Acid-suppressive Drugs Research Articles

Examination on Factors Affecting Symptom Change after Drug Withdrawal in Patients with Mild Erosive Gastroesophageal Reflux Disease Undergoing Symptom-Controlled Maintenance Therapy with Acid-Secretion Inhibition Drugs

Introduction: In patients with gastroesophageal reflux disease (GERD) on maintenance therapy with acid-suppressive drugs, it is not clear what background factors allow patients to discontinue the drugs. The aims of this study were to examine the relationship of the changes in the frequency and severity of gastrointestinal symptoms after discontinuation of acid-secretion inhibitors for erosive GERD (eGERD) with possible patient background factors and to identify factors that influence these changes. Methods: This is a multicenter, open-label, interventional, exploratory study. eGERD patients with mild mucosal injury whose symptoms were under control and who were on maintenance therapy with acid-suppressive drugs were withdrawn from the drug treatment for 4 weeks. We examined the relationship of patient backgrounds (sex, age, body mass index, alcohol consumption, smoking habits), esophageal hiatal hernia, Helicobacter pylori infection, pepsinogen I and II concentrations and I/II ratios, blood gastrin levels before and after drug discontinuation with total score change in Frequency Scale for the Symptoms of GERD (FSSG). Results: Of the 92 patients whose symptoms could be assessed before and after drug withdrawal, 66 patients (71.7% of the total) had FSSG <8 and no symptom relapse after the withdrawal. Furthermore, patient background factors that may be related to symptom relapse/non-relapse were examined, but no related factors were detected. The maintenance medications before discontinuation in the above 92 patients were a proton pump inhibitor (PPI) and vonoprazan (VPZ, a potassium ion competitive acid blocker). Since PPI and VPZ were administered to about the same number of patients, though incidentally, we additionally examined the relationship between patient background factors and symptom relapse/non-relapse by treatment group. As a result, no relevant background factors were detected in both groups. Although there were no significant differences between the two groups, the severity and frequency of symptom recurrence in the VPZ group tended to be higher than in the PPI group. Conclusions: Consideration of background factors is unlikely to be required in the discontinuation of maintenance therapy for eGERD. There was no significant difference in the extent of disease or frequency of recurrence during the discontinuation period, regardless of whether the drug before discontinuation was a PPI or VPZ.

Exposure to Commonly Used Drugs and the Risk of Gastric Cancer: An Umbrella Review of Meta-Analyses.

Recently, attention has been paid to some medications and gastric cancer (GC) risk. This review aimed to evaluate associations between commonly used drugs and GC risk and to grade evidence from published systematic reviews and meta-analyses. This umbrella review was registered in PROSPERO (CRD42022320276). The systematic reviews and meta-analyses of observational studies were retrieved by searching Embase, PubMed, and Web of Science. The evidence strength of commonly used drugs and GC risk was categorized into four grades: weak, suggestive, highly suggestive, and strong. Of 19 associations between commonly used drugs and GC risk and its subtypes, none was supported by convincing or highly suggestive evidence. The risk of GC related to non-steroidal anti-inflammatory drugs (NSAIDs), non-aspirin NSAIDs, and acid-suppressive drugs, as well as the risk of non-cardia GC related to NSAIDs and aspirin, was supported by suggestive evidence. The results showed that a reduced GC risk was associated with two drug types (NSAIDs and non-aspirin NSAIDs), and an increased GC risk was associated with acid-suppressing drugs at the suggestive evidence level. Moreover, NSAIDs and aspirin reduced non-cardia GC risk as supported by suggestive evidence. However, the evidence supporting statins or metformin in reducing GC risk was weak, and thus future studies are required to clarify these associations.

Incidence and type of adverse events in patients taking vonoprazan: A systematic review and meta-analysis.

