Proton Pump Inhibitors Intake Research Articles

Abstract PO1-01-08: The impact of drug-drug interactions between palbociclib and proton pump inhibitors on clinical outcomes of patients with hormone receptor positive, HER2-negative, early breast cancer: an exploratory analysis of the PALLAS study

Abstract Background: Data suggest that concomitant intake of proton pump inhibitors (PPI) may create drug-drug interactions, potentially impacting efficacy of agents including palbociclib, which is widely used in the treatment of metastatic hormone-receptor-positive/HER2-negative (HR+/HER2-) breast cancer. In the open label, randomized, phase 3 PALLAS trial, the addition of palbociclib for two years to standard adjuvant endocrine therapy (ET) in patients with HR+/HER2- early breast cancer (EBC) did not improve invasive disease-free survival (IDFS) compared to adjuvant ET alone. We explored whether concomitant use of PPIs could have affected clinical outcomes in patients treated with palbociclib in PALLAS. Methods: This is an exploratory, unplanned analysis of the PALLAS trial (AFT-05/ABCSG-42/PrE0109/BIG-14-13, NCT02513394), which enrolled 5796 patients with stage II-III HR+/HER2- EBC. Patients were randomized to receive either 2 years of palbociclib (125 mg oral capsules once daily on days 1-21 of a 28-day cycle) with adjuvant ET or ET alone. Primary endpoint was IDFS in the intention-to-treat population. The present exploratory analysis included patients who received at least one dose of palbociclib. Definitions of IDFS, distant relapse-free survival (DRFS) and overall survival (OS) were according to the PALLAS protocol (STEEP criteria), using first day of palbociclib intake as start date. Only PPI concomitant intake during palbociclib treatment was considered. To determine the association of concomitant PPI use with IDFS, DRFS, and OS, uni- and multivariable Cox models with time-dependent PPI (the latter adjusted for age, prior chemotherapy, progesterone receptor, grade, tumor stage, nodal stage, body mass index (BMI)) were used. Also, the association between PPI use and neutropenia was investigated in patients initiating PPI prior to randomization vs never. Odds ratios (OR) unadjusted and adjusted for age and BMI estimated with logistic regression models are reported. Results: Of 2840 patients treated with palbociclib + ET, 533 (18.8%) had concomitant PPI and palbociclib intake. Median duration of PPI intake was 10.8 months (interquartile range 2.3-22.3). Most patients received omeprazole as PPI (n=265, 49.7%). PPI intake was significantly associated with older age, post-menopausal status, use of aromatase inhibitors as ET, higher BMI, and worse ECOG status (all p< 0.001). Concomitant PPI intake was not significantly associated with survival outcomes (Table 1). Unadjusted all grade neutropenia rates were slightly lower in patients who initiated PPI prior study start vs patients never initiating (79% vs 85%, unadjusted OR 0.66, 95%CI 0.50-0.88). After adjustment for BMI and age, the difference between the groups decreased (adjusted OR = 0.77, 95%CI 0.57-1.04). Similar effect sizes were found for grade 3/4 neutropenia rates (54% vs 64%, unadjusted OR 0.66, 95%CI 0.52-0.83, adjusted OR 0.81, 95%CI 0.64-1.03). Conclusions: Our exploratory analysis did not demonstrate a statistically significant relationship between concomitant use of PPIs and palbociclib and survival outcomes of patients in the PALLAS trial. Nonetheless, careful consideration of concomitant medications and of drug-drug interactions is important when studying novel agents in the adjuvant breast cancer setting. Support: AFT, Pfizer; https://acknowledgments.alliancefound.org Table 1. Association between PPI intake and survival outcomes. Citation Format: Elisa Agostinetto, Georg Pfeiler, Dominik Hlauschek, Erica Mayer, Matteo Lambertini, Evandro de Azambuja, Meritxell Bellet- Ezquerra, Jane Meisel, Gabor Rubovszky, Nicholas Zdenkowski, Yelena Novik, Manuel Ruíz - Borrego, Karen Gelmon, Eleftherios Mamounas, Hiroji Iwata, Dongrui Lu, Lidija Sölkner, Christian Fesl, Michael Gnant, Angela DeMichele. The impact of drug-drug interactions between palbociclib and proton pump inhibitors on clinical outcomes of patients with hormone receptor positive, HER2-negative, early breast cancer: an exploratory analysis of the PALLAS study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-08.

