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.

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.

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.

Evaluation of Appropriateness of Proton Pump Inhibitors (PPIs) Use in the Region of Sharjah, United Arab Emirates (UAE)

Background: Proton pump inhibitors (PPIs) are drugs that reduce the production of acid in the stomach. Recently, the use of PPI has been increasing among communities, whether with or without prescription. As a part of the healthcare team, the pharmacist should not only dispense medications but also ensure the appropriate use of these medications. Studies conducted within 16 countries showed substantial variation in the appropriateness of the use of PPI drugs. Aim: To evaluate the appropriateness of PPIs use in Sharjah, UAE based on surveys answered by pharmacists, physicians, and patients. Methods: A cross-sectional survey study was conducted on December 2017 at Sharjah, UAE as an example of information obtained from the Middle East. Two different surveys were conducted on physicians and pharmacists. Both Physicians and Pharmacists were chosen randomly from Yellow Pages. The results obtained from both studies were used to develop a patient’s survey, which was distributed among University of Sharjah students, their families and random people at Shopping Malls and Clinics. Results: The results obtained from the patients’ survey showed that ~39% of PPI users from the region of Sharjah are 25 - 44 years old. Approximately 79% are using PPI according to physicians’ prescriptions. Prescriptions’ duration is varied between 1 month (39%) and 6 months (22%), where 52% of PPI users ask their physicians to prescribe PPIs when needed. Suggested reasons for the use of PPI included inappropriate food habits (52%), use of other medications (16%) or bacterial infection (13%). Around 52% of the patients did not receive any recommendations regarding the deprescribing of PPIs. According to the pharmacists’ surveys, an average sale of 5 - 10 PPI packages is reported per day, and around 50% are sold without a prescription. Most pharmacists were not fully aware of the health conditions and side effects of PPI drugs. On the other hand, physicians’ surveys showed that PPIs were mainly prescribed in the case of GERD and ulcer and for a maximum of 2 - 4 weeks. Approximately 75% of physicians recommend changing regimen by reducing the dose and stopping in case of chronic use of PPIs. Conclusion: The results from this survey study indicated that even though most PPI consumers at Sharjah, UAE are well aware of the use of PPI drugs and they follow the instructions given by the Physicians’, there is some discrepancy in the information obtained by the physicians, pharmacists, and patients. The reason for this discrepancy may be attributed to the missing role of the pharmacists which is currently just dispensing the medications without appropriate counseling. Thus the appropriate role of the pharmacists should be implemented according to the known international guidelines.

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.

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.

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.

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.

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.

Proton pump inhibitors therapy vs H_2 receptor antagonists therapy for upper gastrointestinal bleeding after endoscopy: A meta-analysis

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.

Protons pump inhibitor treatment and lower gastrointestinal bleeding: Balancing risks and benefits

Proton pump inhibitors(PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal antiinflammatory drugs(NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding(LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients.

Proton pump inhibitor for non-erosive reflux disease:A meta-analysis

AIM:To evaluate the efficacy,safety and influential factors of proton pump inhibitor(PPI)treatment for non-erosive reflux disease(NERD).METHODS:PubMed,MEDLINE,EMBASE and the Cochrane Library were searched up to April 2013 to identify eligible randomized controlled trials(RCTs)that probed into the efficacy,safety and influential factors of PPI treatment for NERD.The rates of symptomatic relief and adverse events were measured as the outcomes.After RCT selection,assessment and data collection,the pooled RRs and 95%CI were calculated.This meta-analysis was performed using the Stata 12.0 software(Stata Corporation,College Station,Texas,United States).The level of evidence was estimated by the Grading of Recommendations Assessment,Development and Evaluation system.RESULTS:Seventeen RCTs including 6072 patients met the inclusion criteria.The results of the metaanalysis showed that PPI treatment was significantly superior to H2receptor antagonists(H2RA)treatment(RR=1.629,95%CI:1.422-1.867,P=0.000)and placebo(RR=1.903,95%CI:1.573-2.302,P=0.000)for the symptomatic relief of NERD.However,there were no obvious differences between PPI and H2RA(RR=0.928,95%CI:0.776-1.110,P=0.414)or PPI and the placebo(RR=1.000,95%CI:0.896-1.116,P=0.997)regarding the rate of adverse events.The overall rate of symptomatic relief of PPI against NERD was 51.4%(95%CI:0.433-0.595,P=0.000),and relief was influenced by hiatal hernia(P=0.030).The adverse rate of PPI against NERD was 21.0%(95%CI:0.152-0.208,P=0.000),and was affected by hiatal hernia(P=0.081)and drinking(P=0.053).CONCLUSION:PPI overmatched H2RA on symptomatic relief rate but not on adverse rate for NERD.Its relief rate and adverse rate were influenced by hiatal hernia and drinking.

Nissen fundoplication vs proton pump inhibitors for laryngopharyngeal reflux based on p H-monitoring and symptom-scale

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.

Proton pump inhibitors as a risk factor for recurrence of Clostridium-difficile-associated diarrhea

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.