries higher risks of adverse reactions, prompting this study's analysis. Methods. We have performed a systematic review of 30 articles, which include a total of 762 505 pediatric patients. Results. Adverse effects were encountered in 6.98% of the population. The 5 most common adverse effects were respiratory tract complications, gastrointestinal complications, urinary tract infections, asthma, and ENT infections. Conclusion. Hence, PPIs should be prescribed only when necessary, and physicians should prioritize patient education when considering their use.

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.

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.

Proton pump inhibitor (PPI) administration and Clostridioides difficile infection - is this a real clinical problem? A critical review of the literature

Background: Proton pump inhibitors (PPIs) are widely used drugs that reduce gastric acid secretion. In recent years, there has been a gradual increase in their use. The safety of prolonged PPI therapy and the potential for cumulative side effects of these drugs raise legitimate concerns. An association between PPI administration and the risk of Clostridioides difficile infection has been suggested. The findings regarding this phenomenon require further unequivocal verification.&#x0D; Material and methods: A review of publications obtained from the PubMed database and published between 2016-2023. Based on the keywords "proton pump inhibitor", "PPI" and "Clostridium", 132 articles were selected. Finally, 6 meta-analyses were included in the analysis.&#x0D; Results: Studies conducted in recent years have shown a statistically significant increase in the risk of C. difficile infection in patients taking PPIs compared to those who avoid this therapy. The aforementioned relationship was observed in both adults and pediatric patients. One study proved that the risk remained high even up to 1 year after the end of treatment. The described relationship is still a matter of debate due to the fact that patients using antacids are usually elderly, have several comorbidities and a higher risk of developing C. difficile infection regardless of PPI use.&#x0D; Conclusions: The relationship between the use of PPIs and the risk of developing C. difficile infection is still controversial, which justifies the need for continued clinical trials to objectively resolve this issue. PPIs exert high efficacy in the treatment of acid-dependent diseases, but due to the many ambiguities surrounding possible side effects, caution in their administration seems warranted, especially for long-term therapy in elderly patients with polypharmacy.

Intestinal metaplasia in follow-up endoscopies among Asian patients with short-segment Barrett's esophagus: Regression, sampling error, and associated factors

The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors. Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin-eosin staining. Only patients with negative hematoxylin-eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error. Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25. In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25.

The association between duration of and indications for proton pump inhibitor use and risk of gastric polyps.

The development of fundic gland polyps (FGPs) is the most common side effect of long-term proton pump inhibitor (PPI) use; however, the effect of drug use characteristics and their impact on the risk of other gastric polyp development remain unclear. We aimed to identify the influence of PPI administration, as well as its duration and dose, in the development of gastric polyps. A prospective cohort study was conducted on consecutive patients who underwent gastroscopy between September 2017 and August 2019. Detailed characteristics of gastric polyps, Helicobacter pylori infection, and PPI use were analyzed. Among the 2723 patients included, gastric polyps (75% FGPs, 22% hyperplastic) were detected in 16.4%, and 60% were prescribed PPI. The risk of FGPs and hyperplastic polyps according to the duration of PPI use were as follows: 2-5 years [odds ratio (95% confidence interval); 2.86 (2.00-4.11) and 2.82 (1.69-4.78)]; 6-9 years [7.42 (5.03-11.01) and 2.32 (1.05-4.78)]; ≥10 years [14.94 (10.36-21.80) and 3.52 (1.67-7.03)]. Multivariate analysis confirmed that the risk of FGPs was 17.16 (11.35-26.23) for ≥10 years of PPI use. Portal hypertension-related conditions were associated with hyperplastic polyps [4.99 (2.71-9.20)]. Duration of and indications for PPI use are the most predictive factors for the development of gastric polyps. Prolonged PPI use increases the risk of polyp development and the number of patients with polyps, which may burden endoscopic practice. Highly selected patients may require particular care despite minimal risk of dysplasia and bleeding generally.

Effects of prolonged proton pump inhibitor treatment on nutritional status and respiratory infection risk in cystic fibrosis: A matched cohort study.