Vonoprazan, a novel acid-suppressive drug, is non-inferior to proton pump inhibitors (PPIs) for the management of gastric acid-related diseases. However, the safety of vonoprazan has not been systematically evaluated yet. To elucidate the incidence and type of adverse events (AEs) in patients taking vonoprazan. Systematic review and meta-analysis. PubMed, EMBASE, and Cochrane Library databases were searched for all studies reporting the safety of vonoprazan. The incidences of any AEs, drug-related AEs, serious AEs, AEs leading to drug discontinuation, and common AEs were pooled. Odds ratios (ORs) were calculated to compare the incidence of AEs between patients taking vonoprazan and PPIs. Seventy-seven studies were included. The pooled incidences of any AEs, drug-related AEs, serious AEs, and AEs leading to drug discontinuation were 20, 7, 1, and 1%, respectively. The incidences of any AEs (OR = 0.96, p = 0.66), drug-related AEs (OR = 1.10, p = 0.44), serious AEs (OR = 1.14, p = 0.36), and AEs leading to drug discontinuation (OR = 1.09, p = 0.55) were not significantly different between patients taking vonoprazan and PPIs. In subgroup analyses, patients with peptic ulcer disease (PUD) had higher incidences of any AEs, serious AEs, and AEs leading to drug discontinuation than those with gastroesophageal reflux disease (GERD), Helicobacter pylori (H. pylori) infection, and artificial ulcer after gastric endoscopic submucosal dissection (ESD), but patients with H. pylori infection had a higher incidence of drug-related AEs than those with PUD, GERD, and artificial ulcer after gastric ESD. The incidence of AEs was higher in patients taking long-term use of vonoprazan than those taking short-term use of vonoprazan. Vonoprazan is well tolerated and shows similar safety compared to PPIs. The safety of vonoprazan may be primarily influenced by its indications and duration. PROSPERO CRD42022314982.

Treatment of Acid-related Diseases Using Potassium-competitive Acid Blockers

Proton pump inhibitors (PPIs) have several limitations to their efficacy including insufficient acid suppression, slow onset of action, and variable efficacy among patients due to CYP2C19 metabolism. Potassium-competitive acid blockers inhibit H+-K+-ATPase in a reversible and K+-competitive manner, are novel acid suppressive drugs with rapid onset of action, meal independence, and prolonged control of intragastric acidity compared to PPIs. Potassium-competitive acid blockers exhibited non-inferior therapeutic efficacies on reflux esophagitis, gastric ulcers, and Helicobacter pylori eradication. The review is focused on the unmet needs across the acid-related diseases and recent updates on clinical studies using vonoprazan and tegoprazan.

Short antibiotic treatment followed by regular administration of acid suppressant (proton pump inhibitor) reduce AB42 load in the brain and in the gut.

AbstractBackgroundFecal microbiota transplantation (FMT) from healthy mice, microbiota depletion with antibiotic treatment (ABT) or with germ free mice have been associated with a reduction of cerebral amyloid load in Alzheimer’s disease (AD) mice models, indicating that the gut microbiota can modulate amyloid load in the brain. Interestingly, amyloid can also deposit in the gut, particularly within proximity to vasculature, nerves, and nerve plexuses. Additionally, acid suppressant drug such as proton pump inhibitors (PPI) have been shown to modify the gut microbial population. Here we postulate that ABT+PPI could modulate the gut microbiota and amyloid load in the gut and in the brain.MethodSixty female, two‐year old 3xTg mice (APPSWE, PS1M146V and TauP301L) were divided in 2 groups and received: (1) 2‐weeks of ABT to deplete the microbiota followed by recurrent PPI administration simultaneously with (FMT) once a week for 2 months or (2) FMT only at same frequency. The FMTs consisted in i) water, ii) litter mate mice and, iii) bacteria isolated from 1 young and 1 cognitively unimpaired elderly donor to test different microbiota.ResultAfter 60 days of treatment, Ab42 and Ab40 were measured by ELISA in the hippocampus and the colon. We observed that ABT‐PPI treatment reduced the soluble and insoluble form of Ab42 in the hippocampus (ANOVA p&lt;0.05) and, interestingly, also in the colon (ANOVA p&lt;0.05), independently of the microbiota transplanted. This was specific to the Ab42 isoform as no differences was observed in the levels of AB40.ConclusionThe results suggest that ABT‐PPI can reduced Ab42 in the brain as well as in the gut in an AD mice model, independently of the microbiota transplanted. The link between the amyloid in the gut and in the brain remain a black box. More research is needed to rule out that the Ab detection in the gut is not due to randomly deposited circulating amyloid from blood. Also, the short ABT intervention and the 2 months delay before sample collection suggests that the driver of the effect observed is the PPI. This will be confirmed by testing the administration of PPI only.

