Long-term Proton Pump Inhibitor Therapy Research Articles

Long-term proton pump inhibitors therapy and prevalence of hyperprolactinemia. a cross-sectional study in outpatient gastroenterology clinics

Objective: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. Method: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. And comprised patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for >3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. Results: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinemia and 70(42%) with hypreprolactinemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Pateints having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinemia. Conclusion: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management. Key Words: Proton pump inhibitors, Long-term therapy, Hyperprolactinemia, Omeprazole, Prolactin.

Inappropriate Use of Proton Pump Inhibitor Among Elderly Patients in British Columbia: What are the Long-term Adverse Events?

Proton pump inhibitors (PPIs) are one of the most used classes of drugs. For most indications, PPIs are only recommended up to 8 weeks duration. However, PPI use continues to expand. Regular and prolonged use of PPIs should be avoided because of the risk of adverse events. The main objective of this study was to (1) investigate the extent of PPI usage in people aged 65 or older in the province of British Columbia (BC), Canada, (2) provide an overview of the harms associated with the long-term use of PPIs. We examined utilization trends of the PPIs in BC since the year 2009 using PharmaNet, BC's medication dispensing database where the information is accessible to community pharmacists. We performed a comprehensive literature search for relevant reviews reporting harms associated with long-term use of PPIs. A search was conducted from January 2014 to June 2022. Between 2000 and 2018 BC's population grew by 20%, but the use of PPIs escalated to 257%. Of these older British Columbians, 62% had a cumulative exposure exceeding 2 years and 42% exceeded 5 years. This is alarming because the recommended treatment duration is 4-12 weeks for common indications including reflux esophagitis, and duodenal and gastric ulcers. Only 13.5% were dispensed PPIs for 90 days or less. Patients on long-term PPI therapy should be reassessed. Adverse events of PPI use are common among older adults. We identified over 217 systematic reviews published during the last 8 years of specific harms associated with long-term daily usage of PPIs. These harms include increased risks of death, cardiovascular disease, acute renal injury, chronic kidney disease, dementia, fractures, hypomagnesemia, iron deficiency, vitamin B12 deficiency, enteric infection (including C. difficile), pneumonia, and neoplasia (gastric cancer, carcinoids, and colon cancer), and drug interactions. This study revealed a high prevalence of PPI use among elderly populations in BC, Canada. The overutilization of PPIs is often a result of failure to re-evaluate the need for continuation of therapy. Published studies identified signals of serious harm from long-term PPI exposure. Healthcare providers with patients can reverse the relentless expansion of long-term PPI exposure by discussing the expected benefits and potential harms.

Лекарственная безопасность: в фокусе – долгосрочная терапия ингибиторами протонной помпы. Возможные побочные эффекты

Proton pump inhibitors (PPIs) are the most effective drugs for the treatment of acid-related diseases. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines note that when prescribing PPIs in large doses for a long period, the possibility of side effects should be taken into account. In a clinical context, a reasonable definition of long-term PPI use would be PPI use for more than 8 weeks in patients with symptoms of gastroesophageal reflux disease and more than 4 weeks in patients with peptic ulcers or functional dyspepsia. There are no reviews in the domestic literature on the safety of PPIs during long-term use. In this regard, a search was conducted in the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to November 15, 2023, which showed that long-term use of PPIs is associated with the possible development of numerous side effects. The first publication examined the possible side effects of long-term use of PPIs: the development of infections, an increased risk of fractures and kidney pathology. This review examines the most possible side effects associated with long-term PPI therapy: the development of cancer and electrolyte disturbances. If there are indications for long-term use of PPIs in accordance with clinical guidelines (Barrett's esophagus, erosive esophagitis C/D and a number of others), oncological vigilance should be exercised and monitoring aimed at identifying electrolyte disturbances should be carried out.

