Risk factors associated with a decrease ≥2 g/dL in haemoglobin and/or ≥10% haematocrit in osteoarthritis patients taking celecoxib or a nonselective NSAID plus a PPI in a large randomised controlled trial (CONDOR).

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.

Haemoglobin decreases in NSAID users over time: an analysis of two large outcome trials.

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.

Cost-effectiveness analysis: cardiovascular benefits of proton pump inhibitor co-therapy in patients using aspirin for secondary prevention.

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 cost-effectiveness 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 10000 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 $19000 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.

Prophylactic 5-Fr pancreatic duct stents are superior to 3-Fr stents: a randomized controlled trial.

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.

Mesenteric venous collateral vessels mimicking cystic pancreatic neoplasm.

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.

Underutilization of gastroprotection for at-risk patients undergoing percutaneous coronary intervention: Spain compared with the United States.

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.

Extraribosomal functions associated with the C terminus of the 37/67 kDa laminin receptor are required for maintaining cell viability.

The 37/67 kDa laminin receptor (LAMR) is a multifunctional protein, acting as an extracellular receptor, localizing to the nucleus, and playing roles in rRNA processing and ribosome assembly. LAMR is important for cell viability; however, it is unclear which of its functions are essential. We developed a silent mutant LAMR construct, resistant to siRNA, to rescue the phenotypic effects of knocking down endogenous LAMR, which include inhibition of protein synthesis, cell cycle arrest, and apoptosis. In addition, we generated a C-terminal-truncated silent mutant LAMR construct structurally homologous to the Archaeoglobus fulgidus S2 ribosomal protein and missing the C-terminal 75 residues of LAMR, which displays more sequence divergence. We found that HT1080 cells stably expressing either silent mutant LAMR construct still undergo arrest in the G1 phase of the cell cycle when treated with siRNA. However, the expression of full-length silent mutant LAMR rescues cell viability, whereas the expression of the C-terminal-truncated LAMR does not. Interestingly, we also found that both silent mutant constructs restore protein translation and localize to the nucleus. Our findings indicate that the ability of LAMR to regulate viability is associated with its C-terminal 75 residues. Furthermore, this function is distinct from its role in cell proliferation, independent of its ribosomal functions, and may be regulated by a nonnuclear localization.

Changing perceptions and practices regarding aspirin, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs among US primary care providers.

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.

Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report.

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.

Efficacy of esomeprazole for resolution of symptoms of heartburn and acid regurgitation in continuous users of non-steroidal anti-inflammatory drugs.

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

Review article: acid-related disease--what are the unmet clinical needs?

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.

Gastroenterologists utilize the referral for EGD to enhance colon cancer screening more effectively than primary care physicians.

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.

Primary care physician perceptions of non-steroidal anti-inflammatory drug and aspirin-associated toxicity: results of a national survey.

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.

Effect of cyclooxygenase-2 inhibition on human Helicobacter pylori gastritis: mechanisms underlying gastrointestinal safety and implications for cancer chemoprevention.

UNLABELLED: 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.

Role of endoscopic ultrasonography in screening and treatment of pancreatic endocrine tumours in asymptomatic patients with multiple endocrine neoplasia type 1.

BACKGROUND: Patients with multiple endocrine neoplasia (MEN) type 1 risk premature death from pancreatic endocrine tumours (PETs). Endoscopic ultrasonography (EUS) is the most sensitive imaging modality for small PETs. A screening and therapeutic approach for asymptomatic patients is delineated in which EUS plays a pivotal role. METHODS: This was a retrospective study of 15 patients with MEN-1 but with no symptoms of a PET. All patients underwent serum hormone measurement, including gastrin, and EUS. The findings were used to facilitate operative treatment. RESULTS: Six of 15 patients had a normal basal gastrin level and nine had a raised level. EUS demonstrated PETs in 14 patients and identified multiple lesions in 12. There was no predictive relationship between age or gastrin level and the number or size of PETs discovered. Thirteen patients have undergone enucleation or resection of PETs and two remain under observation. Nine of the 13 patients underwent transduodenal exploration to excise gastrinoma(s). One patient had lymph node metastases found at operation. There was no death. Self-limiting pancreatic fistula in five patients and biliary fistula in one. CONCLUSION: Early and aggressive screening using EUS identifies PETs in asymptomatic patients with MEN-1. Detection of tumours at an early stage, before the development of symptoms, lymph node metastases or liver metastases, may facilitate prompt surgical intervention and improve prognosis.

