BACKGROUND Exposure to proton pump inhibitors(PPIs)has been reported to have a potential role in the development of diabetes.AIM To determine the association between PPIs and diabetes.METHODS This meta-analysis is reg...BACKGROUND Exposure to proton pump inhibitors(PPIs)has been reported to have a potential role in the development of diabetes.AIM To determine the association between PPIs and diabetes.METHODS This meta-analysis is registered on PROSPERO(CRD42022352704).In August 2022,eligible studies were identified through a comprehensive literature search.In this study,odds ratios were combined with 95%confidence intervals using a random-effects model.The source of heterogeneity was assessed using sensitivity analysis and subgroup analysis.The publication bias was evaluated using Egger’s test and Begg’s test.RESULTS The meta-analysis included 9 studies with a total of 867185 participants.Results showed that the use of PPIs increased the risk of diabetes(odds ratio=1.23,95%confidence interval:1.05-1.43,n=9,I2=96.3%).Subgroup analysis showed that geographic location and study type had significant effects on the overall results.Both Egger’s and Begg’s tests showed no publication bias(P>0.05).Sensitivity analysis also confirmed the stability of the results.CONCLUSION The results of this study indicated that the use of PPIs was related to an increased risk of diabetes.However,more well-designed studies are needed to verify these results in the future.展开更多
Aspirin,other antiplatelet agents,and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases.A concomitant proton pump inhibitor(PPI)treatment is often prescribed in these p...Aspirin,other antiplatelet agents,and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases.A concomitant proton pump inhibitor(PPI)treatment is often prescribed in these patients,as gastrointestinal complications are relatively frequent.On the other hand,a potential increased risk of cardiovascular events has been suggested in patients treated with PPIs;in particular,it has been discussed whether these drugs may reduce the cardiovascular protection of clopidogrel,due to pharmacodynamic and pharmacokinetic interactions through hepatic metabolism.Previously,the concomitant use of clopidogrel and omeprazole or esomeprazole has been discouraged.In contrast,it remains less known whether PPI use may affect the clinical efficacy of ticagrelor and prasugrel,new P2Y12 receptor antagonists.Current guidelines recommend PPI use in combination with antiplatelet treatment in patients with risk factors for gastrointestinal bleeding,including advanced age,concurrent use of anticoagulants,steroids,or non-steroidal anti-inflammatory drugs,and Helicobacter pylori(H.pylori)infection.In patients taking oral anticoagulant with risk factors for gastrointestinal bleeding,PPIs could be recommended,even if their usefulness deserves further data.H.pylori infection should always be investigated and treated in patients with a history of peptic ulcer disease(with or without complication)treated with antithrombotic drugs.The present review summarizes the current knowledge regarding the widespread combined use of platelet inhibitors,anticoagulants,and PPIs,discussing consequent clinical implications.展开更多
BACKGROUND Endoscopic variceal treatment(EVT)is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis.Proton pump inhibitors(PPIs)ar...BACKGROUND Endoscopic variceal treatment(EVT)is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis.Proton pump inhibitors(PPIs)are widely used for various gastric acid-related diseases.However,the effects of PPIs on the development of post-EVT complications,especially gastrointestinal bleeding(GIB),remain controversial.AIM To evaluate the effects of postoperative use of PPIs on post-EVT complications in patients with liver cirrhosis during hospitalization.METHODS Patients with a diagnosis of liver cirrhosis who were admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command,treated by an attending physician between January 2016 and June 2020 and underwent EVT during their hospitalization were included.Logistic regression analyses were performed to explore the effects of postoperative use of PPIs on the development of post-EVT complications during hospitalization.Odds ratios(ORs)with 95%confidence intervals(CIs)were calculated.RESULTS A total of 143 patients were included.The incidence of post-EVT GIB and other post-EVT complications was 4.90%and 46.85%,respectively.In the overall analyses,postoperative use of PPIs did not significantly reduce the risk of post-EVT GIB(OR=0.525,95%CI=0.113-2.438,P=0.411)or other post-EVT complications(OR=0.804,95%CI=0.413-1.565,P=0.522).In the subgroup analyses according to the enrollment period,type and route of PPIs after the index EVT,use of PPIs before the index EVT,use of vasoactive drugs after the index EVT,indication of EVT(prophylactic and therapeutic),and presence of portal venous system thrombosis,ascites,and hepatocellular carcinoma,the effects of postoperative use of PPIs on the risk of post-EVT GIB or other post-EVT complications remain not statistically significant.CONCLUSION Routine use of PPIs after EVT should not be recommended in patients with liver cirrhosis for the prevention of post-EVT complications during hospitalization.展开更多
Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarat...Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.展开更多
During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[Mt10]t intrigued us,as it couldn't be assigned to any literature k...During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[Mt10]t intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[Mt10]t has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ionization.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a′).Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.展开更多
AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to i...AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.展开更多
AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patie...AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patients diagnosed with CDAD between January 2006 and December 2007 were collected by medical chart review.Collected data included patient characteristics at baseline,underlying medical disease, antibiotic history before receiving a diagnosis of CDAD, duration of hospital stay,severity of CDAD,concurrenttreatment with PPIs,laboratory parameters,response to CDAD therapy,and recurrence of disease within 90 d of successful treatment.Various clinical and laboratory parameters were compared in patients in whom CDAD did or did not recur. RESULTS:Of the 125 patients(mean age,67.6± 13.9 years)that developed CDAD,98(78.4%)did not experience recurrence(non-recurrent group)and 27 (21.6%)experienced one or more recurrences(recurrent group).Prior to the development of CDAD,96% of the 125 patients were prescribed antibiotics,and 56(44.8%)of the patients received PPIs.Age older than 65 years(P=0.021),feeding via nasogastric tube(NGT)(P=0.045),low serum albumin level(P =0.025),and concurrent use of PPIs(P=0.014) were found to be risk factors for CDAD recurrence by univariate analysis.However,sex,length of hospital stay,duration and type of antibiotics used,severity of disease,leukocyte count and C-reactive protein(CRP) were not associated with risk of CDAD recurrence.On multivariate analysis,the important risk factors were advanced age(>65 years,adjusted OR:1.32,95% CI:1.12-3.87,P=0.031),low serum albumin level(< 2.5 g/dL,adjusted OR:1.85,95%CI:1.35-4.91,P= 0.028),and concurrent use of PPIs(adjusted OR:3.48, 95%CI:1.64-7.69,P=0.016). CONCLUSION:Advanced age,serum albumin level< 2.5 g/dL,and concomitant use of PPIs were found to be significant risk factors for CDAD recurrence.展开更多
AIM To determine the sensitivity and specificity of the ^(13)C-urea breath test(UBT) in patients taking proton pump inhibitors(PPIs), using a new test meal Refex. METHODS One hundred and fourteen consecutive patients ...AIM To determine the sensitivity and specificity of the ^(13)C-urea breath test(UBT) in patients taking proton pump inhibitors(PPIs), using a new test meal Refex. METHODS One hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori(H. pylori) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the ^(13)C-UBT with the new test meal was performed the next morning. RESULTS The sensitivity of the ^(13)C-UBT with a cut off 2.5‰ was92.45%(95%CI: 81.79%-97.91%) by per-protocol(PP) analysis and 78.13 %(95%CI: 66.03%-87.49%) by intention-to-treat(ITT) analysis. The specificity of the ^(13)C-UBT test was 96.00 % in the ITT population(95%CI: 86.29%-99.51%) and 97.96% in the PP population(95%CI: 89.15%-99.95%).CONCLUSION The new test meal based ^(13)C-UBT is highly accurate in patients on PPIs and can be used in those unable to stop their PPI treatment.展开更多
AIM To investigate whether the use of proton pump inhibitors(PPIs) increases the incidence of spontaneous bacterial peritonitis(SBP) in patients with cirrhosis and ascites.METHODS An historical cohort study was carrie...AIM To investigate whether the use of proton pump inhibitors(PPIs) increases the incidence of spontaneous bacterial peritonitis(SBP) in patients with cirrhosis and ascites.METHODS An historical cohort study was carried out in cirrhotic outpatients with ascites followed in a specialized clinic at a tertiary hospital in Southern Brazil. Patient charts were reviewed to collect information on the variables of interest as the use of PPIs. Primary outcome was defined as development of SBP during the study period. SBP was diagnosed based on ascitic fluid polymorphonuclear cell count ≥ 250 cells/mm3 without evidence of an intraabdominal, surgically treatable source of infection.RESULTS Of 738 cirrhotic patients, 582(58.2% male) were enrolled, with mean age of 53.6 ± 12 years. Hepatitis C virus infection(36.2%) and alcohol abuse(25.6%) were the main etiologies of cirrhosis. The presence of ascites was detected in 299(51.4%) patients during the development of the study. Nineteen patients with previous diagnosis of SBP undergoing secondary prophylaxis and 22 patients with insufficient PPI data were further excluded. Of 258 patients with ascites, 151 used PPIs, and 34 developed SBP(22.5%). Among 107 non-users of PPIs, 23 developed SBP(21.5%)(HR = 1.44, 95%CI: 0.85-2.47, P = 0.176). The median follow-up time of patients using PPI was 27 mo vs 32 mo for non-users. Univariate analysis of the risk factors associated with the development of SBP revealed a significant association of SPB with the severity of liver disease according to the Child-Turcotte-Pugh(CTP) score. Multivariate analysis confirmed that CTP score was the only independent variable influencing the occurrence of SBP. Survival at 60 mo(Kaplan-Meier analysis) was similar in users and non-users of PPI, independently of the presence of SBP(58.4% vs 62.7% respectively, P = 0.66). For patients with SBP, survival at 60 mo was 55.1%, vs 61.7% in patients without SBP(P = 0.34). CONCLUSION In conclusion, the rate of SBP was not significantly different in users or non-users of PPIs in this cohort of cirrhotic with ascites.展开更多
