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.

Clinical evidence of interaction between clopidogrel and proton pump inhibitors

Clopidogrel is approved for reduction of atherothrombotic events in patients with cardiovascular(CV)and cerebrovascular disease.Dual antiplatelet therapy with aspirin and clopidogrel decreases the risk of major adverse cardiac events after acute coronary syndrome or percutaneous coronary intervention,compared with aspirin alone.Due to concern about gastrointestinal bleeding in patients who are receiving clopidogrel and aspirin therapy,current guidelines recommend combined use of a proton pump inhibitor(PPI)to decrease the risk of bleeding.Data from previous pharmacological studies have shown that PPIs,which are extensively metabolized by the cytochrome system,may decrease the ADP-induced platelet aggregation of clopidogrel. Results from retrospective cohort studies have shown a higher incidence of major CV events in patients re-ceiving both clopidogrel and PPIs than in those without PPIs.However,other retrospective analyses of randomized clinical trials have not shown that the concomitant PPI administration is associated with increased CV events among clopidogrel users.These controversial results suggest that large specific studies are needed. This article reviews the metabolism of clopidogrel and PPIs,existing clinical data regarding the interaction between clopidogrel and PPIs,and tries to provide recommendations for health care professionals.

Rebuilding trust in proton pump inhibitor therapy

Introduction of proton pump inhibitor(PPI)therapy into clinical practice has revolutionized treatment approach to acid-related diseases.With its clinical success came a widespread use of PPI therapy.Subsequently,several studies found that PPIs were oftentimes overprescribed in primary care and emergency setting,likely attributed to seemingly low side-effect profile and physicians having low threshold to initiate therapy.However,now there is a growing concern over PPI side-effect profile among both patients and providers.We would like to bring more awareness to the currently available guidelines on PPI use,discuss clinical indications for PPIs and the evidence behind the reported sideeffects.We hope that increased awareness of proper PPI use will make the initiation or continuation of therapy a well informed and an evidence-based decision between patient and physician.We also hope that discussing evidence behind the reported side-effect profile will help clarify the growing concerns over PPI therapy.

Obscure bleeding colonic duplication responds to proton pump inhibitor therapy

We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding.Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5and 2 years previously.An emergency abdominal computed tomography scan,gastroscopy and colonoscopy,performed after hemodynamic stabilization,were considered normal.High-dose intravenous proton pump inhibitor(PPI)therapy was initiated and bleeding stopped spontaneously.Two other massive rectal bleeds occurred 8 h after each cessation of PPI which led to a hemostatic laparotomy after negative gastroscopy and small bowel capsule endoscopy.This showed long tubular duplication of the right colon,with fresh blood in the duplicated colon.Obscure lower gastrointestinal bleeding is a difficult medical situation and potentially life-threatening.The presence of ulcerated ectopic gastric mucosa in the colonic duplication explains the partial efficacy of PPI therapy.Obscure gastrointestinalbleeding responding to empiric anti-acid therapy should probably evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel’s diverticulum or gastrointestinal duplication,and gastroenterologists should be aware of this potential medical situation.

Role of proton pump inhibitors in the management of peptic ulcer bleeding

Peptic ulcer bleeding is a serious medical problem with significant morbidity and mortality.Endoscopic therapy significantly reduces further bleeding,surgery and mortality in patients with bleeding peptic ulcers and is now recommended as the first hemostatic modality for these patients.The efficacy of large-dose proton pump inhibitor(PPI) therapy in reducing re-bleeding after endoscopic therapy has been supported by evidence derived from randomized controlled trials.It may be premature to recommend small-dose intravenous injection PPI after endoscopic hemostasis in patients with bleeding ulcers.An updated systematic review shows that PPI therapy before endoscopy significantly reduces the proportion with major stigmata and requirement for endoscopic therapy at index endoscopy.Some studies show that there is no significant difference between oral and intravenous PPIs in raising intragastric pH.However,clinical data is lacking in patients with peptic ulcer bleeding to date.