Лекарственная безопасность: в фокусе долгосрочная терапия ингибиторами протонной помпы. Вероятные побочные эффекты

Currently, an important component of rational pharmacotherapy is drug safety. Proton pump inhibitors (PPIs) are the most effective drugs for the treatment of acid-related diseases. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines note that when prescribing PPIs in large doses for a long period, the possibility of side effects should be taken into account. In recent years, a number of foreign reviews have been published that examine the connections between PPIs and a number of diseases/conditions, but in the domestic literature there are no reviews on the safety of PPIs during long-term use. A search was conducted in the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to November 15, 2023. However, long-term use of PPIs is associated with numerous side effects, and it is not possible to discuss all of them in detail in one review. This review examines the most likely side effects associated with long-term PPI therapy: the development of infections, increased risk of fractures and kidney pathology. The association of long-term use of PPIs with the development of these side effects is not denied or questioned in recent reviews.

Proton pump inhibitors and chronic kidney disease risk: a comparative study with histamine-2 receptor antagonists

This observational study explored the association between proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use and the risk of chronic kidney disease (CKD). Using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) and six-hospital electronic health record (EHR) databases, CKD incidence was analyzed among PPI and H2RA users. Propensity score matching was used to balance baseline characteristics, with 1,869 subjects each in the PPI and H2RA groups from the NHIS-NSC, and 5,967 in EHR databases. CKD incidence was similar for both groups (5.72/1000 person-years vs. 7.57/1000 person-years; HR = 0.68; 95% CI, 0.35–1.30). A meta-analysis of the EHR databases showed no significant increased CKD risk associated with PPI use (HR = 1.03, 95% CI: 0.87–1.23). These results suggest PPI use may not increase CKD risk compared to H2RA use, but the potential role of PPI-induced CKD needs further research. Clinicians should consider this when prescribing long-term PPI therapy.

CYP2C19 genotypes and osteoporotic fractures in long-term users of proton pump inhibitors: A hospital-based study.

Proton pump inhibitors (PPIs) are commonly prescribed medications. The existing data suggest that individuals at a high risk of fractures have been exposed to high doses of PPIs for prolonged durations. CYP2C19 plays a pivotal role in metabolism of PPIs and thereby influences their pharmacokinetic profile. Hence, we hypothesize that CYP2C19 genotypes may be associated with fragility fracture among PPIs users due to PPI exposure. This study aimed to investigate the association between CYP2C19 genotypes, bone mineral density (BMD), and osteoporotic fracture in a hospital-based population. This retrospective cohort study enrolled patients who were prescribed long-term PPIs at Taichung Veterans General Hospital using data extracted from the Taiwan Precision Medicine Initiative between January 2010 and April 2021. Associations between CYP2C19 phenotypes, comorbidities, and fractures in PPI users were analyzed. We enrolled 1518 long-term PPI users; 571 (38%), 727 (48%), and 220 (14%) CYP2C19 normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs), respectively. Among them, 49 (3.2%) patients developed fractures within the 1-year follow-up period; 20 (3.5%) fractures in NMs, 24 (3.3%) in IMs, and 5 (2.3%) in PMs, respectively. No significant difference was observed among CYP2C19 genotypes and fracture. Additionally, BMD measurements during the 1-year follow-up period were made available among 75 participants. No significant difference in BMD between CYP2C19 PMs and non-PMs was found. This real-world, hospital-based study concludes that CYP2C19 PMs/IMs are not associated with an increased risk for fractures or reduced BMD in individuals on long-term PPI therapy.

Comparing the Safety and Efficacy of Proton Pump Inhibitors and Histamine-2 Receptor Antagonists in the Management of Patients With Peptic Ulcer Disease: A Systematic Review.