BACKGROUND The proton pump inhibitors(PPIs),used to reduce gastric acid secretion,represent one of the most widely used pharmaceutical classes in the world.Their consumption as a risk factor for the evolution of sever...BACKGROUND The proton pump inhibitors(PPIs),used to reduce gastric acid secretion,represent one of the most widely used pharmaceutical classes in the world.Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been investigated as well as the mortality of these patients.These risks also appear to be linked to the duration and the dosage.On the other hand,several studies have emerged with regard to the protective or therapeutic effects of these drugs.More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs.In addition,their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells.AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019(COVID-19)in patients affected by SARS-CoV-2 infection,with the main objective of evaluating the outcomes related to severity and mortality.METHODS A literature review was performed in November 2020.The MEDLINE/PubMed,Cochrane Library,EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic.The search terms were identified by means of controlled vocabularies,such as the National Library of Medicine’s MESH(Medical Subject Headings)and keywords.The MESH terms and keywords used were as follows:“COVID-19”,“proton pump inhibitors”,“PPIs”,“SARS-CoV-2”,“outcomes”,“severity”and“mortality”.The inclusion criteria regarding the studies considered in our analysis were:meta-analysis,casecontrol,hospital-based case-control,population-based case-control,retrospective studies,online survey,as well as cohort-studies,while articles not published as full reports,such as conference abstracts,case reports and editorials were excluded.We tried to summarize and pool all the data if available.RESULTS A total of 9 studies were found that described the use of PPIs,of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients.Our pooled incidence analysis of severe events did not differ between patients with and without PPIs(odds ratio 1.65,95%confidence interval:0.62-4.35)(P=0.314),or for mortality(odds ratio 1.77,95%confidence interval:0.62-5.03)(P=0.286).CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.展开更多
Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) pa...Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) palbociclib a drug interaction with PPi was hypothesized. It was shown in a retrospective study that this association was an independent predictive factor for worse progression-free survival (PFS). Objective: To verify the impact of concomitant administration of PPi with Ci on overall survival (OS) and PFS. Material and Methods: This is a retrospective cohort study of patients treated with Ci for HR+HER2-ABC in the period from Feb/2017 to Aug/2020. SPSS software was used for data processing. Univariate analysis was done by the Kaplan-Meier method and log-rank test, and multivariate analysis by COX regression. P-value < 0.05 was considered significant. Results: 80 patients were included. The median age at diagnosis of ABC was 56 years (25 - 75). Treatment with Ci was 1st line for ABC in 68.8%. Choice of Ci was palbociclib in 73.8% (n = 59) and ribociclib in 26.3% (n = 21). The hormone partner was a nonsteroidal aromatase inhibitor in 45.0%, and fulvestrant in 55.0% of cases. 37.5% of patients were on PPi, and 70.0% of them were during the entire treatment (23.3% omeprazole, 73.4% pantoprazole, 3.3% others). Patients taking concomitant PPi and Ci had lower OS (OS-3 years 42.6% vs. 63.4%, p = 0.254) and PFS (PFS med 15 m. vs. 21 m., p = 0.733), although with no statistically significant difference. Discussion: In the sample, there was a numerical difference, without the statistical significance in the use of PPi in the survival of patients under Ci. This difference could be more evident with a longer follow-up and a larger sample size. This study intends to alert to the growing importance of checking for drug interactions. Polymedication, advanced age and the presence of several comorbidities are real problems in patients with ABC. Conclusion: Real-world data from this center demonstrate a negative, non-statistically significant impact of PPi treatment on survival outcomes, in patients treated with Ci for HR+HER2-ABC.展开更多
AIM To compare the outcomes between laparoscopic Nissen fundoplication(LNF)and proton pump inhibitors(PPIs)therapy in patients with laryngopharyngeal reflux(LPR)and typeⅠhiatal hernia diagnosed by oropharyngeal p H-m...AIM To compare the outcomes between laparoscopic Nissen fundoplication(LNF)and proton pump inhibitors(PPIs)therapy in patients with laryngopharyngeal reflux(LPR)and typeⅠhiatal hernia diagnosed by oropharyngeal p H-monitoring and symptom-scale assessment.METHODS From February 2014 to January 2015,70 patients who were diagnosed with LPR and type I hiatal hernia and referred for symptomatic assessment,oropharyngeal p H-monitoring,manometry,and gastrointestinal endoscopy were enrolled in this study.All of the patients met the inclusion criteria.All of the patients underwent LNF or PPIs administration,and completed a2-year follow-up.Patients’baseline characteristics and primary outcome measures,including comprehensive and single symptoms of LPR,PPIs independence,and satisfaction,and postoperative complications were assessed.The outcomes of LNF and PPIs therapy were analyzed and compared. RESULTS There were 31 patients in the LNF group and 39patients in the PPI group.Fifty-three patients(25 in the LNF group and 28 in the PPI group)completed reviews and follow-up.Oropharyngeal p H-monitoring parameters were all abnormal with high acid exposure,a large amount of reflux,and a high Ryan score,associated reflux symptom index(RSI)score.There was a significant improvement in the RSI and LPR symptom scores after the 2-year follow-up in both groups(P<0.05),as well as typical symptoms of gastroesophageal reflux disease.Improvement in the RSI(P<0.005)and symptom scores of cough(P=0.032),mucus(P=0.011),and throat clearing(P=0.022)was significantly superior in the LNF group to that in the PPI group.After LNF and PPIs therapy,13 and 53 patients achieved independence from PPIs therapy(LNF:44.0%vs PPI:7.14%,P<0.001)during follow-up,respectively.Patients in the LNF group were more satisfied with their quality of life than those in the PPI group(LNF:62.49±28.68 vs PPI:44.36±32.77,P=0.004).Body mass index was significantly lower in the LNF group than in the PPI group(LNF:22.2±3.1kg/m^2 vs PPI:25.1±2.9 kg/m^2,P=0.001).CONCLUSION Diagnosis of LPR should be assessed with oropharyngeal p H-monitoring,manometry,and the symptom-scale.LNF achieves better improvement than PPIs for LPR with type I hiatal hernia.展开更多