Proton pump inhibitor step-down therapy for GERD:A multi-center study in Japan

AIM:To investigate the predictors of success in stepdown of proton pump inhibitor and to assess the quality of life(QOL).METHODS:Patients who had heartburn twice a week or more were treated with 20 mg omeprazole(OPZ) once daily for 8 wk as an initial therapy(study 1).Patients whose heartburn decreased to once a week or less at the end of the initial therapy were enrolled in study 2 and treated with 10 mg OPZ as maintenance therapy for an additional 6 mo(study 2).QOL was in-vestigated using the gastrointestinal symptom rating scale(GSRS)before initial therapy,after both 4 and 8 wk of initial therapy,and at 1,2,3,and 6 mo after starting maintenance therapy.RESULTS:In study 1,108 patients were analyzed.Their characteristics were as follows;median age:63(range: 20-88)years,sex:46 women and 62 men.The success rate of the initial therapy was 76%.In the patients with successful initial therapy,abdominal pain,indigestion and reflux GSRS scores were improved.In study 2,83 patients were analyzed.Seventy of 83 patients completed the study 2 protocol.In the per-protocol analysis,80%of 70 patients were successful for stepdown.On multivariate analysis of baseline demographic data and clinical information,no previous treatment for gastroesophageal reflux disease(GERD)[odds ratio (OR)0.255,95%CI:0.06-0.98]and a lower indigestion score in GSRS at the beginning of step-down therapy(OR 0.214,95%CI:0.06-0.73)were found to be the predictors of successful step-down therapy.The improved GSRS scores by initial therapy were maintained through the step-down therapy.CONCLUSION:OPZ was effective for most GERD patients.However,those who have had previous treatment for GERD and experience dyspepsia before stepdown require particular monitoring for relapse.

Treatment with clopidogrel and proton pump inhibitors in combination: a review of emerging evidence

Proton pump inhibitors often are prescribed in combination with clopidogrel to decrease risk of gastrointestinal bleeding after acute coronary syndrome. Clopidogrel is a prodrug that has to be metabolized in the liver to generate the active metabolite. Both medications are metabolized largely by the CYP2C19 enzyme;therefore, concerns exist that a drug-drug interaction during concomitant treatment with clopidogrel and a proton pump inhibitor may result in reduction of platelet inhibition. We have reviewed observational and randomized control studies that have evaluated the potential influence of proton pump inhibitors on the platelet inhibitory effect of clopidogrel, along with cardiovascular outcomes. We also have summarized regulatory and academic guidelines for treatment of patients in which concomitant therapy with clopidogrel and proton pump inhibitors may be indicated. Confounding issues, including differential effects of individual proton pump inhibitors on the pharmacodynamics of clopidogrel and variation in clopidogrel metabolism mediated by CYP2C19 gene polymorphisms, also are discussed.

Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial

BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

Are proton pump inhibitors a new antidiabetic drug? A cross sectional study

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.

Positive predictors for gastroesophageal reflux disease and the therapeutic response to proton-pump inhibitors

AIM: To identify objective and subjective predictors for the reliable diagnosis of gastroesophageal reflux disease (GERD) and the response to proton pump inhibitor (PPI) therapy.

Clopidogrel and proton pump inhibitors-where do we stand in 2012?

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

Treatment and prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy

Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding complications such as gastrointestinal bleeding, which is one of the most common life-threatening complications. Early endoscopy is recommended for most patients with acute upper gastrointestinal bleeding. After successful endoscopic hemostasis, immediate resumption of antiplatelet therapy with proton-pump inhibitors(PPIs) is recommended to prevent further ischemic events. PPI prophylaxis during antiplatelet therapy reduces the risk of upper gastrointestinal bleeding. The potential negative metabolic interaction between PPIs and clopidogrel is still unclear.

