Proton Pump Inhibitors Group Research Articles

Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study

Cough may be a manifestation of gastro-oesophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain. To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. Subjects were nonsmokers without history of asthma, with chronic cough for >8 weeks. All subjects underwent a baseline 24-h pH/impedance study, methacholine challenge test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores and change in laryngeal findings. Forty subjects were randomised (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores. Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18) and 31.8% (seven of 22) in the placebo and PPI groups respectively. In subjects with chronic cough and rare or no heartburn, high-dose proton pump inhibitor does not improve cough-related quality of life or symptoms.

Platelet Activity Associated with Concomitant Use of Clopidogrel and Proton Pump Inhibitors in Children with Cardiovascular Disease

In adults with acute coronary syndrome, decreased platelet inhibition associated with concomitant use of clopidogrel and proton pump inhibitors (PPI) has been reported. To evaluate platelet activity associated with PPI + clopidogrel vs. clopidogrel alone in children enrolled in the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial of clopidogrel in children with a cardiac condition at risk for arterial thrombosis. Patients 0-24 m randomized to active therapy in the PICOLO trial were included in the present analysis. Platelet aggregation inhibition at baseline and steady state were evaluated in patients taking clopidogrel + PPI vs. clopidogrel only in the overall cohort and sub-group of clopidogrel responders. A total of 49 patients were included (44 clopidogrel only, five clopidogrel + PPI); median age 38 days (interquartile range [IQR] 17-157 days). The majority of patients in each group had undergone systemic-to-pulmonary artery shunt. Compared with the clopidogrel group, patients in the clopidogrel + PPI group had a trend toward lower percent inhibition of maximum extent of platelet aggregation overall (median 6%, IQR 0-44% vs. 49%, IQR 19-63%, P= 0.09), and a significant reduction in the clopidogrel responders sub-group (median 25%, IQR 3-45% vs. 53%, IQR 38-65%, P= 0.04). There was no difference in percent inhibition of rate of platelet aggregation. Concomitant use of PPI + clopidogrel may be associated with decreased platelet inhibition in children with cardiac disease. Further study in a larger population and assessment of associated clinical outcomes is warranted.

Spontaneous Bacterial Peritonitis and Proton Pump Inhibitors: Correlation of Disease Process?

Purpose: Bacterial infections are a significant cause of morbidity and mortality in cirrhosis, the most common of which is spontaneous bacterial peritonitis (SBP). Proton pump inhibitors (PPI) are one of the most widely used medications to treat peptic ulcer disease in order to eliminate gastric acid in the stomach and relieve symptoms. This, however, allows orally ingested bacteria to colonize and proliferate in the stomach and small intestine, thereby increasing bacterial overgrowth and leading to SBP. We intend to explore this association in a community based setting in this retrospective chart review. Methods: We conducted a 5-year retrospective review of patients at teaching hospital diagnosed with ascites, cirrhosis, and SBP using ICD 9 codes, from January 1st 2004 to December 31st 2008. Each patient with a diagnosis of ascites, cirrhosis, and SBP were stratified into two groups: one with home PPI use (Study), and those without home PPI use (Control). Both groups were matched 1:1 based on age (decade), sex, Child-Turcotte-Pugh scores, and MELD scores (intervals of 10). If the patients had more than one episode of SBP, then the first episode was the only one analyzed. Results: A total of eight patients had a diagnosis of ascites, cirrhosis, and SBP and were on a home PPI regiment of some kind. Mean age of the both groups was 51 yrs+/-6.8 SD, while the experimental/PPI group of patients were slightly older when compared to our control population, 53.7+/- 9.7 vs. 49.7+/- 4.2 (P value < 0.35). 90% of all the patients in both groups were males. We found no significant difference between the two groups in terms of CTP or MELD score severity. 42.8% of the both groups had ETOH liver cirrhosis; however, that was not statistically significant between the two populations. PPI group had a lower ascitic fluid albumin level (0.55 +/- 0.5, CI 0.3-1.05) compared to the control group. Mortality was 25% higher in the PPI group. Only 37% of the PPI group had documented indication for PPI use. Conclusion: SBP is common problem with cirrhotic patients. There are many risk factors which can be associated with developing SBP, and one of those was thought to be the use of PPI. Although our study sample is small, our study found that the misuse of PPI's lowers ascitic albumin level and may prone patients to more severe infections and increase mortality. This is an important consideration when prescribing cirrhotic patients PPIs.