The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its c...The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its coccoid form,which is resistant to antibiotics.On these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be administered.Therefore,several tricks need to be used to optimize eradication rate of different regimens.The administration of the highest dose as possible of PPI,by doubling or increasing the number of pills/day,has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies,even if specific trials have not been performed.A pre-treatment with PPI before starting antibiotics does not seem to be effective,therefore it is discouraged.However,the choice of PPI molecule could have a certain weight,since second-generation substances(esomeprazole,rabeprazole)are likely more effective than those of first generation(omeprazole,lansoprazole).A possible explanation is due to their metabolism,which has been proven to be less dependent on cytochrome P450(CYP)2C19 genetic variables.Finally,vonoprazan,a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy,due to both its highest acid inhibition power and rapid pharmacologic effect.However current data come only from Eastern Asia,therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.展开更多
AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLIN...AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLINE, EMBASE and Pub Med for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios(OR) and mean difference with 95% confidence interval(CI). Rev Man 5.3.3 software and Stata 12.0 software were used for data analyses. RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors(PPI) group and the remaining 605 subjects were in the H2 receptor antagonists(H2RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H2 RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate(OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate(OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality(OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference(WMD),-0.70 unit; 95%CI:-1.64- 0.25] and the time that patients remained hospitalized [WMD,-0.77 d; 95%CI:-1.87- 0.34]. The Begg's test(P = 0.283) and Egger's test(P = 0.339) demonstrated that there was no publication bias in our meta-analysis.CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H2 RA, PPI may be a more effective therapy.展开更多
AIM:To assess the potential benefits of mosapride plus proton pump inhibitors(PPIs)in the treatment of gastroesophageal reflux disease.METHODS:A literature search was performed through MEDLINE,EMBASE,and the ISI Web o...AIM:To assess the potential benefits of mosapride plus proton pump inhibitors(PPIs)in the treatment of gastroesophageal reflux disease.METHODS:A literature search was performed through MEDLINE,EMBASE,and the ISI Web of Knowledge.The clinical trials that compared the benefit of mosapride plus PPI treatment with that of PPI monotherapy were analyzed.The rate of responders was evaluated by the pooled relative risk(PRR)and improvement in symptom scores was assessed by single effect size of a standardized mean,while Hedges’g was used as the effect size.Pooled effect sizes with 95%CIs were calculated using a fixed-effects model.Between-study heterogeneity was assessed using Q test and I2analyses.In addition,studies that assessed the additional efficacy of mosapride in PPI-resistant patients were also reviewed.RESULTS:This systematic review included information on a total of 587 patients based on 7 trials.Four trials compared the efficacy of combination therapy of mosapride plus a PPI with that of PPI monotherapy.The statistical analysis for the effect of additional mosapride showed equivocal results(PRR=1.132;95%CI:0.934-1.372;P=0.205;Hedges’g=0.24;95%CI:0.03-0.46;P=0.023).No heterogeneity and publication bias were found among the studies.Three openlabeled trials assessed the additional efficacy of mosapride in PPI-resistant patients.However,since these trials did not set the control group,the results may be considerably biased.CONCLUSION:Mosapride combined therapy is not more effective than PPI alone as first-line therapy.Whether it is effective in PPI-resistant patients needs to be determined.展开更多
AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven ...AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.展开更多
AIM: To investigate the influence of proton pump inhibitors(PPIs) exposure on the diagnosis of Helicobacter pylori(H. pylori) gastritis and intestinal metaplasia.METHODS: Chronic PPI use is associated with masking of ...AIM: To investigate the influence of proton pump inhibitors(PPIs) exposure on the diagnosis of Helicobacter pylori(H. pylori) gastritis and intestinal metaplasia.METHODS: Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed(H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System.RESULTS: Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old(range: 20-87). The histological types of gastritis were classified as H. pylori gastritis(n = 156, 52%) and non-H. pylori gastritis(n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure(71% vs 34.2%, P < 0.001). Intestinal metaplasiawas more likely to be detected in the latter patients(1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure(OR = 0.217, 95%CI: 0.123-0.385), GERD(OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake(OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia.CONCLUSION: The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.展开更多
AIM: To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. METHODS: A crosssectional study of consecutive in-patients admitted to hospital in any departmen...AIM: To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. METHODS: A crosssectional study of consecutive in-patients admitted to hospital in any department during the fi rst semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a diagnosis of hyperglycemic decompensation, diabetic onset or pregnancy. It compared HbA1c levels of those taking PPIs and those not. RESULTS: A total of 97 patients were recruited. The average HbA1C level was 7.0% ± 1.2%. Overall PPI consumption was 55.7%. HbA1c was signif icantly lower in individuals who took PPIs: -0.6%, 95% CI: -0.12 to-0.83. People who used PPIs with some type of insulin therapy had a HbA1c reduction by -0.8%, 95% CI: -0.12 to -1.48. For the rest of subgroup analysis based on the antidiabetic drug used, PPI consumption always exhibited lower HbA1c levels. CONCLUSION: PPIs seems to be consistently associated with better glycemic control in type 2 diabetes. HbA1c reduction observed is similar to incretin-based therapies.展开更多
BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopat...BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.展开更多
Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastri...Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.展开更多
文摘BACKGROUND Exposure to proton pump inhibitors(PPIs)has been reported to have a potential role in the development of diabetes.AIM To determine the association between PPIs and diabetes.METHODS This meta-analysis is registered on PROSPERO(CRD42022352704).In August 2022,eligible studies were identified through a comprehensive literature search.In this study,odds ratios were combined with 95%confidence intervals using a random-effects model.The source of heterogeneity was assessed using sensitivity analysis and subgroup analysis.The publication bias was evaluated using Egger’s test and Begg’s test.RESULTS The meta-analysis included 9 studies with a total of 867185 participants.Results showed that the use of PPIs increased the risk of diabetes(odds ratio=1.23,95%confidence interval:1.05-1.43,n=9,I2=96.3%).Subgroup analysis showed that geographic location and study type had significant effects on the overall results.Both Egger’s and Begg’s tests showed no publication bias(P>0.05).Sensitivity analysis also confirmed the stability of the results.CONCLUSION The results of this study indicated that the use of PPIs was related to an increased risk of diabetes.However,more well-designed studies are needed to verify these results in the future.
文摘Aspirin,other antiplatelet agents,and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases.A concomitant proton pump inhibitor(PPI)treatment is often prescribed in these patients,as gastrointestinal complications are relatively frequent.On the other hand,a potential increased risk of cardiovascular events has been suggested in patients treated with PPIs;in particular,it has been discussed whether these drugs may reduce the cardiovascular protection of clopidogrel,due to pharmacodynamic and pharmacokinetic interactions through hepatic metabolism.Previously,the concomitant use of clopidogrel and omeprazole or esomeprazole has been discouraged.In contrast,it remains less known whether PPI use may affect the clinical efficacy of ticagrelor and prasugrel,new P2Y12 receptor antagonists.Current guidelines recommend PPI use in combination with antiplatelet treatment in patients with risk factors for gastrointestinal bleeding,including advanced age,concurrent use of anticoagulants,steroids,or non-steroidal anti-inflammatory drugs,and Helicobacter pylori(H.pylori)infection.In patients taking oral anticoagulant with risk factors for gastrointestinal bleeding,PPIs could be recommended,even if their usefulness deserves further data.H.pylori infection should always be investigated and treated in patients with a history of peptic ulcer disease(with or without complication)treated with antithrombotic drugs.The present review summarizes the current knowledge regarding the widespread combined use of platelet inhibitors,anticoagulants,and PPIs,discussing consequent clinical implications.
文摘BACKGROUND Endoscopic variceal treatment(EVT)is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis.Proton pump inhibitors(PPIs)are widely used for various gastric acid-related diseases.However,the effects of PPIs on the development of post-EVT complications,especially gastrointestinal bleeding(GIB),remain controversial.AIM To evaluate the effects of postoperative use of PPIs on post-EVT complications in patients with liver cirrhosis during hospitalization.METHODS Patients with a diagnosis of liver cirrhosis who were admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command,treated by an attending physician between January 2016 and June 2020 and underwent EVT during their hospitalization were included.Logistic regression analyses were performed to explore the effects of postoperative use of PPIs on the development of post-EVT complications during hospitalization.Odds ratios(ORs)with 95%confidence intervals(CIs)were calculated.RESULTS A total of 143 patients were included.The incidence of post-EVT GIB and other post-EVT complications was 4.90%and 46.85%,respectively.In the overall analyses,postoperative use of PPIs did not significantly reduce the risk of post-EVT GIB(OR=0.525,95%CI=0.113-2.438,P=0.411)or other post-EVT complications(OR=0.804,95%CI=0.413-1.565,P=0.522).In the subgroup analyses according to the enrollment period,type and route of PPIs after the index EVT,use of PPIs before the index EVT,use of vasoactive drugs after the index EVT,indication of EVT(prophylactic and therapeutic),and presence of portal venous system thrombosis,ascites,and hepatocellular carcinoma,the effects of postoperative use of PPIs on the risk of post-EVT GIB or other post-EVT complications remain not statistically significant.CONCLUSION Routine use of PPIs after EVT should not be recommended in patients with liver cirrhosis for the prevention of post-EVT complications during hospitalization.
文摘Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82030107 and 81872831)the National Science and Technology Major Projects for significant new drugs creation of the 13th five-year plan(Grant Nos.:2017ZX09101001 and 2018ZX09721002007).
文摘During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[Mt10]t intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[Mt10]t has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ionization.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a′).Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.
