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BARREL is a multiple-balloon investigation designed to study electron losses from Earth's Radiation Belts. Selected as a NASA Living with a Star Mission of Opportunity, BARREL augments the Radiation Belt Storm Probes mission by providing measurements of relativistic electron precipitation with a pair of Antarctic balloon campaigns that will be conducted during the Austral summers (January-February) of 2013 and 2014. During each campaign, a total of 20 small (∼20 kg) stratospheric balloons will be successively launched to maintain an array of ∼5 payloads spread across ∼6 hours of magnetic local time in the region that magnetically maps to the radiation belts. Each balloon carries an X-ray spectrometer to measure the bremsstrahlung X-rays produced by precipitating relativistic electrons as they collide with neutrals in the atmosphere, and a DC magnetometer to measure ULF-timescale variations of the magnetic field. BARREL will provide the first balloon measurements of relativistic electron precipitation while comprehensive in situ measurements of both plasma waves and energetic particles are available, and will characterize the spatial scale of precipitation at relativistic energies. All data and analysis software will be made freely available to the scientific community. [ABSTRACT FROM AUTHOR]

Background Nonsteroidal anti-inflammatory drugs are associated with gastrointestinal ( GI) damage. The Celecoxib vs. Omeprazole and Diclofenac for At- Risk Osteoarthritis and Rheumatoid Arthritis Patients ( CONDOR) trial showed that a haemoglobin drop ≥2 g/dL adjudicated as either of defined or presumed GI origin was the most frequent component/event for the composite GI primary end point. This adverse event is potentially clinically relevant in long-term NSAID treatment. Aim To define potential risk factors associated with a decrease in haemoglobin/haematocrit. Methods Post hoc analysis of the CONDOR trial was conducted in the intention-to-treat population. Clinically significant blood loss was defined as: (i) a haemoglobin drop ≥2 g/dL and/or a haematocrit drop ≥10%; and (ii) blood loss adjudicated as either of defined or presumed GI origin. Fifteen risk factors were evaluated by stepwise logistic regression. Each factor had to be significant at <0.20 α to be included in the model. Results A total of 64/3774 (1.7%) osteoarthritis ( OA) patients had decreased haemoglobin/haematocrit and were adjudicated to the GI endpoint. Significant risk factors, at the 0.20 α level found to be associated with clinically significant blood loss in OA patients included [odds ratio (80% CI)] baseline C-reactive protein ( CRP) levels [2.27 (1.46-3.53)], history of gastritis and history of GI intolerance [1.55 (1.06-2.28)], positive Helicobacter pylori at screening [1.54 (1.07-2.22)], increasing age [1.17 (1.04-1.32)] and body mass index [ BMI; 1.03 (1.00-1.06)]. Conclusions Monitoring for decreases in haemoglobin should be considered for all OA patients and especially those with an increased age, BMI, history of gastritis and GI intolerance, CRP levels >1 mg/dL and/or positive H. pylori status, as this may affect their clinical management. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Patients undergoing percutaneous coronary intervention require dual antiplatelet therapy. Proton-pump inhibitor (PPI) therapy is recommended for the prevention of upper GI complications. No study has determined the rate and type of GI bleeding events in such patients in routine clinical practice. DESIGN: Observational study with a prospective follow-up to confirm medication use and occurrence of events, which were validated. PATIENTS AND SETTING: We have followed up a cohort of 1219 consecutive patients admitted for percutaneous coronary intervention in Zaragoza (Spain). MAIN OUTCOME MEASURES: Major GI bleeding and cardiovascular events. RESULTS: At discharge, 96.7% of patients were on dual antiplatelet therapy and 76.6% on PPI therapy, which increased up to 87.9% during follow-up of 2107.6 patient (pt) s-years (1.72±1.07 years/patient). There were eight patients who developed GI bleeding during hospitalisation and 27 patients during follow-up, (1.52 bleeds per 100 pt-years). Most GI bleeding events (81.4%) occurred during the first year (mean time to bleeding event: 7.03±7.65 months) and 84.6% of patients were on long-term PPI at the time of the bleed. Lower GI bleeding occurred more frequently than upper GI bleeding (74% lower vs 26% upper). Peptic ulcer history and concomitant warfarin therapy were the only risk factors identified for upper or lower GI bleeding respectively. CONCLUSIONS: Among patients on dual antiplatelet therapy and PPI co-therapy, gastrointestinal bleeding episodes are more frequent in the lower GI tract. This changing pattern of bleeding may reflect the success of gastroprotection and focuses attention on research to address lower GI bleeding in this population. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2011; 34: 808-816 Summary Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with clinically significant decreases in haemoglobin dependent and independent of acute bleeding events. Aim To evaluate the incidence and time to a clinically meaningful decrease in haemoglobin in two double-blind, prospective randomised clinical trials comparing NSAIDs in patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Methods In CLASS, patients with OA/RA who were aged ≥18 years and required continuous NSAID treatment were included; patients who were Helicobacter pylori positive and/or using aspirin were not excluded. In contrast, in the CONDOR trial, comparing celecoxib alone to diclofenac sustained release (plus omeprazole), patients were aged ≥60 years or ≥18 years with a history of gastroduodenal ulcer and were H. pylori negative; aspirin or other anti-platelet users were excluded. To make a parallel post hoc analysis we limited our study to 6 months and the populations to only the non-aspirin users in CLASS and those patients receiving either celecoxib or diclofenac. A decrease in haemoglobin of ≥2 g/dL defined the primary end point. Results At 6 months, in the CLASS and CONDOR trials, 1.9% and 2.0% of patients treated with celecoxib and 3.3% and 5.7% of patients treated with diclofenac developed a ≥2 g/dL decrease in haemoglobin, respectively, [CLASS: odds ratio (OR) 1.80 (95% confidence interval (CI), 1.22-2.65) and CONDOR: OR 2.93 (95% CI, 2.06-4.15), respectively]. Conclusion In these two large, independent trials, clinically-meaningful decreases in haemoglobin ≥2 g/dL occurred in a relatively similar fashion over time despite differences in trial designs. [ABSTRACT FROM AUTHOR]