Long-Term Intake of Proton-Pump Inhibitors Could Be Associated with an Increased Incidence of Liver Cancer in Women.

Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in gastroenterology. Although PPIs are mostly well tolerated, long-term PPI intake has been linked with diabetes mellitus, osteoporosis and infectious disease. In the present study, we evaluated a potential association between PPI intake and a subsequent diagnosis of liver cancer in a large real-world cohort of outpatients in Germany. A total of 1766 patients with liver cancer, as well as 8830 propensity-score-matched controls, were identified from the Disease Analyzer database (IQVIA). The outcome of the study was the association between PPI use and a subsequent diagnosis of liver cancer, which was evaluated using multivariable logistic regression analyses. Overall, 42.9% of the liver cancer patients and 39.0% of the controls received at least one PPI prescription before the index date. PPI prescriptions at any time before the index date were associated with an increased risk of subsequent liver cancer (OR: 1.18; 95% CI: 1.06-1.31). The positive association was observed in all age groups, as well as in women and men, but only in women (OR: 1.30; 95% 1.09-1.55) did it reach the predefined level of significance (p < 0.01). When considering the duration of PPI therapy, only PPI therapy for at least two years was significantly associated with an increased risk of liver cancer (OR: 1.28; 95% 1.09-1.50). In an analysis stratified by age and sex, this association was strongest in the age group < 60 years (OR: 1.99; 95% 1.21-3.26). Our data suggest that long-term PPI intake in women as well as in patients < 60 years might be associated with an increased risk of liver cancer. These findings support current efforts to reduce the inappropriate use of PPIs in routine clinical practice and to link PPI prescribing to a clear medical indication.

Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment.

The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients. Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI. We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.

Analysis of impact of consumption of proton pump inhibitor on osseo integration of dental implants to the alveolar bone: A systematic critical appraisal.

Proton pump inhibitors are one of the most frequently prescribed medicines primarily for reducing the production of gastric acid. Every medicine has some adverse effects associated with it, including effects on the bone tissues. Dental implant is one of the most preferred options for teeth replacement. The current literature review was planned to evaluate the association between intake of proton pump inhibitors and its impact on the bone around the dental implant. Literature review entailed search on Google Scholar, Web of Science and PubMed databases using a range of search terms. Chronic intake of proton pump inhibitors has been associated with decrease in the density of bone, which eventually leads to increased risk of dental implant failure. However, since limited studies have been carried out, further research is required, especially clinical trials, to evaluate the relationship between the intake of proton pump inhibitors and the failure of dental implants.

Efficacy of a computer based discontinuation strategy to reduce PPI prescriptions: a multicenter cluster-randomized controlled trial

Deprescribing of inappropriate long-term proton pump inhibitors (PPI) is challenging and there is a lack of useful methods for general practitioners to tackle this. The objective of this randomized controlled trial was to evaluate the effectiveness of the electronic decision aid tool arriba-PPI on reduction of long-term PPI intake. Participants (64.5 ± 12.9 years; 54.4% women) with a PPI intake of at least 6 months were randomized to receive either consultation with arriba-PPI from their general practitioner (n = 1256) or treatment as usual (n = 1131). PPI prescriptions were monitored 6 months before, 6 and 12 months after study initiation. In 49.2% of the consultations with arriba-PPI, the general practitioners and their patients made the decision to reduce or discontinue PPI intake. At 6 months, there was a significant reduction by 22.3% (95% CI 18.55 to 25.98; p < 0.0001) of defined daily doses (DDD) of PPI. A reduction of 3.3% (95% CI − 7.18 to + 0.62) was observed in the control group. At 12 months, the reduction of DDD-PPI remained stable in intervention patients (+ 3.5%, 95% CI − 0.99 to + 8.03), whereas control patients showed a reduction of DDD-PPI (− 10.2%, 95% CI − 6.01 to − 14.33). Consultation with arriba-PPI led to reduced prescription rates of PPI in primary care practices. Arriba-PPI can be a helpful tool for general practitioners to start a conversation with their patients about risks of long-term PPI intake, reduction or deprescribing unnecessary PPI medication.