Use of acid suppressive therapy in hospitalized non-critically ill patients

AIM: To assess the appropriateness of prescribing acid suppressive therapy (AST) in a general medicine service in a tertiary care hospital. METHODS: In this retrospective observational study, we reviewed the inpatient records of all patients admitted to the general medical service in a tertiary care hospital in Beirut, Lebanon, from April 1 to May 31, 2011. Treatment with AST was considered appropriate if the patient had a specific indication or appropriate treatment purpose [e.g. , gastro-esophageal reflux disease (GERD), peptic ulcer disease, dyspepsia, acute or suspected gastrointestinal (GI) bleeding]. Appropriate administration of stress ulcer prophylaxis (SUP) was derived from an internal guideline that is based on the American Society of Health System Pharmacists guidelines. Prophylaxis was considered appropriate if a patient had 1 absolute indication (coagulopathy or requiring mechanical ventilation), or 2 or more relative indications (sepsis, occult bleeding, use of high dose corticosteroids, recent use of non-steroidal anti-inflammatory drugs for more than 3 mo, renal or liver failure, enteral feeding and anticoagulant use). RESULTS: Of the 153 patient admissions during the study period, 130 patients (85%) were started on AST, out of which 11 (8.5%) had a diagnosis that sup-ports the use of this therapy (GI bleed, gastritis and GERD), 16 (12.3%) had an absolute indication for SUP, 59 (45.4%) had 2 or more relative indications for SUP, and 44 (33.8%) received AST without an appropriate indication. In addition, one patient with an absolute indication for SUP and four with two or more relative indications did not receive AST. Rabeprazole was the most frequently used AST (59.2%), followed by omeprazole (24.6%), esomeprazole (11.6%) and ranitidine (4.6%). The dose of AST was appropriate in 126 patients (96.9%) and the route of administration was appropriate in 123 patients (94.6%). Fifteen of the admitted patients (10%) were discharged on AST, 7 of which (47%) did not have an appropriate indication. CONCLUSION: AST is overused in hospitalized noncritically ill patients and many patients are discharged on unnecessary AST which can increase cost, drug interactions and adverse events. Potential interventions include implementation of institutional protocols and prescriber education.

Current status of Helicobacter pylori eradication and risk factors for eradication failure

BACKGROUND The Helicobacter pylori(H.pylori)eradication rate is decreasing in the general population of China.AIM To evaluate the H.pylori eradication status in real-world clinical practice and to explore factors related to eradication failure.METHODS Patients with H.pylori infection who were treated with standard 14-d quadruple therapy and received a test of cure at a provincial medical institution between June 2018 and May 2019 were enrolled.Demographic and clinical data were recorded.Eradication rates were calculated and compared between regimens and subgroups.Multivariate analysis was performed to identify predictors of eradication failure.RESULTS Of 2610 patients enrolled,eradication was successful in 1999(76.6%)patients.Amoxicillin-containing quadruple regimens showed a higher eradication rate than other quadruple therapy regimens(83.0%vs 69.0%,P<0.001).The quadruple therapy containing amoxicillin plus clarithromycin achieved the highest eradication rate(83.5%).Primary therapy had a higher eradication rate than rescue therapy(78.3%vs 66.5%,P<0.001).In rescue therapy,the amoxicillinand furazolidone-containing regimens achieved the highest eradication rate(80.8%).Esomeprazole-containing regimens showed a higher eradication rate than those containing other proton pump inhibitors(81.8%vs 74.9%,P=0.001).Multivariate regression analysis found that older age,prior therapy,and use of omeprazole or pantoprazole were associated with an increased risk of eradication CONCLUSION The total eradication rate is 76.6%.Amoxicillin-containing regimens are superior to other regimens.Age,prior therapy,and use of omeprazole or pantoprazole are independent risk factors for eradication failure.

Correlation between Distribution of Helicobacter Pylori in Oral Cavity and Chronic Stomach Conditions

In this study,the colonization and distribution of Helicobacter pylori（Hp） in patients with chronic gastric diseases were investigated and the relationship between the periodontal initial treatment and presence of Hp in oral cavity was examined to better understand the connection between Hp infection and chronic diseases.Primers for PCR amplification were designed according to ureC gene and cagA genes of Hp.Specimens were harvested from different sites of 96 patients with chronic gastric diseases and the specimens of dental plaques,gargles and dorsal mucosa were tested for Hp.The 96 patients were treated by bismuth triple therapy and among them,52 subjects were additionally given periodontal initial therapy.The eradication rate of gastric Hp and oral Hp detection rate were determined 4 weeks and 1 year after the treatment.The results showed that the detection rates of oral specimens were in the order of dental plaques（82.3%）,gargles（51.1%） and scrapings of dorsal mucosa of tongue（37.5%）.One year after bismuth triple therapy or the triple therapy in combination with periodontal initial treatment,the eradication rate of gastric Hp was significantly higher in the combination treatment group than in group treated by the triple therapy alone（62.8% vs.32.4%,P0.05）.Moreover,the Hp detection rate was significantly lower in the combination group than in the group treated only with the triple therapy.We are led to conclude that Hp is present at various parts of oral cavity,oral Hp might be an important source of gastric Hp and the triple therapy plus periodontal initial treatment can enhance the long-term eradication rate of gastric Hp in patient with both chronic gastric diseases and chronic periodontitis.