Background Many patients with cardiovascular (CV) disease will stop aspirin (ASA) because of ASA-related dyspepsia. Proton pump inhibitor (PPI) co-therapy may reduce ASA-related dyspepsia, enhancing ASA adherence and improving CV outcomes. Aim To explore the impact of PPI co-therapy on CV outcomes in long-term, low-dose ASA users. Methods We modified a previously published Markov model to assess the long-term impact of PPI co-therapy on CV and upper gastrointestinal bleeding (UGIB) outcomes among patients using ASA for secondary CV prevention. UGIB events, recurrent myocardial infarctions (MIs) and incremental costeffectiveness ratios (ICERs) were measured. The perspective taken was that of a long-term payer. Results Compared with ASA alone, ASA plus PPI resulted in fewer lifetime UGIB events (3.4% vs. 7.2%) and increased ASA adherence (74% vs. 71%). Increased ASA adherence resulted in fewer recurrent MIs (26 fewer events per 10 000 patients). On average, the ASA plus PPI strategy resulted in 38 additional days of life per patient, with the majority of this benefit (61%) because of a reduction in CV mortality (rather than UGIB-related mortality). ASA plus PPI was also more costly than ASA alone, with an ICER of $19 000 per life-year saved. Results were sensitive to cost of PPI and impact of PPI on ASA adherence. Conclusions Proton pump inhibitor co-therapy has the potential to impact not only GI, but also CV outcomes in patients with CV disease using ASA and such co-therapy is likely to be cost-effective. Future studies should better quantify the CV benefits of PPI co-therapy. [ABSTRACT FROM AUTHOR]