Cardiovascular and gastrointestinal events of three antiplatelet therapies: clopidogrel, clopidogrel plus proton-pump inhibitors, and aspirin plus proton-pump inhibitors in patients with previous gastrointestinal bleeding

Concomitant use of antiplatelet agents and proton-pump inhibitors (PPIs) has been recommended in patients with a history of gastrointestinal (GI) hemorrhage. However, recent studies have reported that PPIs may alter clopidogrel's pharmacokinetics and potentially lead to an increased risk of recurrent adverse cardiovascular (CV) events. Using Taiwan's 2000-2006 National Health Insurance database, this population-based retrospective cohort study assessed CV and GI events in patients who had a prior history of GI bleeding and had been prescribed ongoing antiplatelet therapy after acute coronary syndrome (ACS) discharge. We identified 3,580 ACS patients and categorized them into (1) those taking clopidogrel alone, (2) those taking clopidogrel plus PPIs, and (3) those taking aspirin plus PPIs. Cox proportional hazards models were used to assess the association between the use of antiplatelet therapies and CV/GI events. The clopidogrel only group and the clopidogrel plus PPI group were found to be at lower risk for GI events than the aspirin plus PPI group [adjusted hazard ratio (HR) 0.23 (95% confidence interval; CI 0.14-0.36) and HR 0.70 (0.52-0.96), respectively]. However, while the clopidogrel only group had a lower risk of CV events than the aspirin plus PPI group [HR 0.57 (0.38-0.84)], the clopidogrel plus PPI group had a significantly higher CV risk than the aspirin plus PPI group [HR 1.59 (1.18-2.13)]. Our findings suggest that although the use of clopidogrel plus PPIs provides GI benefits, with this treatment, there is an increased CV risk among patients with a history of GI bleeding.

Clopidogrel and PPI, warfarin management, and rural pharmacists' competence

Clopidogrel and PPI Stockl et al.1 concluded that “patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone.” Patients taking clopidogrel and a proton pump inhibitor (PPI) (n = 1,033) were compared with a matched group of patients taking clopidogrel alone. Propensity score matching corrected potential selection bias by balancing covariates between the two groups of patients. Patients included in the clopidogrel plus PPI group were dispensed a PPI with one or more days’ supply overlapping the index date and at least one refill within 90 days. The clopidogrel-alone group patients were not dispensed a PPI 90 days before or after the index date. Patients who received clopidogrel plus a PPI had a 93% higher risk of rehospitalization for myocardial infarction (MI) (adjusted hazard ratio 1.93 [95% CI 1.05–3.54]; P = 0.03) and a 64% higher risk of rehospitalization for MI or coronary stent placement (1.64 [1.16– 2.32]; P = 0.005) than patients receiving clopidogrel alone. Implications. Patients taking clopidogrel and a PPI were at higher risk of rehospitalization. Reduced action of clopidogrel may result from competitive metabolic effects of the PPIs on cytochrome P450 (CYP)2C19. Also, CYP2C19 variant allele carriers have lower capacity to metabolize clopidogrel into its active metabolite and inhibit platelet activation.2 Does the higher risk of rehospitalization associated with taking a PPI potentially have a genetic component? Further study is needed of therapy based on genetic testing among patients at high risk of acute gastrointestinal bleeding where a PPI is indicated.