Proton pump inhibitors and myocardial infarction: an application of active comparators in a self-controlled case series.

Previous studies investigating potential cardiovascular adverse events of acid-suppressing drugs are susceptible to protopathic bias and confounding. We aimed to investigate the association between short-term risk of myocardial infarction (MI) and proton pump inhibitors (PPIs) using a self-controlled case series (SCCS) with an active comparator. We conducted a SCCS using a population-wide database from Hong Kong from 2003-2014. Adult with ≥1 outpatient oral PPI prescription or H2 receptor antagonist (H2RA) and MI during the observation period were included. We used both simple ratio and effect modifier approaches to SCCS with active comparators to obtain comparator adjusted estimates. A total of 2802 and 1889 people with MI who had exposure to PPIs and H2RA were included respectively. We observed a higher risk of MI during days 1-14 following the start of PPI prescription (Incidence rate ratio (IRR): 2.30, 95% confidence interval (CI): 1.76-3.00) versus baseline. Similarly, we observed a higher risk of MI during days 1-14 following the start of H2RA prescription (IRR: 2.46, 95%CI: 1.92-3.16) versus baseline. In the novel SCCS analyses, comparator adjusted estimates were 0.93 (95%CI: 0.57-1.30) and 0.83 (95%CI: 0.58-1.20) during days 1-14 in simple ratio and effect modifier approach, respectively. We observed no difference in risk of MI associated with PPIs compared with baseline using H2RA as the active comparator. The elevated risk of MI associated with PPIs is likely due to protopathic bias. More studies are required to explore the feasibility of using active comparators in SCCS to address protopathic bias in addition to confounding.

Proton pump inhibitor usage associates with higher risk of first episodes of pneumonia and peritonitis in peritoneal dialysis patients

Background A large number of studies have shown that proton pump inhibitors (PPIs) are associated with infection events. Therefore, we retrospectively evaluated the association of PPI therapy with the occurrence of first pneumonia and peritoneal dialysis(PD)-related peritonitis events in the maintenance PD patients. Methods We collected PD patients in two large hospitals from January 1, 2012 to December 31, 2016, and divided them into the PPI group and the non-PPI group. Multivariate Cox proportional hazards models were applied to evaluate the cumulative incidence and hazard ratios (HRs). Inverse probability of treatment weight (IPTW) method was used to adjust for covariate imbalance between the two groups and further confirm our findings. Results Finally, 656 PD patients were included for data analysis, and the results showed that PPI usage was associated with an increased risk of pneumonia [HR 1.71; 95% CI 1.06-2.76; p = 0.027] and peritonitis [HR 1.73; 95% CI 1.24-2.40; p = 0.001]. IPTW-adjusted HRs for the association of PPIs with pneumonia and peritonitis were 1.58 (95% CI:1.18-2.12; p = 0.002) and 2.33 (95% CI:1.91-2.85; p < 0.001), respectively. Moreover, the competitive risk model proved that under the conditions of competition for other events(including transfer to hemodialysis therapy, kidney transplant, transfer from our research center, loss to follow-up, and death), the differences in endpoints events between the two groups were still statistically significant (p = 0.009, p < 0.001, respectively). Conclusions PPIs was associated with an increased risk of first pneumonia and PD-related peritonitis events in PD patients, which reminds clinicians to be cautious when prescribing acid-suppressing drugs for PD patients.

An Unusual Cause of Esophagitis

An Unusual Cause of Esophagitis

Association between Acid-Suppressive Drugs and Clinical Outcomes in Patients with Nonvalvular Atrial Fibrillation.