Aluminum phosphate gel reduces early rebleeding in cirrhotic patients with gastric variceal bleeding treated with histoacryl injection therapy

BACKGROUND Esophageal-gastro varices bleeding(EGVB)is the most widely known cause of mortality in individuals with cirrhosis,with an occurrence rate of 5%to 15%.Among them,gastric varices bleeding(GVB)is less frequent than esophageal varices bleeding(EVB),but the former is a more critical illness and has a higher mortality rate.At present,endoscopic variceal histoacryl injection therapy(EVHT)is safe and effective,and it has been recommended by relevant guidelines as the primary method for the treatment of GVB.However,gastric varices after endoscopic treatment still have a high rate of early rebleeding,which is mainly related to complications of its treatment,such as bleeding from drained ulcers,rebleeding of varices etc.Therefore,preventing early postoperative rebleeding is very important to improve the quality of patient survival and outcomes.AIM To assess the efficacy of aluminium phosphate gel(APG)combined with proton pump inhibitor(PPI)in preventing early rebleeding after EVHT in individuals with GVB.METHODS Medical history of 196 individuals with GVB was obtained who were diagnosed using endoscopy and treated with EVHT in Shenzhen People's Hospital from January 2016 to December 2021.Based on the selection criteria,101 patients were sorted into the PPI alone treatment group,and 95 patients were sorted into the PPI combined with the APG treatment group.The incidences of early rebleeding and corresponding complications within 6 wk after treatment were compared between both groups.Statistical methods were performed by two-sample t-test,Wilcoxon rank sum test andχ2 test.RESULTS No major variations were noted between the individuals of the two groups in terms of age,gender,Model for End-Stage Liver Disease score,coagulation function,serum albumin,hemoglobin,type of gastric varices,the dose of tissue glue injection and EV that needed to be treated simultaneously.The early rebleeding rate in PPI+APG group was 3.16%(3/95),which was much lower than that in the PPI group(12.87%,13/101)(P=0.013).Causes of early rebleeding:the incidence of gastric ulcer bleeding in the PPI+APG group was 2.11%(2/95),which was reduced in comparison to that in the PPI group(11.88%,12/101)(P=0.008);the incidence of venous bleeding in PPI+APG group and PPI group was 1.05%(1/95)and 0.99%(1/101),respectively,and there was no significant difference between them(0.999).The early mortality rate was 0 in both groups within 6 wk after the operation,and the low mortality rate was related to the timely hospitalization and active treatment of all patients with rebleeding.The overall incidence of complications in the PPI+APG group was 12.63%(12/95),which was not significantly different from 13.86%(14/101)in the PPI group(P=0.800).of abdominal pain in the PPI+APG group was 3.16%(3/95),which was lower than that in the PPI group(11.88%,12/101)(P=0.022).However,due to aluminum phosphate gel usage,the incidence of constipation in the PPI+APG group was 9.47%(9/95),which was higher than that in the PPI group(1.98%,2/101)(P=0.023),but the health of the patients could be improved by increasing drinking water or oral lactulose.No patients in either group developed spontaneous peritonitis after taking PPI,and none developed hepatic encephalopathy and ectopic embolism within 6 wk of EVHT treatment.CONCLUSION PPI combined with APG can significantly reduce the incidence of early rebleeding and postoperative abdominal pain in cirrhotic patients with GVB after taking EVHT.

Effects of proton pump inhibitor on gastroesophageal varices in patients with cirrhosis:A randomized controlled trial from China