041 Clopidogrel and proton pump inhibitors: can near patient testing help to inform dual prescription?

Clopidogrel is relatively contraindicated in patients at risk of gastrointestinal bleeding. To reduce this risk, proton-pump inhibitors (PPI) which are often co-prescribed. Many PPIs undergo hepatic metabolism by the cytochrome (CYP) P450 isoenzymes, thus CYP P450-metabolised drugs, including clopidogrel become vulnerable to drug-drug interaction. Gilard et al first highlighted the negative impact of PPIs, on the pharmacodynamic response to clopidogrel in the randomised, double-blind Omeprazole CLopidogrel Aspirin (OCLA) trial. A randomised trial of omeprazole and pantoprazole conducted by Cuisset et al also demonstrated that after 1 month, patients receiving pantoprazole had significantly better platelet response to clopidogrel than those receiving omeprazole. Population-based studies have suggested that concomitant use of PPI with clopidogrel results in significantly increased risk of adverse outcomes. Anxieties brought on by such studies have been largely allayed by the recently presented results of the COGENT trial. This major randomised controlled trial, comparing clopidogrel with omeprazole vs clopidogrel alone demonstrated no difference in the risk of cardiovascular events between groups. We assessed the impact of PPI co-prescription on clopidogrel response using a verified near patient test, prospectively in 269 patients (mean age 63±11, 85 female) admitted with high risk ACS (characterised by electrocardiographic changes of ischaemia and/or raised troponin I). Loading and maintenance of clopidogrel was as per contemporary UK practice. Eighty-eight patients were prescribed a PPI concomitantly as in-patients. Platelet response to clopidogrel in whole blood samples, taken at the time of angiography, was assessed using a VerifyNow analyser (Accumetrics, California, US). Of the 269 patients recruited, 151 (56%) proceeded to PCI, 40 (15%) underwent coronary artery bypass grafting (CABG), 78 (29%) were treated medically. The clinical endpoint was adverse clinical events (ACE) at 18 months (death, MI, repeat revascularisation, CABG, stroke or unplanned cardiovascular hospitalisation). Co-administration of PPI and clopidogrel was associated with significantly reduced clopidogrel P2Y12 activity (p=0.022) (Abstract 41 Figure 1a) but not clinical outcome (ACE, p=0.123, Abstract 41 Figure 1b). Groups were well matched for age, gender, body mass index, current smoking, presence of diabetes and hyperlipidaemia. More patients in the PPI group had suffered a previous MI (36% vs 20%, p=0.007) and had received previous PCI treatment (20% vs 8%, p=0.005). As near patient tests of clopidogrel activity find their position in the care of patients with ischaemic heart disease, physicians may wish to use this technology to test patients at high risk of stent thrombosis who are also taking medications which pose a risk of inhibiting platelet clopidogrel response.

Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: A randomized, crossover, controlled clinical trial

Proton pump inhibitors (PPIs) are the most potent gastric acid suppressing drugs available, and their use is widespread. An emerging concern about chronic PPI therapy is whether these drugs impair intestinal calcium absorption, resulting in a negative calcium balance and thereby potentially causing bone loss. The objective of this study was to evaluate the acute effect of the PPI esomeprazole or placebo on intestinal calcium absorption in healthy adults. Twelve young adults participated in a placebo-controlled, double-blind, crossover study. There were two 3-week interventions that included a 14-day adjustment period (designed to stabilize calcium homeostasis) followed by 6 days of a diet containing 800 mg of calcium and 2.1 g/kg of protein (intervention). During the last 3 days of the adjustment period and throughout the intervention period, subjects consumed esomeprazole or placebo. Half the subjects underwent 24-hour continuous gastric acid pH monitoring. Intestinal calcium absorption was measured using dual-stable calcium isotopes at the end of each intervention. Treatment with esomprazole significantly increased gastric pH (mean pH on PPI 5.38 +/- 0.13, mean pH on placebo 2.70 +/- 0.44, p = .005). Neither calcium absorption (PPI 34.2% +/- 2.4%, placebo 31.5% +/- 2.1%, p = .24) nor urinary calcium (PPI 321 +/- 38 mg/34 hours, placebo 355 +/- 37 mg/34 hours, p = .07) differed between the PPI and placebo groups. It is concluded that short-term gastric acid suppression by PPIs does not attenuate intestinal calcium absorption in healthy young adults.

Bleeding and pneumonia in intensive care unit patients given proton pump inhibitor or histamine-2 receptor antagonist for prevention of stress ulcer: a Meta analysis

To assess the efficacy and safety of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H(2)RA) in intensive care unit patients for stress ulcer prophylaxis. A systematic search of MEDLINE (1966 to March 2009), Ebsco and CNKI was made. Two reviewers were assigned to assess the quality of studies and extracted data independently. Six items were evaluated for each trial (patient selection, patient characteristics, randomization, blinding, definition of bleeding and of pneumonia). Disagreements were resolved through discussion. RevMan 4.2.2 software developed by the cochrane collaboration was used for Meta-analysis. Four series of clinical use involving 771 patients were included. Meta-analysis showed that the incidence of clinically significant bleeding was significantly lower in the PPI group (2.2% vs. 6.8%) as compared to H(2)RA group [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.21 to 0.96, P=0.04]. There was no significant difference of the incidence of nosocomial pneumonia (10.0% vs. 9.9%, OR 1.03, 95%CI 0.63 to 1.70, P=0.89) and mortality (14.5% vs. 14.3%,OR 1.17, 95%CI 0.76 to 1.80, P=0.47) between two groups. In comparison with H(2)RA, PPI is more effective in the prevention of stress ulcer bleeding (SUB) in patients under intensive care. There is no significant difference in the incidence of nosocomial pneumonia and mortality between two groups. There were very few randomized controlled clinical trials on prevention of stress ulcer, and these findings were based on a small number of patients, therefore a steadfast conclusion cannot presently be reached. More randomized, multicenter studies with sufficient sample size are warranted.