PurposeAcid-suppressive drugs (ASDs) are often prescribed for patients with nonvalvular atrial fibrillation (NVAF) taking oral anticoagulants (OACs). However, the risk-benefit balance of ASDs prescription for patients with NVAF taking OACs is still unclear. This study aimed to assess the association between ASDs and clinical outcomes in patients taking OACs for NVAF.MethodsThis study is a subanalysis of an historical registry study from 71 centers in Japan. We included patients taking vitamin K antagonists for NVAF and excluded those with mechanical heart valves or a history of pulmonary thrombosis or deep vein thrombosis. We registered consecutive patients in February 2013 and followed them up until February 2017. The primary outcomes were ischemic events, major bleedings, and all-cause mortality. Ischemic stroke, acute myocardial infarction, and hemorrhagic stroke comprised the secondary outcomes.ResultsWe included 7826 patients with a mean age of 73 years, 5274 (67%) of whom were males. The adjusted hazard ratios (95% confidence intervals) for ischemic events, major bleedings, and all-cause mortality in the ASD group compared with the no-ASD group were 0.998 (0.78–1.27), 0.98 (0.81–1.18), and 1.22 (1.02–1.47), respectively, while those for ischemic stroke, acute myocardial infarction, and hemorrhagic stroke were 0.96 (0.74–1.24), 0.82 (0.36–1.88), and 1.17 (0.69–1.99), respectively.ConclusionsASDs were significantly associated with all-cause mortality in patients with NVAF taking OACs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40268-022-00392-5.

Acid Suppressive Drugs

Histamine H2 receptor antagonists (H2RAs) suppress gastric acid production by blocking H2 receptors in parietal cells. Studies have shown that proton pump inhibitors (PPIs) are superior to H2RAs as a treatment for acid-related disorders, such as peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). PPIs reduce gastric acid production by irreversibly inhibiting the H+/K+ ATPase pump, and they also increase gastric emptying. Although PPIs have differing pharmacokinetic properties, each PPI is effective in managing GERD and PUDs. However, PPIs have some limitations, including short plasma half-lives, breakthrough symptoms (especially at night), meal-associated dosing, and concerns associated with long-term PPI use. Potassium-competitive acid blockers (P-CABs) provide more rapid and profound suppression of intragastric acidity than PPIs. P-CABs are non-inferior to lansoprazole in healing erosive esophagitis and peptic ulcers, and may also be effective in improving symptoms in patients with non-erosive reflux disease. Acid suppressive drugs are the most commonly used drugs in clinical practice, and it is necessary to understand the pharmacological properties and adverse effects of each drug.

Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans

Fexuprazan is a potassium-competitive acid blocker (P-CAB). The compounds in this newly developed drug family suppress intragastric acidity. As there are already other acid-suppressing drugs on the market, such as H2 antagonists and proton pump inhibitors (PPIs), it would be informative to compare the biological effects of fexuprazan against another approved drug with the same indication. The drug concentration predicted by the pharmacokinetic (PK) model could serve as an input function for a pharmacodynamic (PD) model. The apparent pharmacokinetics of fexuprazan could be described by a simpler model. However, a physiologically based pharmacokinetic (PBPK) model was developed in a previous study. A one-compartment model was also proposed in the present study. Both the newly suggested model and the previously validated PBPK model were used as input functions of the PD models. Our simulation revealed that the effects of fexuprazan could be effectively simulated by the proposed PK–PD models. A PK–PD model was also proposed for the oral administration of the PPI reference drug esomeprazole. A model-based analysis was then performed for intragastric pH using several dosing methods. The expected pH could be predicted for both drugs under several dosing regimens using the proposed PK–PD models.

Risk factors of furazolidone-associated fever.

