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 compl...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.展开更多
AIM:To evaluate the current practice of stress ulcer prophylaxis (SUP) in Lebanese Health care centers.METHODS:A multi-center prospective chart review study was conducted over 8 mo.A questionnaire was distributed to p...AIM:To evaluate the current practice of stress ulcer prophylaxis (SUP) in Lebanese Health care centers.METHODS:A multi-center prospective chart review study was conducted over 8 mo.A questionnaire was distributed to pharmacy students who collected data on demographics,SUP medications,dose,route,duration and associated risk factors.The appropriateness of SUP use was determined as per American Society of Health-System Pharmacists guidelines.Institutional review board approval was obtained from each hospital center.RESULTS:A total of 1004 patients were included.67% of the patients who received prophylaxis did not have an indication for SUP.The majority (71.6%) of the patients who were administered parenteral drugs can tolerate oral medications.Overall,the regimen of acid-suppressant drugs was suboptimal in 87.6% of the sample.This misuse was mainly observed in non-teaching hospitals.CONCLUSION:This study highlighted the need,in Lebanese hospitals,to establish clinical practice guidelines for the use of SUP;mainly in non-critical care settings.展开更多
Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestin...Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.展开更多
Background：Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors （PPIs） combined with clopidogrel therapy,causing much un...Background：Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors （PPIs） combined with clopidogrel therapy,causing much uncertainty in clinical practice.We sought to evaluate the safety of PPIs use among high-risk cardiovascular patients who underwent percutaneous coronary intervention （PCI） in a long-term follow-up study.Methods：A total of 7868 consecutive patients who had undergone PCI and received dual antiplatelet therapy （DAPT） at a single center from January 2013 to December 2013 were enrolled.Adenosine diphosphate （ADP）-induced platelet aggregation inhibition was measured by modified thromboelastography （mTEG） in 5042 patients.Propensity score matching （PSM） was applied to control differing baseline factors.Cox proportional hazards regression was used to evaluate the 2-year major adverse cardiovascular and cerebrovascular events （MACCEs）,as well as individual events,including all-cause death,myocardial infarction,unplanned target vessel revascularization,stent thrombosis,and stroke.Results：Among the whole cohort,27.2% were prescribed PPIs.The ADP-induced platelet aggregation inhibition by mTEG was significantly lower in PPI users than that in non-PPI users （42.0 ± 30.9% vs.46.4 ± 31.4%,t =4.435,P 〈 0.001）.Concomitant PPI use was not associated with increased MACCE through 2-year follow-up （12.7% vs.12.5%,x2 =0.086,P =0.769）.Other endpoints showed no significant differences after multivariate adjustment,regardless of PSM.Conclusion：In this large cohort of real-world patients,the combination of PPIs with DAPT was not associated with increased risk of MACCE in patients who underwent PCI at up to 2 years of follow-up.展开更多
AIM:To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal(GI) injury with combined protective medications.METHODS:A retrospective drug util...AIM:To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal(GI) injury with combined protective medications.METHODS:A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital,School of Medicine,Zhejiang University.The hospital has 2300 beds and 2.5 million outpatient visits annually.Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011.Concomitant use of proton-pump inhibitors(PPIs),histamine 2-receptor antagonists(H2RA) and mucoprotective drugs(MPs) were analyzed.A defined daily dose(DDD) methodology was applied to each MP.A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs(NSAIDs),corticosteroids and clopidogrel and warfarin] or intestinal protective drugs(misoprostol,rebamipide,teprenone and gefarnate).Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records.The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients.RESULTS:Prescriptions for aspirin users receiving PPIs,H2RA and MPs(n = 1039) accounted for only 3.46% of total aspirin prescriptions(n = 30 015).The ratios of coadministration of aspirin/PPI,aspirin/H2RA,aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%,0.12%,0.40% and 0.12%,respectively.No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs,H2RA or MPs.The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs(2.82% vs 0.40%,P < 0.05) and aspirin/H2RA(2.82% vs 0.12%,P < 0.05).The values of DDDs of MPs in descending order were as follows:gefarnate,hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium gualenate granules > rebamipide > sucralfate chewable tablets.The ratio of MP plus aspirin p展开更多