The Therapeutic Effect of Proton Pump Inhibitors on Helicobacter pylori-positive Gastric Ulcers

The aim of the present study was to elucidate the risk factors that could delay gastric ulcer healing when either a proton pump inhibitor or an H2-receptor antagonist is used for gastric ulcer treatment. Endoscopically-diagnosed gastric ulcer patients (216 men and 96 women, mean age: 57+/-13 years) were investigated. All patients were consecutively recruited and randomly assigned to receive H2-receptor antagonist (n = 196) or proton pump inhibitor (n = 116) treatment for eight weeks. Chi-squared tests and multivariate analysis to determine factors influencing ulcer healing were used to analyse the patients profiles, endoscopic findings, and Helicobacter pylori-infection status. In the H2-receptor antagonist group, the most important risk factor was a large ulcer size (> 2 cm diam.), followed by a linear shape of the ulcer, undermining tendency of ulcer, previous history of gastric ulcer, and H. pylori infection. In the proton pump inhibitor group, linear shape of the ulcer was the only significant risk factor for slow ulcer healing; other factors, including H. pylori infection, were insignificant. These results indicate that ulcer morphology may be the most important information for predicting ulcer healing, and that H. pylori infection does not delay gastric ulcer healing when proton pump inhibitor treatment is used.

Relation of Proton Pump Inhibitor Use After Percutaneous Coronary Intervention With Drug-Eluting Stents to Outcomes

Recent evidence has shown that clopidogrel and proton pump inhibitors (PPIs) are metabolized by the same pathway and that patients taking both drugs have greater levels of platelet reactivity and more adverse outcomes than patients taking only clopidogrel. We sought to examine the effect of a PPI at discharge from the hospital after percutaneous coronary intervention with drug-eluting stents on the incidence of major adverse cardiac events (MACE) at 1 year. We compared 502 patients who were not prescribed a PPI at discharge and 318 patients who were prescribed a PPI. All patients were taking clopidogrel. We followed patients for 1 year with regard to MACE, including death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. We performed multivariate Cox regression to adjust for confounding variables, including compliance with clopidogrel, to assess the effect of a PPI at discharge on the 1-year outcomes. The baseline characteristics of patients discharged with a PPI were similar to those of patients discharged without a PPI. Univariate survival analysis of the outcomes showed a greater rate of MACE (13.8% vs 8.0%, p = 0.008) and overall mortality (4.7% vs 1.8%, p = 0.02) in the PPI group. After multivariate analysis, the adjusted MACE hazard ratio for PPI at discharge was 1.8 (95% confidence interval 1.1 to 2.7, p = 0.01). In conclusion, in patients undergoing percutaneous coronary intervention with drug-eluting stents and receiving clopidogrel, the prescription of a PPI at discharge was associated with a greater rate of MACE at 1 year.

Effectiveness and Safety of Proton Pump Inhibitors in Infantile Gastroesophageal Reflux Disease

To evaluate the efficacy and safety of proton pump inhibitors (PPIs) in the treatment of gastroesophageal reflux disease (GERD) in infants <1 year of age. A literature search was conducted through PubMed (up to December 2009), International Pharmaceutical Abstracts (1970-December 2009), and The Cochrane Library (up to December 2009) using combinations of the following key search terms: proton pump inhibitor, GERD, infant, children, pediatric, omeprazole, rabeprazole, lansoprazole, esomeprazole, and pantoprazole. Reference citations from identified articles were also reviewed. All double-blind, placebo-controlled trials published in English that evaluated the safety and efficacy of PPIs in infants with GERD were included in this review. Trials involving children older than 12 months were not included. GERD is a source of pain and discomfort in adults; yet, in infants, symptoms that are thought to be indicative of painful stimuli have no clear cause-and-effect relationship with infant GERD. PPIs are beneficial in relieving symptoms of GERD in the adult population, but their usefulness in decreasing GERD-associated behaviors in infants is still questionable, despite a large increase in PPI prescribing for children <1 year of age. In all studies reviewed, infants treated with PPIs did not experience a significant decrease in behaviors perceived to be caused by GERD. The largest placebo-controlled trial to date found that rates of adverse events were increased in the PPI group compared with the placebo group, whereas the other trials reviewed reported no difference in adverse effects with the use of PPIs. Clinical trials reveal that PPI therapy is not an effective treatment for common infant GERD-associated symptoms. Evidence supporting safety of PPI use in infants is conflicting, and more large-scale, randomized, placebo-controlled trials are necessary to better establish the role of PPIs in infant GERD.