Furazolidone is a synthetic nitrofuran with a broad spectrum of antimicrobial action and has been widely used in the treatment of Helicobacter pylori (H. pylori) infection. However, its safety profile has not been clarified. Moreover, the drug fever associated with its use is frequently misdiagnosed. The aim of this study was to explore the risk factors of furazolidone-associated fever to increase awareness and stimulate further research on this topic. This was a retrospective case-control study of patients referred to a specialist clinic for furazolidone-containing quadruple regimens for H. pylori infection at a tertiary care hospital located in Eastern China between July 2018 and September 2018. We evaluated adult patients who received furazolidone treatment for Helicobacter pylori infection. The exclusion criteria were as follows: (1) patients were pregnant or breastfeeding; (2) patients received furazolidone treatment not for Helicobacter pylori infection; (3) patients had taken antibiotics or any acid suppressant or non-steroidal anti-inflammatory drug in the last 4 weeks; (4) patients had chronic hepatic, renal, or pulmonary disease. Pertinent information was retrieved from medical records and telephone follow-up. All statistical analysis was performed in SPSS version 22.0. A total of 1499 patients received furazolidone and met the overall inclusion criterion. Of these 1499 patients, 27 (1.80%) developed drug fever. The mean time between initiation of furazolidone and the onset of fever is 11.00 ± 1.84 days, and the median peak fever was 38.87 ± 0.57°C. We found no differences in age and past drug allergy between the non-fever and fever groups. Through multiple logistic regression analysis, we found two variables as independent risk factors for furazolidone-associated fever, including gender (OR, 3.16; 95% CI, 1.26-7.91; P = 0.014) and clarithromycin (OR, 4.83; 95% CI, 2.17-10.79; P<0.001). This retrospective cohort study identified two risk factors for furazolidone-associated fever, which were female and clarithromycin. We also analyzed the characteristics of drug fever during anti-Helicobacter pylori therapy. However, the underlying mechanisms are uncertain and require further research.

The role of Proton Pump Inhibitors in COVID-19

The use of proton pump inhibitors (PPIs) has been associated with an increased risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and severe outcomes. This may be because the gut is the most important immune organ in the body and the virus reach and replicate rapidly in the absence of gastric acid. Therefore, the use of PPIs as acid suppressant drugs may have a negative impact on COVID-19. We aimed to identify the relationship between the use of PPIs with the incidence of Covid-19 and the severity of outcomes. This case-control study was conducted on 246 participants who were pretested for Covid-19 in Herat city, Afghanistan. We investigated the incidence rate and risk of severe clinical symptoms and outcomes (mechanical ventilation, intensive care unit (ICU) admission, and requirement of oxygen therapy) in COVID-19 patients. The incidence of Covid-19 was insignificantly higher among PPI users than non-users (OR 1.29, 95% CI 0.74 – 2.25). Moreover, the symptoms including respiratory, digestive and systemic complains, taste and smell disturbances and outcome of the disease were more severe in PPI users {OR (95% CI)}, 2.47 (0.71 – 8.63), 2.16 (0.97 – 4.84), 2.32 (1.01 – 5.31), 2.23 (1.05 – 4.72), 2.62 (1.23 – 5.45), 4.38 (2.01 – 9.51), 7.56 (2.93 – 19.61) and 5.99 (2.52 – 14.30) respectively. In Conclusion, we found a significantly increased risk of COVID-19 negative outcomes in PPIs users. Further studies with a larger sample size are needed to find the exact role of PPIs use on COVID-19.

Use of acid-suppressive drugs in gastrointestinal tract lesions in COVID-19

This review is devoted to the clinical picture, approaches to the diagnosis and treatment of gastrointestinal diseases in the novel coronavirus SARS-CoV-2.

Current real-world treatments for Japanese patients with eosinophilic esophagitis

A total of 306 patients with eosinophilic esophagitis (EoE) were analyzed at our department. Proton pump inhibitors or potassium-competitive acid blockers were used as the first-line treatment in 286 (93.5%) patients. Fifty-five (18.0%) patients received topical steroid swallowing therapy. During 17.7-month mean follow-up, 46.4% of the patients were followed-up with no medications, 37.3% of the patients received maintenance or on-demand therapy using acid-suppressive drugs, and 9.8% of the patients received maintenance therapy with steroid swallowing. The majority of patients with EoE were treated using a therapeutic strategy similar to that used for gastroesophageal reflux disease. However, some patients were refractory to the treatment. Current real-world treatment strategies for Japanese patients with EoE are clarified.

Use of acid-suppressive drugs and risk of fracture in children and young adults: a meta-analysis of observational studies.

