Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management:Delphi consensus study

BACKGROUND Gastro-esophageal reflux disease(GERD)may affect the upper digestive tract;up to 20%of population in Western nations are affected by GERD.Antacids,histamine H2-receptor antagonists,and Proton Pump Inhibitors(PPIs)are considered the referring medications for GERD.Nevertheless,PPIs must be managed carefully because their use,especially chronic,could be linked with some adverse effects.An effective and safe alternative pharmacological tool for GERD is needed.After the identification of potentially new medications to flank PPIs,it is mandatory to revise and improve good clinical practices even through a consensus process.AIM To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi method.METHODS The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel,subject of the consensus,is the basic prerequisite for the consensus itself.A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of GERD.The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations:Gastroenterology,otolaryngology,geriatrics,and general medicine.A scientific committee analyzed the literature,determined areas that required investigation(in agreement with the multiple-choice questionnaire results),and identified two topics of interest:(1)GERD disease;and(2)GERD treatment.Statements for each of these topics were then formulated and validated.The Delphi process involved two rounds of questioning submitted to the panel experts using an online platform.RESULTS According to their routinary GERD practice and current clinical evidence,the panel members provided feedback to each questionnaire statement.The experts evaluated 15 statements and reached consensus on all 15.The statements regarding the GERD disease showed high levels of agreement,with consensus ranging from 70%to 92%.The statements regarding the GERD treatment also showed very high levels of agreement,with consensus ranging from 90%to 100%.This Delphi process was able to reach consensus among physicians in relevant aspects of GERD management,such as the adoption of a new approach to treat patients with GERD based on the overlapping between PPIs and Nux vomica-Heel.The consensus was unanimous among the physicians with different specializations,underlying the uniqueness of the agreement reached to identify in the overlapping approach between PPIs and Nux vomica-Heel a new intervention model for GERD management.The results support that an effective approach to deprescribe PPIs through a progressive decalage timetable(reducing PPIs administration to as-needed use),should be considered.CONCLUSION Nux vomica-Heel appears to be a valid opportunity for GERD treatment to favor the deprescription of PPIs and to maintain low disease activity together with the symptomatology remission.

Helicobacter pylori,esophageal precancerous lesions,and proton pump inhibitor overuse

This article reviews the cohort study published in the World Journal of Gastroenterology,which reported low rates of Helicobacter pylori(H.pylori)infection among esophageal cancer(EC)patients,coupled with proton pump inhibitor(PPI)overuse.These findings suggest a potential protective role of H.pylori against EC and indicate a possible association between PPI use and increased cancer risk.In light of these findings,our article examines the complex relationship between H.pylori and esophageal precancerous lesions,exploring the potential underlying mechanisms.We also address growing concerns regarding PPI overuse,including its potential effects on cancer therapy efficacy and the risk of drug interactions.Ultimately,this article highlights the urgent need for further research to evaluate the safety and efficacy of PPIs in cancer patients and to better understand their broader implications.

Critical analysis of the effects of proton pump inhibitors on inflammatory bowel disease:An updated review

This letter critically evaluates the effects of proton pump inhibitors(PPIs)on inflammatory bowel disease,particularly focusing on Crohn's disease(CD)and ulcerative colitis(UC),as discussed in Liang et al’s recent review.While the review provides significant insights,it relies heavily on cross-sectional and observational studies,which limits the ability to draw causal inferences.The heterogeneous study populations and inconsistent definitions of long-term PPI use further complicate the findings.This letter also highlights the need for rigorous control of confounding factors and considers the potential publication bias in the existing literature.The implications of these issues are discussed in the context of both CD and UC,and future research directions are proposed to address these shortcomings.