基金Supported by First Affiliated Hospital,Guangxi Medical University
文摘AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.
基金Supported by A Seoul National University Boramae Hospital Grant(03-2007-1)
文摘AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patients diagnosed with CDAD between January 2006 and December 2007 were collected by medical chart review.Collected data included patient characteristics at baseline,underlying medical disease, antibiotic history before receiving a diagnosis of CDAD, duration of hospital stay,severity of CDAD,concurrenttreatment with PPIs,laboratory parameters,response to CDAD therapy,and recurrence of disease within 90 d of successful treatment.Various clinical and laboratory parameters were compared in patients in whom CDAD did or did not recur. RESULTS:Of the 125 patients(mean age,67.6± 13.9 years)that developed CDAD,98(78.4%)did not experience recurrence(non-recurrent group)and 27 (21.6%)experienced one or more recurrences(recurrent group).Prior to the development of CDAD,96% of the 125 patients were prescribed antibiotics,and 56(44.8%)of the patients received PPIs.Age older than 65 years(P=0.021),feeding via nasogastric tube(NGT)(P=0.045),low serum albumin level(P =0.025),and concurrent use of PPIs(P=0.014) were found to be risk factors for CDAD recurrence by univariate analysis.However,sex,length of hospital stay,duration and type of antibiotics used,severity of disease,leukocyte count and C-reactive protein(CRP) were not associated with risk of CDAD recurrence.On multivariate analysis,the important risk factors were advanced age(>65 years,adjusted OR:1.32,95% CI:1.12-3.87,P=0.031),low serum albumin level(< 2.5 g/dL,adjusted OR:1.85,95%CI:1.35-4.91,P= 0.028),and concurrent use of PPIs(adjusted OR:3.48, 95%CI:1.64-7.69,P=0.016). CONCLUSION:Advanced age,serum albumin level< 2.5 g/dL,and concomitant use of PPIs were found to be significant risk factors for CDAD recurrence.
文摘AIM To determine the sensitivity and specificity of the ^(13)C-urea breath test(UBT) in patients taking proton pump inhibitors(PPIs), using a new test meal Refex. METHODS One hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori(H. pylori) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the ^(13)C-UBT with the new test meal was performed the next morning. RESULTS The sensitivity of the ^(13)C-UBT with a cut off 2.5‰ was92.45%(95%CI: 81.79%-97.91%) by per-protocol(PP) analysis and 78.13 %(95%CI: 66.03%-87.49%) by intention-to-treat(ITT) analysis. The specificity of the ^(13)C-UBT test was 96.00 % in the ITT population(95%CI: 86.29%-99.51%) and 97.96% in the PP population(95%CI: 89.15%-99.95%).CONCLUSION The new test meal based ^(13)C-UBT is highly accurate in patients on PPIs and can be used in those unable to stop their PPI treatment.
文摘AIM To investigate whether the use of proton pump inhibitors(PPIs) increases the incidence of spontaneous bacterial peritonitis(SBP) in patients with cirrhosis and ascites.METHODS An historical cohort study was carried out in cirrhotic outpatients with ascites followed in a specialized clinic at a tertiary hospital in Southern Brazil. Patient charts were reviewed to collect information on the variables of interest as the use of PPIs. Primary outcome was defined as development of SBP during the study period. SBP was diagnosed based on ascitic fluid polymorphonuclear cell count ≥ 250 cells/mm3 without evidence of an intraabdominal, surgically treatable source of infection.RESULTS Of 738 cirrhotic patients, 582(58.2% male) were enrolled, with mean age of 53.6 ± 12 years. Hepatitis C virus infection(36.2%) and alcohol abuse(25.6%) were the main etiologies of cirrhosis. The presence of ascites was detected in 299(51.4%) patients during the development of the study. Nineteen patients with previous diagnosis of SBP undergoing secondary prophylaxis and 22 patients with insufficient PPI data were further excluded. Of 258 patients with ascites, 151 used PPIs, and 34 developed SBP(22.5%). Among 107 non-users of PPIs, 23 developed SBP(21.5%)(HR = 1.44, 95%CI: 0.85-2.47, P = 0.176). The median follow-up time of patients using PPI was 27 mo vs 32 mo for non-users. Univariate analysis of the risk factors associated with the development of SBP revealed a significant association of SPB with the severity of liver disease according to the Child-Turcotte-Pugh(CTP) score. Multivariate analysis confirmed that CTP score was the only independent variable influencing the occurrence of SBP. Survival at 60 mo(Kaplan-Meier analysis) was similar in users and non-users of PPI, independently of the presence of SBP(58.4% vs 62.7% respectively, P = 0.66). For patients with SBP, survival at 60 mo was 55.1%, vs 61.7% in patients without SBP(P = 0.34). CONCLUSION In conclusion, the rate of SBP was not significantly different in users or non-users of PPIs in this cohort of cirrhotic with ascites.