Peptic ulcer disease (PUD) refers to the occurrence of an open erosion in the inner lining of the stomach, duodenum, or sometimes lower esophagus. Treatments like proton pump inhibitors (PPIs) or histamine 2 receptor antagonists (H2RAs) are available on the market to efficiently treat the break in the mucosal lining. However, there is little evidence about the effects of the medication on the type and location of the ulcer and the epigastric pain caused by disintegration and increased acidity in the stomach. Given the above, we conducted a systematic review comparing the safety and efficacy of PPIs and H2RAs in various ulcer locations (gastric, duodenal, and pre-pyloric) and the effect of prolonging the treatment with the same medication or changing into a drug from another class in treatment-resistant ulcers. We employed major research literature databases and search engines such as PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Science Direct, and Google Scholar to find relevant articles. After a thorough screening, a quality check using various tools, and applying filters that suited our eligibility criteria, we identified eight articles, of which five were random clinical trials (RCTs), two review articles, and one meta-analysis. This study compares the different side effects of PPIs and H2RAs. Most studies concluded that omeprazole is superior in healing ulcers and bringing pain relief and that patients resistant to H2RAs can be treated better when switched to a PPI. This study also discusses the adverse effects of chronic use, such as diarrhea, constipation, headaches, and gastrointestinal infections. Patients on long-term PPI therapy are required to take calcium supplements to prevent the risk of fractures in older adults. Regarding long-term outcomes, PPIs remain the mainstay of treatment for peptic ulcer disease, based on the papers we reviewed.

Long-Term Proton Pump Inhibitor Therapy Increases the Risk of Infection in Patients with Incident Hemodialysis

Background: Infection is one of the most common causes of death in patients with chronic kidney disease (CKD). Proton pump inhibitors (PPIs) are not only widely used in patients with CKD but also represent a known risk factor for infection in the general population. Here, we investigated associations between PPIs and infection events in patients with incident hemodialysis. Methods: We analyzed data from 485 consecutive patients with CKD who started hemodialysis at our hospital between January 2013 and December 2019. We analyzed associations between infection events and long-term (≥6 months) PPI use before and after propensity score-matched analysis. Results: Of the 485 patients, PPIs were administered to 177 patients (36.5%). During 24 months of follow-up, infection events occurred in 53 patients (29.9%) with PPIs and 40 patients (13.0%) without PPIs (p < 0.001). Patients with PPIs had a significantly higher cumulative incidence rate of infection events than those without PPIs (hazard ratio [HR] 2.13, 95% confidence interval [CI]: 1.36–3.32; p < 0.001). Even after propensity score-matched analysis (132 patients matched in each), the rate of infection events was higher for patients with PPIs (28.8% vs. 12.1%, HR 2.88, 95% CI: 1.61–5.16; p < 0.001). Similar results were obtained for severe infection events in both unmatched (14.1% vs. 4.5%, HR 2.97, 95% CI: 1.47–6.00; p = 0.002) and propensity score-matched analyses (14.4% vs. 3.8%, HR 4.54, 95% CI: 1.85–11.13; p < 0.001). Conclusions: In patients with incident hemodialysis, long-term PPI use increases the risk of infection. Clinicians should be wary of unnecessarily prolonging PPI therapy.

Do the benefits outweigh the risks? Potential dangers associated with long-term therapy of proton pump inhibitors

Introduction:Proton pump inhibitors (PPIs) are one of the most popular and also one of the most commonly prescribed medications worldwide. In many conditions associated with excessive secretion of hydrochloric acid in the stomach, they are the first-line treatment. When they are used in a balanced manner in strict indications, they have a high level of efficacy and a favorable safety profile. The low rate of side effects refers mainly to their short-term use. With the over-the-counter availability of PPIs, increasing dangerous trend of their abuse has provided new evidence suggesting the presence of numerous, more serious side effects of long-term PPI therapy.&#x0D; Purpose:The purpose of this review is to summarize current reports regarding the potential risks and causal relationship of adverse effects occurring as a consequence of long-term use of proton pump inhibitors.&#x0D; Material and methods:This literature review based on the available scientific literature, published between 2015 and 2023 in the Pubmed database, searched using the terms, listed under "keywords”.&#x0D; Conclusion:PPIs are relatively safe drugs. However, they are not completely free of side effects. There are a lot of reports suggesting a potential connection between their long-term use and the development of complications, such as: various infections, decreased absorption of nutrients, kidney disease, liver disease, pancreatic disease, musculoskeletal disease, nervous system disease, cardiovascular disease, dementia, hypergastrinemia and even cancer. However, some of them are fraught with errors, and another often provide contradictory results. More precisely designed studies are needed to draw clear conclusions, especially in view of the ever-increasing abuse of PPIs worldwide. It is worth noting that patients with strictly defined indications for long-term PPI therapy, may benefit significantly outweighing the potential dangers.