Aims:Proton pump inhibitors(PPI)are widely used for gastroesophageal varices in patients with cirrhosis after endoscopic therapy,although the effect of PPI on these patients remains controversial.This study aimed to evaluate the effect of PPI on gastroesophageal varices in patients with cirrhosis after endoscopic therapy,including variceal bleeding and adverse events.Methods:Cirrhotic patients with endoscopically confirmed gastroesophageal varices were enrolled in this study between May 2017 and June 2019.Eligible patients were randomized into two groups:one group received PPI for 14 days and the other group did not receive PPI treatment(n=53 in each group).All patients were followed for 8 weeks.Results:During the follow‐up period,three patients(5.66%)in the PPI group experienced variceal bleeding on days 9,16,and 25 after endoscopic therapy,including two patients with acute bleeding and one with primary prophylaxis.In the non‐PPI group,three patients(5.66%)experienced variceal bleeding on days 7,42,and 56 after endoscopic therapy,including one patient with acute bleeding and two with secondary prophylaxis(p=0.990).The incidence of adverse events was similar between the two groups(37.74%vs.28.30%,p=0.30).Conclusions:PPI did not appear to reduce variceal bleeding and adverse events in patients with cirrhosis after endoscopic therapy.

Comparative effectiveness of first-line therapies for eradication of antibiotic-resistant Helicobacter pylori strains:A network metaanalysis

BACKGROUND As a first-line treatment regimen for Helicobacter pylori(H.pylori)infection,antibiotic therapy is widely used worldwide.However,the question of increasing antibiotic resistance must be considered.Given this issue,we need to find ways to reduce drug resistance.This study examined all currently available first-line regimens and compared them with standard triple treatment through a network meta-analysis of randomized controlled trials(RCTs).AIM To compare first-line treatment regimens for eradication of antibiotic-resistant H.pylori strains.METHODS To compare the effectiveness of the first-line regimens for treating H.pylori infection,a Bayesian network meta-analysis was applied to process data extracted from RCTs.The plausible ranking for each regimen was assessed by the surface under the cumulative ranking curve(SUCRA).In addition,we conducted a relevant search by reference citation analysis.RESULTS Twenty-five RCTs involving 12029 participants[including 1602 infected with clarithromycin(CAM)-resistant strains and 1716 infected with metronidazole(MNZ)-resistant strains]were included,in which a total of seven regimens were used for H.pylori eradication.The results showed that dual therapy containing a high-dose proton pump inhibitor(HDDT)[odds ratio(OR):4.20,95%confidence interval(CI):2.29-8.13]was superior to other therapies for all patients,including those with CAM/MNZ-resistant H.pylori infection.In the comparative effectiveness ranking,for CAM-resistant H.pylori,HDDT(OR:96.80,95%CI:22.46-521.9)had the best results,whereas standard triple therapy ranked last(SUCRA:98.7%vs 0.3%).In the subgroup of high cure rates(≥90%),HDDT was also generally better than other therapies.CONCLUSION For the eradication of CAM-and MNZ-resistant H.pylori strains,HDDT exhibited considerable advantages.The studies of CAM-resistant H.pylori were based on small samples due to a lack of antibiotic sensitivity tests in many RCTs,but the results showed that all patients,including those with CAM-resistant H.pylori infection,had a concordant trend.Overall,HDDT may be a reference for RCTs and other studies of H.pylori eradication.

Risk Factors for Gastrointestinal Injuries in Acute Coronary Syndrome Patients with Double Antiplatelet Therapy in One-Year Follow-Up

Background: The goal is to determine the incidence of symptomatic gastrointestinal (GI) injuries in acute coronary syndrome (ACS) patients receiving double antiplatelet therapy (DAPT). The risk factors for serious GI complications are also evaluated. Methods: 603 eligible patients from the Department of Cardiology at Zhongda Hospital between January 2014 and August 2015 were enrolled and the occurrence of GI injuries within one year assessed. The risk factors for serious GI complications were identified using cox regression analysis. Results: After one-year follow-up, 108 (17.9%) out of 603 patients developed symptomatic GI injuries: 22 (3.65%) with serious GI complications and 86 (14.2%) with GI symptoms. Drinking habit (95% CI: 1.512 - 8.796;P = 0.004) and previous peptic injury (95% CI: 2.307 - 18.080;P = 0.001) are independent predictors of serious GI complications, while proton pump inhibitor (PPI) was protective (95% CI: 0.120 - 0.699;P = 0.006) per cox regression analysis. Additionally, GI injuries of both serious GI complications and GI symptoms peaked in the first three months. Conclusions: Symptomatic GI injuries were relatively common in ACS patients with DAPT, especially in the first three months. Previous peptic injury and drinking habit were significant independent risk factors for serious GI complications, while PPI played a protective role in ACS with DAPT.