Gastric and esophageal cancers are multifactorial and multistage-involved malignancy.While the impact of gut microbiota on overall human health and diseases has been well documented,the influence of gastric and esopha...Gastric and esophageal cancers are multifactorial and multistage-involved malignancy.While the impact of gut microbiota on overall human health and diseases has been well documented,the influence of gastric and esophageal microbiota on gastric and esophageal cancers remains unclear.This review will discuss the reported alteration in the composition of gastric and esophageal microbiota in normal and disease conditions,and the potential role of dysbiosis in carcinogenesis and tumorigenesis.This review will also discuss how dysbiosis stimulates local and systemic immunity,which may impact on the immunotherapy for cancer.展开更多
Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers...Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.展开更多
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 thera...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 alt展开更多
AIM： To compare the efficacy of the proton-pump inhibitor, rabeprazole, with that of the H2-receptor antagonist, ranitidine, as on-demand therapy for relieving symptoms associated with non-erosive reflux disease （N...AIM： To compare the efficacy of the proton-pump inhibitor, rabeprazole, with that of the H2-receptor antagonist, ranitidine, as on-demand therapy for relieving symptoms associated with non-erosive reflux disease （NEED）.METHODS： This is a single center, prospective, randomized, open-label trial of on-demand therapy with rabeprazole （group A） vs ranitidine （group B） for 4 wk. Eighty-three patients who presented to the American University of Beirut Medical Center with persistent gas- troesophageal reflux disease （GERD） symptoms and a normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A （n = 44） were al-lowed a maximum rabeprazole dose of 20 mg twice daily, while those in group B （n = 39） were allowed a maximum ranitidine dose of 300 mg twice daily. Ef- ficacy was assessed by patient evaluation of global symptom relief, scores of the SF-36 quality of life （QoL） questionnaires, total number of pills used, and number of medication-free days.RESULTS： Among the 83 patients who were enrolled in the study, 76 patients （40 in the rabeprazole group and 36 in the ranitidine group） completed the 4-wk trial. Baseline characteristics were comparable between both groups. After 4 wk, there was no significant difference in the subjective global symptom relief between the rabeprazole and the ranitidine groups （71.4% vs 65.4%, respectively; P = 0.9）. There were no statistically significant differences between mean cumulative scores of the SF-36 QoL questionnaire for the two study groups （rabeprazole 22.40±27.53 vs ranitidine 17.28 ± 37.06; P = 0.582）. There was no significant difference in the mean number of pills used （rabeprazole 35.70±29.75 vs ranitidine 32.86±26.98; P = 0.66）. There was also no statistically significant difference in the mean number of medication-free days between both groups.CONCLUSION： Rabeprazole has a comparable efficacy compared to ranitidine when given on-demand for the treatment of NERD. Both medications were associ展开更多
Since the early reports nearly a decade ago, proton-pump inhibitor-induced hypomagnesemia （PPIH） has become a well-recognized phenomenon. While many observational studies in the inpatient and outpatient populations ...Since the early reports nearly a decade ago, proton-pump inhibitor-induced hypomagnesemia （PPIH） has become a well-recognized phenomenon. While many observational studies in the inpatient and outpatient populations have confirmed the association of PPI exposure and serum magnesium concentrations, there are no prospective,controlled studies to support causation. Molecular mechanisms of magnesium transporters, including the pH-dependent regulation of transient receptor potential melastatin-6 transporters in the colonic enterocyte, have been proposed to explain the effect of PPIs on magnesium reabsorption, but may be a small part of a more complicated interplay of molecular biology, pharmacology, and genetic predisposition. This review explores the current state of research in the feld of PPIH and the proposed mechanisms of this effect.展开更多
Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori(H.pylori)infection associated duodenal ulcers should undergo eradication therapy.There are m...Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori(H.pylori)infection associated duodenal ulcers should undergo eradication therapy.There are many regimens offered for H.pylori eradication which include triple,quadruple,or sequential therapy regimens.The central aim of this systematic review is to evaluate the evidence for H.pylori therapy from a meta-analytical outlook.The consequence of the dose,type of proton-pump inhibitor,and the length of the treatment will be debated.The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.展开更多