Proton pump inhibitors and all-cause mortality risk among cancer patients

BACKGROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related disorders.Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes,including greater mortality.AIM To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias.METHODS This retrospective cohort study used data from the TriNetX research network,with electronic health records from multiple healthcare organizations.The study employed a new-user,active comparator design,which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists(H2RA)users among adult cancer patients.Newly prescribed PPIs(esomeprazole,lansoprazole,omeprazole,pantoprazole,or rabeprazole)users were compared to non-users or newly prescribed H2RAs(cimetidine,famotidine,nizatidine,or ranitidine)users.The primary outcome was all-cause mortality.Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects.Multivariable Cox regression models were used to estimate hazard ratios(HRs)and 95% confidence interval(CI).RESULTS During the follow-up period(median 5.4±1.8 years for PPI users and 6.5±1.0 years for non-users),PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year,2 years,and at the end of follow up(HRs:2.34-2.72).Compared with H2RA users,PPI users demonstrated a higher rate of all-cause mortality HR:1.51(95%CI:1.41-1.69).Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure,confirming the robustness of these findings.In a sensitivity analysis,we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs,providing insights into the long-term effects of past PPI use.In addition,at 1-year follow-up,the analysis revealed a significant difference in mortality rates between former PPI users and non-users(HR:1.84;95%CI:1.82-1.96).CONCLUSION PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users.These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible.However,further studies are needed to corroborate our findings,given the significant adverse outcomes in cancer patients.

Endoscopic full-thickness plication along with argon plasma coagulation for treatment of proton pump inhibitor dependent gastroesophageal reflux disease

BACKGROUND Most endoscopic anti-reflux interventions for gastroesophageal reflux disease(GERD)management are technically challenging to practice with inadequate data to support it utility.Therefore,this study was carried to evaluate the effectiveness and safety newer endoscopic full-thickness fundoplication(EFTP)device along with Argon Plasma Coagulation to treat individuals with GERD.AIM To evaluate the effectiveness and safety newer EFTP device along with Argon Plasma Coagulation to treat individuals with GERD.METHODS This study was a single-center comparative analysis conducted on patients treated at a Noble Institute of Gastroenterology,Ahmedabad,hospital between 2020 and 2022.The research aimed to retrospectively analyze patient data on GERD symptoms and proton pump inhibitor(PPI)dependence who underwent EFTP using the GERD-X system along with argon plasma coagulation(APC).The primary endpoint was the mean change in the total gastroesophageal reflux disease health-related quality of life(GERD-HRQL)score compared to the baseline measurement at the 3-month follow-up.Secondary endpoints encompassed enhancements in the overall GERD-HRQL score,improvements in GERD symptom scores at the 3 and changes in PPI usage at the 3 and 12-month time points.RESULTS In this study,patients most were in Hill Class II,and over half had ineffective esophageal motility.Following the EFTP procedure,there were significant improvements in heartburn and regurgitation scores,as well as GERDHRQL scores(P<0.001).PPI use significantly decreased,with 82.6%not needing PPIs or prokinetics at end of 1 year.No significant adverse events related to the procedures were observed in either group.CONCLUSION The EFTP along with APC procedure shows promise in addressing GERD symptoms and improving patients'quality of life,particularly for suitable candidates.Moreover,the application of a lone clip with APC yielded superior outcomes and exhibited greater cost-effectiveness.

Identification,structure elucidation and origin of a common pyridinium-thiocyanate intermediate in electrospray mass spectrometry among the benziamidazole-class proton pump inhibitors

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.

Exposure to proton pump inhibitors and risk of diabetes:A systematic review and meta-analysis

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.

Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view

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.

Effects of postoperative use of proton pump inhibitors on gastrointestinal bleeding after endoscopic variceal treatment during hospitalization

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.

Progress in the Study of Vonoprazan Fumarate vs. Proton Pump Inhibitors in the Treatment of Gastroesophageal Reflux Disease

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.

Studies on the Proton Pumping Activity of H^+-ATPase in Tonoplast Vesicles of Populus euphratica

Tonoplast-enriched vesicles were prepared from suspension-cultured Populus euphratica Oliv. cells by differential centrifugation and discontinuous sucrose density gradient centrifugation. The properties of the proton pumping activity of H+-ATPases in tonoplast vesicles were studied by acridine orange fluorescent quenching measured at 22 degreesC. The proton pumping activity of ATPase was ATP-dependent with apparent Michaelis-Menten Constant (K-m) for ATP about 0.65 mmol/L. The optimal pH for H+-ATPases activity was 7.5. The proton pumping activity of H+-ATPase could be initiated by some divalent cations, Mg2+ being highly efficient, much more than Fe2+; and Ca2+, Cu2+ and Zn2+ were inefficient under the experimental condition. The proton translocation could be stimulated by halide anions, with potencies decreasing in the order Cl- > Br- > I- > F-. The proton pumping activity was greatly inhibited by N-ethylmaleimide (NEM), N, N'-dicyclohexylcarbodiimide (DCCD), NO3- and Bafilomycin A(1), but not by orthovanadate and azide. These results demonstrated that the H+-ATPase in the tonoplast of Populus euphratica belonged to vacuolar type ATPase. This work was the first time that tonoplast-enriched vesicles were isolated from Populus euphratica cells.