Influence of Proton Pump Inhibitor Use in Gastrointestinal Polyps

Proton pump inhibitors (PPIs) are the most potent anti-acid agents and are extensively used worldwide. PPI-induced hypergastrinemia is one of the very few side effects associated with these drugs. However, because hypergastrinemia is related to the occurrence of colonic adenomatous polyps, the purpose of this study was to analyze the relationship between the occurrence of gastrointestinal polyps and hypergastrinemia induced by PPIs. This study included 259 patients who underwent colonoscopy and esophagogastroduodenoscopy between January and August 2007. Chart records, including medication history and fasting plasma gastrin level, were reviewed and analyzed. Any subtle polypoid lesions in the stomach and colon were sampled by biopsy for histological examination. Helicobacter pylori infection status was examined by a rapid urea test during esophagogastroduodenoscopy. All patients underwent endoscopy examinations. A total of 122 patients were receiving PPI treatment for either peptic ulcer disease or reflux esophagitis and were included as the study group. The remaining 137 patients were not treated with PPIs and served as the non-PPI group. The mean fasting gastrin level in PPI users versus non-PPI users was 121.8 ng/L versus 56.8 ng/L, respectively (p < 0.001). Although the prevalence of gastric gland polyps was higher in the PPI group (65.6% vs. 37.2%, p < 0.001), there was no difference in the prevalence of colonic adenomatous polyps observed (22.13% vs. 22.62%, p = 0.928). In conclusion, the prevalence of gastric polyps, particularly fundic gland polyps, was higher among PPI users. However, the prevalence of colonic polyps was not affected by PPI use, regardless of past history of colonic adenomatous polyps.

Increased Incidence of Small Intestinal Bacterial Overgrowth During Proton Pump Inhibitor Therapy

Proton pump inhibitors (PPIs) can cause diarrhea, enteric infections, and alter the gastrointestinal bacterial population by suppressing the gastric acid barrier. Among patients that received long term PPI treatment, we evaluated the incidence of small intestinal bacterial overgrowth (SIBO; assessed by glucose hydrogen breath test [GHBT]), the risk factors for development of PPI-related SIBO and its clinical manifestations, and the eradication rate of SIBO after treatment with rifaximin. GHBTs were given to 450 consecutive patients (200 with gastroesophageal reflux disease who received PPIs for a median of 36 months; 200 with irritable bowel syndrome [IBS], in absence of PPI treatment for at least 3 years; and 50 healthy control subjects that had not received PPI for at least 10 years). Each subject was given a symptoms questionnaire. SIBO was detected in 50% of patients using PPIs, 24.5% of patients with IBS, and 6% of healthy control subjects; there was a statistically significant difference between patients using PPIs and those with IBS or healthy control subjects (P < .001). The prevalence of SIBO increased after 1 year of treatment with PPI. The eradication rate of SIBO was 87% in the PPI group and 91% in the IBS group. SIBO, assessed by GHBT, occurs significantly more frequently among long term PPI users than patients with IBS or control subjects. High dose therapy with rifaximin eradicated 87%-91% of cases of SIBO in patients who continued PPI therapy.