Long-Term Proton Pump Inhibitor Therapy and its Effect on Endocrine Hormones in Selected Patient Population.

To evaluate the impacts of long-term utilization of proton pump inhibitors on male reproductive hormones and its clinical outcomes. A cross-sectional study was performed in two out-patients gastroenterology clinics in Khyber Pakhtunkhwa province. Male patients who were using proton pump inhibitors regularly for ≥3 months were enrolled in this study. Among 65 enrolled participants, patients with sexual complaints have significant variations in mean serum levels of prolactin (p<0.001), sex hormone binding globulins (p=0.043), total testosterone (p<0.001) and progesterone (p=0.001) as compared to patients without sexual complaints. Significantly high values of prolactin mean ranks were observed in patient with sexual complaints (p<0.001). There were statistically significant correlations of serum levels of sex hormone binding globulins (p=0.003), total testosterone (p=0.008) and progesterone (p<0.001) with serum prolactin levels. Similarly, statistically significant variation was observed for decreased libido(p=0.001), erectile dysfunction (p=0.001) and decreased semen mass ((p<0.001) between normal and hyperprolactinemic PPI users. Highly significant differences were observed in serum sex hormone binding globulins (p<0.001), total testosterone (p<0.001) and progesterone (p<0.001) values in normal and hyperprolactinemic groups. Long-term utilization of PPI may induce endocrine hormone disruption with subsequent sexual complications.

Appropriateness of Proton Pump Inhibitor Prescription Evaluated by Using Serological Markers.

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy.

Evaluation and management of gastroesophageal reflux disease: A brief look at the updated guidelines.

Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disorder seen in primary care offices and is usually managed with proton pump inhibitors (PPIs). The authors present an overview of the updated guidelines from the American College of Gastroenterology, which address the evaluation and management of GERD, including the consequences of long-term PPI therapy and emerging therapies.

Risk of gastric and oesophageal adenocarcinoma following discontinuation of long-term proton-pump inhibitor therapy

BackgroundThere is uncertainty whether long-term use of proton-pump inhibitors can cause gastric adenocarcinoma (GAC) and oesophageal adenocarcinoma (OAC). This study aimed to determine how discontinuation of long-term PPI therapy influences the risk of GAC and OAC.MethodsThis population-based cohort study included all long-term users of PPI therapy in Sweden in 2005–2018 was based on Swedish nationwide health registry data. The exposure was discontinuation of long-term PPI therapy, defined as no dispensation of PPI following inclusion and used as a time-varying variable, compared to remaining on PPI. Main outcomes were GAC and OAC, while oesophageal squamous cell carcinoma (OSCC) was included as a comparison outcome. Incidence rate ratios (IRR) with 95% CI adjusted for age, sex, comorbidity, obesity, diabetes, hyperlipidaemia, NSAIDs/aspirin, and statins were calculated with Poisson regression.ResultsAmong 730,176 long-term PPI users (mean age 65.6 years, 58.4% females) with 4,210,925 person-years at risk (median 5.5 person-years), 439,390 (60.2%) discontinued PPIs. In total, 495 developed GAC, 598 OAC, and 188 developed OSCC. PPI discontinuation was associated with decreased risk of GAC (IRR 0.81, 95% CI 0.67–0.98) and OAC (IRR 0.80, 95% CI 0.68–0.96), but not OSCC (IRR 1.10, 95% CI 0.82–1.49) compared to continued PPI use. Stratified analyses showed decreased point estimates across most age categories and both sexes for GAC and OAC risk among participants discontinuing PPI therapy.ConclusionDiscontinuation of long-term PPI therapy may decrease the risk of GAC and OAC, suggesting that physicians should consider ceasing prescribing long-term PPI in patients without continued indication for its use.