Background: Temporary prophylactic pancreatic duct stenting effectively reduces post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients, but the optimal stent remains unclear. We compared rate of spontaneous passage, and technical difficulty of placement for 3-Fr and 5-Fr stents. Methods: A randomized controlled trial at a single academic medical center. Patients deemed high risk for PEP randomly received 5-Fr or 3-Fr pancreatic duct stents. Primary outcome was spontaneous stent passage by 2 weeks. Secondary outcomes were ease and time for stent placement, and number of guide wires required for the entire procedure. Results: Patients (69 female [89 %]; mean age 44.9 years, standard deviation [SD] 16.8) were randomly assigned to receive 5-Fr (n = 38) and 3-Fr (n = 40) stents. Indications for stenting were similar. Seven patients in the 3-Fr group actually received a 5-Fr stent, and two in the 5-Fr group had a 3-Fr stent. Spontaneous passage or non-passage was confirmed in 64 (83 %). No statistically significant difference in spontaneous passage rates was seen (5-Fr group, 68.4 %; 3-Fr group 75.0 %; P = 0.617). Non-passage rates were 10.5 % (5-Fr group) and 10.0 % (3-Fr group) (P = 1.00). The study was stopped after a futility analysis for the primary end point. Placement of 5-Fr stents was rated easier, at a mean score of 1.8 (5-Fr) vs. 3.4 (3-Fr), P < 0.001, with a trend towards being faster, 9.2 vs. 11.1 minutes (P = 0.355). Fewer guide wires were required for 5-Fr stent placement, 1.5 vs. 1.9 (P = 0.002). PEP rates did not differ (P = 0.519). Conclusion: Placement of 5-Fr compared to 3-Fr pancreatic duct stents for PEP prophylaxis is easier, faster, and requires fewer wires. No statistically significant difference in spontaneous passage was found between the two sizes. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 689–695 Background Proton pump inhibitors (PPIs) are the preferred agents for the prevention of aspirin-associated upper gastrointestinal bleeding (UGIB). Data are limited to determine whether PPIs are being used to reduce UGIB risk. Aim To evaluate the implementation of PPI treatment to reduce the GI risk in two cardiology centres from Europe and the United States. Methods A retrospective cross-sectional study was carried out at the University of Michigan and University Hospital-Zaragoza in 429 consecutive patients hospitalized for percutaneous coronary intervention (PCI) on dual antiplatelet therapy. Results Admission for PPI co-therapy was similar (34% vs. 30%) in both centres. At discharge, the proportion of high-risk patients receiving PPI therapy in the Spanish centre (75.4%) was higher than their American peers (55.6%) (OR: 2.5; 95% CI; 1.3–4.7). No differences in PPI prescription rates were found among Spanish patients with/without GI risk factors. The opportunity to initiate PPI co-therapy in high-risk patients was missed in 81.8% (36/44) of those not on PPI at admission in US patients vs. 24.1% (19/79) ( P < 0.0001) in Spanish patients. Conclusions There are important differences concerning PPI prescription and risk stratification in the two centres when managing PCI patients. Efforts to stratify risks and utilize appropriate strategies for UGIB prophylaxis in high-risk patients are warranted. [ABSTRACT FROM AUTHOR]

We report an unusual case of intrapancreatic mesenteric venous collateral vessels following partial pancreatic surgical resection resembling pancreatic neoplasm upon greyscale sonographic and unenhanced CT examinations. [ABSTRACT FROM AUTHOR]

Background Our understanding of the benefits and risks of aspirin non steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) selective NSAIDs and gastro-protective agents (GPAs) continues to expand. Aim To assess the perceptions and practices of US primary care physicians (PCPs) regarding the use of aspirin, NSAIDs, COX-2 selective NSAIDs and GPA. Methods A 34-question survey was administered to 1000 US PCPs via the internet. Questions addressed issues involving aspirin, NSAIDs, COX-2 selective NSAIDs, and GPAs. Around 491 of 1000 PCPs had participated in a similar survey conducted in 2003. Results Eighty-five per cent of PCPs reported that >25% of their patients were taking aspirin for preventive reasons. Nineteen per cent performed a risk calculation when deciding whether to start aspirin for cardioprotection. Fifty-four per cent recommended a proton pump inhibitor (PPI) for a patient with a recently healed ulcer who required ongoing aspirin. Thirty-one per cent reported prescribing NSAIDs more often and 52% were more likely to recommend a GPA with an NSAID than in 2003. Although PCPs were less likely to recommend a COX-2 selective NSAID compared to 2003, only 41% felt that rofecoxib increased cardiovascular risk. One-third felt that celecoxib and traditional NSAIDs were associated with increased cardiac risk. Conclusion This survey identified several areas of ongoing confusion regarding aspirin, NSAIDs, COX-2 selective NSAIDs and GPAs, which should help direct future educational efforts regarding the benefits, risks and appropriate use of these agents. [ABSTRACT FROM AUTHOR]

Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate. [ABSTRACT FROM AUTHOR]

Background The use of non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal symptoms such as heartburn and acid regurgitation. Aim To assess the efficacy of esomeprazole 20 and 40 mg for resolution of heartburn and acid regurgitation in continuous NSAIDs. Methods A post hoc analysis of five clinical trials was performed. Two identically designed, placebo-controlled, 4-week studies (NASA1, SPACE1) enrolled non-ulcer, NSAIDs-treated patients with upper abdominal pain, discomfort or burning. PLUTO and VENUS were identically designed, placebo-controlled, 6-month studies that enrolled patients at risk of NSAIDs-induced ulcers. Study 285 was an 8-week comparative study with ranitidine (300 mg/day) in patients with NSAIDs-induced gastric ulcers. Resolution of investigator-assessed heartburn and acid regurgitation was defined as symptom severity of ‘none’ in the last 7 days. Results In NASA1/SPACE1, heartburn resolved in 61% and 62% of patients taking esomeprazole 20 and 40 mg, respectively (vs. 36% on placebo, P < 0.001), and acid regurgitation resolved in 65% and 67% (vs. 48%, P < 0.001). Resolution of both symptoms was greater with esomeprazole than with placebo in PLUTO/VENUS ( P ≤ 0.001), and than with ranitidine in study 285 ( P < 0.05 for esomeprazole 20 mg). Conclusion Heartburn and regurgitation are common in patients taking NSAIDs and esomeprazole is efficacious for resolution of these symptoms. [ABSTRACT FROM AUTHOR]