Comparative study of therapeutic effects of PPI and H2RA on ulcers during continuous aspirin therapy

To compare the therapeutic effects of proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) on gastroduodenal ulcers under continuous use of low-dose aspirin. Sixty patients who had a gastroduodenal ulcer on screening endoscopy but required continuous use of low-dose aspirin were randomly assigned to receive PPI (lansoprazole 30 mg, n = 30) or H2RA (famotidine 40 mg or if famotidine had been administered before assignment, ranitidine 300 mg, n = 30). The therapeutic effects were evaluated by endoscopy after 8-wk treatment. The presence or absence of Helicobacter pylori (H. pylori) was determined by urea breath test before treatment. Abdominal symptoms were compared with the gastrointestinal symptom rating scale (GSRS) questionnaire before and after treatment. Twenty-six patients in the PPI group and 26 patients in the H2RA group, excluding dropouts, were analyzed. There were no significant differences in median age, sex, underlying disease, smoking status, H. pylori infection, prevalence of ulcers before treatment, and lesion site between the two groups. The therapeutic effects were endoscopically evaluated as healed in 23 patients (88.5%) and not healed in 3 patients in the PPI group and as healed in 22 patients (84.6%) and not healed in 4 patients in the H2RA group. Abdominal symptoms before treatment were uncommon in both groups; the GSRS scores were not significantly reduced after treatment as compared with before treatment. The healing rate of gastroduodenal ulcers during continuous use of low-dose aspirin was greater than 80% in both the PPI group and the H2RA group, with no significant difference between the two groups.

PPIs are not associated with a lower incidence of portal-hypertension-related bleeding in cirrhosis

To determine if proton pump inhibitor use in cirrhotic patients with endoscopic findings of portal hypertension is associated with a lower frequency of gastrointestinal bleeding. Patients with cirrhosis and endoscopic findings related to portal hypertension, receiving or not receiving proton pump inhibitor (PPI) therapy, were included retrospectively. We assigned patients to two groups: group 1 patients underwent PPI therapy and group 2 patients did not undergo PPI therapy. One hundred and five patients with a median age of 58 (26-87) years were included, 57 (54.3%) of which were women. Esophageal varices were found in 82 (78%) patients, portal hypertensive gastropathy in 72 (68.6%) patients, and gastric varices in 15 (14.3%) patients. PPI therapy was used in 45.5% of patients (n = 48). Seventeen (16.1%) patients presented with upper gastrointestinal bleeding; in 14/17 (82.3%) patients, bleeding was secondary to esophageal varices, and in 3/17 patients bleeding was attributed to portal hypertensive gastropathy. Bleeding related to portal hypertension according to PPI therapy occurred in 18.7% (n = 9) of group 1 and in 14% (n = 8) of group 2 (odds ratio: 0.83, 95% confidence interval: 0.5-1.3, P = 0.51). Portal hypertension bleeding is not associated with PPI use. These findings do not support the prescription of PPIs in patients with chronic liver disease with no currently accepted indication.

Two stomach-originatedlactobacillusstrains improveHelicobacter pyloriinfected murine gastritis

To investigate the potential anti-Helicobacter pylori (H. pylori) and anti-inflammation in vivo effects of two lactobacillus strains from human stomach. Forty H. pylori infected Balb/c mice were randomly divided into 4 groups: proton pump inhibitor and antibiotics triple treated group, Lactobacillus fermenti (L. fermenti) treated group, Lactobacillus acidophilus treated group and normal saline control group. Ten uninfected mice were also included as blank control group. The infection of H. pylori was detected by rapid urease tests, Giemsa staining and bacterial culture. The colonization of H. pylori was assessed in bacterial density score and gastric inflammation was assessed in histological score. The colonization of L. fermenti was performed by fluorescent probe. Histopathologic evaluation showed significant release of mucosal inflammation in gastric antrum and gastric body in lactobacillus treated groups and triple treated group. H. pylori eradication rate in both lactobacillus treated groups and triple treated group were higher than normal saline control group. Lactobacillus treated groups and triple treated group showed significant decrease of H. pylori bacterial density. Both lactobacillus strains have a significant anti-H. pylori activity; L. fermenti displays more efficient antagonistic activity in vivo against H. pylori infection.

Rebound Symptoms After PPI Use: Priming the Pump?