Trends of Proton Pump Inhibitor Uses among Pharmaceutical Promotional Workers

Background: Proton pump inhibitors (PPIs) are one of the most frequently used drugs in the world for the management of gastric- acid related diseases. The aim of this study was to assess the trend of PPIs uses among the pharmaceutical promotional workers in Bangladesh. Methods: A questionnaire-based survey was conducted on pharmaceutical promotional workers from different regions in Bangladesh. The study data were collected which includes demographics, PPIs uses in terms of duration, dose, generics, symptoms for which they took PPIs and effects of PPIs on symptoms. Drugs or diseases that influenced the intake of PPIs were also recorded. Results: Among six hundred surveys issued for the study, 581 valid questionnaires were returned. Among the respondents 520 individuals (89.5%) were male and 61 individuals (10.5%) were female. Common indications for taking PPIs were abdominal discomfort (51.5%), vomiting (34.1%) and abdominal pain (24.6%). Two hundred seventy (48.56%) respondents had satisfactory relief of symptoms, 125 (22.48%) had symptoms reappeared after stopping PPIs and 77 (13.85%) had complete cure of symptoms. Most of the participants (42.60%) were on PPIs therapy for up to one year. Most of the participants (64.49%) took PPI once daily. Most of the participants (60.75%) started PPI by themselves. Esomeprazole (40.1%) and rabeprazole (30.1%) were the most frequently used PPIs. Conclusion: PPI is found to be a frequently used medication among pharmaceutical promotional workers. Further well-designed study with adequate work up may be designed to see misuse and overuse of PPI among workers of pharmaceutical sector as well as general population. Sir Salimullah Med Coll J 2023; 31: 41-46

Long-term patient-reported outcomes after anti-reflux surgery for gastroesophageal reflux disease and hiatal hernia repair: a single-center experience.

Patients with gastroesophageal reflux disease (GERD) and hiatal hernia who are candidates for surgery should be treated with minimally invasive partial or total fundoplication. As data on long-term clinical and functional outcomes after laparoscopic surgery for GERD are limited, the aim of this study was to evaluate the long-term effectiveness of fundoplication in terms of patient-reported symptoms and proton pump inhibitor (PPI) use. The data of 88 patients who underwent laparoscopic anti-reflux surgery for GERD between January 2007 and September 2020 were retrospectively reviewed. Preoperative and postoperative patient-reported outcomes were investigated after surgery using a 13-items Likert-Scale questionnaire based on the frequency (events/week) and severity of typical and atypical symptoms, dysphagia, and dyspepsia. Furthermore, variations in the use of PPIs were investigated as a secondary endpoint. A total of 76 patients participated in the questionnaire survey. The median follow-up duration was 77 (2-165) months. The postoperative rate of mild and severe typical symptoms was significantly lower than the preoperative rate (P<0.01). Similarly, the atypical symptom rates decreased after surgery (P<0.05). Dysphagia was more frequent after fundoplication (P<0.01). Before the anti-reflux surgery, 94.7% of the patients were prescribed a PPI. At the time of follow-up, this proportion had decreased to 73.7% (P<0.01). However, the PPI intake rate was 90.9% in the group of patients interviewed >10 years after surgery. In this cohort of patients, laparoscopic anti-reflux fundoplication reduced the rate typical and atypical symptoms of GERD. However, surgery appeared to have no impact on PPI intake over time.

Intake of Proton-Pump Inhibitors and Gastric Cancer within the Stomach Cancer Pooling (StoP) Project.