Reappraisal of non-invasive management strategies for uninvestigated dyspepsia: a cost-minimization analysis.

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.

Can endoscopic ultrasound or magnetic resonance cholangiopancreatography replace ERCP in patients with suspected biliary disease? A prospective trial and cost analysis.

OBJECTIVES: ERCP is the gold standard for pancreaticobiliary evaluation but is associated with complications. Less invasive diagnostic alternatives with similar capabilities may be cost-effective, particularly in situations involving low prevalence of disease. The aim of this study was to compare the performance of endoscopic ultrasound (EUS) with magnetic resonance cholangiopancreatography (MRCP) and ERCP in the same patients with suspected extrahepatic biliary disease. The economic outcomes of EUS-, MRCP-, and ERCP-based diagnostic strategies were evaluated. METHODS: Prospective cohort study of patients referred for ERCP with suspected biliary disease. MRCP and EUS were performed within 24 h before ERCP. The investigators were blinded to the results of the alternative imaging studies. A cost-utility analysis was performed for initial ERCP, MRCP, and EUS strategies for these patients. RESULTS: A total of 30 patients were studied. ERCP cholangiogram failed in one patient, and another patient did not complete MRCP because of claustrophobia. The final diagnoses (N = 28) were CBD stone (mean = 4 mm; range = 3-6 mm) in five patients; biliary stricture in three patients, and normal biliary tree in 20. Two patients had pancreatitis after therapeutic ERCP, one after precut sphincterotomy followed by a normal cholangiogram. EUS was more sensitive than MRCP in the detection of choledocolithiasis (80% vs 40%), with similar specificity. MRCP had a poor specificity and positive predictive value for the diagnosis of biliary stricture (76%/25%) compared to EUS (100%/100%), with similar sensitivity. The overall accuracy of MRCP for any abnormality was 61% (95% CI = 0.41-0.78) compared to 89% (CI = 0.72-0.98) for EUS. Among those patients with a normal biliary tree, the proportion correctly identified with each test was 95% for EUS and 65% for MRCP (p < 0.02). The cost for each strategy per patient evaluated was $1346 for ERCP, $1111 for EUS, and $1145 for MRCP. CONCLUSIONS: In this patient population with a low disease prevalence, EUS was superior to MRCP for choledocholithiasis. EUS was most useful for confirming a normal biliary tree and should be considered a low-risk alternative to ERCP. Although MRCP had the lowest procedural reimbursement, the initial EUS strategy had the greatest cost-utility by avoiding unnecessary ERCP examinations.

Aspirin as an adjunct to screening for prevention of sporadic colorectal cancer. A cost-effectiveness analysis.

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.

First cut, then blend: an electrocautery technique affecting bleeding at sphincterotomy.

BACKGROUND AND STUDY AIMS: The use of pure cut electrocautery current for endoscopic sphincterotomy lowers pancreatitis rates following endoscopic retrograde cholangiopancreatography (ERCP), but at the expense of greater localized bleeding which partially obscures the endoscopic view. We hypothesized that localized bleeding could be decreased by using blended current at the end of the sphincterotomy, without losing the benefit associated with pure cut current of lower post-ERCP pancreatitis benefit. PATIENTS AND METHODS: Patients undergoing sphincterotomy were randomly allocated to receive pure cut current alone or a sequential combination of pure cut then blended current. In the sequential combination patients, the first 75 - 80 % of the sphincterotomy was done using pure cut current at 30 W and the remainder completed at a blend 2 setting (pure cut plus coagulation current), also at 30 W. RESULTS: 142 patients were enrolled in the study. No statistical difference was noted between the two groups in the rates of overall pancreatitis or bleeding requiring transfusion. When comparing visible bleeding rates (more than a few drops), we found that there was significantly more bleeding (P < 0.05) in the pure cut group (31/75, 41 %) at the time of sphincterotomy compared with the sequential combination group (16/67, 23 %). CONCLUSIONS: A sequential combination of pure cut and blended current for sphincterotomy caused less visible bleeding than pure cut alone. This occurred without a change in the rate of post-ERCP pancreatitis.