Source: Reimer C, Sondergaard BO, Hilsted L, et al. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009;137(1):80–87; doi:10.1053/j.gastro.2009.03.058Danish investigators conducted a randomized, double-blind, placebo-controlled trial to determine the clinical relevance of rebound acid hypersecretion (RAHS) after proton pump inhibitor (PPI) use. Healthy adult volunteers without acid-related disease or symptoms were randomized to receive either 12 weeks of placebo or 8 weeks of esomeprazole 40 mg once daily followed by 4 weeks of placebo. Subjects completed the Gastrointestinal Symptom Rating Scale (GSRS), a 15-item instrument, weekly. A GSRS score of >2 for any one of three symptoms (dyspepsia, heartburn, or acid regurgitation) was defined as clinically relevant. Plasma levels of gastrin and chromogranin A (CgA) were measured at weeks 4, 8, and 12. Antacid tablets were allowed for bothersome acid-related symptoms during the study.One hundred twenty adults were enrolled with a mean age of approximately 25 years. No difference in GSRS scores between the treatment and placebo groups was seen in the first nine weeks of the study period. During weeks 10 to 12 the treatment group had significantly higher overall mean GSRS scores than placebo recipients. During weeks 9 to 12, significantly more study participants in the esomeprazole-treated group reported clinically relevant symptoms lasting one week or more than those in the placebo group (44% vs 15%). Among those with symptoms, 52% in the esomeprazole-treated group used antacids as compared to only 11% in the placebo group. At the end of the study more of those in the esomeprazole-treated group had symptoms of heartburn, acid regurgitation, or dyspepsia than those in the placebo group (20.7% vs 1.7%). The only preexisting risk factor associated with withdrawal symptoms was a history of heartburn before participating in the trial (OR 4.4; 95% CI, 1.4–13.6).Plasma gastrin levels were within normal range in both groups at weeks 0, 4, 8, and 12, but significantly higher in the esomeprazole-treated group during treatment. Plasma gastrin levels were significantly correlated with GSRS scores at week 8. Plasma chromogranin A levels peaked above the normal range and were significantly higher in the esomeprazole-treated group at both weeks 8 and 12.The authors conclude that PPI therapy induces acid-related symptoms in healthy adult volunteers after withdrawal.Drs Alexander and LeLeiko have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.This trial suggests that isolated acid-related symptoms are experienced by a majority of healthy adults occasionally. While RAHS has been reported,1 this study reliably confirmed for the first time that new acid-related symptoms can be induced after eight weeks of therapy with a PPI. The strengths of this study include sample size, design, the use of online validated questionnaires, and the low dropout rate. Its limitations include the fact that only healthy volunteers were studied. Hence the results from this study may not be applicable to patients who are prescribed PPIs for acid-related or dyspeptic symptoms. Although there was no direct measurement of acid secretion in this study, the temporal elevation of plasma gastrin levels and of plasma chromogranin A levels (indicative of enterochromaffin cell hyperplasia causing RAHS even after stopping therapy) correlated well with the GSRS scores in the PPI group as compared to the placebo group.Although this study was done in adults, effects in children may be similar. The empiric use of PPI in infants and children for presumptive gastroesophageal reflux disease and for dyspepsia is widespread and increasing. In a recent study of the use of lansoprazole in irritable infants with presumed GERD, there was no difference between treated and placebo groups in symptom resolution, but there was an increase in serious adverse events in the PPI-treated group of infants.2 Since PPI therapy results in RAHS on withdrawal in adults, the possibility of new-onset acid-related symptoms upon withdrawal in children warrants careful selection of patients for treatment with these very potent drugs.This study drives yet another nail in the coffin of PPI inhibitors. Extrapolation of its findings to pediatric patients suggests that indiscriminate use of acid suppression treatment in children and adolescents should be discouraged. Since it is neither feasible nor appropriate to subject every symptomatic child to an invasive diagnostic procedure prior to instituting treatment, thorough history and physical examination seems to us prudent. (See Editors’ Note, AAP Grand Rounds, July 2009;22:2.)

Impact of Proton Pump Inhibitors on Benign Anastomotic Stricture Formations After Esophagectomy and Gastric Tube Reconstruction