Background: Clopidogrel is a prodrug metabolized by cytochrome P450-2C19. Drugs inhibiting this enzyme might reduce its antiplatelet activity. In order to reduce gastrointestinal bleedings, proton-pump inhibitors are ...Background: Clopidogrel is a prodrug metabolized by cytochrome P450-2C19. Drugs inhibiting this enzyme might reduce its antiplatelet activity. In order to reduce gastrointestinal bleedings, proton-pump inhibitors are usually prescribed in association with clopidogrel. The study aims at assessing the clinical importance of interactions between clopidogrel and inhibitors of CYP2C19. It also aims to evaluate any possible factors that may reduce the therapeutic efficacy of the drug. Particular attention was devoted to possible gender differences in responsiveness to treatment with clopidogrel or clopidogrel plus proton-pump inhibitors. This analysis is a retrospective case-control observational study carried out by the University Hospital of Ferrara. Methods: Subjects were patients who had received clopidogrel from 01-01-2008 to 31-12-2008. For them, we analysed hospital admissions and data of drug prescriptions relative to dispensing of drugs cytochrome P-450-2C19 inhibitors. Patients were subdivided into case and control groups based on the occurrence or not of cardiovascular or cerebrovascular secondary events during therapy with clopidogrel. Results: The study focused on 781 patients, 20.1% of which (n.157) experienced secondary effects. The mean age is 70 years old. Men (67% of the analyzed population) experienced secondary events more than women (OR 1.54;CI 95% 1.04 - 2.28;p < 0.03). 70% of patients took PPIs and we noticed that the risk of secondary events increased by 2.2% with respect to the remaining patients (20.77% vs 18.57%;OR 1.15;CI 0.78 - 1.70;p = NS). Among PPIs, lansoprazole is the most used. For this subgroup the risk is 5.2% higher (risk in those exposed of 23.75% vs 18.57% in those not exposed;or 1.37, 95% CI 0.92 - 2.03;p = NS). The interaction with PPIs is particularly interesting only among women, with a risk 6.3% higher (17.46% exposed, 11.11% non exposed). The risk remains the same among men. Conclusions: Analyzed data show an increase in cardiovascular or cerebral secondary events for patie展开更多
Gastro-esophageal reflux disease(GERD)is a condition which is frequently faced by primary care physicians and gastroenterologists.Improving management of GERD is crucial to maximise both patient care and resource util...Gastro-esophageal reflux disease(GERD)is a condition which is frequently faced by primary care physicians and gastroenterologists.Improving management of GERD is crucial to maximise both patient care and resource utilization.In fact,the management of patients with GERD is complex and poses several questions to the clinician who faces them in clinical practice.For instance,many aspects should be considered,including the appropriateness of indication to endoscopy,the quality of the endoscopic examination,the use and interpretation of ambulatory reflux testing,and the choice and management of anti-reflux treatments,i.e.,protonpump inhibitors and surgery.Aim of the present review was to provide a comprehensive update on the clinical management of patients with GERD,through a literature review on the diagnosis and management of patients with GER symptoms.In details,we provide practice-oriented concise answers to clinical questions,with the aim of optimising patient management and healthcare resource use.展开更多
Proton-pump inhibitors （PPIs） are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters ...Proton-pump inhibitors （PPIs） are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for 〉3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients （258 samples） used PPIs for at least 3 months before semen collection. In regression models, PPI use （either as the only medication or when used in combination with other nonspermatotoxic medications） was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.展开更多
Objective： To determine whether patients maintain symptom control after discontinuation of PPI （proton-pump inhibitor） therapy through intervention of a pharmacist-led medication utilization program and determine a...Objective： To determine whether patients maintain symptom control after discontinuation of PPI （proton-pump inhibitor） therapy through intervention of a pharmacist-led medication utilization program and determine annual clinic cost-savings per prescription. Design： The study was conducted as a prospective, medication use evaluation. Using an electronic medical record system at a clinic, reports generated all patients receiving PP1 therapy from January 2013-June 2015. Patients were encouraged to participate in a PPI discontinuation trial through a pharmacist-led educational session. Participants were followed-up three months post enrollment to assess their quality of life through a survey assessing severity and frequency of symptoms. Participants unable to maintain symptom control after the intervention were referred back to their primary care physician for further evaluation. Results： Of one hundred participants, 25% （n = 25） were able to discontinue the use of PPI by lifestyle modifications, 43% （n = 43） refused to discontinue PP1 therapy and lifestyle changes due to the severity of their symptoms, 17% （n = 17） switched to over-the-counter H2 receptor antagonist daily to control their symptoms, 9% （n = 9） used PPIs only as needed, and 6% （n = 6） of participants were dropped from the study after three failed communication attempts. The clinic saved approximately $11 thousand annually for every one prescription of PPI＇s. Conclusions： Discontinuation of PPI or step-down therapy was possible for patients with mild-moderate GERD （Gastroesophageal Reflux Disease） symptoms when mediated by pharmacist counseling and follow-up. Also, the annual PPI expenditure at this clinic will decrease due to participant＇s discontinuation of therapy.展开更多