BACKGROUND: Low-dose aspirin (75-325 mg/day) is widely used for the prevention of cardiovascular disease. However, due to its action on cyclo-oxygenase (COX), aspirin is associated with upper gastrointestinal (GI) side effects including ulcers and bleeding. SCOPE: This was a comprehensive review of the literature available on the side effects associated with low-dose aspirin, together with the available treatment and prevention options, which was based on the authors' expertise in the field and a supplementary PubMed search limited to papers published in English during the last 10 years, up to November 2006. FINDINGS: Although the risk of upper GI side effects is smaller with low-dose aspirin compared with non-selective, non-steroidal anti-inflammatory drugs (NSAIDs), it is nevertheless a substantial healthcare issue. Factors associated with an increased risk of upper GI complications during low-dose aspirin therapy include aspirin dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of NSAIDs (including COX-2-selective NSAIDs), and Helicobacter pylori infection. Co-administration of a gastroprotective agent such as proton pump inhibitors (PPIs) may be useful for alleviating the upper GI side effects associated with use of low-dose aspirin. Eradication of H. pylori also appears to reduce the risk of these side effects, especially in those at high risk. The use of other antiplatelet agents such as clopidogrel does not seem to provide a safer alternative to low-dose aspirin in at-risk patients. CONCLUSIONS: Prophylactic low-dose aspirin therapy is associated with an increased risk of developing upper GI side effects. Administration of a PPI seems the most effective therapy for the prevention and/or relief of such side effects in at-risk patients. H. pylori eradication therapy further reduces the risk of upper GI bleeding in these patients. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors have dramatically improved the management options available for patients with acid-related disorders. In patients with gastro-oesophageal reflux disease, currently available proton pump inhibitors provide an excellent outcome for the majority; however, they do not provide optimal pH control in many. Proton pump inhibitors co-therapy reduces, but does not eliminate, the risk of gastrointestinal ulcers and complications in patients taking non-steroidal anti-inflammatory drugs, while in patients with upper gastrointestinal bleeding, it may be difficult to reach and maintain the current therapeutic target of intragastric pH of 6–7. This article reviews the effectiveness of current antisecretory therapy in these three acid-related diseases and areas of unmet clinical need. The potential role of a proton pump inhibitor with an extended duration of action and enhanced acid control from a single daily dose, particularly improved control at night, is discussed. Finally, therapy that could be administered without regard to time of day and/or food intake would offer dosing flexibility and thus have a positive effect on patients’ compliance. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer screening rates among patients with upper gastrointestinal symptoms undergoing oesophagogastroduodenoscopy have not been previously established. We hypothesize that gastroenterologists seize this opportunity more frequently than primary care providers. Aims To assess colorectal cancer screening rates at the time of direct access oesophagogastroduodenoscopy and gastrointestinal clinic evaluation for upper gastrointestinal symptoms. To compare rates in the 6 months following the oesophagogastroduodenoscopy in both cohorts of patients. Methods Retrospective review. primary care physician group: direct access oesophagogastroduodenoscopy ( n = 247) vs. gastrointestinal group ( n = 278). Multivariable regression analysis utilized to assess predictors of screening outcome. Results Colorectal cancer screening at the time of referral was 54%. Among the 243 unscreened patients, an additional 29% in the primary care physician group vs. 59% in the gastrointestinal group completed colorectal cancer screening in 6 months of follow-up. Nearly 60% patients evaluated in gastrointestinal clinic for upper symptoms had documented discussion, and 99% of those patients underwent colonoscopy ( P < 0.001). Gastrointestinal consultation increased the probability of colorectal cancer screening completion eightfold (95% CI 3.69–18.96). Conclusions At the time of evaluation for upper symptoms, half of patients were not current with colorectal cancer screening recommendations. Referrals for the direct access oesophagogastroduodenoscopy and, more importantly, the gastroenterology consult represent key opportunities for colorectal cancer screening education and improved compliance. [ABSTRACT FROM AUTHOR]