The primary aim of this study was to evaluate if the use of proton pump inhibitors (PPIs) reduced the prevalence of benign anastomotic strictures after uncomplicated esophagectomies with gastric tube reconstruction and circular stapled anastomoses. Benign anastomotic strictures are associated with anastomotic leaks or conduit ischemia. Also patients without those complications develop benign anastomotic strictures. We hypothesize that patients without postoperative anastomotic complications may develop benign anastomotic strictures due to exposure of acid gastric tube contents to the anastomotic area, and that the formation of such strictures may be reduced by prophylactic use of PPIs. Eighty patients without preoperative chemo- or radiotherapy, without clinical or radiological signs of anastomotic leaks were included in this clinical trial. The patients were randomized to b.i.d. PPIs or no treatment for 1 year. Benign anastomotic strictures were defined as anastomotic narrowing not allowing a standard diagnostic endoscope to pass without dilatation. The study was registered in the EudraCT database (2009-009997-28) for clinical trials. : Seventy-nine patients were evaluated. Benign anastomotic strictures developed in 5/39 (13%) patients in the PPI group and in 18/40 (45%) in the control group (RR 5.6, 95% CI: 2.0-15.9, P = 0.001). The use of a narrower 25 mm cartridge as compared to a wider 28 or 31 mm cartridge significantly increased stricture formations (RR 2.9, 95% CI: 1.1-7.6, P = 0.025). Prophylactic PPI treatment reduced the prevalence of benign anastomotic strictures following esophagectomy with gastric tube reconstruction and circular stapled anastomoses. Larger sized circular staple cartridges additionally reduced the stricture prevalence.

Comparison Between Oral vs. Intravenous Administration of PPI with Gastric pH

Purpose: In patients with peptic ulcer bleeding, a proton pump inhibitor (PPI) is administered intravenously (IV) following endoscopic treatment. However, if oral administration (PO) of the PPI obtains the same antisecretory effect as IV administration of the PPI (IV PPI), PO PPI treatment will be more advantageous in shortening the length of a patient's hospital stay compared to IV PPI administration. Methods: The subjects of the current study included 51 patients with peptic ulcer bleeding who did not undergo endoscopic therapy and in whom a visible vessel or blood clot was present. These patients were randomized into two groups, one group receiving IV administration of the PPI (IV PPI group (n=26)) and a group in which the PPI was administered orally (PO PPI group (n=25)). The 24-hour intragastric pH was measured andthe hemostasis rate was compared between the two groups. Results: The hemostasis rate was 92.3% (24/26) in the IV PPI group and 92.0% (23/25) in the PO PPI group (p=0.936). The median 24-hour gastric pH value was 5.93±1.92 in the IV PPI group and 5.73±1.74 in the PO PPI group (p=0.748). Daytime median intragastric pH was 5.94±2.00 in the IV PPI group and 5.58±1.69 in the PO PPI group (p=0.861). Night-time median pH was 5.91±1.95 in the IV PPI group and 5.68±1.86 in the PO PPI group (p=0.624). The mean percent of cases in which gastric pH exceeded 6 was 62.3% in the IV PPI group and 58.5% in the PO PPI group (p=0.672). The difference in the cumulative frequency of cases did not reach a statistical significance. Conclusion: In patients with bleeding peptic ulcer, in which a visible vessel or blood clot was present, there were no significant differences in the intragastric pH and hemostasis rate between intravenous infusion of a PPI and the oral administration of a PPI.

A Randomized, Single‐Blind Study of Lansoprazole for the Prevention of Exacerbations of Chronic Obstructive Pulmonary Disease in Older Patients

To investigate whether proton pump inhibitor (PPI) therapy reduces the frequency of common colds and exacerbations in patients with chronic obstructive pulmonary disease (COPD). Twelve-month, randomized, observer-blind, controlled trial. A university hospital and three city hospitals in Miyagi prefecture in Japan. One hundred patients with COPD (mean age +/- SD 74.9 +/- 8.2) participated. They were all ex-smokers and had received conventional therapies for COPD, including smoking cessation and bronchodilators. Patients with gastroesophageal reflux disease or gastroduodenal ulcer were excluded. Patients were randomly assigned to conventional therapies (control group) or conventional therapies plus PPI (lansoprazole 15 mg/d; PPI group) and observed for 12 months. Frequency of common colds and COPD exacerbations. The number of exacerbations per person in a year in the PPI group was significantly lower than that in the control group (0.34 +/- 0.72 vs 1.18 +/- 1.40; P<.001). The adjusted odds ratio with logistic regression for having exacerbation (> or =once/year) in the PPI group compared with the control group was 0.23 (P=.004). In contrast, there was no significant difference in the numbers of common colds per person per year between the PPI group and the control group (1.22 +/- 2.09 vs 2.04 +/- 3.07; P=.12). PPI therapy significantly reduced the risk of catching frequent common colds (> or =3 times/year), the adjusted odds ratio of which was 0.28 (P=.048). In this single-blind, nonplacebo-controlled trial, lansoprazole was associated with a significant decrease in COPD exacerbations. More definitive clinical trials are warranted.