The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed tha...The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed that new PPIs should have the following features:(1) number of ring II = number of ring I+ 1;(2) preferably five, six, or seven-membered heteroatomic ring for stability;and (3) 1<pKa1<4. Six molecular scaffolds based on the aforementioned criteria were constructed, and R groups were extracted from compounds in extensive data sources. A virtual molecule dataset was established, and the pKa values of specific atoms on the molecules in the dataset were calculated to select the molecules with required pKa values. Drug-likeness screening was further conducted to obtain the candidates that significantly reduced the adverse effects of long-term PPI use. This study provided insights and tools for designing targeted molecules in silico that are suitable for practical applications.展开更多
Background:Asymptomatic low-grade(Los Angeles Classification Grades A and B)esophagitis is common in clinical practice with unclear clinical outcomes.This study aimed to explore the clinical outcomes of asymptomatic l...Background:Asymptomatic low-grade(Los Angeles Classification Grades A and B)esophagitis is common in clinical practice with unclear clinical outcomes.This study aimed to explore the clinical outcomes of asymptomatic low-grade esophagitis.Methods:This was a multicenter cohort study conducted by three academic hospitals in China.Asymptomatic low-grade esophagitis patients between January 2015 and December 2019 were included.Mucosal healing condition 1year after initial diagnosis,symptomoutcomes,and proton-pump inhibitor(PPI)use within 1year after initial diagnosis were studied and compared.Results:A total of 248 asymptomatic low-grade esophagitis patients were included.Esophagitis disappeared in 76.2%of patients 1 year after initial diagnosis.In terms of symptom outcomes,89.9%of patients did not present gastroesophageal reflux disease(GERD)symptoms within 1 year after initial diagnosis.No significant difference was found in the proportion of patients who presented GERD symptoms and in the proportion of patients with persistent esophagitis between the PPI group and the non-PPI group(all P>0.05).Patients with initial Grade B esophagitis were more likely to present follow-up GERD symptoms(16.0%vs 7.5%,P=0.041)and had more severe follow-up esophagitis than those with Grade A(P<0.001).Patients with follow-up GERD symptoms were more likely to have persistent esophagitis than those without.Conclusions:This study demonstrated that asymptomatic low-grade esophagitis had relatively benign clinical outcomes.Patients with initial Grade B esophagitis and patients with follow-up GERD symptoms were more likely to be those who are in genuine need of further follow-up and treatments.展开更多
Background:Gastroesophageal reflux disease(GERD)is a common disorder.Overall,≤35%of GERD patients fail the standard dose of proton-pump-inhibitor(PPI)treatment.Due to the high prevalence and low satisfaction rate wit...Background:Gastroesophageal reflux disease(GERD)is a common disorder.Overall,≤35%of GERD patients fail the standard dose of proton-pump-inhibitor(PPI)treatment.Due to the high prevalence and low satisfaction rate with treatment failure,there is an unmet need for new treatment.Our aim was to evaluate whether the use of the transcutaneous electrical stimulation system(TESS)can reduce esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI.Methods:We enrolled 10 patients suffering from heartburn and regurgitation with an abnormal esophageal-acid exposure(off PPIs)who failed standard-dose PPI.After the placement of a wireless esophageal pH capsule,all patients were treated with TESS.The primary end point was the reduction in the baseline(pretreatment)24-hour percent total time pH<4 and/or DeMeester score by 50%.Results:Seven GERD patients(five females and two males,aged 49.3610.1 years)completed the study.At baseline,the mean percent total time pH<4 was 12.064.9.Following TESS,the mean percent total time pH<4 dropped to 5.563.4,4.562.6,3.762.9,and 4.462.5 on Days 1,2,3,and 4,respectively.At baseline,the mean DeMeester score was 39.0618.5.After TESS,the mean DeMeester score dropped to 15.869.2,13.266.8,11.269.4,and 12.066.8 on Days 1,2,3,and 4,respectively.Conclusion:TESS is a safe and potentially effective modality in reducing esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI.A larger and prospective controlled study is needed to verify these preliminary results.展开更多
文摘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.