Aim To assess primary care physician perceptions of non-steroidal anti-inflammatory drug (NSAID) and aspirin-associated toxicity. Methods A group of gastroenterologists and internal medicine physicians created a survey, which was administered via the Internet to a large number of primary care physicians from across the US. Results One thousand primary care physicians participated. Almost one-third of primary care physicians recommended 325 mg rather than 81 mg of aspirin/day for cardioprotection. Fifty-nine percent thought enteric-coated or buffered aspirin reduced the risk of upper gastrointestinal (GI) bleeding. Seventy-six percent believed that Helicobacter pylori infection increased the risk of NSAID ulcers but fewer than 25% tested NSAID users for this infection. More than two-thirds were aware that aspirin co-therapy decreased the GI safety benefits of the cyclo-oxygenase 2 selective NSAIDs. However, 84% felt that aspirin with a cyclo-oxygenase 2 selective NSAID was safer than aspirin with a non-selective NSAID. When presented a patient at high risk for NSAID-related GI toxicity, almost 50% of primary care physicians recommended a proton pump inhibitor and cyclo-oxygenase 2 selective NSAID. Conclusions This survey has identified areas of misinformation regarding the risk–benefit of NSAIDs and aspirin and the utilization of gastroprotective strategies. Further education on NSAIDs for primary care physicians is warranted. [ABSTRACT FROM AUTHOR]

Summary Cyclooxygenase (COX)-2 expression and prostaglandin production is increased by Helicobacter pylori infection. Non-selective COX inhibitors reduce prostaglandins and mucosal proliferation in infected mucosa and may reduce gastric cancer risk, but ulceration precludes their use. COX-2 inhibitors cause fewer ulcers and may be chemopreventive. Physiological studies of COX-2 inhibitors in humans with H. pylori infection have not been performed. Aim: To study the impact of COX-2 specific inhibition on gastric prostaglandin levels, H. pylori gastritis and proliferation. Methods: Twenty infected (eight males, 12 females; age 38 ± 1.8) and six uninfected (four males, two females; age 36 ± 3.5) healthy volunteers received rofecoxib 25 mg daily for 14 days. Endoscopic biopsies were evaluated for prostaglandin E2 (PGE2 ) content, gastritis and proliferation. Results: Before drug therapy, compared to uninfected, H. pylori -infected subjects had significantly higher: (a) gastric mucosal PGE2 (pg/mg tissue) in the gastric body and antrum, (b) H. pylori score in body and antrum and (c) mid-gland proliferation index in antrum and body. The COX-2 inhibitor did not significantly affect PGE2 levels, gastritis scores or proliferation indices in the body or antrum in the H. pylori- positive or -negative subjects. Conclusion: The predominant source of increased gastric PGE2 in H. pylori infection appears to be COX-1-derived. In non-ulcerated H. pylori gastritis, COX-2 inhibition does not affect cellular proliferation. Rofecoxib's lack of effect on gastric prostaglandin levels and proliferation in H. pylori -infected mucosa may explain the absence of an increased ulcer risk among COX-2 inhibitor users with H. pylori infection. The lack of significant effect on intermediate biomarkers raises uncertainty regarding the potential of specific COX-2 inhibitors for chemoprevention of gastric cancer. [ABSTRACT FROM AUTHOR]

Summary Background : The benefits of the Helicobacter pylori test-and-treat strategy are attributable largely to the cure of peptic ulcer disease while limiting the use of endoscopy. Aim : To reappraise the test-and-treat strategy and empirical proton pump inhibitor therapy for the management of uninvestigated dyspepsia in the light of the decreasing prevalence of H. pylori infection, peptic ulcer disease and peptic ulcer disease attributable to H. pylori . Methods : Using a decision analytical model, we estimated the cost per patient with uninvestigated dyspepsia managed with the test-and-treat strategy ($25/test; H.pylori treatment, $200) or proton pump inhibitor ($90/month). Endoscopy ($550) guided therapy for persistent or recurrent symptoms. Results : In the base case (25%H. pylori prevalence, 20% likelihood of peptic ulcer disease, 75% of ulcers due to H.pylori ), the cost per patient is $545 with the test-and-treat strategy and $529 with proton pump inhibitor, and both strategies yield similar clinical outcomes at 1 year. H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H.pylori are important determinants of the least costly strategy. At an H. pylori prevalence below 20%, proton pump inhibitor is consistently less costly than the test-and-treat strategy. Conclusions : As the H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H. pylori decrease, empirical proton pump inhibitor becomes less costly than the test-and-treat strategy for the management of uninvestigated dyspepsia. Given the modest cost differential between the strategies, the test-and-treat strategy may be favoured if patients without peptic ulcer disease derive long-term benefit from H.pylori eradication. [ABSTRACT FROM AUTHOR]