A potential association between proton-pump inhibitors (PPI) and gastric cancer remains undefined. Thus, we aimed to evaluate such association within the Stomach cancer Pooling (StoP) Project. Data from five case-control studies of the StoP Project were included (1,889 cases and 6,517 controls). We assessed the impact of different exposure definitions, specifically any reported use of PPIs and exposure definitions based on the duration of PPI intake. Additionally, we modeled the dose-response relationship between the cumulative duration of PPI intake and gastric cancer. Significant associations between PPI intake and gastric cancer, both overall and in the stratified analyses, were limited to exposure definitions based on short durations of intake. The overall odds ratio (OR) for any reported PPI intake was 1.78 [95% confidence interval (CI): 0.76-4.14]. In the dose-response analysis, the ORs of gastric cancer were found to be higher for short durations of PPI intake (6 months: OR 3.26; 95% CI: 2.40-4.42; one year: OR 2.14; 95% CI: 1.69-2.70; 2 years: OR 1.50; 95% CI: 1.22-1.85; 3 years: OR 1.27; 95% CI: 1.03-1.56), with the association becoming not significant for durations longer than 3 years. Our findings suggest that the observed association between PPIs and gastric cancer might be mainly due to reverse causality. The results of this study suggest that PPIs are a safe therapeutic choice regarding their effect on the occurrence of gastric cancer. See related commentary by Richman and Leiman, p. 1127.

#4068 EVALUATION OF CHRONIC TOXIC EFFECT OF PROTON PUMP INHIBITORS (PPIS) ABUSE ON MAGNESIUM LEVEL IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Proton Pump Inhibitors are widely used in haemodialysis patients for the prevention and treatment of uremic gastritis, peptic ulcer, gastritis, esophagitis and gastro oesophageal reflux. Hypomagnesaemia is reported recently in some patients who abuse intake of Proton Pump Inhibitors (PPIs) but this problem is still not well studied yet. Our study aims to evaluate the chronic toxic effect of Proton Pump Inhibitor on Magnesium level in Egyptian haemodialysis patients, especially those who suffer from abuse of intake without medical prescriptions. Method The study was conducted at the haemodialysis centre and clinic of Alzawya One-Day Surgery Hospital in Cairo including 60 end stage renal disease patients after their consents and approval of ethical committee in our hospital. PPIs use and duration were investigated. The patients were dialyzed using a dialysate magnesium level of 0.5 mmol/L and Calcium level 1.5 mmol/L in all groups, after at least one month of haemodialysis with the mentioned dialysate, laboratory tests were performed. The patients participating in this study after their consents were divided into 3 groups: • Group A: - 20 patients on Proton Pump Inhibitors regularly with long term intake for more than 6 months on high dose above or equal280 mg/week [1] • Group B: -20 patients on Proton Pump Inhibitors irregularly for less than 6 months on low dose below 280 mg/week. • Group C: -20 patients not intake Proton Pump Inhibitors. The magnesium level in haemodialysis patients was evaluated by comparison between the 3 groups, and its correlation with duration of its use, Calcium and Phosphorus level in blood. Dialysate magnesium and calcium concentration in all groups were fixed and abuse of intake of PPIs without medical prescription in the participated patients was evaluated. Results Show highly statistically significant higher mean value in Non-intake of PPI group, followed by PPI intake ≤6m group and the lowest value in PPI intake &amp;gt;6m group according to magnesium “mg/dl”, with p-value (p&amp;lt;0.001). There is no statistically significant difference between groups according to calcium “mg/dl”; with p-value (p&amp;gt;0.05). Conclusion Proton Pump Inhibitors regularly with long term intake for more than 6 months on high dose above or equal 280 mg/week associated with hypomagnesaemia. So we recommend stoppage of abuse intake of PPIs in haemodialysis patients.

Biliary microbial patterns in primary sclerosing cholangitis are linked to poorer transplant-free survival.