文摘AIM:To evaluate the current practice of stress ulcer prophylaxis (SUP) in Lebanese Health care centers.METHODS:A multi-center prospective chart review study was conducted over 8 mo.A questionnaire was distributed to pharmacy students who collected data on demographics,SUP medications,dose,route,duration and associated risk factors.The appropriateness of SUP use was determined as per American Society of Health-System Pharmacists guidelines.Institutional review board approval was obtained from each hospital center.RESULTS:A total of 1004 patients were included.67% of the patients who received prophylaxis did not have an indication for SUP.The majority (71.6%) of the patients who were administered parenteral drugs can tolerate oral medications.Overall,the regimen of acid-suppressant drugs was suboptimal in 87.6% of the sample.This misuse was mainly observed in non-teaching hospitals.CONCLUSION:This study highlighted the need,in Lebanese hospitals,to establish clinical practice guidelines for the use of SUP;mainly in non-critical care settings.
文摘Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81470486）, and the National Key Research and Development Program of China during the 13^th 5-Year Plan Period （No. 2016YFC1301301）.
文摘Background：Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors （PPIs） combined with clopidogrel therapy,causing much uncertainty in clinical practice.We sought to evaluate the safety of PPIs use among high-risk cardiovascular patients who underwent percutaneous coronary intervention （PCI） in a long-term follow-up study.Methods：A total of 7868 consecutive patients who had undergone PCI and received dual antiplatelet therapy （DAPT） at a single center from January 2013 to December 2013 were enrolled.Adenosine diphosphate （ADP）-induced platelet aggregation inhibition was measured by modified thromboelastography （mTEG） in 5042 patients.Propensity score matching （PSM） was applied to control differing baseline factors.Cox proportional hazards regression was used to evaluate the 2-year major adverse cardiovascular and cerebrovascular events （MACCEs）,as well as individual events,including all-cause death,myocardial infarction,unplanned target vessel revascularization,stent thrombosis,and stroke.Results：Among the whole cohort,27.2% were prescribed PPIs.The ADP-induced platelet aggregation inhibition by mTEG was significantly lower in PPI users than that in non-PPI users （42.0 ± 30.9% vs.46.4 ± 31.4%,t =4.435,P 〈 0.001）.Concomitant PPI use was not associated with increased MACCE through 2-year follow-up （12.7% vs.12.5%,x2 =0.086,P =0.769）.Other endpoints showed no significant differences after multivariate adjustment,regardless of PSM.Conclusion：In this large cohort of real-world patients,the combination of PPIs with DAPT was not associated with increased risk of MACCE in patients who underwent PCI at up to 2 years of follow-up.
基金Supported by Zhejiang Provincial Bureau of Health,No. 2012KYA090Zhejiang Provincial Bureau of Education, No.20070227
文摘AIM:To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal(GI) injury with combined protective medications.METHODS:A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital,School of Medicine,Zhejiang University.The hospital has 2300 beds and 2.5 million outpatient visits annually.Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011.Concomitant use of proton-pump inhibitors(PPIs),histamine 2-receptor antagonists(H2RA) and mucoprotective drugs(MPs) were analyzed.A defined daily dose(DDD) methodology was applied to each MP.A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs(NSAIDs),corticosteroids and clopidogrel and warfarin] or intestinal protective drugs(misoprostol,rebamipide,teprenone and gefarnate).Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records.The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients.RESULTS:Prescriptions for aspirin users receiving PPIs,H2RA and MPs(n = 1039) accounted for only 3.46% of total aspirin prescriptions(n = 30 015).The ratios of coadministration of aspirin/PPI,aspirin/H2RA,aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%,0.12%,0.40% and 0.12%,respectively.No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs,H2RA or MPs.The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs(2.82% vs 0.40%,P < 0.05) and aspirin/H2RA(2.82% vs 0.12%,P < 0.05).The values of DDDs of MPs in descending order were as follows:gefarnate,hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium gualenate granules > rebamipide > sucralfate chewable tablets.The ratio of MP plus aspirin p
基金supported by the Comprehensive Cancer Center Support Grant of the Ohio State University as part from the National Institutes of Health P30 CA16058-32(to X.Z.)R01 CA185055 from the National Cancer InstituteS10 OD025230 from the National Heart,Lung,and Blood Institute(to Z.P.).