Background: Aspirin may decrease colorectal cancer incidence, but its role as an adjunct to or substitute for screening has not been evaluated.Objective: To examine the potential cost-effectiveness of aspirin chemoprophylaxis in relation to screening.Design: Markov model.Data Sources: Literature on colorectal cancer epidemiology, screening, costs, and aspirin chemoprevention (1980-1999).Target Population: General U.S. population.Time Horizon: 50 to 80 years of age.Perspective: Third-party payer.Intervention: Aspirin therapy in patients screened with sigmoidoscopy every 5 years and fecal occult blood testing every year (FS/FOBT) or colonoscopy every 10 years (COLO).Outcome Measures: Discounted cost per life-year gained.Results Of Base-case Analysis: When a 30% reduction in colorectal cancer risk was assumed, aspirin increased costs and decreased life-years because of related complications as an adjunct to FS/FOBT and cost $149 161 per life-year gained as an adjunct to COLO. In patients already taking aspirin, screening with FS/FOBT or COLO cost less than $31 000 per life-year gained.Results Of Sensitivity Analysis: Cost-effectiveness estimates depended highly on the magnitude of colorectal cancer risk reduction with aspirin, aspirin-related complication rates, and the screening adherence rate in the population. However, when the model's inputs were varied over wide ranges, aspirin chemoprophylaxis remained generally non-cost-effective for patients who adhere to screening.Conclusions: In patients undergoing colorectal cancer screening, aspirin use should not be based on potential chemoprevention. Aspirin chemoprophylaxis alone cannot be considered a substitute for colorectal cancer screening. Public policy should focus on improving screening adherence, even in patients who are already taking aspirin. [ABSTRACT FROM AUTHOR]

Introduction: Although it is incontrovertible that Helicobacter pylori causes peptic ulcer disease, controversy persists regarding the impact of H. pylori infection on the incidence of NSAID-related complications and whether H. pylori eradication reduces the rate of adverse events. Methods: A symptom-driven decision analytic model was developed to compare the clinical and economic impact of H. pylori screening compared to a strategy of no H. pylori testing for individuals requiring chronic NSAID therapy. In the principal analysis, it was assumed that untreated H. pylori infection increased the ulcer risk by 50% and that successful eradication reduced the risk of adverse events to that of uninfected patients. Patients’ ulcer risk and the protective effect of H. pylori eradication were evaluated using sensitivity analysis. Results: When compared to no H. pylori testing, H. pylori screening led to fewer symptomatic ulcers (no test, 5.4; H. pylori test, 4.6 per 100 patient years) and ulcer complications (no test, 2.6; H. pylori test, 2.3 per 100 patient years) and a higher cost per patient (no test, $435; H. pylori test, $556). The incremental cost attributable to the H. pylori screening strategy to prevent a symptomatic and complicated ulcer was $16 805 and $31 842, respectively. The clinical and cost-effectiveness advantage of H. pylori screening improved as patients’ ulcer risk increased or the protective effect of H. pylori eradication was enhanced. Conclusions: Based upon the available evidence, H. pylori screening has the potential to reduce NSAID-related adverse events for average-risk patients at an incremental cost. Until controlled investigations definitively quantify the effect of H. pylori eradication on clinically significant NSAID-related adverse events, a compelling argument can be made for H. pylori testing for chronic NSAID users at increased risk of ulcer disease. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the efficacy of lansoprazole, clarithromycin, and metronidazole (LCM) administered twice daily for 7 days. Because there is growing concern about the development of metronidazole-resistant H. pylori (HP) strains, we also tested a novel regimen consisting of lansoprazole, clarithromycin, and bismuth subsalicylate (LCB). Methods: Patients with active HP infection and peptic ulcer, a history of peptic ulcer, or nonulcer dyspepsia were randomized to either lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d, or lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and bismuth subsalicylate 524 mg b.i.d. (LCB) for 7 days. Compliance and side effects were recorded by using a diary. Results: "Per protocol" eradication with LCM was achieved in 41 of 47 (87%). By using "intention to treat" analysis, LCM eradicated HP infection in 43 of 53 patients (81%). By using "per protocol" analysis, LCB eradicated HP infection in 40 of 47 patients (85%). On an "intention to treat" basis, LCB led to HP eradication in 42 of 52 (81%). The most common significant side effects observed with LCM were altered taste (39%) and abdominal pain (19%). With LCB, the most common significant side effects were altered taste (23%) and dark stools (23%). Conclusions: LCB for 7 days was as effective in eradicating HP infection as a 7-day course of LCM. Further studies evaluating the role of bismuth compounds in proton-pump inhibitor based triple therapy are warranted. Such therapy may have particular importance in areas where high metronidazole resistance is a concern. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effect of lansoprazole and high dose ranitidine on the accuracy of the 14C-urea breath test (UBT). Using intragastric pH recordings, we correlated the effect of these agents on the UBT with their potency of gastric acid suppression. Methods: Patients with active Helicobacter pylori infection underwent a baseline UBT before receiving 14 days of lansoprazole (30 mg/day) or ranitidine (300 mg b.i.d.). During therapy, patients were asked to undergo 24-h intragastric pH monitoring. Repeat breath testing was performed 1 day after completion of the study drugs. If the UBT was equivocal or negative (14CO2 excretion was < 200 dpm), further UBTs were completed until the 14CO2 excretion was > 200 dpm. Results: Thirteen patients received lansoprazole. Eight of thirteen patients developed a negative or equivocal UBT. All patients had 14CO2 excretion > 200 dpm 5 days after the cessation of lansoprazole. Eleven patients received ranitidine. Ranitidine led to equivocal or false negative UBTs in 2 of 11 cases. This effect resolved within 5 days of stopping ranitidine. Intragastric pH recordings revealed that the patients who experienced the most profound gastric acid suppression were those that developed equivocal or false negative UBTs. Conclusions: Lansoprazole significantly affected the accuracy of the UBT, causing equivocal or false negative results in 61%. High dose ranitidine affected the breath test in only 18%. The ability of these drugs to suppress gastric acid secretion predicted those patients who developed equivocal or false-negative UBTs. The effect on the accuracy of the UBT resolved within 5 days of drug cessation. [ABSTRACT FROM AUTHOR]