文摘BACKGROUND The proton pump inhibitors(PPIs),used to reduce gastric acid secretion,represent one of the most widely used pharmaceutical classes in the world.Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been investigated as well as the mortality of these patients.These risks also appear to be linked to the duration and the dosage.On the other hand,several studies have emerged with regard to the protective or therapeutic effects of these drugs.More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs.In addition,their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells.AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019(COVID-19)in patients affected by SARS-CoV-2 infection,with the main objective of evaluating the outcomes related to severity and mortality.METHODS A literature review was performed in November 2020.The MEDLINE/PubMed,Cochrane Library,EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic.The search terms were identified by means of controlled vocabularies,such as the National Library of Medicine’s MESH(Medical Subject Headings)and keywords.The MESH terms and keywords used were as follows:“COVID-19”,“proton pump inhibitors”,“PPIs”,“SARS-CoV-2”,“outcomes”,“severity”and“mortality”.The inclusion criteria regarding the studies considered in our analysis were:meta-analysis,casecontrol,hospital-based case-control,population-based case-control,retrospective studies,online survey,as well as cohort-studies,while articles not published as full reports,such as conference abstracts,case reports and editorials were excluded.We tried to summarize and pool all the data if available.RESULTS A total of 9 studies were found that described the use of PPIs,of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients.Our pooled incidence analysis of severe events did not differ between patients with and without PPIs(odds ratio 1.65,95%confidence interval:0.62-4.35)(P=0.314),or for mortality(odds ratio 1.77,95%confidence interval:0.62-5.03)(P=0.286).CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.
文摘Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) palbociclib a drug interaction with PPi was hypothesized. It was shown in a retrospective study that this association was an independent predictive factor for worse progression-free survival (PFS). Objective: To verify the impact of concomitant administration of PPi with Ci on overall survival (OS) and PFS. Material and Methods: This is a retrospective cohort study of patients treated with Ci for HR+HER2-ABC in the period from Feb/2017 to Aug/2020. SPSS software was used for data processing. Univariate analysis was done by the Kaplan-Meier method and log-rank test, and multivariate analysis by COX regression. P-value < 0.05 was considered significant. Results: 80 patients were included. The median age at diagnosis of ABC was 56 years (25 - 75). Treatment with Ci was 1st line for ABC in 68.8%. Choice of Ci was palbociclib in 73.8% (n = 59) and ribociclib in 26.3% (n = 21). The hormone partner was a nonsteroidal aromatase inhibitor in 45.0%, and fulvestrant in 55.0% of cases. 37.5% of patients were on PPi, and 70.0% of them were during the entire treatment (23.3% omeprazole, 73.4% pantoprazole, 3.3% others). Patients taking concomitant PPi and Ci had lower OS (OS-3 years 42.6% vs. 63.4%, p = 0.254) and PFS (PFS med 15 m. vs. 21 m., p = 0.733), although with no statistically significant difference. Discussion: In the sample, there was a numerical difference, without the statistical significance in the use of PPi in the survival of patients under Ci. This difference could be more evident with a longer follow-up and a larger sample size. This study intends to alert to the growing importance of checking for drug interactions. Polymedication, advanced age and the presence of several comorbidities are real problems in patients with ABC. Conclusion: Real-world data from this center demonstrate a negative, non-statistically significant impact of PPi treatment on survival outcomes, in patients treated with Ci for HR+HER2-ABC.
文摘AIM To compare the outcomes between laparoscopic Nissen fundoplication(LNF)and proton pump inhibitors(PPIs)therapy in patients with laryngopharyngeal reflux(LPR)and typeⅠhiatal hernia diagnosed by oropharyngeal p H-monitoring and symptom-scale assessment.METHODS From February 2014 to January 2015,70 patients who were diagnosed with LPR and type I hiatal hernia and referred for symptomatic assessment,oropharyngeal p H-monitoring,manometry,and gastrointestinal endoscopy were enrolled in this study.All of the patients met the inclusion criteria.All of the patients underwent LNF or PPIs administration,and completed a2-year follow-up.Patients’baseline characteristics and primary outcome measures,including comprehensive and single symptoms of LPR,PPIs independence,and satisfaction,and postoperative complications were assessed.The outcomes of LNF and PPIs therapy were analyzed and compared. RESULTS There were 31 patients in the LNF group and 39patients in the PPI group.Fifty-three patients(25 in the LNF group and 28 in the PPI group)completed reviews and follow-up.Oropharyngeal p H-monitoring parameters were all abnormal with high acid exposure,a large amount of reflux,and a high Ryan score,associated reflux symptom index(RSI)score.There was a significant improvement in the RSI and LPR symptom scores after the 2-year follow-up in both groups(P<0.05),as well as typical symptoms of gastroesophageal reflux disease.Improvement in the RSI(P<0.005)and symptom scores of cough(P=0.032),mucus(P=0.011),and throat clearing(P=0.022)was significantly superior in the LNF group to that in the PPI group.After LNF and PPIs therapy,13 and 53 patients achieved independence from PPIs therapy(LNF:44.0%vs PPI:7.14%,P<0.001)during follow-up,respectively.Patients in the LNF group were more satisfied with their quality of life than those in the PPI group(LNF:62.49±28.68 vs PPI:44.36±32.77,P=0.004).Body mass index was significantly lower in the LNF group than in the PPI group(LNF:22.2±3.1kg/m^2 vs PPI:25.1±2.9 kg/m^2,P=0.001).CONCLUSION Diagnosis of LPR should be assessed with oropharyngeal p H-monitoring,manometry,and the symptom-scale.LNF achieves better improvement than PPIs for LPR with type I hiatal hernia.