枇杷果实液泡膜V-ATPase D亚基基因的克隆及表达

提取枇杷果实总RNA,根据RNAseq数据库查找得到的(液泡膜质子泵V-ATPase)基因片段序列11个。设计引物,采用RACE技术,获得质子泵V-ATPase cDNA的全长,对测序结果进行分析,并将序列在NCBI上进行blast比对,结果显示核苷酸序列和氨基酸同源性均在80%以上,为质子泵酶基因V-ATPase D亚基基因。经qPCR分析表明,该基因对枇杷果实有机酸具有明显调控作用。

Risk factors for proton pump inhibitor refractoriness in Chinese patients with non-erosive reflux disease

AIM:To analyze risk factors for refractoriness to proton pump inhibitors(PPIs) in patients with non-erosive reflux disease(NERD).METHODS:A total of 256 NERD patients treated with the PPI esomeprazole were enrolled.They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia(QolRad) scale.All subjects completed questionnaires on psychological status(self-rating anxiety scale;selfrating depression scale) and quality of life scale(Short Form 36).Multivariate analysis was used to determine the predictive factors for PPI responses.RESULTS:According to QolRad,97 patients were confirmed to have residual reflux symptoms,and the remaining 159 patients were considered symptom free.There were no significant differences between the two groups in lifestyle factors(smoking and alcohol consumption),age,Helicobacter pylori infection,and hiatal hernia.There were significant differences between the two groups in relation to sex,psychological distress including anxiety and depression,body mass index(BMI),and irritable bowel syndrome(IBS)(P < 0.05).Logistic regression analysis found that BMI < 23,comorbid IBS,anxiety,and depression were major risk factors for PPI resistance.Symptomatic patients had a lower quality of life compared with symptom-free patients.CONCLUSION:Some NERD patients are refractory to PPIs and have lower quality of life.Residual symptoms are associated with psychological distress,intestinal disorders,and low BMI.

Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease

Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.

New aspects in the pathomechanism and diagnosis of the laryngopharyngeal reflux-clinical impact of laryngeal proton pumps and pharyngeal p H metry in extraesophageal gastroesophageal reflux disease

AIM:To determine the laryngeal H+K+-ATPase and pharyngeal p H in patients with laryngopharyngeal reflux(LPR)-symptoms as well as to assess the symptom scores during PPI therapy.METHODS:Endoscopy was performed to exclude neoplasia and to collect biopsies from the posterior cricoid area(immunohistochemistry and PCR analysis).Immunohistochemical staining was performed with monoclonal mouse antibodies against human H+K+-ATPase.Quantitative real-time RT-PCR for each of the H+K+-ATPase subunits was performed.The p H values were assessed in the aerosolized environment of the oropharynx(Dxp H Catheter) and compared to a subsequently applied combined p H/MII measurement.RESULTS:Twenty patients with LPR symptoms were included.In only one patient,the laryngeal H+K+-ATPase was verified by immunohistochemical staining.In another patient,real-time RT-PCR for each H+K+-ATPase subunit was positive.Fourteen out of twenty patients had pathological results in Dxp H,and 6/20 patients had pathological results in p H/MII.Four patients had pathological results in both functional tests.Nine out of twenty patients responded to PPIs.CONCLUSION:The laryngeal H+K+-ATPase can only be sporadically detected in patients with LPR symptoms and is unlikely to cause the LPR symptoms.Alternative hypotheses for the pathomechanism are needed.The role of pharyngeal p H-metry remains unclearand its use can only be recommended for patients in a research study setting.

Optimizing proton pump inhibitors in Helicobacter pylori treatment:Old and new tricks to improve effectiveness

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.

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

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.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

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.

Efficacy of mosapride plus proton pump inhibitors for treatment of gastroesophageal reflux disease: A systematic review

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.