Objectives: Gastrointestinal symptoms, particularly pyrosis, complicate nonsteroidal anti-inflammatory drug (NSAID) use. NSAIDs cause esophageal injury, and H2 blockers are often prescribed for, and successfully control, NSAID-related symptoms. To determine whether NSAIDs can induce gastroesophageal reflux, we studied the effect of a commonly used NSAID, naproxen, on reflux parameters and esophageal function. Methods: Nine healthy volunteers (five males, four females, age 23-34 yr) were studied. After basal measurements were taken, the subjects randomly received naproxen 500 mg p.o. b.i.d. or placebo for 1 wk. On day 6, the subjects underwent esophageal manometry with a water-perfused system and Dent sleeve. Body pressures, contraction velocity, and duration of contraction were recorded in the distal 7 cm of the esophagus. The lower esophageal sphincter pressure (LESP) and number of transient relaxations (TLESRs) were monitored. This was followed by 24-h pH monitoring. The subjects then crossed over to the other drug after a minimum 14-day wash-out period. Results: No subject experienced any GI symptoms during the study. One subject developed reflux-induced symptoms a few months after completing the study and was excluded from the analysis. The total fraction of time (pH < 4) was 4.9 ± 1.0% in the basal state, 5.5 ± 1.4% on placebo, and 5.4 ± 1.5% on naproxen. These differences were not significant. The number of reflux episodes and the esophageal clearance time were not affected by naproxen. The LESP in the basal state was 32.1 ± 5.6 mm Hg, 32.3 ± 4.2 mm Hg on placebo, and 29.9 ± 3.3 mm Hg on naproxen (p = NS). The number of TLESRs per 30 minutes in the basal state was 3.5 ± 0.9, 4.6 ± 1.2 on placebo, and 5.8 ± 1.0 on naproxen (p = NS). The speed and duration of contractions were not affected by naproxen. The excluded subject had... [ABSTRACT FROM AUTHOR]

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers. AIMS: To assess whether the somatostatin analogue octreotide prevents NSAID induced mucosal gastrointestinal damage in both animals and humans. The effect of octreotide on neutrophil adhesion to the endothelium was also evaluated. METHODS: Male Sprague-Dawley rats were pretreated either with saline (0.3 ml subcutaneously) or octreotide (0.001-1 ng/kg subcutaneously). After 30 minutes gastric ulcers were induced by the intragastric application of NSAIDs (20 mg/kg indomethacin, 200 mg/kg aspirin, 200 mg/kg ibuprofen, or 50 mg/kg diclofenac). Four hours later the rats were killed and gastric mucosal lesions were assessed by computed planimetry. To determine whether octreotide could prevent indomethacin induced injury in humans, 20 healthy volunteers were evaluated in a double blind, placebo controlled study. RESULTS: Octreotide prevented NSAID induced gastric mucosal lesions (p < 0.05). The dose response curve was U shaped and the most effective dose was 0.1 ng/kg. Leucocyte adherence in submucosal venules of the stomach was evaluated by in vivo microscopy. Octreotide (0.1 ng/kg subcutaneously) prevented indomethacin (20 mg/kg intragastric) induced leucocyte adherence in gastric submucosal venules (p < 0.05). Healthy human volunteers received 50 mg indomethacin orally thrice a day concomitantly with either an identical placebo or 0.01 microgram, 0.1 microgram, or 1 microgram octreotide subcutaneously thrice a day for three days. Injury was assessed by endoscopy. There was a negative correlation between the octreotide dose and injury score (p < 0.03 for gastric injury, p < 0.001 for duodenal injury). CONCLUSIONS: Octreotide protects the stomach from NSAID induced gastric injury, probably via its ability to reduce NSAID induced neutrophilic adhesion to the microvasculature. Octreotide also ameliorated indomethacin induced gastric and duodenal injury in humans. [ABSTRACT FROM PUBLISHER]