文摘Gastric and esophageal cancers are multifactorial and multistage-involved malignancy.While the impact of gut microbiota on overall human health and diseases has been well documented,the influence of gastric and esophageal microbiota on gastric and esophageal cancers remains unclear.This review will discuss the reported alteration in the composition of gastric and esophageal microbiota in normal and disease conditions,and the potential role of dysbiosis in carcinogenesis and tumorigenesis.This review will also discuss how dysbiosis stimulates local and systemic immunity,which may impact on the immunotherapy for cancer.
基金Supported by Zhejiang Provincial Bureau of Education, No. 20070227Zhejiang Medical Association, No.2007ZYC18Association of Zhejiang Hospital Administration, No. 2007AZHA-KEB312
文摘Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.
文摘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 alt
文摘AIM： To compare the efficacy of the proton-pump inhibitor, rabeprazole, with that of the H2-receptor antagonist, ranitidine, as on-demand therapy for relieving symptoms associated with non-erosive reflux disease （NEED）.METHODS： This is a single center, prospective, randomized, open-label trial of on-demand therapy with rabeprazole （group A） vs ranitidine （group B） for 4 wk. Eighty-three patients who presented to the American University of Beirut Medical Center with persistent gas- troesophageal reflux disease （GERD） symptoms and a normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A （n = 44） were al-lowed a maximum rabeprazole dose of 20 mg twice daily, while those in group B （n = 39） were allowed a maximum ranitidine dose of 300 mg twice daily. Ef- ficacy was assessed by patient evaluation of global symptom relief, scores of the SF-36 quality of life （QoL） questionnaires, total number of pills used, and number of medication-free days.RESULTS： Among the 83 patients who were enrolled in the study, 76 patients （40 in the rabeprazole group and 36 in the ranitidine group） completed the 4-wk trial. Baseline characteristics were comparable between both groups. After 4 wk, there was no significant difference in the subjective global symptom relief between the rabeprazole and the ranitidine groups （71.4% vs 65.4%, respectively; P = 0.9）. There were no statistically significant differences between mean cumulative scores of the SF-36 QoL questionnaire for the two study groups （rabeprazole 22.40±27.53 vs ranitidine 17.28 ± 37.06; P = 0.582）. There was no significant difference in the mean number of pills used （rabeprazole 35.70±29.75 vs ranitidine 32.86±26.98; P = 0.66）. There was also no statistically significant difference in the mean number of medication-free days between both groups.CONCLUSION： Rabeprazole has a comparable efficacy compared to ranitidine when given on-demand for the treatment of NERD. Both medications were associ
文摘Since the early reports nearly a decade ago, proton-pump inhibitor-induced hypomagnesemia （PPIH） has become a well-recognized phenomenon. While many observational studies in the inpatient and outpatient populations have confirmed the association of PPI exposure and serum magnesium concentrations, there are no prospective,controlled studies to support causation. Molecular mechanisms of magnesium transporters, including the pH-dependent regulation of transient receptor potential melastatin-6 transporters in the colonic enterocyte, have been proposed to explain the effect of PPIs on magnesium reabsorption, but may be a small part of a more complicated interplay of molecular biology, pharmacology, and genetic predisposition. This review explores the current state of research in the feld of PPIH and the proposed mechanisms of this effect.
文摘Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori(H.pylori)infection associated duodenal ulcers should undergo eradication therapy.There are many regimens offered for H.pylori eradication which include triple,quadruple,or sequential therapy regimens.The central aim of this systematic review is to evaluate the evidence for H.pylori therapy from a meta-analytical outlook.The consequence of the dose,type of proton-pump inhibitor,and the length of the treatment will be debated.The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.