Acid-suppressive drugs (ASDs) are being used by increasing number of children and young adults. However, evidence for a relationship between ASD use and the risk of fracture in these groups of patients is conflicting. We conducted a meta-analysis to evaluate the risk of fracture in children and young adults exposed to ASDs. A literature search was performed using the PUBMED, EMBASE, and Cochrane Library databases from inception to November 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to determine the relationship of ASD use with fracture risk in children and young adults. Six studies reporting the outcomes of more than 900,000 children and young adults with ASD use were included in the meta-analysis. The pooled RR for fracture with the use of proton pump inhibitors (PPIs) versus non-use of these medications was 1.17 (95% CI = 1.1-1.25; P < 0.001) in children and 1.2 (95% CI = 0.87-1.65; P = 0.272) in young adults. By contrast, the use of histamine H2-receptor antagonists (H2RAs) was not significantly associated with fracture risk in children (RR, 1.08, 95% CI = 0.99-1.17; P = 0. 083) or young adults (RR, 1.08, 95% CI = 0.82-1.42; P = 0.589). Significant statistical and clinical heterogeneity among studies were determined for the main analysis and most of the subgroup analyses. Our study provides evidence linking PPI use to an increased risk of fracture in children. Thus, the use of PPIs in these patients should be carefully considered. However, randomized controlled studies are needed to determine causality and the role of unmeasured/residual confounding factors in this association.

A Birds-Eye (Re)View of Acid-Suppression Drugs, COVID-19, and the Highly Variable Literature.

This Perspective examines a recent surge of information regarding the potential benefits of acid-suppression drugs in the context of COVID-19, with a particular eye on the great variability (and, thus, confusion) that has arisen across the reported findings, at least as regards the popular antacid famotidine. The degree of inconsistency and discordance reflects contradictory conclusions from independent, clinical-based studies that took roughly similar approaches, in terms of both experimental design (retrospective, observational, cohort-based, etc.) and statistical analysis workflows (propensity-score matching and stratification into sub-cohorts, etc.). The contradictions and potential confusion have ramifications for clinicians faced with choosing therapeutically optimal courses of intervention: e.g., do any potential benefits of famotidine suggest its use in a particular COVID-19 case? (If so, what administration route, dosage regimen, duration, etc. are likely optimal?) As succinctly put this March in Freedberg et al. (2021), “…several retrospective studies show relationships between famotidine and outcomes in COVID-19 and several do not.” Beyond the pressing issue of possible therapeutic indications, the conflicting data and conclusions related to famotidine must be resolved before its inclusion/integration in ontological and knowledge graph (KG)–based frameworks, which in turn are useful for drug discovery and repurposing. As a broader methodological issue, note that reconciling inconsistencies would bolster the validity of meta-analyses which draw upon the relevant data-sources. And, perhaps most broadly, developing a system for treating inconsistencies would stand to improve the qualities of both 1) real world evidence-based studies (retrospective), on the one hand, and 2) placebo-controlled, randomized multi-center clinical trials (prospective), on the other hand. In other words, a systematic approach to reconciling the two types of studies would inherently improve the quality and utility of each type of study individually.

Acid-Suppressive Drugs and Risk of Fracture in Children and Young Adults: A Meta-Analysis of Observational Studies.

Background: Recent studies have suggested that proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs) may increase the risk of fracture. We performed a meta-analysis to evaluate the risk of fracture with PPIs and H2RAs use in children and young adults.Methods: PubMed, EMBASE database, Cochrane Library, and Web of Science for relevant articles published before May 2021 were searched. We included all the observational studies reporting on the risk of fracture with acid-suppressive drug (PPIs and H2RAs) use in children and young adults. We calculated pooled risk ratios (RRs) for fracture using random-effects models and conducted subgroup analyses.Results: A total of six studies were included in our analysis. Pooled analysis of PPIs use showed significant risk for fracture (RR = 1.23; 95% CI, 1.12–1.34; I 2 = 79.3), but not significant for PPIs combined with H2RAs use (RR = 1.22; 95% CI, 0.94–1.60; I 2 = 44.0%), as well as for H2RAs use alone (RR = 1.08; 95% CI, 0.94-1.24; I 2 = 84.1%). Grouping of studies by region showed a significantly increased fracture risk with PPIs use in North America (RR = 1.24; 95% CI, 1.16–1.32; I 2 =0.0%) than in Europe (RR = 1.23; 95% CI, 1.00–1.52; I 2 = 94.6%) and Asia (RR = 1.10; 95% CI, 0.96–1.25). However, there was no significant association between the H2RAs use and the fracture risk in North America (RR = 1.08; 95% CI, 1.00–1.09; I 2 = 0.0%). Moreover, PPIs use showed an increased risk of fracture in women (RR = 1.13; 95% CI, 1.07–1.19; I 2 = 0.0%), whereas there was no significant association between the PPIs use and the risk of fracture in men (RR = 0.93; 95% CI, 0.66–1.31; I 2 = 0.0%).Conclusion: PPIs use alone could increase the risk of fracture in children and young adults, but not for PPIs combined with H2RAs use or H2RAs use alone. Clinicians should exercise caution when prescribing PPIs for patients.