S442 Utilization of Diagnostic Testing and Indications for Long-Term Twice-Daily Proton Pump Inhibitor (PPI) Therapy for Gastroesophageal Reflux Disease (GERD) in a Large Healthcare System

Introduction: For symptoms potentially associated with GERD, guidance recommends de-prescribing long-term PPI therapy based on symptoms if possible, particularly in the absence of objective diagnostic findings. We assessed the utilization and yield of diagnostic evaluation (upper endoscopy (EGD) and/or reflux monitoring) among patients with GERD diagnoses receiving long-term twice-daily PPI therapy. Methods: From a healthcare system database, adults with GERD diagnoses (per ICD coding) who received prescriptions for twice-daily PPI for at least 90 days from 2018-2021 were identified. CPT analyses were performed to identify the proportions who underwent EGD and reflux monitoring. Characteristics of patients who underwent diagnostic testing were compared to those who did not. Further, those with objective EGD findings potentially warranting long-term PPI (such as erosive or eosinophilic esophagitis, peptic stricture, Barrett’s esophagus, ulcer) were compared to those without such findings on EGD. Factors significant on univariate analysis were included in multivariate models to identify predictors of A) undergoing diagnostic evaluation, and B) having positive EGD findings. Results: 5565 patients (57.7±0.2 yrs; 67.4% female; BMI 31.3±0.1) met inclusion criteria. 2696 (47.7%) had upper endoscopy, 491 (8.7%) had reflux monitoring, and 2735 (48.4%) had either upper endoscopy or reflux monitoring performed. Factors associated with diagnostic testing included younger age, female gender, and non-white race (Table, Figure A). Among those who underwent EGD, 42.2% had endoscopic findings potentially warranting long-term PPI (37.7% for females vs 52.2% for males; 34.7% for non-white patients vs 47.3% for white patients). Factors associated with the presence of EGD findings included older age, male gender, and white race (Figure B). Conclusion: Among patients receiving prescriptions for long-term, twice-daily PPI for GERD diagnoses, over half did not have procedural diagnostic evaluation documented per CPT analysis, suggesting providers may rely on patient symptom reporting to guide long-term PPI prescriptions. Of those with documented EGD, less than half had objective findings to potentially corroborate the need for long-term, twice-daily PPI. These findings warrant further investigation into potential disparities in care around long-term PPI prescribing patterns based on symptoms and symptom response versus diagnostic evidence.Figure 1.: Forest Plots for Multivariate Analysis of Factors Associated with A) Diagnostic Evaluation (Upper Endoscopy and/or Ambulatory Reflux Monitoring) among Patients with GERD Diagnoses Prescribed Twice-Daily Long-Term PPI Therapy; and B) Objective Endoscopic Findings Potentially Warranting Twice-Daily Long-Term PPI Therapy. Odds Ratios are Depicted with Bars Representing Associated 95% Confidence Intervals; Values Not Crossing the Dashed Line at 1 are Significant. Odds ratios for smoking status variables are in reference to no smoking history. Table 1. - Comparisons Between Patients who Underwent Diagnostic Evaluation (with Upper Endoscopy and/or Ambulatory Reflux Monitoring) and Those Patients Who did Not Undergo Diagnostic Evaluation Evaluated (n=2735) Not Evaluated (n=2920) p Values Age (years) 57.1±0.3 58.3±0.3 0.005* Body Mass Index 31.0±0.1 31.6±0.2 0.006* Gender (female) 1898 (69.4%) 1916 (65.6%) 0.002* Race (data missing = 97) White 1681 (62.4%) 1998 (69.8%) < 0.001* Black 838 (31.1%) 672 (23.5%) Asian 62 (2.3%) 77 (2.7%) Other 115 (4.3%) 115 (4.0%) Ethnicity (data missing =109) Non-Hispanic 2505 (93.1%) 2663 (93.3%) 0.71 Hispanic or Latino 187 (7.0%) 191 (6.7%) Married (data missing =58) Married 1526 (56.2%) 1658 (57.5%) 0.32 Not Married 1189 (43.8%) 1224 (42.5%) Smoking Status (data missing = 5) Current 279 (10.2%) 390 (13.4%) < 0.001* Former 974 (35.6%) 945 (32.4%) Never 1481 (54.2%) 1581 (54.2%)

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

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

Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia.

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.