文摘Background: Clopidogrel is a prodrug metabolized by cytochrome P450-2C19. Drugs inhibiting this enzyme might reduce its antiplatelet activity. In order to reduce gastrointestinal bleedings, proton-pump inhibitors are usually prescribed in association with clopidogrel. The study aims at assessing the clinical importance of interactions between clopidogrel and inhibitors of CYP2C19. It also aims to evaluate any possible factors that may reduce the therapeutic efficacy of the drug. Particular attention was devoted to possible gender differences in responsiveness to treatment with clopidogrel or clopidogrel plus proton-pump inhibitors. This analysis is a retrospective case-control observational study carried out by the University Hospital of Ferrara. Methods: Subjects were patients who had received clopidogrel from 01-01-2008 to 31-12-2008. For them, we analysed hospital admissions and data of drug prescriptions relative to dispensing of drugs cytochrome P-450-2C19 inhibitors. Patients were subdivided into case and control groups based on the occurrence or not of cardiovascular or cerebrovascular secondary events during therapy with clopidogrel. Results: The study focused on 781 patients, 20.1% of which (n.157) experienced secondary effects. The mean age is 70 years old. Men (67% of the analyzed population) experienced secondary events more than women (OR 1.54;CI 95% 1.04 - 2.28;p < 0.03). 70% of patients took PPIs and we noticed that the risk of secondary events increased by 2.2% with respect to the remaining patients (20.77% vs 18.57%;OR 1.15;CI 0.78 - 1.70;p = NS). Among PPIs, lansoprazole is the most used. For this subgroup the risk is 5.2% higher (risk in those exposed of 23.75% vs 18.57% in those not exposed;or 1.37, 95% CI 0.92 - 2.03;p = NS). The interaction with PPIs is particularly interesting only among women, with a risk 6.3% higher (17.46% exposed, 11.11% non exposed). The risk remains the same among men. Conclusions: Analyzed data show an increase in cardiovascular or cerebral secondary events for patie
文摘Gastro-esophageal reflux disease(GERD)is a condition which is frequently faced by primary care physicians and gastroenterologists.Improving management of GERD is crucial to maximise both patient care and resource utilization.In fact,the management of patients with GERD is complex and poses several questions to the clinician who faces them in clinical practice.For instance,many aspects should be considered,including the appropriateness of indication to endoscopy,the quality of the endoscopic examination,the use and interpretation of ambulatory reflux testing,and the choice and management of anti-reflux treatments,i.e.,protonpump inhibitors and surgery.Aim of the present review was to provide a comprehensive update on the clinical management of patients with GERD,through a literature review on the diagnosis and management of patients with GER symptoms.In details,we provide practice-oriented concise answers to clinical questions,with the aim of optimising patient management and healthcare resource use.
文摘Proton-pump inhibitors （PPIs） are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for 〉3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients （258 samples） used PPIs for at least 3 months before semen collection. In regression models, PPI use （either as the only medication or when used in combination with other nonspermatotoxic medications） was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.
文摘Objective： To determine whether patients maintain symptom control after discontinuation of PPI （proton-pump inhibitor） therapy through intervention of a pharmacist-led medication utilization program and determine annual clinic cost-savings per prescription. Design： The study was conducted as a prospective, medication use evaluation. Using an electronic medical record system at a clinic, reports generated all patients receiving PP1 therapy from January 2013-June 2015. Patients were encouraged to participate in a PPI discontinuation trial through a pharmacist-led educational session. Participants were followed-up three months post enrollment to assess their quality of life through a survey assessing severity and frequency of symptoms. Participants unable to maintain symptom control after the intervention were referred back to their primary care physician for further evaluation. Results： Of one hundred participants, 25% （n = 25） were able to discontinue the use of PPI by lifestyle modifications, 43% （n = 43） refused to discontinue PP1 therapy and lifestyle changes due to the severity of their symptoms, 17% （n = 17） switched to over-the-counter H2 receptor antagonist daily to control their symptoms, 9% （n = 9） used PPIs only as needed, and 6% （n = 6） of participants were dropped from the study after three failed communication attempts. The clinic saved approximately $11 thousand annually for every one prescription of PPI＇s. Conclusions： Discontinuation of PPI or step-down therapy was possible for patients with mild-moderate GERD （Gastroesophageal Reflux Disease） symptoms when mediated by pharmacist counseling and follow-up. Also, the annual PPI expenditure at this clinic will decrease due to participant＇s discontinuation of therapy.