Effectiveness and safety of proton pump inhibitors for treating acute pancreatitis: A protocol for systematic review and meta analysis.

Background:Previous studies have showed that anti-acid therapy with proton pump inhibitors (PPIs) can inhibit pancreatic secretion and it may be used in treating acute pancreatitis (AP). But at present, there is no systematic reviews for the evidence and the therapeutic effectiveness and safety of anti-acid therapy with PPIs in AP were not unclear. Therefore, we will undertake a systematic review of the literature to summarize previous evidence regarding this topic, in order to clarify the effectiveness and safety of anti-acid therapy with PPIs in AP.Methods:We will search the EMBASE, WANFANG DATA, Web of Knowledge, China National Knowledge Infrastructure, PubMed, ClinicalTrials.gov and Cochrane Library from inception to June 30,2021 to retrieve relevant studies using the search strategy: (“Proton pump inhibitors” OR “PPI” OR “PPIs” OR “Omeprazole” OR “Tenatoprazole” OR “Pantoprazole” OR “acid suppression therapy” OR “acid suppression drugs”) AND (“pancreatitis” OR “pancreatitides”). Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I2 statistic.Results:This study assessed the efficiency and safety of proton pump inhibitors for treating acute pancreatitis.Conclusions:This study will provide reliable evidence-based evidence for the clinical application of PPIs for treating AP.Ethics and dissemination:Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.

Association between acid‐suppressive drug use and atopic dermatitis in patients with upper gastrointestinal diseases: A population‐based retrospective cohort study

Proton-pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are two of the most widely used acid-suppressive drugs (ASDs). Some studies have reported that prenatal ASD exposure may increase the risk of asthma and other allergic diseases. This study investigated the effects of ASDs on the risk of atopic dermatitis in patients with upper gastrointestinal diseases. This population-based retrospective cohort study used data of 289,850 patients with at least two diagnoses of upper gastrointestinal diseases (UGIDs) between 1 January 2001 and 31 December 2005, from Taiwan's National Health Insurance Research Database. The AD risks among ASD users and nonusers were compared. Differences in sociodemographic characteristics and potential covariates were examined. AD hazard ratios were estimated, and groups were compared using Cox proportional hazards regression analysis after adjustment for age, sex and other covariates. In total, 109,980 patients were included. The adjusted hazard ratio (HR) of AD risk in ASD users relative to that in nonusers was 1.52 (95% confidence interval [CI]: 1.40-1.64, p<0.001). For a dose-effect sub-analysis, patients were divided into four groups based on their defined daily dose. ASDs dose-dependently affected the AD risk (p for trend <0.01). Furthermore, the adjusted HR of the AD risk among ASD nonusers was 2.30 (95% CI: 2.06-2.57) relative to that in the comparison group (ASD nonusers without UGIDs). Among patients with UGIDs, ASD users had a higher AD risk than ASD nonusers. A subgroup analysis revealed only H2RA use was associated with an increased AD risk (adjusted HR 1.70, 95% CI: 1.53-1.89, p<0.001). These results indicate that the use of H2RAs was associated with an increased risk of AD among patients with UGIDs, and the increase in risk appeared to be dose-dependent. ASDs should be used only in situations where clear clinical benefits can be obtained.