Evidence on the effectiveness of proton pump inhibitors (PPI) as adjuvant therapy to improve maldigestion in people with cystic fibrosis (pwCF) is limited and there is increasing concern on possible side effects. We conducted a matched cohort study based on paediatric and adult pwCF who received PPI for ≥3 months. Treated patients were matched to a group of patients who never received PPI using a nearest neighbour propensity score matching based on sex, year of birth, CFTR genotype and pancreatic insufficiency. The study included 160 pwCF: 80 treated and 80 untreated patients. Over a median follow-up of 2 years, no significant differences in changes in BMI z-score were detected between groups (adjusted mean difference: 0.06, 95% CI: -0.17-0.30). At baseline 25% (n=20) of the treated patients and 22.5% (n=18) of the untreated patients had a positive culture for P. aeruginosa (Pa). At follow-up percentages of Pa positive cultures increased to 47.5% (n=38) in the treated group and to 26.3% (n=21) in the untreated group (adjusted mean difference: 23.1%, 95% CI: 10.8-35.3). Prolonged PPI therapy should be used cautiously in pwCF since it may increase the risk of respiratory infection by Pa. In addition, such treatment does not seem to improve nutritional status.

Applicability of tools to identify potentially inappropriate prescribing in elderly during medication review: Comparison of STOPP/START version 2, Beers 2019, EU(7)-PIM list, PRISCUS list, and Amsterdam tool-A pilot study.

Potentially inappropriate prescribing (PIP) is one of the major risk factors of adverse drug events in elderly patients. Pharmacotherapy assessment criteria may help reduce the instances of PIP among geriatric patients. This study aimed to verify the applicability of selected tools designed to assess prescribing appropriateness in elderly and to identify PIP in the study population. Based on pharmacist-led medication reviews that were performed among patients attending senior day-care centers based in Poland, aged 65 years and over, the following tools were applied for assessing the appropriateness of pharmacotherapy: PILA (patient-in-focus listing approach): STOPP/START v.2 and Amsterdam tool, DOLA (drug-oriented listing approach): PRISCUS list, and DOLA+: Beers criteria v.2019 and the EU(7)-PIM list–the criteria oriented on medications requiring indications. Fifty patients participated in the study. The prevalence of prescribing issues in the study population was very high and ranged from 28% to 100%, depending on the criteria applied. The highest number of PIP cases was identified based on the PILA criteria: STOPP/START v.2 (171, a mean of 3.4 PIP cases per patient), and the Amsterdam criteria (124, a mean of 2.5 PIP cases per patient). The lack of protective vaccinations against pneumococci identified using the START criterion was found to be the most common PIP (identified in 96% of the patients). Proton-pump inhibitors (PPIs) were identified as the most problematic group of medications. The STOPP, EU(7)-PIM and Beers criteria revealed cases of inappropriate prolonged PPI use, whereas the Amsterdam tool identified cases where PPIs should have been prescribed but were not. The highest number of PIP cases in the study population were identified with the PILA tools, and on this basis the most comprehensive assessment of pharmacotherapy appropriateness in geriatric patients was conducted. Further studies should be designed, covering a larger group of patients across different healthcare settings (inpatient and outpatient), with access to comprehensive patient data.

Ticagrelor monotherapy after coronary stenting in patients requiring proton pump inhibitor and prolonged antiplatelet therapy.

Key Points Approximately half of patients undergoing coronary stenting are discharged on a proton‐pump inhibitor (PPI). Post‐hoc analysis of the large GLOBAL LEADERs trial finds PPI treatment and aspirin monotherapy after a year of dual antiplatelet therapy (DAPT) is associated with increased risk of ischemic events. In contrast, PPI treatment and continued ticagrelor monotherapy are not associated with increased ischemic events in the second year after stenting. This observational evidence suggests the GLOBAL LEADERS tested ticagrelor monotherapy regimen could be considered in patients requiring both prolonged antiplatelet therapy (&gt;12 months) and PPI for increased bleeding risk.

The Inappropriate Use of Proton Pump Inhibitors: An Internal Medicine Residency Clinics Effort to Deprescribe

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications, and are often prescribed for unnecessarily extended courses. A variety of adverse outcomes have been attributed to prolonged PPI use. Outpatient deprescribing strategies aimed at decreasing the burden of these adverse effects have been infrequently described

Risk Factors Associated With Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Positive Cultures in a Cohort of US Veterans.