Factors that determine individual disease course of patients with primary sclerosing cholangitis (PSC) are poorly understood. Although an association between gut microbes and disease outcome has been suggested, little is known about the role of microbes in the biliary tract. We analyzed microbial cultures from bile specimens obtained during routine endoscopic retrograde cholangiopancreatography (ERCP) and intraoperatively before liver transplantation in 114 patients with PSC in our tertiary academic center. The presence of bacterial and fungal species was correlated with clinical characteristics and outcome data. A total of 87 patients (76%) had positive bile culture results. The presence of concomitant inflammatory bowel disease (IBD) was associated with positive bile culture results in multivariate analysis (OR, 4.707; 95% CI, 1.688-13.128; p=0.003). Enterococcus spp. in the bile was associated with a more frequent occurrence of liver transplantation and/or death (OR, 2.778; 95% CI, 1.147-6.728; p=0.021) and recurrent (≥3) cholangitis episodes (OR, 2.839; 95% CI, 1.037-7.768; p=0.037). Biliary candidiasis was linked to a higher frequency of recurrent (≥3) cholangitis episodes (OR, 5.677; 95% CI, 1.940-16.616; p=0.001). Proton pump inhibitor intake conferred a clinical feature associated with biliary candidiasis in multivariate analysis (OR, 3.559; 95% CI, 1.275-9.937; p=0.016). Our data indicate that in patients with PSC, presence of Enterococcus spp. and Candida spp. in bile is associated with an adverse outcome. Concomitant IBD is linked to presence of microbes in bile, and proton pump inhibitor intake is a feature associated with biliary candidiasis in patients with PSC.

Association between occurrence of multiple white and flat elevated gastric lesions and oral proton pump inhibitor intake.

Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p<0.001). Moreover, the occurrence of MWFL was significantly higher in patients with hypergastrinemia (p=0.005). In the multivariate analyses, oral PPI intake was the only significant independent factor associated with the presence of MWFL (p=0.001; odds ratio, 5.78; 95% confidence interval, 2.06-16.2). Our findings suggest that oral PPI intake is associated with the presence of MWFL (UMINCTR 000030144).

Esophagogastrostomy with fundoplication versus double-tract reconstruction after laparoscopic proximal gastrectomy for gastric cancer.

346 Background: Upper-third gastric cancer has been increasing in incidence worldwide and performance of laparoscopic proximal gastrectomy has become increasing common. Various reconstructive procedures after laparoscopic proximal gastrectomy have been reported, but the optimal reconstructive procedure is unclear. Methods: This single-center retrospective study included 53 consecutive patients with early gastric cancer in the upper third of the stomach who received laparoscopic proximal gastrectomy at our hospital between September 2013 and November 2019. Of these 53 patients, 39 underwent esophagogastrostomy with fundoplication. In the 14 patients requiring resection of the abdominal esophagus or where the size of the remnant stomach was 50% or less, we performed double-tract reconstruction. We compared the surgical and nutritional outcomes of patients who underwent esophagogastrostomy or double-tract reconstruction after laparoscopic proximal gastrectomy. Results: There was no significant difference between the two groups regarding blood loss, incidence of postoperative complications, occurrence of gastroesophageal reflux disease, food intake, reflux symptoms, or usage of proton pump inhibitors. There was no significant difference in the rate of body weight change at 6 or 12 months, or in biochemical markers (hemoglobin, total protein and albumin) at 12 months. However, eight patients (21%) in the esophagogastrostomy group had extreme body weight loss (≥20%) within 12 months. Conversely, in the double-tract reconstruction group, no patients had any extreme body weight loss ( P = 0.013). Conclusions: Double-tract reconstruction is useful after laparoscopic proximal gastrectomy, especially in terms of preventing extreme body weight loss.

Is an optimization of the use of proton pump inhibitors feasible in the real world medical practice?

The review deals with the data on negative health impact of prolonged and inadequate use of proton pump inhibitors (PPI). Since their advent at the end of 1980s, their worldwide use has been continuously increasing. However, up to 70% of PPI use is not based on clear indications. Inadequate treatment with PPI not complying with clinical guidelines results in a higher risk of adverse events, especially in the elderly. Prolonged (more than 8 weeks) intake of PPI increases the risk of osteoporotic fractures, promotes Clostridioides difficile infection and gut microbiota abnormalities, community-acquired pneumonia, vitamin B12 deficiency, renal disease, dementia, risk of gastric cancer, etc. Most potential side effects of PPI are the results of hypochlorhydria and reflex hypergastrinemia. The main safety principle for PPI is adherence to short duration of treatment and minimally effective doses. Rational strategies for safe and effective PPI treatment are supported by the evidence-based deprescribing in gastroesophageal reflux disease and include dose tapering or therapy as needed after the treatment course for a specific indication has been finished, or stopping the treatment in patients with no adequate indications to PPI administration. Increased awareness of medical personnel and patients on the proper PPI use and their side effects would make it possible to optimize the use of these agents in the real world medical practice.