TGF-α inhibits gastric acid secretion andmay play an important role in epithelial repair. Wequantitated regional levels of TGF-α in the humanproximal gastrointestinal tract and determined whether they are affected by acid suppression oraspirin-induced injury. Ten healthy volunteers werestudied. After baseline endoscopy with biopsy, fiverandomly received no treatment, aspirin, omeprazole, orcimetidine for one week. Endoscopy was repeated and priorunhealed biopsy sites quantitated. TGF-α levelswere measured by RIA. Five additional subjects thencompleted an extended protocol of three weeks' duration. All subjects were free of H. pylori infection.TGF-α levels in the antrum, 34.76 ± 5.54 pgTGF-α/μg DNA were threefold higher than in thegastric body and duodenum (11.03 ± 2.60 and 10.41± 1.64 respectively, P < 0.01). The number of unhealed sites inthe aspirin group was significantly greater than in thecontrol or acid inhibition groups; however, TGF-αlevels were not different from the surrounding mucosa. TGF-α increased in the controls afterbiopsy; the increase was significant in the body at week2 only. Aspirin significantly increased TGF-αlevels in the gastric body and duodenum after one week. The rise in antral TGF-α appeared delayedand blunted by the aspirin treatment compared tocontrol. There was no relationship between the number ofvisible biopsy sites, degree of aspirin-induced injury, and the TGF-α level. Acid suppression wasassociated with a significant increase in TGF-α inthe gastric body and antrum at one week. Immunochemicalstaining did not demonstrate differences inproliferation in any treatment group compared to controls.TGF-α levels vary by location in the proximalgastrointestinal tract, with significantly greaterlevels in the antrum. After biopsy, TGF-α levelsincrease; short-term aspirin and acid inhibitors modulatethis effect. Aspirin significantly impaired the healingof endoscopic biopsies in the antrum; however, this wasnot associated with changes in TGF-α levels. TGF-α levels did not change in responseto acid secretory state. Further studies of mucosallevels of TGF-α in response to aspirin-inducedinjury in humans appear warranted. [ABSTRACT FROM AUTHOR]

The article focuses on the cardiovascular and chemopreventive benefits of aspirin. Aspirin has been studied as a means of primary and secondary prevention of cardiovascular events. The role of aspirin as a potential chemopreventive agent for colorectal and other gastrointestinal cancers continues to evolve, supported by the results of epidemiological observations and randomized-controlled studies. In those receiving non-steroidal anti-inflammatory drugs (NSAIDs), the concurrent use of aspirin substantially increases the risk for gastrointestinal events. Because the evidence for colorectal cancer prevention comes only from secondary prevention trials, it is premature to recommend the use of aspirin or any NSAID as a primary cancer chemopreventive strategy.

The article presents the authors' response to a commentary on the findings of their study on the risk factors for gastrointestinal bleeding in users of non-steroidal anti-inflammatory drugs (NSAIDs). They state that small bowel lesions linked with the use of NSAID is a new area of interest and have a clinical relevance. They add that there must be further studies to better define the mechanisms and factors the decrease of haemoglobin linked with NSAID use.

An abstract of the article "Esomeprazole Maintains Control of Upper GI Symptoms in Patients on NSAID Therapy," by J. M. Scheiman, N. Yeomans, C. J. Hawkey, N. J. Talley, and J. Sung R. Jones is presented.

An abstract of the article "Esomeprazole Relieves NSAID-Associated Upper GI Symptoms in Patients Taking Either Continuous Cox-2 Selective NSAIDs or Non-Selective NSAIDs," by N. Yeomans, J. Scheiman, J. Sung, N. J. Talley, R. Jones and C. J. Hawkey is presented.

An abstract of the article "Esomeprazole Reduces Gastric and Duodenal Ulcer Development Among High Risk NSAID Users," by J.M. Schieman and colleagues is presented.