Gastric mucosa condition in patients with coronary artery disease and high risk of gastrointestinal bleeding (register REGATTA-1)

To assess the upper gastrointestinal mucosal condition by endoscopic and histological methods in patients with stable coronary arteries disease receiving long-term antiplatelet therapy with gastrointestinal bleeding (GIB) history or with high risk of this complication. The study included patients from the single-center prospective registry of long-term antithrombotic therapy REGATTA-1. The gastric mucosa endoscopic examination with biopsy was performed in 20 patients with gastrointestinal bleeding history less than 1 year ago and in 24 patients without GIB, which have concomitant risk factors such as erosions and ulcers history and/or persistent dyspepsia clinical signs. The mucosal condition (erosions and ulcers) was estimated using a modified Lanz scale. The presence of Helicobacter pylori was determined by Histological verification. The inflammatory process characteristics were evaluated according to the modified Sydney classification. All participants received antithrombotic therapy at the time of esophagogastroduodenoscopy; 81.8% of patients received proton pump inhibitors. Chronic inflammation (93.2%), atrophy (59.1%), multiple erosions (45.5%) or ulcers (18.2%) were the most frequent endoscopic finding. H. pylori infection, found in mucosal samples in 90.9% of patients was one of the most important pathogenesis mechanism, which support the gastrointestinal mucosa damage. Mucosal damage endoscopic signs remains despite long-term proton pump inhibitors therapy in patients with coronary arteries disease and concomitant GIB risk factors, receiving antithrombotic therapy. H. pylori contamination may be the cause of these changes. Therefore, its active screening and eradication is necessary in such patients.

REBOUND PHENOMENON OF PROTON PUMP INHIBITOR THERAPY

Proton pump inhibitors (PPIs) are the most potent drugs for suppressing gastric acid secretion. They are used in the treatment of acid-peptic disorders, including peptic ulcer disease, gastroesophageal reflux disease, Zollinger Ellison syndrome, in the eradication of Helicobacter pylori infection and ulcer prophylaxis. In the pharmacotherapy of these disorders, they have significantly suppressed the use of H2 blockers, like other, older groups of antisecretory drugs. Long-term PPI therapy leads to moderate hypergastrinemia (increased gastrin secretion) in 20-25% of patients. This hypergastrinemia results in rebound acid hypersecretion (RAHS) in 30-40% patients, who abruptly discontinue PPI. Most patients who abruptly discontinue PPI have symptoms of dyspepsia and gastroesophageal reflux, most commonly heartburn and a burning sensation in the esophagus. Therefore, care should be taken to properly discontinue PPI and reduce the dose of the drug before complete discontinuation. A less effective acid blocker (H2 blocker) can be switched, since H2 receptor blockers cause less pronounced hypergastrinemia and hyperplasia of enterochromaffin-like cells (ECL cells) compared to PPI.

A pharmacovigilance study of association between proton pump inhibitor and dementia event based on FDA adverse event reporting system data

Proton pump inhibitor (PPI) was widely used around the world. Studies suggested conflicting results between PPI treatment and dementia event. This study examined the association between six PPI agents and dementia event by mining the US FDA Adverse Event Reporting System (FAERS) database from 2004 to 2020. We employed proportional reporting ratio (PRR) and information element (IC) methods to detect the signals of dementia relevant to PPI. We also analyzed characteristics of PPI and positive control reports, compared dementia event between long- and short-duration of PPI treatment. Finally, we identified 2396 dementia cases with PPI treatment. We did not detect significant signal between PPI and dementia event: PRR = 0.98, 95%CI 0.94 to 1.02, IC = −0.03, 95%CI − 0.17 to 0.10, even in gastroesophageal reflux disease cases: PRR = 0.65, 95%CI 0.59 to 0.72, IC = −0.62, 95%CI − 0.97 to − 0.27. No significant differences of dementia event were detected between long- and short- duration groups, the OR (95%CI) of the 3 years, 5 years and 10 years comparison were 0.70 (0.48 to 1.02), 0.72 (0.45 to 1.15) and 1.65 (0.75 to 3.63), respectively. Based on the current FAERS data mining, we discovered no association between PPI use and dementia event, even in long-term PPI therapy case.

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.