Carbapenem-resistant Enterobacteriaceae (CRE) cause approximately 13 100 infections, with an 8% mortality rate in the United States annually. Carbapenemase-producing CRE (CP-CRE) a subset of CRE infections infections have much higher mortality rates (40%-50%). There has been little research on characteristics unique to CP-CRE. The goal of the current study was to assess differences between US veterans with non-CP-CRE and those with CP-CRE cultures. A retrospective cohort of veterans with CRE cultures from 2013-2018 and their demographic, medical, and facility level covariates were collected. Clustered multiple logistic regression models were used to assess independent factors associated with CP-CRE. The study included 3096 unique patients with cultures positive for either non-CP-CRE or CP-CRE. Being African American (odds ratio, 1.44 [95% confidence interval, 1.15-1.80]), diagnosis in 2017 (3.11 [2.13-4.54]) or 2018 (3.93 [2.64-5.84]), congestive heart failure (1.35 [1.11-1.64]), and gastroesophageal reflux disease (1.39 [1.03-1.87]) were associated with CP-CRE cultures. There was no known antibiotic exposure in the previous year for 752 patients (24.3% of the included patients). Those with no known antibiotic exposure had increased frequency of prolonged proton pump inhibitor use (17.3%) compared to those with known antibiotic exposure (5.6%). Among a cohort of patients with CRE, African Americans, patients with congestive heart failure, and those with gastroesophageal reflux disease had greater odds of having a CP-CRE culture. Roughly 1 in 4 patients with CP-CRE had no known antibiotic exposure in the year before their positive culture.

The Risk of Epilepsy after Long-term Proton Pump Inhibitor Therapy

BackgroundPrescription-event monitoring studies have reported incident epilepsy or seizures in proton pump inhibitor (PPI) recipients. We examined the risk of epilepsy after prolonged PPI exposure and determine what age group was at higher risk of epilepsy. MethodsWe performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000). PPI users with subsequent epilepsy were selected as the case cohort. Controls were PPI users without subsequent epilepsy, matched for age, sex, PPI use indication, enrollment time, end point time, follow-up period, overall systemic health, and comorbidities. The total dose of PPI was defined as the cumulative defined daily dose (cDDD). Prolonged PPI use was defined as a cDDD > 365. A logistic regression analysis was performed. Population attributable risk was calculated. ResultsEpilepsy occurred 4.13 years after the initiation of PPI use. PPI users with the highest risk of incident epilepsy received a cDDD > 365 [odds ratio = 1.63, 95% confidence interval = 1.37–1.95], followed by 121–365 cDDD (1.33, 1.18–1.51) and 31–120 cDDD (1.15, 1.02–1.29), compared to those receiving a cDDD ≤ 30, after adjusting for potential confounders. Prolonged PPI use increased the risk of epilepsy in all age groups, and the risk was highest for those older than 80 years (3.11, 1.67–5.79). The population attributable risk was 12.2% (> 365 cDDD vs ≤ 30 cDDD). DiscussionProlonged PPI therapy was associated with an increased risk of epilepsy, particularly in the elderly population.

Gastric Perforation due to Candida Infection in Association with Prolonged Proton Pump Inhibitor Use: A Report of Two Cases

Fungus as a cause of gastric perforation is very rare. Very low pH of stomach usually does not support fungal growth. It is usually associated with immunocompromised state or is seen in debilitated patients like patients receiving steroid therapy, patients with Diabetes Mellitus (DM) and Human Immunodeficiency Virus (HIV) infection, patients undergoing transplant. Prolonged use of strong antacids can also be a predisposing factor for gastric fungal infection; although this theory is controversial, authors could find few studies which were similar to present study. Here, authors are reporting two cases of gastric perforation leading to peritonitis, in otherwise healthy individuals due to prolonged Proton Pump Inhibitors (PPIs) use, due to Candida infection, in the following case report. Both patients (48-year-old male and 65-year-old female) had history of chronic PPI use, had gastric perforation and underwent exploratory laparotomy. On histopathological examination of perforation edge biopsy yeast forms and few pseudohyphae of Candida species were identified. Postoperatively one of the patients survived with systemic antifungal, antibiotic therapy along with replacement of PPI with histamine H2 receptor blockers. The other patient could not survive and died postoperatively due to septicaemia. Fungal aetiology in gastric perforation should prompt further evaluation to look for underlying cause. This case report highlights the effects of unjust and over use of strong antacids for prolonged period.