Scheduling Dosage of Proton Pump Inhibitors Using Constrained Optimization With Gastric Acid Secretion Model

Dosage schedule of the Proton Pump Inhibitors (PPIs) is critical for gastric acid disorder treatment. In this paper, we develop a constrained optimization based approach for scheduling the PPIs dosage. In particular, we exploit a mathematical prediction model describing the gastric acid secretion, and use it within the optimization algorithm to predict the acid level. The dosage of the PPIs which is used to enforce acid level constraints is computed by solving a constrained optimization problem. Simulation results show that the proposed approach can successfully suppress the gastric acid level with less PPIs intake compared with the conventional fixed PPIs dosage regimen, which may reduce the long-term side effects of the PPIs.

Usefulness of Molecular Methods for Helicobacter pylori Detection in Pediatric Patients and Their Correlation with Histopathological Sydney Classification

Helicobacter pylori infections, as one of the most prevalent among humans, are generally acquired during childhood, and are one of the main causes of chronic gastritis and peptic ulcer disease. A bacterial culture from a gastric biopsy is the gold standard and is the only method that has 100% specificity. However, its sensitivity varies, depending on experience of the laboratory staff, applied culture media, specimen transport conditions, biopsy site, and quality of the sample. The same factors compromise all invasive methods and a culture-based H. pylori infection diagnostic, as well as a recent intake of antibiotics, bismuth-containing compounds, and proton pump inhibitors. Molecular methods have been used for clinical microbiology investigation since the beginning of the 21st century. However, their usefulness for H. pylori infections diagnosis remains unclear, especially in pediatric patients. The aim of the study was to assess the incidence of H. pylori infections in a group of 104 pediatric patients and to compare the results of the PCR test with the corresponding histopathological investigation effects. Among the biopsy samples collected from 104 children, 44 (42.3%) were positive in PCR, while 43 (41.3%) and 39 (37.5%) presented histologically-confirmed signs of inflammation and H. pylori colonization, respectively. Moreover, the mean grades of the parameters of the histopathological examination were higher in the group of PCR-positive samples. The compatibility of both research methods was confirmed, emphasizing the usefulness of molecular methods for detecting H. pylori infections in pediatric patients. Considering that the PCR-based method gives reliable results and is less time-consuming and costly, it is worth discussing this method as a new standard in the diagnosis of H. pylori infections, at least among pediatric patients, for which culture-based diagnostics is not sufficient or histopathological examination is negative, while inflammation signs are observed macroscopically.

Post COVID-19 irritable bowel syndrome

ObjectivesThe long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut–brain interaction after hospitalisation...

The Effects of Proton Pump Inhibitors in Acid Hypersecretion-Induced Vitamin B12 Deficiency: A Systematic Review (2022).

Gastroesophageal reflux disease (GERD) is the most common disease, for which proton pump inhibitors (PPIs) are a widely used class of drugs. Due to their efficacy and relative safety profile, PPIs are used chronically by GERD patients. Although it is a safe drug, particular attention focuses on the long-term adverse effects of PPI. The association with vitamin deficiencies has received additional focus since chronic PPI treatment increases the incidence of vitamin B12 deficiency, especially in the elderly. However, numerous studies regarding the establishment of an association between PPI and vitamin B12 status revealed conflicting results. In this systematic review, we systematically examined observational studies that focused on the impact of chronic PPI effects on vitamin B12 absorption and diagnostic biomarkers of vitamin B12 deficiency. Our review showed significant changes in diagnostic biomarkers of vitamin B12 status in long-term PPI users, including elevated homocysteine and methylmalonic acid (MMA) concentration levels defining cellular vitamin B12 deficiency. Although there is uncertainty regarding the exact mechanism, it supports the concept that long-term intake of PPI can have clinical implications for vitamins.