文摘The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its coccoid form,which is resistant to antibiotics.On these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be administered.Therefore,several tricks need to be used to optimize eradication rate of different regimens.The administration of the highest dose as possible of PPI,by doubling or increasing the number of pills/day,has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies,even if specific trials have not been performed.A pre-treatment with PPI before starting antibiotics does not seem to be effective,therefore it is discouraged.However,the choice of PPI molecule could have a certain weight,since second-generation substances(esomeprazole,rabeprazole)are likely more effective than those of first generation(omeprazole,lansoprazole).A possible explanation is due to their metabolism,which has been proven to be less dependent on cytochrome P450(CYP)2C19 genetic variables.Finally,vonoprazan,a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy,due to both its highest acid inhibition power and rapid pharmacologic effect.However current data come only from Eastern Asia,therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.
基金Supported by National Natural Science Funds of China,No.81102784/H2803the key project in scientific research from ministry of education,No.212032Liaoning Innovative Research Team in University,No.LT2013022
文摘AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLINE, EMBASE and Pub Med for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios(OR) and mean difference with 95% confidence interval(CI). Rev Man 5.3.3 software and Stata 12.0 software were used for data analyses. RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors(PPI) group and the remaining 605 subjects were in the H2 receptor antagonists(H2RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H2 RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate(OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate(OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality(OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference(WMD),-0.70 unit; 95%CI:-1.64- 0.25] and the time that patients remained hospitalized [WMD,-0.77 d; 95%CI:-1.87- 0.34]. The Begg's test(P = 0.283) and Egger's test(P = 0.339) demonstrated that there was no publication bias in our meta-analysis.CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H2 RA, PPI may be a more effective therapy.
基金Supported by National Natural Science Foundation of China,No.31171106,No.81070302 and No.81270463
文摘AIM:To assess the potential benefits of mosapride plus proton pump inhibitors(PPIs)in the treatment of gastroesophageal reflux disease.METHODS:A literature search was performed through MEDLINE,EMBASE,and the ISI Web of Knowledge.The clinical trials that compared the benefit of mosapride plus PPI treatment with that of PPI monotherapy were analyzed.The rate of responders was evaluated by the pooled relative risk(PRR)and improvement in symptom scores was assessed by single effect size of a standardized mean,while Hedges’g was used as the effect size.Pooled effect sizes with 95%CIs were calculated using a fixed-effects model.Between-study heterogeneity was assessed using Q test and I2analyses.In addition,studies that assessed the additional efficacy of mosapride in PPI-resistant patients were also reviewed.RESULTS:This systematic review included information on a total of 587 patients based on 7 trials.Four trials compared the efficacy of combination therapy of mosapride plus a PPI with that of PPI monotherapy.The statistical analysis for the effect of additional mosapride showed equivocal results(PRR=1.132;95%CI:0.934-1.372;P=0.205;Hedges’g=0.24;95%CI:0.03-0.46;P=0.023).No heterogeneity and publication bias were found among the studies.Three openlabeled trials assessed the additional efficacy of mosapride in PPI-resistant patients.However,since these trials did not set the control group,the results may be considerably biased.CONCLUSION:Mosapride combined therapy is not more effective than PPI alone as first-line therapy.Whether it is effective in PPI-resistant patients needs to be determined.
文摘AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.
基金the Lebanese American University for the funding support in purchasing the immunochemical staining products
文摘AIM: To investigate the influence of proton pump inhibitors(PPIs) exposure on the diagnosis of Helicobacter pylori(H. pylori) gastritis and intestinal metaplasia.METHODS: Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed(H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System.RESULTS: Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old(range: 20-87). The histological types of gastritis were classified as H. pylori gastritis(n = 156, 52%) and non-H. pylori gastritis(n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure(71% vs 34.2%, P < 0.001). Intestinal metaplasiawas more likely to be detected in the latter patients(1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure(OR = 0.217, 95%CI: 0.123-0.385), GERD(OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake(OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia.CONCLUSION: The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.
文摘AIM: To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. METHODS: A crosssectional study of consecutive in-patients admitted to hospital in any department during the fi rst semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a diagnosis of hyperglycemic decompensation, diabetic onset or pregnancy. It compared HbA1c levels of those taking PPIs and those not. RESULTS: A total of 97 patients were recruited. The average HbA1C level was 7.0% ± 1.2%. Overall PPI consumption was 55.7%. HbA1c was signif icantly lower in individuals who took PPIs: -0.6%, 95% CI: -0.12 to-0.83. People who used PPIs with some type of insulin therapy had a HbA1c reduction by -0.8%, 95% CI: -0.12 to -1.48. For the rest of subgroup analysis based on the antidiabetic drug used, PPI consumption always exhibited lower HbA1c levels. CONCLUSION: PPIs seems to be consistently associated with better glycemic control in type 2 diabetes. HbA1c reduction observed is similar to incretin-based therapies.
文摘BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.
文摘Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.