基金National Natural Science Foundation of China (Nos.31200986 and 41530105)(to RZ)Natural Science Foundation, the Shanghai Committee of Science and Technology (No.16ZR1449800)(to RZ)+4 种基金the Fundamental Research Funds for the Central Universities (Nos.10247201546 and 2000219083)(to RZ)a departmental start-up fund (to LZ)the Peter and Tommy Fund,Inc.,Buffalo,NY (to LZ),Funds from the University at Buffalo Community of Excellence in GenomeEnvironment and Microbiome (GEM)(to LZ)UTHealth Innovation for Cancer Prevention Research Training Program Post-doctoral Fellowship (Cancer Prevention and Research Institute of Texas,grant #RP160015)(to HK).
文摘The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed that new PPIs should have the following features:(1) number of ring II = number of ring I+ 1;(2) preferably five, six, or seven-membered heteroatomic ring for stability;and (3) 1<pKa1<4. Six molecular scaffolds based on the aforementioned criteria were constructed, and R groups were extracted from compounds in extensive data sources. A virtual molecule dataset was established, and the pKa values of specific atoms on the molecules in the dataset were calculated to select the molecules with required pKa values. Drug-likeness screening was further conducted to obtain the candidates that significantly reduced the adverse effects of long-term PPI use. This study provided insights and tools for designing targeted molecules in silico that are suitable for practical applications.
基金supported by the National Natural Science Foundation of China[grant numbers 81770544,81970479].
文摘Background:Asymptomatic low-grade(Los Angeles Classification Grades A and B)esophagitis is common in clinical practice with unclear clinical outcomes.This study aimed to explore the clinical outcomes of asymptomatic low-grade esophagitis.Methods:This was a multicenter cohort study conducted by three academic hospitals in China.Asymptomatic low-grade esophagitis patients between January 2015 and December 2019 were included.Mucosal healing condition 1year after initial diagnosis,symptomoutcomes,and proton-pump inhibitor(PPI)use within 1year after initial diagnosis were studied and compared.Results:A total of 248 asymptomatic low-grade esophagitis patients were included.Esophagitis disappeared in 76.2%of patients 1 year after initial diagnosis.In terms of symptom outcomes,89.9%of patients did not present gastroesophageal reflux disease(GERD)symptoms within 1 year after initial diagnosis.No significant difference was found in the proportion of patients who presented GERD symptoms and in the proportion of patients with persistent esophagitis between the PPI group and the non-PPI group(all P>0.05).Patients with initial Grade B esophagitis were more likely to present follow-up GERD symptoms(16.0%vs 7.5%,P=0.041)and had more severe follow-up esophagitis than those with Grade A(P<0.001).Patients with follow-up GERD symptoms were more likely to have persistent esophagitis than those without.Conclusions:This study demonstrated that asymptomatic low-grade esophagitis had relatively benign clinical outcomes.Patients with initial Grade B esophagitis and patients with follow-up GERD symptoms were more likely to be those who are in genuine need of further follow-up and treatments.
文摘Background:Gastroesophageal reflux disease(GERD)is a common disorder.Overall,≤35%of GERD patients fail the standard dose of proton-pump-inhibitor(PPI)treatment.Due to the high prevalence and low satisfaction rate with treatment failure,there is an unmet need for new treatment.Our aim was to evaluate whether the use of the transcutaneous electrical stimulation system(TESS)can reduce esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI.Methods:We enrolled 10 patients suffering from heartburn and regurgitation with an abnormal esophageal-acid exposure(off PPIs)who failed standard-dose PPI.After the placement of a wireless esophageal pH capsule,all patients were treated with TESS.The primary end point was the reduction in the baseline(pretreatment)24-hour percent total time pH<4 and/or DeMeester score by 50%.Results:Seven GERD patients(five females and two males,aged 49.3610.1 years)completed the study.At baseline,the mean percent total time pH<4 was 12.064.9.Following TESS,the mean percent total time pH<4 dropped to 5.563.4,4.562.6,3.762.9,and 4.462.5 on Days 1,2,3,and 4,respectively.At baseline,the mean DeMeester score was 39.0618.5.After TESS,the mean DeMeester score dropped to 15.869.2,13.266.8,11.269.4,and 12.066.8 on Days 1,2,3,and 4,respectively.Conclusion:TESS is a safe and potentially effective modality in reducing esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI.A larger and prospective controlled study is needed to verify these preliminary results.