Learning curve for peroral endoscopic myotomy in therapeutic endoscopy experts and nonexperts: Large single-center experience.

Reports on learning curve for peroral endoscopic myotomy (POEM) in therapeutic endoscopy nonexperts are limited. We aimed to assess the number of cases required to achieve POEM proficiency for endoscopic submucosal dissection (ESD) experts and nonexperts. This is a retrospective study at the largest POEM referral center in Japan. POEM between April 2014 and December 2020 were included. Nonexperts and ESD experts were divided by training phases: A, 1-20; B, 21-40; C, 41-60; D, 61-80; and E, 81-100 cases. Primary outcome was operation time, and the phase to reach target time (83 min) was investigated. Secondary outcomes were clinical success rate, adverse events, and post-POEM gastroesophageal reflux disease (GERD). Five hundred and sixty-six cases were performed by 14 nonexperts, and 555 cases by 15 ESD experts. As the primary outcome, operation time in nonexperts was: A, 95 (79-115.8); B, 86.5 (71-105); C, 80 (70-100); D, 73 (64.5-100.5); and E, 73.5 (57.8-88.8) min, while in ESD experts: A, 90 (74-128); B, 77 (70-92); and C, 77 (70-93.5) min (median [interquartile range]). Operation time decreased significantly as experience increased in both groups (P < 0.001), and nonexperts required 41-60 cases to achieve proficiency, while experts required 21-40 cases. As secondary outcomes, in nonexperts, clinical success was 96.9-100%, adverse events were 5.0-9.2%, symptomatic GERD was 11.8-26.5%, and proton pump inhibitor (PPI) intake was 11.5-18.7% in each phase. While in experts, clinical success was 96.2-100%, adverse events were 3.0-5.8%, symptomatic GERD was 14.6-22.0%, and PPI intake was 12.6-17.9%. There were no significant differences among training phases. Non-ESD experts require more cases to achieve proficiency in POEM. These results are useful for establishing POEM training programs and institutional implementation of the procedure.

Three cases of symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by proton-pump inhibitors.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), previously termed drug-related baboon syndrome, is an uncommon drug eruption. It is characterized by symmetrical erythema involving the gluteal and/or inguinal area in association with one other intertriginous area in the absence of systemic involvement. It typically develops a few hours to days after drug exposure. The diagnosis is based on clinical presentation and drug history. The treatment consists mainly of withdrawal of the causative agent; corticosteroids (topical or systemic) are prescribed to accelerate the resolution. We present three cases that appeared after proton-pump inhibitors (PPIs) intake.

The effect of the use of proton pump inhibitors, serotonin uptake inhibitors, antihypertensive, and anti-inflammatory drugs on clinical outcomes of functional dental implants: Aretrospective study.

ObjectiveThe present retrospective study investigated the effect of chronic intake of proton pump inhibitors, selective serotonin uptake inhibitors, anti‐inflammatory, and antihypertensive drugs on the survival of dental implants and on the occurrence of peri‐implantitis.Materials and methodsSurvival analyses for implant failure and peri‐implantitis were performed patient level for each drug subcategory and for risk factors. The HR for each drug was calculated with adjusted models as compared with a control group made of subjects not assuming the specific drug. Multilevel logistic regression was used to explore the influence of implant‐level and patient‐level variables on the outcomes.ResultsA total of 270 subjects receiving 1118 dental implants were included, with a mean follow‐up time of 5.19 ± 4.22 years. After 10 years, the survival rate was 86.9% (patient level), and according to survival analysis, 61.3% of subjects were free from peri‐implantitis. The use of anti‐inflammatory medicines produced a significant effect (p = .04) on peri‐implantitis as compared to subjects not using the drug, with a 2.7‐year drop in the mean survival time. The HR was slightly above the level of significance in a semiadjusted model (p = .058). The multilevel analysis found a significant effect on the entire sample and not when considering only subjects with implants with more than 1‐year follow‐up.ConclusionsWe found a possible relationship between anti‐inflammatory drug use and the occurrence of peri‐implantitis in the examined cohort of patients, and no correlation for the other drugs.